Haemostasis and Clotting Mechanisms
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Questions and Answers

What is the main purpose of haemostasis?

  • To prevent and control bleeding while maintaining blood fluidity (correct)
  • To increase blood viscosity after injury
  • To enhance blood flow to injured areas
  • To promote excessive bleeding during injury

Which elements form the clotting trilogy?

  • Blood vessels, platelets, and coagulation factors (correct)
  • Red blood cells, white blood cells, and plasma
  • Endothelial cells, fibroblasts, and growth factors
  • Vasoconstrictors, platelets, and fibrinolytic factors

What is primary haemostasis?

  • The maintenance of normal blood flow during injury
  • The initial response to vessel injury involving a platelet plug (correct)
  • The interaction of fibrin strands to strengthen a clot
  • The process that removes clots after vessel healing

What role does fibrin play in secondary haemostasis?

<p>It reinforces and stabilizes the primary clot (A)</p> Signup and view all the answers

What is fibrinolysis?

<p>The process of degrading the fibrin clot once healing is complete (A)</p> Signup and view all the answers

Which layer of the blood vessel wall is responsible for regulating vascular tone?

<p>Media (B)</p> Signup and view all the answers

What is the primary function of the adventitia layer in blood vessels?

<p>To provide structural support and protection (A)</p> Signup and view all the answers

What is the role of the intima in blood vessels?

<p>To provide a smooth lining for blood flow (D)</p> Signup and view all the answers

What initiates the extrinsic pathway of the coagulation cascade?

<p>Tissue factor binding to proenzyme factor VII (D)</p> Signup and view all the answers

What is the primary role of the TF-FVIIa complex in coagulation?

<p>Activates factor X (A)</p> Signup and view all the answers

What does factor Xa do in the context of the extrinsic pathway?

<p>Converts prothrombin to thrombin (C)</p> Signup and view all the answers

Which component is NOT part of the extrinsic prothrombinase complex?

<p>Vitamin K (D)</p> Signup and view all the answers

What is the function of calcium ions (Ca²⁺) in the coagulation cascade?

<p>Facilitate the formation of complexes (C)</p> Signup and view all the answers

What role does factor Va (FVa) serve in the coagulation process?

<p>Acts as a co-factor for factor Xa (C)</p> Signup and view all the answers

Which of the following is a natural inhibitor of the coagulation process?

<p>Antithrombin (A)</p> Signup and view all the answers

How does protein C act as an inhibitor in coagulation?

<p>Inactivates factors Va and VIIIa (A)</p> Signup and view all the answers

What is the main storage location of vitamin B12 in the body?

<p>Liver (D)</p> Signup and view all the answers

What characterizes megaloblastic anemia?

<p>Delayed nuclear maturation of erythroblasts (A)</p> Signup and view all the answers

What is a major cause of megaloblastic anemia?

<p>Deficiencies of vitamin B12 or folate (A)</p> Signup and view all the answers

What occurs during the amplification stage of coagulation?

<p>Generation of additional thrombin (C)</p> Signup and view all the answers

What is the main role of thrombin in the coagulation process?

<p>Promotes platelet activation and fibrinogen conversion (D)</p> Signup and view all the answers

What is the primary source of vitamin B12 for animals?

<p>Microbial synthesis (C)</p> Signup and view all the answers

How is a factor assay result interpreted?

<p>Using a reference curve of standard human plasma (A), Using a reference curve of pooled normal plasma (D)</p> Signup and view all the answers

Which type of inhibitors are known to lose activity over time?

<p>Time-dependent inhibitors (A)</p> Signup and view all the answers

What is a Bethesda Unit (BU) used to measure?

<p>The strength of an inhibitor in plasma (C)</p> Signup and view all the answers

What is the purpose of the Ristocetin Cofactor assay?

<p>To determine the functional activity of vWF (D)</p> Signup and view all the answers

What symptoms are commonly associated with bleeding disorders?

<p>Epistaxis and heavy menstrual bleeding (A)</p> Signup and view all the answers

In which scenario does a deficiency of a specific factor manifest during a factor assay?

<p>The plasma cannot compensate for the absent factor (D)</p> Signup and view all the answers

Which of the following factors are vitamin K-dependent?

<p>Factors II, VII, IX, and X (D)</p> Signup and view all the answers

What is the role of gamma-carboxylation in the vitamin K cycle?

<p>It allows for calcium ion binding in proteins (D)</p> Signup and view all the answers

What is a common cause of vitamin K deficiency?

<p>Malabsorption of fat-soluble vitamins (B)</p> Signup and view all the answers

Which conditions are classified as acquired bleeding disorders?

<p>Vitamin K deficiency and liver disease (B)</p> Signup and view all the answers

How does vitamin K deficiency affect clotting times?

<p>It prolongs PT and APTT (A)</p> Signup and view all the answers

What type of assay is used to detect Factor VIII inhibitors?

<p>Bethesda Assay (B)</p> Signup and view all the answers

What happens to vitamin K-dependent factors in the body during vitamin K deficiency?

<p>They remain stable but ineffective (D)</p> Signup and view all the answers

What are the three main components of haemostatic mechanisms?

<p>Primary haemostasis, secondary haemostasis, and fibrinolysis (A)</p> Signup and view all the answers

What is the primary role of von Willebrand factor (vWF) in haemostasis?

<p>To facilitate platelet adhesion to injury sites (B)</p> Signup and view all the answers

How is the platelet plug primarily formed?

<p>Through the formation of fibrin bridges between platelets (C)</p> Signup and view all the answers

What initiates the process of secondary haemostasis?

<p>The exposure of subendothelial collagen (C)</p> Signup and view all the answers

Which statement best describes thromboxane A2's role in procoagulation?

<p>It binds to platelet receptors, promoting aggregation (A)</p> Signup and view all the answers

Where is von Willebrand factor (vWF) primarily produced?

<p>In Weibel-Palade bodies of endothelial cells (A)</p> Signup and view all the answers

What benign role does protein C serve in anticoagulation?

<p>It inactivates coagulation factors Va and VIIIa (A)</p> Signup and view all the answers

How is fibrinolysis inhibited during the procoagulation process?

<p>By the activity of plasminogen activator inhibitor-1 (PAI-1) (D)</p> Signup and view all the answers

What is the role of tissue factor in the coagulation process?

<p>It initiates the coagulation cascade (A)</p> Signup and view all the answers

Which factor is crucial for the localized activation of coagulation factors?

<p>Calcium ions (Ca²⁺) (B)</p> Signup and view all the answers

What is the structure of von Willebrand factor (vWF)?

<p>A large multimeric glycoprotein (D)</p> Signup and view all the answers

How does protein S function in the anticoagulation pathway?

<p>It acts as a co-factor for protein C (C)</p> Signup and view all the answers

Why is it important for the coagulation factor activation to occur at membrane surfaces?

<p>It prevents the activation of all circulating factors simultaneously (C)</p> Signup and view all the answers

What is indicated by increased levels of serum methylmalonic acid (MMA)?

<p>Vitamin B12 deficiency (A)</p> Signup and view all the answers

What do normal levels of both methylmalonic acid and homocysteine suggest?

<p>Clinically significant B12 deficiency is ruled out (B)</p> Signup and view all the answers

What is the gold standard test for determining the cause of B12 deficiency?

<p>Schilling test (D)</p> Signup and view all the answers

What is the first step in the Schilling test?

<p>Giving an intramuscular injection of vitamin B12 (C)</p> Signup and view all the answers

Which of these is a main cause of B12 deficiency?

<p>Autoimmune attack on gastric mucosa (C)</p> Signup and view all the answers

Why is folic acid often administered with B12 treatment?

<p>To address potential folate deficiency (C)</p> Signup and view all the answers

What is a possible consequence of pancreatic enzyme insufficiency?

<p>Inability of intrinsic factor to bind B12 (B)</p> Signup and view all the answers

Which condition is NOT associated with folate deficiency?

<p>Congenital lack of intrinsic factor (D)</p> Signup and view all the answers

What does a blood test showing macrocytic cells typically indicate?

<p>Vitamin B12 or folate deficiency (C)</p> Signup and view all the answers

What is the primary role of reticuloendothelial macrophages in relation to iron?

<p>Supply of iron for hemoglobin synthesis (D)</p> Signup and view all the answers

Which of the following is NOT a mechanism by which anemia can occur?

<p>Increased red blood cell formation (A)</p> Signup and view all the answers

What is a common factor in cases of folate deficiency?

<p>Long-term use of certain antibiotics (A)</p> Signup and view all the answers

What is the primary function of transferrin in the body?

<p>To deliver iron to developing erythroid precursors (D)</p> Signup and view all the answers

Which vitamin is primarily associated with the absorption issues identified in the Schilling test?

<p>Vitamin B12 (A)</p> Signup and view all the answers

What dietary inclusions are recommended for increasing B12 intake?

<p>Red meat, fish, and dairy (C)</p> Signup and view all the answers

Where is the majority of stored iron primarily found in the body?

<p>In liver hepatocytes (D)</p> Signup and view all the answers

What is the primary mechanism by which dietary iron is absorbed in mammals?

<p>Via the duodenal epithelium of the small intestine (D)</p> Signup and view all the answers

How is ferric iron (Fe³⁺) converted to ferrous iron (Fe²⁺) for absorption?

<p>Through enzymatic reduction by duodenal cytochrome b (A)</p> Signup and view all the answers

Which of the following statements regarding hepcidin is accurate?

<p>It is the master regulator of iron metabolism (B)</p> Signup and view all the answers

What effect does a transferrin saturation of less than 20% indicate?

<p>Iron deficiency (A)</p> Signup and view all the answers

What factors are assessed in an extrinsic pathway factor assay?

<p>Factors II, VII, and X (B)</p> Signup and view all the answers

Which factor does NOT influence hepcidin synthesis?

<p>Exercise (B)</p> Signup and view all the answers

What does it suggest if both PT and APTT are prolonged?

<p>A defect in the common clotting pathway (C)</p> Signup and view all the answers

What are the characteristic features observed in a blood film of an individual with iron deficiency anemia?

<p>Microcytic and hypochromic red blood cells (C)</p> Signup and view all the answers

How is the total iron-binding capacity (TIBC) measured?

<p>By saturating transferrin with a predetermined amount of iron (D)</p> Signup and view all the answers

What is the primary diagnostic application of a D-dimer test?

<p>To exclude thromboembolic events (D)</p> Signup and view all the answers

What condition can lead to a prolonged APTT?

<p>Factor deficiencies (C)</p> Signup and view all the answers

What is the standard oral treatment regimen for iron deficiency anemia (IDA)?

<p>200 mg ferrous sulfate taken twice daily (B)</p> Signup and view all the answers

What does the Perls stain test specifically assess?

<p>Haemosiderin stores in bone marrow (A)</p> Signup and view all the answers

How is thrombin time (TT) prolonged?

<p>In patients with heparin therapy (B)</p> Signup and view all the answers

What happens to zinc protoporphyrin levels in iron deficiency anemia?

<p>They will increase (B)</p> Signup and view all the answers

What does a normal PT with an abnormal APTT suggest?

<p>A defect in the intrinsic pathway (D)</p> Signup and view all the answers

What is a limitation of the bleeding time test?

<p>It is operator-dependent (C)</p> Signup and view all the answers

Which of the following is NOT a form of stored iron in the body?

<p>Transferrin (A)</p> Signup and view all the answers

Which mechanism primarily leads to iron overload in the body?

<p>Increased dietary intake of iron (C)</p> Signup and view all the answers

What does a mixing study indicate if the APTT corrects?

<p>A factor deficiency (C)</p> Signup and view all the answers

What is required for the Clauss fibrinogen test?

<p>A reference plasma with known fibrinogen levels (C)</p> Signup and view all the answers

In which condition are D-dimers raised?

<p>Thromboembolic diseases (B)</p> Signup and view all the answers

What condition is indicated by a prolonged APTT and normal PT?

<p>Intrinsic pathway defect (D)</p> Signup and view all the answers

What treatment options are available for patients who cannot tolerate or are unresponsive to oral iron?

<p>Parenteral iron treatment via IV or IM (B)</p> Signup and view all the answers

What indicates the presence of lupus anticoagulant when performing a mixing study?

<p>No correction in APTT (D)</p> Signup and view all the answers

What is the function of a Clauss fibrinogen test?

<p>To measure fibrinogen levels in plasma (C)</p> Signup and view all the answers

What is a significant risk associated with parenteral iron treatment?

<p>High cost and potential side effects (A)</p> Signup and view all the answers

When is a blood transfusion warranted for patients with iron deficiency anemia (IDA)?

<p>For patients with symptomatic anemia unresponsive to iron therapy (A)</p> Signup and view all the answers

What factor deficiencies cannot be detected by APTT?

<p>Factor VII and XIII (B)</p> Signup and view all the answers

What indicates a positive response to IDA treatment?

<p>Hemoglobin returns to normal after 2-4 months (A)</p> Signup and view all the answers

What does a dimorphic blood film signify during treatment for IDA?

<p>Response to therapy with mixed cell morphology (A)</p> Signup and view all the answers

What does primary haemostatic testing primarily assess?

<p>Platelet function (A)</p> Signup and view all the answers

What substance do chief cells in the stomach secrete that is crucial for protein digestion?

<p>Pepsin (A)</p> Signup and view all the answers

Which test is commonly used in secondary haemostatic testing?

<p>Prothrombin Time (PT) (A)</p> Signup and view all the answers

What is critical in sample collection for coagulation tests?

<p>Adding sodium citrate as an anticoagulant (A)</p> Signup and view all the answers

What happens to vitamin B12 after it binds to R-protein in the stomach?

<p>It remains unabsorbed until digestion of R-protein occurs. (D)</p> Signup and view all the answers

What happens if poor venepuncture technique is used during sample collection?

<p>Sample contamination can introduce tissue factor (B)</p> Signup and view all the answers

Why is intrinsic factor (IF) essential for vitamin B12 absorption?

<p>B12-IF complexes are required for absorption in the intestines. (B)</p> Signup and view all the answers

What occurs to vitamin B12 after being absorbed in the terminal ileum?

<p>It binds to transcobalamin for transport. (C)</p> Signup and view all the answers

What do platelet function assays evaluate?

<p>The process of platelet adhesion and aggregation (D)</p> Signup and view all the answers

What is the typical sample volume needed for platelet function assays?

<p>800 µL of whole blood in sodium citrate (D)</p> Signup and view all the answers

What percentage of vitamin B12 can be absorbed in the absence of intrinsic factor?

<p>1% (A)</p> Signup and view all the answers

Which condition is NOT evaluated by the prothrombin time (PT) test?

<p>Fibrinogen levels (C)</p> Signup and view all the answers

How does folate deficiency develop compared to vitamin B12 deficiency?

<p>More rapidly due to a faster turnover rate. (D)</p> Signup and view all the answers

What is a hallmark feature of megaloblastic anaemia observed in neutrophils?

<p>Hypersegmented neutrophils (D)</p> Signup and view all the answers

How is the INR (International Normalized Ratio) calculated?

<p>Patient PT divided by normal PT multiplied by ISI (A)</p> Signup and view all the answers

What does an INR greater than 5.0 indicate?

<p>High risk of bleeding requiring urgent assessment (A)</p> Signup and view all the answers

What complication can arise due to a deficiency in transcobalamin despite adequate vitamin B12 intake?

<p>Megaloblastic anaemia (A)</p> Signup and view all the answers

What happens to folate once it enters the cell?

<p>It is converted to folate polyglutamates. (B)</p> Signup and view all the answers

What causes hypersegmented neutrophils in megaloblastic anaemia?

<p>Delayed DNA synthesis with intact segmentation mechanism. (A)</p> Signup and view all the answers

How are serum iron and ferritin levels typically affected in megaloblastic anaemia?

<p>Both are normal. (D)</p> Signup and view all the answers

What is macrocytosis and how is it related to B12 deficiency?

<p>Enlarged red blood cells indicating early B12 deficiency. (D)</p> Signup and view all the answers

Why is there an increase in serum unconjugated bilirubin in megaloblastic anaemia?

<p>Breakdown of marrow cells leads to increased bilirubin. (A)</p> Signup and view all the answers

What happens to serum homocysteine levels in individuals with both B12 and folate deficiency?

<p>They increase significantly. (D)</p> Signup and view all the answers

What is the first clotting factor to be reduced in liver disease?

<p>Factor VII (FVII) (C)</p> Signup and view all the answers

What condition is characterized by the depletion of clotting factors and platelets due to ongoing clot formation?

<p>Disseminated Intravascular Coagulation (DIC) (D)</p> Signup and view all the answers

What is considered massive hemorrhage in terms of blood loss within three hours?

<p>Blood loss &gt;50% of circulating volume (D)</p> Signup and view all the answers

What is the main consequence of untreated Disseminated Intravascular Coagulation (DIC)?

<p>Increased risk of organ failure (C)</p> Signup and view all the answers

Which factor is contained in cryoprecipitate?

<p>Factor XIII (A)</p> Signup and view all the answers

What triggers the production of thrombopoietin affecting platelet count?

<p>Liver function (B)</p> Signup and view all the answers

How is Octaplas primarily different in terms of coagulation protein content?

<p>Decreased Protein S levels (D)</p> Signup and view all the answers

Which condition can result from a deficiency of Factor VIII?

<p>Hemophilia A (D)</p> Signup and view all the answers

What is the typical dosage of Fresh Frozen Plasma (FFP) administered?

<p>15 mL/kg body weight (A)</p> Signup and view all the answers

What is a potential risk of transfusion during massive hemorrhage?

<p>Bleeding to death (D)</p> Signup and view all the answers

What percentage of Haemophilia A patients develop inhibitors?

<p>14% (B)</p> Signup and view all the answers

In which condition do autoantibodies commonly develop against clotting proteins?

<p>Autoimmune conditions (A)</p> Signup and view all the answers

Which factor is deficient in Hemophilia C?

<p>Factor XI (A)</p> Signup and view all the answers

What storage condition is required for thawed Fresh Frozen Plasma (FFP)?

<p>At 4°C for 24 hours (B)</p> Signup and view all the answers

What is the primary site of haemopoiesis in adults?

<p>Axial skeleton bone marrow (A)</p> Signup and view all the answers

Which of the following is NOT a stage of erythropoiesis?

<p>Megakaryocyte (C)</p> Signup and view all the answers

What regulates the process of erythropoiesis?

<p>Erythropoietin (A)</p> Signup and view all the answers

How long does it take for a red blood cell to develop from a stem cell?

<p>7 days (A)</p> Signup and view all the answers

Which treatment is used to increase levels of von Willebrand factor?

<p>Desmopressin (DDAVP) (B)</p> Signup and view all the answers

Which of the following is a symptom of platelet disorders?

<p>Nosebleeds (D)</p> Signup and view all the answers

What are the stages of thrombopoiesis?

<p>Megakaryoblast, Promegakaryocyte, Megakaryocyte, Platelets (C)</p> Signup and view all the answers

What characterizes von Willebrand Disease?

<p>Autosomal dominant bleeding disorder (D)</p> Signup and view all the answers

What might increase the risk of infection and thrombosis in haemophilia treatment?

<p>Portacath access (D)</p> Signup and view all the answers

Which type of vWD involves total vWF deficiency?

<p>Type 3 (C)</p> Signup and view all the answers

What is the role of von Willebrand factor (vWF) in blood coagulation?

<p>Protects Factor VIII from degradation (C)</p> Signup and view all the answers

What is a common cause of quantitative platelet disorders?

<p>Decreased production of platelets (C)</p> Signup and view all the answers

Which growth factor is responsible for stimulating granulopoiesis?

<p>Granulocyte-Colony Stimulating Factor (G-CSF) (D)</p> Signup and view all the answers

What is the primary outcome of myelofibrosis?

<p>Bone marrow is replaced by fibrous tissue. (C)</p> Signup and view all the answers

What triggers the production of erythropoietin (EPO)?

<p>Hypoxia in the kidneys. (A)</p> Signup and view all the answers

Which factor is primarily responsible for stimulating platelet production?

<p>Thrombopoietin (TPO) (B)</p> Signup and view all the answers

What defines aplastic anemia?

<p>Failure of the bone marrow to produce all blood cell types. (D)</p> Signup and view all the answers

Where is thrombopoietin (TPO) primarily produced?

<p>Liver and kidneys (C)</p> Signup and view all the answers

What is the primary function of stromal cells in the bone marrow?

<p>They provide structural support and secrete growth factors. (B)</p> Signup and view all the answers

What type of cells are derived from the lymphoid lineage?

<p>B-cells (B)</p> Signup and view all the answers

Which condition is characterized by an overproduction of red blood cells?

<p>Polycythemia vera (B)</p> Signup and view all the answers

What condition results in the bone marrow producing dysfunctional blood cells?

<p>Myelodysplastic syndrome (MDS) (C)</p> Signup and view all the answers

What is the role of adhesion molecules in haemopoiesis?

<p>They facilitate interactions of stem cells with the bone marrow niche. (B)</p> Signup and view all the answers

What role does the transcription factor Hypoxia-Inducible Factor (HIF) play in EPO production?

<p>It activates genes that produce EPO in response to hypoxia. (D)</p> Signup and view all the answers

Which condition can lead to extramedullary haemopoiesis?

<p>Myelofibrosis (B)</p> Signup and view all the answers

What is the primary characteristic of leukemia?

<p>Overproduction of abnormal white blood cells. (A)</p> Signup and view all the answers

What are proplatelets?

<p>Extensions from megakaryocytes that fragment to form platelets. (D)</p> Signup and view all the answers

What factor is crucial for neutrophil production?

<p>Granulocyte-Colony Stimulating Factor (G-CSF) (B)</p> Signup and view all the answers

What is the role of the media layer in the blood vessel wall?

<p>Regulates vascular tone and blood pressure (D)</p> Signup and view all the answers

What is the main purpose of fibrinolysis?

<p>To degrade fibrin clots after healing is complete (A)</p> Signup and view all the answers

Which statement best describes primary haemostasis?

<p>It involves blood vessels, platelets, and von Willebrand factor. (D)</p> Signup and view all the answers

What prevents bleeding from occurring as a normal bodily response?

<p>Formation of a platelet plug (A)</p> Signup and view all the answers

What are the three layers of the blood vessel wall?

<p>Intima, media, adventitia (D)</p> Signup and view all the answers

How does the adventitia layer contribute to blood vessels?

<p>It provides structural support and anchors vessels. (D)</p> Signup and view all the answers

What is the significance of von Willebrand factor (vWF) in primary haemostasis?

<p>It binds platelets to damaged blood vessel sites. (A)</p> Signup and view all the answers

What event marks the transition from primary to secondary haemostasis?

<p>The interaction of coagulation factors to produce fibrin (B)</p> Signup and view all the answers

What initiates the common pathway in the coagulation cascade?

<p>The generation of thrombin (A)</p> Signup and view all the answers

What happens when the extrinsic prothrombinase complex is formed?

<p>It activates prothrombin to thrombin (B)</p> Signup and view all the answers

Which factor assists the thrombin-mediated activation of protein C?

<p>Thrombomodulin (A)</p> Signup and view all the answers

What is the result of factor XIIIa's action on fibrin?

<p>It catalyzes cross-link formation (D)</p> Signup and view all the answers

What best describes the role of the tenase complex in coagulation?

<p>To activate factor X in the intrinsic pathway (C)</p> Signup and view all the answers

Which of these substances is NOT a naturally occurring inhibitor of coagulation?

<p>Thrombomodulin (D)</p> Signup and view all the answers

What is a major cause of macrocytic anaemia?

<p>Vitamin B12 deficiency (A)</p> Signup and view all the answers

Where is intrinsic factor (IF) secreted during the absorption of vitamin B12?

<p>Stomach (D)</p> Signup and view all the answers

Which is NOT a component of the intrinsic tenase complex?

<p>Factor Xa (B)</p> Signup and view all the answers

How does vitamin B12 contribute to DNA synthesis?

<p>By serving as a co-factor for thymidine synthesis (A)</p> Signup and view all the answers

What is a characteristic feature of megaloblastic anaemia observed in the bone marrow?

<p>Asynchronous maturation of erythroblasts (A)</p> Signup and view all the answers

Why is a short-term deficiency of vitamin B12 typically not problematic for the body?

<p>The liver contains sufficient stores (C)</p> Signup and view all the answers

What does an increase in serum methylmalonic acid (MMA) indicate?

<p>B12 deficiency (A)</p> Signup and view all the answers

Which step follows confirming low serum B12 levels in the investigation of macrocytic anemia?

<p>Checking methylmalonic acid levels (C)</p> Signup and view all the answers

What role does FXIIIa play in preventing the degradation of clots?

<p>It binds to α2-antiplasmin (A)</p> Signup and view all the answers

What is the percentage of young adult vegans reported to have subnormal vitamin B12 levels?

<p>50% (C)</p> Signup and view all the answers

What is a likely cause of B12 deficiency associated with intrinsic factor?

<p>Autoimmune attack on gastric mucosa (C)</p> Signup and view all the answers

Which test is considered the gold standard for assessing B12 absorption?

<p>Schilling test (D)</p> Signup and view all the answers

What indicates a deficiency in intrinsic factor during the Schilling test?

<p>Radiolabelled B12 present in urine after Step 2 (C)</p> Signup and view all the answers

What does the presence of radiolabelled B12 in urine after administering antibiotics indicate?

<p>Bacterial overgrowth in the terminal ileum (A)</p> Signup and view all the answers

What is a primary dietary recommendation to treat B12 deficiency?

<p>Increase intake of B12-rich foods (A)</p> Signup and view all the answers

Which is a common cause of folate deficiency?

<p>Chronic digestive tract diseases (B)</p> Signup and view all the answers

What is the primary mechanism leading to the reduction in RBC formation in anemia?

<p>Bone marrow malfunction (D)</p> Signup and view all the answers

Why is folic acid often prescribed along with B12 treatment?

<p>To address concurrent folate deficiency (B)</p> Signup and view all the answers

How is iron primarily supplied for new red blood cell synthesis?

<p>Reticuloendothelial macrophages (A)</p> Signup and view all the answers

What is an indication of significant B12 deficiency in terms of MMA and homocysteine levels?

<p>High levels of both MMA and homocysteine (D)</p> Signup and view all the answers

What is the primary role of transferrin in the body?

<p>To deliver iron to developing erythroid precursors and other tissues (C)</p> Signup and view all the answers

How is dietary non-haem iron typically found before absorption?

<p>Ferric iron (Fe³⁺) (B)</p> Signup and view all the answers

What happens to ferric iron (Fe³⁺) in the enterocytes after absorption?

<p>It is reduced to ferrous iron (Fe²⁺) (C)</p> Signup and view all the answers

What is haemosiderin primarily composed of?

<p>Aggregates of iron, carbohydrates, lipids, and proteins (C)</p> Signup and view all the answers

What role does hepcidin play in iron metabolism?

<p>It negatively regulates iron transport (D)</p> Signup and view all the answers

What characterizes red blood cells in iron deficiency anaemia?

<p>Microcytic and hypochromic (C)</p> Signup and view all the answers

Which factor influences hepcidin synthesis?

<p>Infection and inflammation (D)</p> Signup and view all the answers

What does total iron-binding capacity (TIBC) measure?

<p>The maximum amount of iron needed to saturate transferrin (C)</p> Signup and view all the answers

What would a transferrin saturation of less than 20% indicate?

<p>Iron deficiency (A)</p> Signup and view all the answers

Which method is used to measure serum ferritin?

<p>ELISA (B)</p> Signup and view all the answers

What is zinc protoporphyrin (ZPP)?

<p>A metabolite formed during haem synthesis (A)</p> Signup and view all the answers

What is the recommended oral iron treatment for iron deficiency anaemia (IDA)?

<p>200 mg ferrous sulfate taken twice daily (D)</p> Signup and view all the answers

What is the primary function of the Perls stain in medical diagnostics?

<p>To evaluate iron stores in bone marrow (B)</p> Signup and view all the answers

How is serum iron typically measured?

<p>By a colorimetric method with acidic reagents (A)</p> Signup and view all the answers

What is the primary role of tissue factor in the coagulation cascade?

<p>To initiate the coagulation cascade by binding to factor VIIa (C)</p> Signup and view all the answers

How does thromboxane A2 contribute to the process of haemostasis?

<p>By activating platelets and facilitating their aggregation (B)</p> Signup and view all the answers

What is the main function of protein S in the anticoagulation pathway?

<p>To bind to activated platelets and act as a co-factor for protein C (D)</p> Signup and view all the answers

Why is secondary haemostasis important?

<p>It strengthens the platelet plug with fibrin strands (D)</p> Signup and view all the answers

Which component is primarily responsible for the transitional step from primary to secondary haemostasis?

<p>Fibrinogen (B)</p> Signup and view all the answers

What activates platelets during the process of adhesion following vessel injury?

<p>Collagen exposure (B)</p> Signup and view all the answers

What is the primary mechanism by which vWF protects factor VIII (FVIII)?

<p>By safeguarding it from proteolytic degradation (C)</p> Signup and view all the answers

What role does ADAMTS13 play in the regulation of von Willebrand factor (vWF)?

<p>It cleaves and regulates the activity of vWF (D)</p> Signup and view all the answers

What triggers the process of fibrinolysis?

<p>The completion of healing processes at the injury site (B)</p> Signup and view all the answers

Which of the following factors is critical for localized activation during the coagulation process?

<p>Calcium ions (Ca²⁺) (C)</p> Signup and view all the answers

During which phase of the coagulation cascade does the intrinsic pathway operate?

<p>In the absence of external triggers (A)</p> Signup and view all the answers

How is nitric oxide involved in the regulation of haemostasis?

<p>It inhibits platelet function and acts as a vasodilator (A)</p> Signup and view all the answers

What do chief cells in the stomach primarily secrete?

<p>Pepsin (A)</p> Signup and view all the answers

What binds vitamin B12 after it is freed from dietary proteins?

<p>R-protein (C)</p> Signup and view all the answers

Where are vitamin B12-IF complexes absorbed in the digestive tract?

<p>Terminal ileum (A)</p> Signup and view all the answers

What role does intrinsic factor (IF) play in the absorption of vitamin B12?

<p>It protects B12 from bacterial degradation. (A)</p> Signup and view all the answers

What is the consequence of a lack of intrinsic factor in vitamin B12 absorption?

<p>Partial absorption of vitamin B12 (D)</p> Signup and view all the answers

How does folate deficiency develop more rapidly than vitamin B12 deficiency?

<p>Folate has a faster metabolic turnover rate. (C)</p> Signup and view all the answers

What is a hallmark feature of megaloblastic anaemia in neutrophils?

<p>Presence of hypersegmented neutrophils (D)</p> Signup and view all the answers

What role does transcobalamin play in the body after vitamin B12 absorption?

<p>It delivers B12 to bone marrow and tissues. (B)</p> Signup and view all the answers

What happens to homocysteine levels in the presence of both vitamin B12 and folate deficiency?

<p>They increase (A)</p> Signup and view all the answers

What happens to vitamin B12 after it is absorbed in the terminal ileum?

<p>It binds to transcobalamin and enters the bloodstream. (B)</p> Signup and view all the answers

Why does megaloblastic anaemia occur despite normal intake of vitamin B12?

<p>Deficiency in transcobalamin (A)</p> Signup and view all the answers

What is the primary role of methionine synthetase in folate metabolism?

<p>It converts methyl-THF to THF and methylates homocysteine. (C)</p> Signup and view all the answers

How does low red cell folate reflect folate status in the body?

<p>It is a reliable indicator of tissue folate status. (B)</p> Signup and view all the answers

What is a potential risk associated with parenteral iron treatment?

<p>High cost of treatment (B)</p> Signup and view all the answers

What does a dimorphic blood film during IDA treatment indicate?

<p>A response to therapy with a mix of red blood cell types (C)</p> Signup and view all the answers

When are blood transfusions considered for IDA patients?

<p>For symptomatic patients unresponsive to iron therapy (B)</p> Signup and view all the answers

Which of the following tests is NOT used for secondary haemostatic testing?

<p>Platelet function assays (D)</p> Signup and view all the answers

What is a primary indicator that APTT is prolonged?

<p>Deficiency in factors VIII, IX, or XI (C)</p> Signup and view all the answers

What can occur if poor venepuncture technique is used during sample collection for coagulation tests?

<p>Introduction of tissue factor, activating the sample (C)</p> Signup and view all the answers

What is the purpose of the Clauss fibrinogen test?

<p>To assess the levels of fibrinogen in plasma (A)</p> Signup and view all the answers

How does sodium citrate act as an anticoagulant during sample collection?

<p>By removing calcium ions from the blood (D)</p> Signup and view all the answers

When is thrombin time (TT) typically prolonged?

<p>In patients on heparin therapy (D)</p> Signup and view all the answers

What is the main purpose of using platelet function assays?

<p>To evaluate platelet adhesion and aggregation (B)</p> Signup and view all the answers

What does it indicate if a mixing study does not correct APTT?

<p>A lupus anticoagulant may be present (A)</p> Signup and view all the answers

What is measured during a D-dimer test?

<p>The amount of fibrin degradation products (A)</p> Signup and view all the answers

What does an INR greater than 5.0 typically indicate?

<p>A high risk of bleeding requiring urgent assessment (D)</p> Signup and view all the answers

Which of the following factors is NOT evaluated by prothrombin time (PT)?

<p>Factor XIII (D)</p> Signup and view all the answers

What does a prolonged APTT and PT suggest?

<p>A defect in the common clotting pathway (B)</p> Signup and view all the answers

What is the key limitation of bleeding time tests?

<p>It is operator-dependent (B)</p> Signup and view all the answers

What is the correct order of draw for coagulation samples?

<p>Second order of draw (A)</p> Signup and view all the answers

What is a characteristic finding in Bernard-Soulier Syndrome regarding platelet count?

<p>Mild to moderate thrombocytopenia (A)</p> Signup and view all the answers

What does a 1:10 dilution represent in the Clauss fibrinogen test?

<p>A standard for normal fibrinogen levels (B)</p> Signup and view all the answers

What does the prothrombin time (PT) test NOT assess?

<p>Fibrinogen levels (B)</p> Signup and view all the answers

What conditions can lead to elevated D-dimer levels?

<p>Thromboembolic diseases (C)</p> Signup and view all the answers

What happens to iron stores in patients undergoing effective treatment for iron deficiency anemia?

<p>They can take up to 6 months to be fully replenished (C)</p> Signup and view all the answers

What does a normal thrombin time indicate?

<p>Adequate fibrinogen conversion (B)</p> Signup and view all the answers

In factor assays, which factors are assessed in the intrinsic pathway?

<p>Factors IX, XI, and XII (A)</p> Signup and view all the answers

What is a common use of mixing studies?

<p>Diagnosing and differentiating APTT prolongation causes (D)</p> Signup and view all the answers

What may a prolonged bleeding time suggest?

<p>Platelet dysfunction or low platelet count (D)</p> Signup and view all the answers

How do inhibitors in coagulation affect clotting times?

<p>They neutralize or interfere with clotting factor function. (C)</p> Signup and view all the answers

Which of the following statements accurately describes the Bethesda Unit (BU)?

<p>It measures the amount of inhibitor that neutralizes 50% of normal FVIII:C. (C)</p> Signup and view all the answers

What is the main reason for post-translational modification of vitamin K-dependent proteins?

<p>To enable them to become functionally active. (B)</p> Signup and view all the answers

Which method is commonly used to measure the level of von Willebrand factor antigen?

<p>Enzyme-Linked Immunosorbent Assay (ELISA) (C)</p> Signup and view all the answers

What is the primary function of Ristocetin in the vWF:RCo assay?

<p>To induce platelet agglutination in the presence of functional vWF. (A)</p> Signup and view all the answers

Which condition is NOT associated with vitamin K deficiency?

<p>Bone marrow failure. (A)</p> Signup and view all the answers

What characterizes secondary haemostatic defects compared to primary defects?

<p>They often result in large bruises at unusual sites. (C)</p> Signup and view all the answers

What commonly causes a vitamin K deficiency in newborns?

<p>Decreased vitamin K levels at birth. (B)</p> Signup and view all the answers

What happens to vitamin K-dependent factors in the case of vitamin K deficiency?

<p>They become present but functionally inactive. (A)</p> Signup and view all the answers

Which of the following is a common symptom of bleeding disorders?

<p>Joint bleeds. (B)</p> Signup and view all the answers

In which scenario is a factor assay result not interpretable?

<p>In cases where a patient is deficient in a specific factor. (B)</p> Signup and view all the answers

Which of the following describes how latex immunoassays for vWF antigen work?

<p>Latex particles agglutinate in presence of vWF, correlating turbidity to concentration. (D)</p> Signup and view all the answers

What are known as time-dependent inhibitors?

<p>Inhibitors that degrade in activity as time progresses. (C)</p> Signup and view all the answers

What causes a decreased platelet count in liver disease?

<p>Reduced production of thrombopoietin (B)</p> Signup and view all the answers

What does consumptive coagulation lead to?

<p>Depletion of clotting factors and platelets (C)</p> Signup and view all the answers

What is the definition of massive hemorrhage?

<p>Blood loss &gt;50% of circulating volume within 3 hours (C)</p> Signup and view all the answers

Which blood components are lost during a massive hemorrhage?

<p>Red blood cells, platelets, and coagulation factors (D)</p> Signup and view all the answers

When are platelet transfusions typically indicated?

<p>For treatment of thrombocytopenia or platelet dysfunction (C)</p> Signup and view all the answers

What is the typical dosage for Fresh Frozen Plasma (FFP)?

<p>15 mL/kg body weight (A)</p> Signup and view all the answers

What is the function of thrombin in DIC?

<p>To convert fibrinogen to fibrin (B)</p> Signup and view all the answers

What are the possible causes of Disseminated Intravascular Coagulation (DIC)?

<p>Infections, obstetric complications, malignancies, and widespread tissue damage (C)</p> Signup and view all the answers

What is the role of the F8 gene?

<p>Codes for Factor VIII (B)</p> Signup and view all the answers

Which of the following does not typically characterize the consequences of DIC?

<p>Hypercoagulability (C)</p> Signup and view all the answers

What is a major risk of untreated DIC?

<p>Higher mortality due to uncontrolled bleeding and thrombosis (B)</p> Signup and view all the answers

What typically characterizes von Willebrand Disease (vWD)?

<p>Excessive bleeding from minor wounds (C)</p> Signup and view all the answers

Which factor primarily regulates erythropoiesis?

<p>Erythropoietin (EPO) (B)</p> Signup and view all the answers

What is the role of von Willebrand factor (vWF) in relation to Factor VIII?

<p>Protects Factor VIII from degradation (D)</p> Signup and view all the answers

What is a symptom commonly associated with platelet disorders?

<p>Prolonged bleeding after trauma (D)</p> Signup and view all the answers

How is a major component of thrombopoiesis regulated?

<p>Thrombopoietin (TPO) (C)</p> Signup and view all the answers

What is a main cause of symptoms in individuals with Turner syndrome that can lead to hemophilia?

<p>X-chromosome abnormalities (D)</p> Signup and view all the answers

Which factor affects the severity of bleeding in thrombocytopenia?

<p>Underlying cause of platelet production failure (B)</p> Signup and view all the answers

What are the three distinct types of von Willebrand Disease?

<p>Type 1, Type 2, Type 3 (C)</p> Signup and view all the answers

What is one of the benefits of prophylaxis over on-demand treatment for hemophilia?

<p>It is less expensive (A)</p> Signup and view all the answers

What is the first stage of erythropoiesis?

<p>Proerythroblast (C)</p> Signup and view all the answers

What treatment is used to increase levels of vWF and FVIII in patients with vWD?

<p>DDAVP (Desmopressin) (D)</p> Signup and view all the answers

What is one of the risks associated with prophylaxis in hemophilia treatment?

<p>Inhibitor development (B)</p> Signup and view all the answers

What triggers extramedullary haemopoiesis to occur?

<p>Bone marrow failure or increased demand for blood cells (C)</p> Signup and view all the answers

What does M-CSF primarily regulate?

<p>Monocyte production (C)</p> Signup and view all the answers

Which of the following cytokines stimulates the production of neutrophils?

<p>Granulocyte-Colony Stimulating Factor (G-CSF) (C)</p> Signup and view all the answers

Which condition is characterized by a failure of the bone marrow to produce sufficient blood cells?

<p>Aplastic anaemia (B)</p> Signup and view all the answers

During erythropoiesis, what is the primary role of reticulocytes?

<p>They are immature red blood cells released into circulation (B)</p> Signup and view all the answers

What is the function of proplatelets in thrombopoiesis?

<p>They are extensions from megakaryocytes that fragment to form platelets (B)</p> Signup and view all the answers

What is polycythaemia vera primarily characterized by?

<p>Overproduction of red blood cells (C)</p> Signup and view all the answers

What role do adhesion molecules play in haemopoiesis?

<p>They allow HSCs and progenitor cells to interact with the bone marrow niche (A)</p> Signup and view all the answers

What cytokine is primarily responsible for promoting B-cell development?

<p>Interleukin-7 (IL-7) (C)</p> Signup and view all the answers

What is an autologous bone marrow transplant?

<p>Using the patient’s own stem cells (C)</p> Signup and view all the answers

What do monocytes differentiate into during monocytopoiesis?

<p>Macrophages and dendritic cells (B)</p> Signup and view all the answers

What is a common treatment used to manage neutropenia?

<p>Granulocyte-Colony Stimulating Factor (G-CSF) (D)</p> Signup and view all the answers

What is the primary source of thrombopoietin (TPO) production?

<p>Liver and kidneys (A)</p> Signup and view all the answers

What is the role of platelets during primary haemostasis?

<p>They form a primary haemostatic plug through interactions with blood vessels. (C)</p> Signup and view all the answers

Which function is primarily associated with the media layer of the blood vessel wall?

<p>Regulating vascular tone and blood pressure. (A)</p> Signup and view all the answers

How does fibrinolysis contribute to maintaining blood vessel health?

<p>By degrading fibrin clots to prevent vascular occlusion. (D)</p> Signup and view all the answers

What is the significance of von Willebrand factor (vWF) in the haemostatic process?

<p>It facilitates interactions between platelets and blood vessels. (C)</p> Signup and view all the answers

What occurs during secondary haemostasis?

<p>Coagulation factors interact to generate fibrin strands. (A)</p> Signup and view all the answers

Which layer of the blood vessel wall provides protection and structural support?

<p>Adventitia (A)</p> Signup and view all the answers

Why is fluidity maintenance of blood essential in normal bodily functions?

<p>To ensure efficient nutrient transport. (B)</p> Signup and view all the answers

What is the main function of the intima layer in blood vessels?

<p>To provide a smooth lining for blood flow. (D)</p> Signup and view all the answers

What do chief cells in the stomach secrete?

<p>Pepsin (C)</p> Signup and view all the answers

What is the consequence of a deficiency in intrinsic factor (IF) related to vitamin B12?

<p>Decreased absorption of vitamin B12 (A)</p> Signup and view all the answers

How is free vitamin B12 transported in the body after absorption?

<p>Binds to transcobalamin (B)</p> Signup and view all the answers

What is the primary role of R-protein in vitamin B12 absorption?

<p>Protecting vitamin B12 from enzymatic degradation (B)</p> Signup and view all the answers

Where does the B12-intrinsic factor (IF) complex get absorbed?

<p>Terminal ileum (A)</p> Signup and view all the answers

Why do patients with megaloblastic anemia often have increased serum unconjugated bilirubin?

<p>Breakdown of marrow cells (B)</p> Signup and view all the answers

What is the primary function of thrombomodulin in the anticoagulation process?

<p>It reduces clot formation by binding thrombin (D)</p> Signup and view all the answers

What is the primary form in which non-haem dietary iron is found?

<p>Ferric iron (Fe³⁺) (A)</p> Signup and view all the answers

What is the main effect of endothelial cells during procoagulation?

<p>They release endothelin-1, causing vasoconstriction (C)</p> Signup and view all the answers

What is the effect of vitamin B12 deficiency on red blood cell production?

<p>Decreased cell production (B)</p> Signup and view all the answers

What type of cells in the bone marrow are affected by deficiencies in vitamin B12 and folate?

<p>Immature blasts (C)</p> Signup and view all the answers

What initiates the process of secondary haemostasis in the coagulation cascade?

<p>Exposure of procoagulant material due to vessel injury (A)</p> Signup and view all the answers

What is the role of hepcidin in iron metabolism?

<p>It degrades ferroportin, reducing iron transport. (A)</p> Signup and view all the answers

What is the typical serum ferritin level in iron deficiency anaemia (IDA)?

<p>Decreased (A)</p> Signup and view all the answers

Which of the following statements about folate absorption is accurate?

<p>Folate is absorbed as methyl-THF in the upper small intestine (C)</p> Signup and view all the answers

How does protein S enhance the function of protein C in anticoagulation?

<p>By promoting the binding of activated protein C to phospholipids (C)</p> Signup and view all the answers

What is the main outcome of primary haemostasis?

<p>Formation of a temporary platelet plug (D)</p> Signup and view all the answers

What factor would NOT lead to iron overload?

<p>Iron deficiencies (A)</p> Signup and view all the answers

What occurs to serum homocysteine levels in the case of both vitamin B12 and folate deficiencies?

<p>They increase (A)</p> Signup and view all the answers

What occurs to zinc protoporphyrin levels in iron deficiency?

<p>Increased levels occur (D)</p> Signup and view all the answers

What role does tissue plasminogen play in the regulation of coagulation?

<p>It activates plasminogen to promote clot lysis (D)</p> Signup and view all the answers

How do thromboxane A2 and platelet-activating factor (PAF) enhance the coagulation process?

<p>They activate platelets by binding to von Willebrand factor on the endothelial wall (A)</p> Signup and view all the answers

What is a hallmark finding in the blood associated with megaloblastic anemia?

<p>Hypersegmented neutrophils (A)</p> Signup and view all the answers

How is TIBC (total iron-binding capacity) typically affected in iron deficiency anaemia?

<p>TIBC is elevated (D)</p> Signup and view all the answers

What is the main role of transcobalamin in relation to vitamin B12?

<p>Transport of vitamin B12 to tissues (D)</p> Signup and view all the answers

What is a significant characteristic of von Willebrand factor (vWF) in relation to factor VIII?

<p>It protects FVIII from proteolytic degradation (D)</p> Signup and view all the answers

What is the primary function of the Perls stain?

<p>To assess haemosiderin stores (C)</p> Signup and view all the answers

What happens to vitamin B12 once it binds to intrinsic factor?

<p>It forms a stable complex for absorption (B)</p> Signup and view all the answers

What is the main physiological function of prostacyclin in the context of haemostasis?

<p>Inhibits platelet function and acts as a vasodilator (D)</p> Signup and view all the answers

What is not a characteristic feature of iron deficiency anaemia (IDA)?

<p>Increased white blood cell count (A)</p> Signup and view all the answers

What mechanism inhibits fibrinolysis during procoagulation?

<p>Release of Plasminogen Activator Inhibitor-1 (PAI-1) (A)</p> Signup and view all the answers

In what form is haem iron transported into the enterocyte?

<p>By haem carrier protein 1 (HCP1) (B)</p> Signup and view all the answers

What happens to iron stored in haemosiderin?

<p>Iron is released slowly and not readily available. (B)</p> Signup and view all the answers

What is the primary indication of normal levels of both methylmalonic acid and homocysteine?

<p>Normal B12 and folate status (B)</p> Signup and view all the answers

What is the key role of fibrin in the coagulation process?

<p>It strengthens the platelet plug (D)</p> Signup and view all the answers

What does the intrinsic pathway of coagulation primarily rely on?

<p>Factors that are all present in plasma (A)</p> Signup and view all the answers

Which of the following is NOT a characteristic step in investigating macrocytic anaemia?

<p>High homocysteine without elevated MMA (A)</p> Signup and view all the answers

What is a common cause of iron deficiency?

<p>Insufficient dietary intake (D)</p> Signup and view all the answers

What is the gold standard test for assessing B12 absorption versus dietary intake?

<p>Schilling test (C)</p> Signup and view all the answers

Which of the following statements is true regarding ferritin?

<p>Ferritin is present in low concentrations in the plasma. (C)</p> Signup and view all the answers

What is the primary means through which the body loses iron?

<p>Sloughing of skin cells and bleeding (B)</p> Signup and view all the answers

How does increased blood flow affect platelet rolling during vessel injury?

<p>It promotes further platelets to interact via vWF (C)</p> Signup and view all the answers

What does the administration of intrinsic factor (IF) in Step 2 of the Schilling test help determine?

<p>Intrinsic factor deficiency (D)</p> Signup and view all the answers

What happens to transferrin saturation levels in iron deficiency?

<p>Falls below 20% (D)</p> Signup and view all the answers

What would the presence of radiolabelled B12 in the urine after Step 3 of the Schilling test indicate?

<p>Bacterial overgrowth in the terminal ileum (B)</p> Signup and view all the answers

In which condition is pancreatic enzyme insufficiency likely to affect B12 absorption?

<p>Chronic pancreatitis (D)</p> Signup and view all the answers

What could be a cause of folate deficiency?

<p>Poor dietary intake (B)</p> Signup and view all the answers

Why is folic acid often administered alongside B12 treatment?

<p>To manage potential folate deficiency (C)</p> Signup and view all the answers

What mechanism primarily supplies iron for new red blood cell synthesis?

<p>Reticuloendothelial macrophages (C)</p> Signup and view all the answers

What is the main outcome of the activation of factor X (FX) in the coagulation cascade?

<p>It cleaves prothrombin to thrombin. (B)</p> Signup and view all the answers

What factor is associated with both B12 and folate absorption issues?

<p>Chronic digestive tract diseases (D)</p> Signup and view all the answers

What defines anaemia according to WHO standards in non-pregnant women over 15 years?

<p>Haemoglobin levels below 120 g/L (B)</p> Signup and view all the answers

What initiates the amplification phase of coagulation?

<p>The generation of thrombin. (B)</p> Signup and view all the answers

Which complex is primarily responsible for converting prothrombin to thrombin?

<p>Prothrombinase complex. (D)</p> Signup and view all the answers

What are the two primary mechanisms that result in anaemia?

<p>Reduction in RBC formation and reduced RBC survival (C)</p> Signup and view all the answers

What role does tissue factor pathway inhibitor (TFPI) play in coagulation?

<p>It blocks the TF-FVIIa complex and the extrinsic pathway. (D)</p> Signup and view all the answers

What is the primary consequence of FXIIIa's action on fibrin?

<p>It stabilizes the fibrin clot through cross-linking. (B)</p> Signup and view all the answers

What treatment options are available for patients who are intolerant or unresponsive to oral iron?

<p>Parenteral iron treatment via IV infusion or IM injection (C)</p> Signup and view all the answers

How does factor IXa (FIXa) function within the coagulation cascade?

<p>It assists in the formation of the tenase complex. (D)</p> Signup and view all the answers

What is the role of vitamin K in the coagulation process?

<p>It is essential in the synthesis of prothrombin. (B)</p> Signup and view all the answers

What potential risks are associated with parenteral iron treatment?

<p>High cost and potential side effects (A)</p> Signup and view all the answers

When is a blood transfusion considered for patients with iron deficiency anemia (IDA)?

<p>For patients with symptomatic anemia unresponsive to iron therapy (B)</p> Signup and view all the answers

Which of the following is NOT a key role of thrombin in the coagulation cascade?

<p>Activation of vitamin K. (D)</p> Signup and view all the answers

What signifies that a patient is responding to IDA treatment?

<p>Reticulocyte count peaks at 1-2 weeks (D)</p> Signup and view all the answers

What is the significance of the intrinsic tenase complex?

<p>It activates factor X at a higher efficiency than the extrinsic pathway. (D)</p> Signup and view all the answers

Where is antithrombin primarily produced?

<p>Liver. (C)</p> Signup and view all the answers

What happens during the propagation phase of coagulation?

<p>Formation of the tenase complex and amplification of thrombin generation. (B)</p> Signup and view all the answers

What are the common tests used in secondary haemostatic testing?

<p>PT, APTT, and Fibrinogen levels (D)</p> Signup and view all the answers

Which anticoagulant is used in the collection of coagulation samples?

<p>Sodium citrate (B)</p> Signup and view all the answers

What is the mechanism by which protein C acts to reduce coagulation?

<p>It inactivates factors Va and VIIIa with protein S. (C)</p> Signup and view all the answers

How does sodium citrate act as an anticoagulant?

<p>By removing calcium ions from the sample (B)</p> Signup and view all the answers

How long can the body store vitamin B12 without dietary intake?

<p>3-4 years. (A)</p> Signup and view all the answers

What is the purpose of performing mixing studies in prolonged clotting time investigations?

<p>To assess the presence of inhibitors or factor deficiencies (D)</p> Signup and view all the answers

What type of anaemia is primarily characterized by larger than normal red blood cells?

<p>Megaloblastic anaemia. (A)</p> Signup and view all the answers

What does the prothrombin time (PT) evaluate in the coagulation cascade?

<p>The extrinsic and common pathways of coagulation (A)</p> Signup and view all the answers

Which of the following conditions can lead to megaloblastic anaemia?

<p>Vitamin B12 deficiency. (C)</p> Signup and view all the answers

Which of the following conditions can affect prothrombin time (PT)?

<p>Liver disease (D)</p> Signup and view all the answers

What does an INR greater than 5.0 indicate regarding patient safety?

<p>High risk of bleeding requiring urgent assessment (C)</p> Signup and view all the answers

How should platelet function assay samples be stored prior to testing?

<p>At room temperature and delivered quickly (C)</p> Signup and view all the answers

What aspect of coagulation do optical coagulation analysers primarily measure?

<p>Light absorbance and transmission (D)</p> Signup and view all the answers

What does a prolonged APTT indicate?

<p>Defect in the intrinsic pathway or factor deficiencies (D)</p> Signup and view all the answers

In which scenario might PT and APTT both be prolonged?

<p>Defect in the common clotting pathway (A)</p> Signup and view all the answers

What parameter does the Clauss fibrinogen test primarily measure?

<p>Fibrinogen levels in plasma (A)</p> Signup and view all the answers

Which of the following conditions can lead to a prolonged APTT?

<p>Heparin therapy (C)</p> Signup and view all the answers

When is a D-dimer test most commonly utilized?

<p>To exclude thromboembolic events (B)</p> Signup and view all the answers

What would a normal thrombin time (TT) suggest?

<p>Normal fibrin formation (B)</p> Signup and view all the answers

What does a mixing study that does not correct APTT indicate?

<p>Presence of an inhibitor (B)</p> Signup and view all the answers

Which factors are particularly sensitive to APTT testing?

<p>Factors VIII, IX, and XI (A)</p> Signup and view all the answers

Why is the thrombin time rarely performed in modern labs?

<p>Availability of more precise tests (A)</p> Signup and view all the answers

What does a normal bleeding time indicate?

<p>Normal platelet function and integrity of hemostasis (D)</p> Signup and view all the answers

What is the purpose of a factor assay?

<p>To monitor factor replacement therapy (B)</p> Signup and view all the answers

What can elevated D-dimer levels indicate?

<p>Increased clot formation and breakdown (A)</p> Signup and view all the answers

At what factor level can PT and APTT detect deficiencies?

<p>When decreased to 25-40% of normal (B)</p> Signup and view all the answers

Which therapy is most likely to cause prolonged thrombin time?

<p>Heparin therapy (A)</p> Signup and view all the answers

How does the presence of inhibitors affect the function of specific clotting factors?

<p>They interfere with the normal function of clotting factors. (C)</p> Signup and view all the answers

What is the primary purpose of the Bethesda Assay?

<p>To detect Factor VIII inhibitors. (D)</p> Signup and view all the answers

What do latex immunoassays (LIA) rely on for the detection of vWF antigen?

<p>Agglutination of latex particles in the presence of vWF. (B)</p> Signup and view all the answers

What is a common symptom of primary haemostatic defects?

<p>Epistaxis (nosebleeds). (B)</p> Signup and view all the answers

Which of the following conditions is an example of an inherited bleeding disorder?

<p>Haemophilia. (C)</p> Signup and view all the answers

What condition can lead to the development of inhibitors in patients?

<p>Recombinant factor therapy. (B)</p> Signup and view all the answers

Which vitamin K-dependent factor is involved in inhibiting coagulation?

<p>Protein C. (A)</p> Signup and view all the answers

What does the Ristocetin Cofactor assay specifically measure?

<p>The functional activity of von Willebrand factor. (B)</p> Signup and view all the answers

What happens to vitamin K-dependent factors during vitamin K deficiency?

<p>They are present but non-functional. (C)</p> Signup and view all the answers

What is often observed in patients with secondary haemostatic defects?

<p>Joint and soft tissue bleeds. (B)</p> Signup and view all the answers

What effect does gamma-carboxylation have on vitamin K-dependent proteins?

<p>It enables them to bind to phospholipids. (A)</p> Signup and view all the answers

What treatment is given to newborns for vitamin K deficiency?

<p>Vitamin K injections. (A)</p> Signup and view all the answers

What is a potential cause of vitamin K deficiency?

<p>Use of oral anticoagulants like warfarin. (B)</p> Signup and view all the answers

What is the primary cause of decreased platelet count in liver disease?

<p>Reduced production of thrombopoietin (B)</p> Signup and view all the answers

During massive hemorrhage, what component is NOT typically lost?

<p>White blood cells (B)</p> Signup and view all the answers

What defines consumptive coagulation?

<p>Depletion of clotting factors and platelets from continuous clot formation (C)</p> Signup and view all the answers

What is the storage duration for thawed Fresh Frozen Plasma (FFP)?

<p>4 hours at room temperature (D)</p> Signup and view all the answers

Which of the following is a consequence of Disseminated Intravascular Coagulation (DIC)?

<p>Thrombocytopenia (A)</p> Signup and view all the answers

What is a common trigger for the development of inhibitors in coagulation disorders?

<p>Autoimmune conditions (C)</p> Signup and view all the answers

Which clotting factor is deficient in Hemophilia B?

<p>Factor IX (A)</p> Signup and view all the answers

Octaplas differs from standard Fresh Frozen Plasma in that it has decreased levels of which protein?

<p>Protein S (B)</p> Signup and view all the answers

What is the effect on fibrinogen levels following one adult therapeutic dose of cryoprecipitate?

<p>Increases fibrinogen by 1 g/L (B)</p> Signup and view all the answers

Which of the following factors is part of the cryoprecipitate?

<p>Factor VIII (A)</p> Signup and view all the answers

In terms of blood type compatibility, which of these is crucial for platelet transfusions?

<p>ABO and RhD match where possible (A)</p> Signup and view all the answers

Which enzyme is involved in breaking down fibrin during DIC?

<p>Plasmin (A)</p> Signup and view all the answers

What is the treatment strategy for managing DIC?

<p>Treat the underlying cause and replacement therapy with blood products (B)</p> Signup and view all the answers

Which gene is located on the telomeric end of the X chromosome and associated with Hemophilia A?

<p>F8 (D)</p> Signup and view all the answers

What is the most common inheritance pattern of von Willebrand Disease (vWD)?

<p>Autosomal dominant (D)</p> Signup and view all the answers

What is one of the main risk factors associated with prophylactic treatment for haemophilia?

<p>Increased risk of inhibitor development (D)</p> Signup and view all the answers

Which stage follows the proerythroblast in the process of erythropoiesis?

<p>Basophilic erythroblast (D)</p> Signup and view all the answers

Which factor is essential for the differentiation of proerythroblasts into mature red blood cells?

<p>Erythropoietin (A)</p> Signup and view all the answers

What is a common symptom of von Willebrand Disease?

<p>Epistaxis (nosebleeds) (A)</p> Signup and view all the answers

What regulates thrombopoiesis in the body?

<p>Thrombopoietin (B)</p> Signup and view all the answers

What causes quantitative platelet disorders?

<p>Increased destruction of platelets (D)</p> Signup and view all the answers

Which type of von Willebrand Disease is characterized by total vWF deficiency?

<p>Type 3 (B)</p> Signup and view all the answers

What is the role of von Willebrand factor in relation to Factor VIII?

<p>Protects it from proteolytic degradation (B)</p> Signup and view all the answers

What growth factor stimulates granulopoiesis?

<p>Granulocyte-Colony Stimulating Factor (G-CSF) (B)</p> Signup and view all the answers

What is one potential benefit of using plasma-derived clotting factors for haemophilia treatment?

<p>Reduced cost compared to recombinant factors (C)</p> Signup and view all the answers

What cellular process describes the development of platelets from megakaryocytes?

<p>Fragmentation (C)</p> Signup and view all the answers

What is the role of erythropoietin (EPO) in haemopoiesis?

<p>Regulates red blood cell production (C)</p> Signup and view all the answers

What triggers the occurrence of extramedullary haemopoiesis?

<p>Bone marrow failure or increased blood demand (A)</p> Signup and view all the answers

Which cytokine is primarily responsible for stimulating platelet production?

<p>Thrombopoietin (TPO) (A)</p> Signup and view all the answers

What is myelofibrosis?

<p>A disorder characterized by dense fibrous tissue in the bone marrow (B)</p> Signup and view all the answers

What cells differentiate from the myeloid lineage?

<p>Erythrocytes and myeloblasts (B)</p> Signup and view all the answers

What does the presence of reticulocytes in circulation indicate?

<p>Increased bone marrow activity (B)</p> Signup and view all the answers

Which condition is characterized by the failure of bone marrow to produce sufficient blood cells?

<p>Aplastic anaemia (C)</p> Signup and view all the answers

What are the two types of bone marrow transplants?

<p>Autologous and allogeneic (B)</p> Signup and view all the answers

What stimulates the production of monocytopoiesis?

<p>Monocyte-Colony Stimulating Factor (M-CSF) (A)</p> Signup and view all the answers

What is a common symptom of polycythaemia vera?

<p>Headache (A)</p> Signup and view all the answers

What effect does hypoxia have on erythropoietin (EPO) production?

<p>Stimulates EPO production (A)</p> Signup and view all the answers

What is the primary function of granulocyte-colony stimulating factor (G-CSF)?

<p>Stimulating neutrophil production (D)</p> Signup and view all the answers

Which condition is commonly treated with erythropoietin injections?

<p>Severe anemia (D)</p> Signup and view all the answers

What is the most common stain used for blood films preparation in the UK?

<p>May-Grunwald Giemsa (MGG) stain (A)</p> Signup and view all the answers

What might occur if a blood smear is prepared too thick?

<p>Cell details cannot be seen clearly (A)</p> Signup and view all the answers

What is hypochromia in red blood cells indicative of?

<p>Decreased hemoglobin content (A)</p> Signup and view all the answers

What is the normal myeloid-to-erythroid ratio in bone marrow?

<p>2:1 to 4:1 (B)</p> Signup and view all the answers

What is the primary purpose of fixing a blood smear in methanol before staining?

<p>To preserve cellular shape and morphology (B)</p> Signup and view all the answers

What happens to red blood cells when a smear is too thin?

<p>Red blood cells appear as spherocytes (B)</p> Signup and view all the answers

What is the typical fixation time for bone marrow slides in methanol?

<p>15-20 minutes (B)</p> Signup and view all the answers

Which white blood cell types can be identified on a stained smear?

<p>Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils (C)</p> Signup and view all the answers

What is the normal range for metamyelocytes?

<p>2-13% (C)</p> Signup and view all the answers

What is the primary purpose of a bone marrow aspirate?

<p>To assess cellular composition and abnormalities (C)</p> Signup and view all the answers

What microscopy technique is utilized for examining bone marrow aspirates?

<p>Oil immersion microscopy (C)</p> Signup and view all the answers

What fixative is used for trephine biopsies?

<p>10% formal saline (D)</p> Signup and view all the answers

What is indicated by the presence of tear-drop cells on a blood smear?

<p>Myelofibrosis (D)</p> Signup and view all the answers

Which staining technique is used to assess iron stores in the bone marrow?

<p>Perls’ Prussian Blue (A)</p> Signup and view all the answers

What does a positive Perls’ stain reveal?

<p>Presence of iron (C)</p> Signup and view all the answers

What blood cell findings are typically associated with iron deficiency anaemia?

<p>Microcytosis and hypochromia (B)</p> Signup and view all the answers

What indicates increased reticulin fibers in the bone marrow?

<p>Bone marrow fibrosis (B)</p> Signup and view all the answers

Which condition is characterized by markedly hypocellular marrow and increased fat content?

<p>Aplastic anaemia (A)</p> Signup and view all the answers

What color does PAS-positive material appear when stained?

<p>Magenta or pink (C)</p> Signup and view all the answers

What is the normal cellularity range of bone marrow in adults?

<p>30-70% (C)</p> Signup and view all the answers

What is typically observed in acute leukaemia on a bone marrow smear?

<p>Increased numbers of myeloblasts or lymphoblasts (B)</p> Signup and view all the answers

What is the most critical step in the preparation of a blood film?

<p>Spread the blood drop onto the slide (D)</p> Signup and view all the answers

What is the optimal duration for fixing a bone marrow slide in methanol?

<p>15-20 minutes (B)</p> Signup and view all the answers

Which staining procedure is followed immediately after fixing in methanol in blood smear preparation?

<p>Stain in May-Grunwald (A)</p> Signup and view all the answers

What does anisocytosis refer to in red blood cells?

<p>Variation in the size of red blood cells (C)</p> Signup and view all the answers

What would be the appearance of red blood cells if a blood smear is too thin?

<p>Red blood cells appear as spherocytes (D)</p> Signup and view all the answers

Which stage of a blood smear's preparation is performed after the slide is air dried?

<p>Fixing with methanol (D)</p> Signup and view all the answers

Which staining method is NOT used for trephine biopsies?

<p>Oil Red O (C)</p> Signup and view all the answers

What does a positive Perls’ Prussian Blue stain indicate?

<p>Presence of iron in marrow cells (B)</p> Signup and view all the answers

What is the typical finding in acute leukaemia on a bone marrow smear?

<p>Hypercellular with lymphoblasts or myeloblasts (A)</p> Signup and view all the answers

What role does the May-Grunwald Giemsa (MGG) stain serve?

<p>To stain blood films for cell morphology (D)</p> Signup and view all the answers

What are typical red cell findings in iron deficiency anaemia?

<p>Microcytosis, hypochromia, anisocytosis, poikilocytosis (A)</p> Signup and view all the answers

What is the hallmark finding in myelofibrosis?

<p>Increased reticulin fibers (B)</p> Signup and view all the answers

What is the significance of hypocellular bone marrow?

<p>Reduced blood cell production (B)</p> Signup and view all the answers

What does reticulin staining help assess?

<p>Bone marrow architecture and fibrosis (C)</p> Signup and view all the answers

What are common findings in myelodysplastic syndrome (MDS)?

<p>Dysplastic changes in blood cell lineages (C)</p> Signup and view all the answers

What is the range of normal cellularity in adult bone marrow?

<p>30-70% (D)</p> Signup and view all the answers

What is the role of iron stain (Perls’ reaction) in bone marrow examination?

<p>To assess iron stores (A)</p> Signup and view all the answers

Flashcards

Haemostasis purpose

Preventing and controlling bleeding while keeping blood flowing normally.

Primary haemostasis

Initial stage of clotting involving platelets and vessels to form a temporary plug.

Secondary haemostasis

Later clotting stage using clotting factors to make a stronger fibrin clot.

Fibrinolysis

Process breaking down a clot after healing is complete.

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Blood Vessel Layers

Three layers (intima, media, adventitia) forming the blood vessel wall.

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Intima layer function

Smooth lining for blood flow and regulates blood clotting.

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Media layer function

Controls blood vessel size and pressure.

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Adventitia layer function

Provides support and anchors the vessel.

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Von Willebrand Factor (vWF)

A protein that helps platelets stick to injured blood vessels.

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Platelet Adhesion

Platelets sticking to the damaged blood vessel wall.

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Platelet Activation

Platelets becoming active and recruiting more platelets.

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Platelet Plug

A temporary clump of activated platelets that stops bleeding.

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Coagulation Cascade

A series of reactions activating clotting factors in a specific order.

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Intrinsic Pathway

Part of the coagulation cascade triggered by factors present in the blood.

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Extrinsic Pathway

Part of the coagulation cascade triggered by factors outside the blood.

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Coagulation Factors

Proteins (zymogens) that interact to activate each other in the blood clotting cascade.

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Thrombin

Enzyme that converts fibrinogen to fibrin, crucial for clot formation.

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Fibrin

Insoluble protein forming the framework of a blood clot.

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Platelet Rolling

Movement of platelets along the surface of the damaged vessel.

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GPIb

Platelet receptor for collagen.

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Common pathway in coagulation

Where intrinsic and extrinsic pathways meet to create a fibrin clot.

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Extrinsic pathway initiation

Tissue factor (TF) is exposed, binding to factor VII (FVII).

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TF-FVIIa complex activation

Activates factor X (FX).

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FXa's function

Converts prothrombin (FII) to thrombin (in extrinsic pathway).

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Extrinsic prothrombinase

FXa, FVa, phospholipids, and Ca²⁺, generating thrombin.

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Thrombin's role: Fibrinogen to Fibrin

Transforms soluble fibrinogen into insoluble fibrin.

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FXIIIa's role

Crosslinks fibrin, strengthens clot.

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Vitamin B12 Source

Synthesized by microorganisms; diet for animals.

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Vitamin B12 Storage

Primarily stored in the liver.

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Megaloblastic Anemia Cause

Deficiency of vitamin B12 or folate causing DNA synthesis errors in red blood cell development.

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Intrinsic Factor (IF) Role

Essential for vitamin B12 absorption.

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R-protein role

Binds vitamin B12 in diet.

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Antithrombin Role

Inhibits thrombin and factor Xa. Activitiy enhanced by heparin.

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Protein C activation

Thrombin activating PC with thrombomodulin.

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Protein C function

Inactivates factors Va and VIIIa with protein S.

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Tissue Factor Pathway Inhibitor (TFPI)

Inhibits TF-FVIIa and extrinsic pathway; Protein S assistance.

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Chief cells secretion

Pepsin, a protein-digesting enzyme.

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Pepsin's role in B12

Breaks down dietary proteins, releasing vitamin B12.

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Free B12 binding in stomach

Binds to R-protein from salivary glands.

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B12, R-protein, IF destination

Travel to the duodenum after leaving the stomach.

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Pancreatic enzymes and B12

Pancreatic proteases break down R-protein, freeing vitamin B12.

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B12 after R-protein digestion

Binds to intrinsic factor (IF).

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Intrinsic factor (IF) purpose

Crucial for B12 absorption in the intestines.

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B12-IF complex absorption

Absorbed at the terminal ileum.

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Folate synthesis

Humans cannot produce folate.

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Folate absorption site

Upper small intestine.

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Folate storage

Primarily in the liver.

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Macrocytosis

Enlarged, oval-shaped red blood cells.

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Hypersegmented neutrophils

Neutrophils with 6 or more lobes, a sign of megaloblastic anemia.

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B12 deficiency and folate levels

Folate levels may be normal or high in B12 deficiency.

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Low red cell folate

An indicator of folate deficiency, but also appears in about 60% of B12 deficiency cases.

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Transferrin's role

Delivers iron to developing red blood cells and other tissues.

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Iron storage location

Primarily stored in liver cells (hepatocytes).

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Iron loss mechanisms

Loss through skin/muscle cells and bleeding.

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Iron excretion regulation

No regulated mechanism for iron excretion exists in the body.

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Iron absorption site

Duodenum (first part of small intestine).

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Iron membrane transport

Iron cannot pass through membranes freely.

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Dietary iron form

Typically in ferric (Fe³⁺) form.

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Fe³⁺ to Fe²⁺ conversion

Enzyme Dcytb reduces ferric iron to ferrous iron.

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Haemosiderin location

Primarily stored in macrophages.

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Haemosiderin composition

Aggregates of iron, proteins, carbohydrates, and lipids.

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Hepcidin's role

Negative regulator of iron transport, made in the liver.

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Hepcidin's action

Binds to ferroportin, increasing its degradation, thus reducing iron transport.

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IDA peripheral blood film

Shows microcytic, hypochromic red blood cells, and anisocytosis.

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Serum ferritin in IDA

Low serum ferritin levels are usually seen in IDA.

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Oral IDA treatment

Ferrous sulfate (200mg twice daily) is a common treatment.

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Serum MMA in B12 deficiency

Elevated serum methylmalonic acid (MMA) levels are a specific indicator of vitamin B12 deficiency.

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Normal MMA and homocysteine

Normal levels of both MMA and homocysteine strongly suggest the absence of clinically significant B12 deficiency.

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Macrocytic anemia investigation steps

The process starts with clinical signs, blood tests, and microscopic examination. Low B12 leads to B12 deficiency. Increased MCV suggests low folate, leading to folate deficiency.

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Main cause of B12 deficiency

Poor absorption is the primary cause, including issues with intrinsic factor (IF), IF receptors, or autoimmune attacks on stomach cells.

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Main causes of folate deficiency

Poor diet, pregnancy, long-term antibiotics, drugs affecting folate metabolism, and chronic digestive issues.

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Schilling test

A diagnostic test used to differentiate B12 malabsorption from dietary B12 deficiency.

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Schilling test - Step 1

Administering a dose of radiolabeled B12 after a B12 injection to saturate receptors.

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Schilling test - Step 2

Administering radiolabeled B12 with intrinsic factor (IF).

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Schilling test - Step 3

If Step 2 is inconclusive, antibiotics are added for diagnosing bacterial overgrowth.

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Schilling test - Step 4

Administer radiolabeled B12 with pancreatic enzymes to check for pancreatic insufficiency.

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Drugeffect on B12/Folate

Some drugs impede nucleic acid synthesis, causing deficiencies in B12 and folate.

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B12 treatment

Treatment for B12 deficiency can involve dietary changes and supplements. Severe absorption issues use injections.

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Folate deficiency treatment

Increase dietary folate intake.

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Anaemia

A primary pathological condition of red blood cells, either too few or impaired function.

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Parenteral Iron Treatment

Iron administration via IV infusion or IM injection for patients intolerant or unresponsive to oral iron.

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Risks of Parenteral Iron

High cost and potential side effects such as allergic reactions or iron overload.

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Blood Transfusion for IDA

Considered for symptomatic anaemia patients not responding to iron therapy or at risk of cardiovascular instability due to severe anaemia.

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Lifestyle and Dietary Advice for IDA

Counseling on diet and lifestyle modifications to improve iron intake and absorption.

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IDA Treatment Response Indicators

Reticulocyte count peaks at 1-2 weeks, Hb improves at 3-4 weeks, returns to normal at 2-4 months, iron stores replenish at 6 months.

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Dimorphic Blood Film in IDA Treatment

Indicates a positive response, showing a mix of normal and abnormal red blood cells.

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Primary Haemostatic Testing

Assesses platelet function in the initial stage of blood clotting.

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Secondary Haemostatic Testing

Evaluates the coagulation cascade and the formation of a stable fibrin clot.

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Prolonged Clotting Times Investigation

Investigates the cause of prolonged clotting times using tests like mixing studies, factor assays, inhibitor assays, vWF assays.

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Correct Order of Draw for Coagulation Samples

Coagulation samples are drawn second in the order of draw for blood tests.

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Anticoagulant for Coagulation Samples

Sodium citrate prevents coagulation by removing calcium ions.

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Sodium Citrate Reversibility

Sodium citrate is reversible, adding calcium can reignite the clotting process.

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Centrifugation for Coagulation Samples

Centrifuged at 3500 rpm for 5 minutes to obtain platelet-poor plasma (PPP).

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Poor Venepuncture and Coagulation Samples

Poor technique introduces tissue factor, activating the sample and leading to a short clotting time.

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Analytical Principles of Coagulation Analysers

Coagulation analysers use either light absorbance/transmission (optical) or mechanical/viscosity methods to measure clotting times.

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APTT Evaluation

The Activated Partial Thromboplastin Time (APTT) evaluates the intrinsic and common pathways of the coagulation cascade, which involve factors VIII, IX, XI, and XII, as well as the common pathway factors.

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APTT & Heparin Therapy

Heparin therapy commonly affects APTT by increasing clotting time, as Heparin influences the intrinsic and common pathways.

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Prolonged APTT Causes (1)

Prolonged APTT can be caused by conditions like Heparin therapy, factor deficiencies (VIII, IX, XI, XII), and Lupus anticoagulant.

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Prolonged PT & APTT

If both PT and APTT are prolonged, this suggests a defect in the common clotting pathway involving factors I, II, V, or X, which are crucial for both intrinsic and extrinsic pathways.

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Normal PT, Abnormal APTT

A normal PT but an abnormal APTT suggests a defect in the intrinsic pathway, involving factors VIII, IX, XI, or XII, which only affect the intrinsic clotting mechanism.

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Factor Deficiencies Detection

PT and APTT tests can detect factor deficiencies when factor levels drop to 25-40% of normal, highlighting their sensitivity in detecting significant deficiencies.

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Clauss Fibrinogen Test Purpose

The Clauss fibrinogen test is used to measure fibrinogen levels in plasma, a vital protein in the clotting process.

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Clauss Fibrinogen Test Procedure

The Clauss test adds thrombin to plasma samples with known fibrinogen concentrations and uses a calibration curve to compare clotting times.

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Clauss Fibrinogen Test Requirements

The Clauss fibrinogen test requires a reference plasma with a known fibrinogen level calibrated against an international standard for accurate measurement.

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Fibrinogen Test: Diluted Plasma

In a fibrinogen test, plasma is diluted (1:10 in buffer) and incubated before adding phospholipid, thrombin, and calcium to trigger clotting.

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Thrombin Time (TT) Measurement

Thrombin time (TT) measures the conversion of fibrinogen to fibrin, evaluating a crucial step in clot formation.

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Thrombin Time (TT) Factors

Factors affecting thrombin time are the quality and quantity of fibrinogen, highlighting its sensitivity to fibrinogen availability.

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D-dimer Test

A D-dimer test measures the amount of fibrin degradation products (FDPs) after clot lysis, indicating increased coagulation activity and breakdown.

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Elevated D-dimer

An elevated D-dimer level suggests increased coagulation activity and fibrinolysis, often indicating clotting and breakdown processes in the body.

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D-dimer Diagnostic Use

D-dimer testing is primarily used to exclude thromboembolic events like Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE), especially for patients with low risk.

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Liver disease effect on clotting factors

Liver disease reduces the production of clotting factors, leading to a decreased ability to form clots. The order of factor reduction is VII, II, X, I, and V.

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Thrombopoietin role in platelets

Thrombopoietin, produced in the liver and kidneys, stimulates the production of platelets.

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Liver disease effect on platelet count

Reduced production of thrombopoietin in liver disease leads to a decreased platelet count.

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Liver disease and activated factors

Liver disease impairs the clearance of activated clotting factors and inhibitors.

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Massive haemorrhage definition

Massive haemorrhage is a significant blood loss, either greater than 50% of blood volume in 3 hours or more than 150 mL/minute.

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Components lost in massive haemorrhage

A massive haemorrhage involves the loss of red blood cells, platelets, coagulation factors, and essential proteins like cytokines and chemokines.

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Consumptive coagulation definition

Consumptive coagulation is the depletion of clotting factors and platelets due to ongoing clot formation and breakdown.

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Transfusion risks in massive haemorrhage

Though transfusions carry risks, death from uncontrolled bleeding is always worse.

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Platelet transfusions indication

Platelet transfusions are used to treat or prevent bleeding in patients with low platelet counts or platelet dysfunction.

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Platelet transfusion compatibility

Platelet transfusions should be ABO and RhD matched whenever possible to minimize risks.

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Plasma product thawing time

Plasma products need to be thawed for a minimum of 30 minutes at 37°C.

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Fresh Frozen Plasma (FFP) dose

The typical FFP dose is 15 mL/kg of body weight.

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FFP donor criteria

Fresh Frozen Plasma (FFP) is sourced only from male donors.

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FFP administration ratio

FFP is typically administered in a 1:1 ratio with red blood cells.

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Cryoprecipitate content

Cryoprecipitate contains clotting factors VIII and XIII, von Willebrand factor (vWF), fibrinogen, and fibronectin.

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Extramedullary Haematopoiesis

Blood cell production outside the bone marrow, mainly in the liver and spleen.

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When does extramedullary haematopoiesis occur?

It happens when the bone marrow fails to keep up with blood cell demand, like in myelofibrosis or severe anaemia.

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Erythropoietin (EPO)

A hormone that stimulates red blood cell production, primarily in response to low oxygen levels in the kidneys.

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How is EPO production stimulated?

Hypoxia, low oxygen levels, trigger the kidneys to release EPO.

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Thrombopoietin (TPO)

A hormone produced by the liver and kidneys that regulates platelet production.

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Granulocyte-Colony Stimulating Factor (G-CSF)

A cytokine that stimulates the production of neutrophils, a type of white blood cell.

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Monocyte-Colony Stimulating Factor (M-CSF)

A cytokine that stimulates the production of monocytes, which differentiate into macrophages and dendritic cells.

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Aplastic Anemia

A condition where the bone marrow fails to produce enough red blood cells, white blood cells, and platelets.

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Myelofibrosis

A disorder where the bone marrow is replaced by fibrous tissue, leading to impaired blood cell production.

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Polycythemia Vera

A condition characterized by the overproduction of red blood cells, leading to thicker blood.

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Leukaemia

A cancer of the bone marrow, causing the overproduction of abnormal white blood cells.

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Bone Marrow Transplant

A procedure to replace damaged bone marrow with healthy stem cells.

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Autologous Bone Marrow Transplant

Using the patient's own stem cells for transplantation.

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Allogeneic Bone Marrow Transplant

Using stem cells from a donor, usually a close relative.

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Factor Assay Interpretation

Uses a reference curve from standard human plasma or pooled normal plasma to analyze the level of specific clotting factors in a patient's blood sample.

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Factor Deficiency Impact

When a patient is deficient in a specific clotting factor, their plasma cannot compensate for the missing factor during a factor assay, resulting in a lower reading.

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Coagulation Inhibitors

Antibodies that block the action of specific clotting factors or phospholipids, interfering with normal blood clotting.

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Inhibitor Targets

Coagulation inhibitors target specific clotting factors (like Factor VIII) or phospholipids (like lupus anticoagulant), preventing proper clot formation.

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Inhibitor Effect on Clotting

Coagulation inhibitors slow down or stop the clotting process by interfering with the function of essential clotting factors.

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Time-Dependent Inhibitors

Some inhibitors, like Factor VIII inhibitors, lose their effectiveness over time, while others, like Factor IX inhibitors, stay stronger for longer.

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Inhibitor Development

Inhibitors can occur in patients receiving recombinant clotting factor therapy, especially in individuals with Haemophilia, as their bodies can develop antibodies against the therapy.

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Bethesda Assay

This assay is used to analyze the presence and strength of antibodies against Factor VIII, specifically Factor VIII inhibitors in the blood.

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Bethesda Unit (BU)

A unit of measurement for Factor VIII inhibitors, defined as the amount of inhibitor that neutralizes half of a standard unit of Factor VIII in plasma after a specific incubation time.

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vWF Antigen Test

This test measures the level of von Willebrand factor protein in the blood using various methods, such as ELISA and Latex Immunoassays.

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vWF Antigen Detection Methods

ELISA and Latex Immunoassays are used to measure vWF antigen levels, with latex particles agglutinating in the presence of vWF to indicate its presence.

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vWF Activity Test

Measures the functional activity of von Willebrand factor in plasma, determining its ability to bind to and activate platelets.

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Ristocetin Cofactor (vWF:RCo) Assay

This assay measures vWF activity by analyzing the ability of a patient's plasma to agglutinate platelets in the presence of ristocetin, a substance that activates vWF.

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Ristocetin's Role

In the vWF activity assay, Ristocetin binds to vWF, enabling it to agglutinate platelets, which provides an indication of vWF's functional capacity.

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Bleeding Disorders Symptoms

Common symptoms include nosebleeds, bruising, skin spot formations (purpura and petechiae), heavy menstrual bleeding, joint and muscle bleeds, and chronic anemia.

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Primary Haemostatic Defects

Characterized by minor bleeding, typically from small cuts, mucous membranes, and after dental procedures, but without major internal bleeding.

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Secondary Haemostatic Defects

Involve deeper bleeding into tissues and organs, including large bruises, haematomas, joint bleeds, blood in the urine, and prolonged bleeding after injury or surgery.

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Factor IX Gene Location

The gene responsible for producing Factor IX is located on the long arm of the X chromosome, specifically at position Xq27.

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Factor IX Protein Size

The Factor IX protein, which is encoded by the F9 gene, has a chain of 415 amino acids.

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F9 Gene Mutations

Over 1095 different mutations have been identified within the F9 gene, causing a variety of haemophilia conditions.

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Haemophilia in Females

Females can inherit haemophilia due to various factors, including X-chromosome inactivation, Turner syndrome, true haemophilia, and von Willebrand disease.

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Prophylactic Haemophilia Treatment

Preventive measures to manage haemophilia include using plasma-derived clotting factors, recombinant clotting factors, and the drug DDAVP.

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Prophylaxis vs. On-Demand Treatment

Prophylactic treatment for haemophilia offers benefits over on-demand treatment by reducing bleeding episodes and being more cost-effective.

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Risks of Prophylaxis in Haemophilia

Prophylactic treatment can lead to increased inhibitor development and an increased risk of infection and thrombosis due to portacath access.

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What is von Willebrand Disease?

An inherited bleeding disorder affecting about 1% of the population, characterized by varying clinical severity due to deficiencies or dysfunction of the von Willebrand factor (vWF).

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vWD Presentation

Von Willebrand disease typically presents with mild to moderate bleeding, often manifesting as nosebleeds, bruising, and excessive bleeding from minor wounds.

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Types of vWD

There are three distinct types of von Willebrand disease, differentiated by the nature of the vWF deficiency: Type 1 (partial deficiency), Type 2 (dysfunction), and Type 3 (complete deficiency).

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vWF's Role in Factor VIII Protection

vWF plays a crucial role in protecting Factor VIII (FVIII) from degradation by enzymes in the blood.

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Treatments for von Willebrand Disease

Treatments for vWD include DDAVP (increasing vWF and FVIII levels), vWF/FVIII concentrates, antifibrinolytic drugs, and topical agents to control bleeding.

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Platelet Transfusions in vWD

Platelet transfusions can be helpful in some patients with Type 3 vWD, but they are not the primary treatment.

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Cryoprecipitate and FFP in vWD

Cryoprecipitate and fresh-frozen plasma (FFP) can be used to restore vWF and Factor VIII levels in patients with vWD.

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What are Platelet Disorders?

These disorders arise from abnormalities in platelets, leading to abnormal or excessive bleeding due to either low platelet count (thrombocytopenia) or dysfunctional platelets.

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Quantitative Platelet Disorders

These disorders are characterized by low platelet count (thrombocytopenia), caused by either increased destruction or decreased production of platelets.

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Qualitative Platelet Disorders

These disorders involve dysfunctional platelets, meaning they cannot function properly despite normal count due to defects in their structure or activation.

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Platelet Disorders Symptoms

Common symptoms include spontaneous bruising, bleeding from mucous membranes, and prolonged bleeding after minor injuries. Bleeding severity depends on the cause.

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Thrombocytopenia Bleeding Severity

Bleeding is more severe in cases where thrombocytopenia is caused by decreased platelet production, as opposed to increased destruction.

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Intima Layer

The inner layer of the blood vessel, made of endothelial cells, helps regulate clotting.

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Media Layer

The middle layer of the blood vessel, made of smooth muscle, regulates blood pressure.

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Adventitia Layer

The outer layer of the blood vessel, made of connective tissue, provides support and anchors the vessel.

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What are the main components of haemostatic mechanisms?

The primary, secondary, and fibrinolysis stages. Primary haemostasis forms a platelet plug. Secondary haemostasis strengthens the plug with fibrin. Fibrinolysis breaks down the clot once healing is complete

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What is von Willebrand factor (vWF)?

vWF is a protein that helps platelets stick to the site of vessel injury during the primary haemostasis stage.

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What is the function of thrombomodulin in anticoagulation?

Thrombomodulin binds free thrombin to reduce clot formation.

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How does heparin sulphate contribute to anticoagulation?

Heparin sulphate enhances antithrombin's inhibition of coagulation factors and activates protein C.

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What does protein C do in the anticoagulation process?

Protein C inactivates factors Va and VIIIa. This reduces clot formation and promotes breakdown of existing clots.

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How does tissue plasminogen function in anticoagulation?

Tissue plasminogen promotes clot lysis, helping break down a clot after healing.

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What is tissue factor's role in procoagulation?

Tissue factor initiates the coagulation cascade by binding with factor VIIa.

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How does thromboxane A2 and PAF function in procoagulation?

They activate platelets by binding to vWF on the endothelial cell wall. This promotes platelet aggregation and clot formation.

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How is fibrinolysis inhibited in procoagulation?

Fibrinolysis is inhibited by PAI-1 (plasminogen activator inhibitor) to reduce unwanted clot breakdown.

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How does von Willebrand factor (vWF) contribute during vessel injury?

Exposure of vWF activates and recruits circulating platelets by binding to the GPIb receptor complex on the platelet surface, leading to platelet adhesion.

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What is platelet activation?

Once platelets adhere, they become activated and release chemicals, recruiting and activating additional platelets to the injured site.

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What are coagulation factors?

Coagulation factors are inactive enzymes (zymogens) that participate in a complex series of reactions to form a blood clot.

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What does the localization of coagulation factor activation achieve?

Focusing the clotting process to the injury site, preventing widespread clotting.

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What is the intrinsic pathway in the coagulation cascade?

It requires enzymes and factors that are all present in plasma. This pathway is activated by contact with a foreign surface.

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What is the extrinsic pathway in the coagulation cascade?

The extrinsic pathway is activated by factors outside the blood, like tissue factor released from damaged tissue.

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Common Pathway

The point where the intrinsic and extrinsic pathways converge to form a fibrin clot.

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Tissue Factor (TF) & Factor VII Activation

The TF-FVIIa complex forms, activating factor X (FX).

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Factor Xa (FXa) Function

FXa converts prothrombin (FII) to thrombin, a key step in the extrinsic pathway.

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Extrinsic Prothrombinase Complex

FXa, FVa, phospholipids, and Ca²⁺ work together to produce thrombin.

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Prothrombinase Complex Function

The complex converts prothrombin (FII) to thrombin, essential for clot formation.

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Factor XIIIa Role in Clot Formation

FXIIIa crosslinks fibrin strands, making the clot stronger and more stable.

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Amplification Stage

A small amount of thrombin activates factors V, VIII, and platelets, creating a cascade effect.

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Factor Va (FVa) Role

FVa works with FXa (factor Xa) to amplify thrombin production.

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Factor IXa (FIXa) Function

FIXa moves to activated platelets, contributing to the generation of more thrombin.

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Propagation Stage

During this stage, FVIIIa is formed, and the tenase complex (FIXa + FVIIIa + FX) is created, leading to more thrombin production.

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Tenase Complex (FIXa + FVIIIa + FX)

This complex is 50 times more efficient than TF-FVIIa in activating factor X.

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Prothrombinase Complex

FXa + FVa (co-factor) + phospholipids + Ca²⁺, which cleaves prothrombin to generate thrombin.

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Thrombin Function

Thrombin plays numerous roles, including fibrinogen conversion, activation of other factors, and platelet activation.

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Fibrinogen Conversion to Fibrin

Thrombin converts soluble fibrinogen into insoluble fibrin, forming the clot's framework.

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What is vitamin B12?

A water-soluble vitamin essential for cell growth and development, especially for red blood cell production and nerve function.

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How do we get vitamin B12?

It's mainly obtained through animal-based foods like meat, fish, poultry, dairy, and eggs.

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How is vitamin B12 absorbed in the gut?

It requires a special protein called intrinsic factor (IF) released by stomach cells to be absorbed in the terminal ileum.

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What's the role of pepsin in vitamin B12 absorption?

Pepsin, a stomach enzyme, breaks down dietary proteins to release vitamin B12.

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What does vitamin B12 do in the cell?

It's a co-factor for certain enzymes involved in DNA and RNA synthesis. It's also important for myelin production.

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What happens when vitamin B12 is deficient?

It leads to megaloblastic anemia (larger than normal red blood cells) and neurologic problems.

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Can humans synthesize folate?

No, humans rely on dietary sources for pre-formed folate.

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What are the best sources of folate?

Green leafy vegetables, legumes, and fortified foods like cereal provide significant amounts.

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How is folate absorbed?

Dietary folates are absorbed in the upper small intestine as methyl tetrahydrofolate.

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What's the connection between folate and vitamin B12?

Both are essential for DNA synthesis and red blood cell production.

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What happens when there's a folate deficiency?

It also leads to megaloblastic anemia due to impaired DNA synthesis.

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What is macrocytosis?

The presence of larger than normal red blood cells, which can be a sign of vitamin B12 or folate deficiency.

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What are hypersegmented neutrophils?

Neutrophils (white blood cells) with more than the usual number of lobes (segments) in the nucleus. It's a characteristic sign of megaloblastic anemia.

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What is red cell folate?

A measure of folate stored in red blood cells, giving an idea of overall folate status.

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Why is red cell folate a better indicator than serum folate?

Red cell folate reflects long-term folate status, while serum folate can fluctuate more.

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MMA in B12 deficiency

Levels of serum methylmalonic acid (MMA) increase specifically in B12 deficiency.

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Macrocytic anemia investigation

The process starts with clinical signs, then blood tests, examining blood smear. Low B12 indicates deficiency. High MCV implies low folate.

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B12 deficiency cause

Poor absorption of B12 is the main cause, due to issues with intrinsic factor, receptors, or autoimmune attacks on stomach cells.

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Folate deficiency causes

Inadequate intake, pregnancy, long-term antibiotics, drugs affecting folate, and digestive issues are major causes.

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Schilling test purpose

This test distinguishes between B12 malabsorption and dietary B12 deficiency.

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B12 treatment methods

Treatment includes dietary changes, supplements, and for severe cases or absorption issues, B12 injections.

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Folate treatment

The key treatment is increasing dietary intake of folate-rich foods.

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Anaemia definition

A condition of insufficient RBCs or impaired RBC function, leading to reduced oxygen carrying capacity.

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Iron location and supply

Most iron is in bone marrow and RBCs, supplied primarily from iron-containing macrophages.

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Ferric Iron Reduction

Dietary iron is typically in the ferric (Fe³⁺) form. It needs to be reduced to ferrous (Fe²⁺) for absorption.

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Dcytb: The Iron Reducer

Duodenal cytochrome b (Dcytb) is the protein that reduces ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) in the duodenum.

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DMT1: The Iron Transporter

Divalent metal transporter 1 (DMT1) is the protein that moves ferrous iron (Fe²⁺) into enterocytes.

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Ferritin: The Iron Safe

Ferritin is a protein that stores iron and releases it when needed. It's like a safe for iron.

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Haemosiderin: The Iron Reserve

Haemosiderin is another form of stored iron found mainly in macrophages. It's like a 'stash' of iron.

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Hepcidin: The Iron Gatekeeper

Hepcidin is a hormone made in the liver that regulates iron levels. It's like a gatekeeper for iron.

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Hepcidin's Action on Ferroportin

Hepcidin binds to ferroportin, the iron exporter protein, and causes its degradation. This reduces iron transport.

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Iron Deficiency Anaemia Signs

Iron deficiency anaemia (IDA) is characterized by small, pale red blood cells (microcytic, hypochromic) and variation in red blood cell size (anisocytosis).

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TIBC in Iron Deficiency

Total Iron-Binding Capacity (TIBC) measures how much iron transferrin can bind. In IDA, TIBC is usually high.

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Transferrin Saturation Calculation

Transferrin saturation measures how much iron is bound to transferrin. It's calculated as (serum iron / TIBC) x 100%

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Treatment of Iron Deficiency Anaemia

Oral iron supplements, such as ferrous sulfate (200 mg twice daily), are commonly used to treat iron deficiency anaemia.

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Factor Deficiency Effect

If a patient lacks a specific clotting factor, their plasma cannot compensate for the deficiency in the factor-deficient plasma used in the assay.

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Inhibitor Development in Patients

Inhibitors can occur in patients receiving recombinant factor therapy, like those with hemophilia.

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vWF Antigen Test Methods

Common methods for measuring vWF antigen include ELISA (Enzyme-Linked Immunosorbent Assay) and automated Latex Immunoassays (LIA).

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Latex Immunoassay (LIA) for vWF

Latex micro-particles are coated with an antibody to human vWF. In the presence of vWF, the latex particles agglutinate, and the turbidity is proportional to the concentration of vWF:Ag in the plasma sample.

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Ristocetin's Role in vWF Activity Assay

Ristocetin induces platelet agglutination when vWF is functionally active, helping to assess vWF's ability to bind platelets.

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Factor Xa (FXa) Testing

A common test used to assess the function of Factor Xa, a key enzyme in both intrinsic and extrinsic coagulation pathways. It helps determine if the clotting process is working correctly.

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APTT (Activated Partial Thromboplastin Time)

A test measuring the time it takes for blood to clot, specifically evaluating the intrinsic and common coagulation pathways. It provides information on the health of factors VIII, IX, XI, and XII.

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APTT and Heparin

Heparin therapy commonly affects APTT by increasing the clotting time, as it influences the intrinsic and common coagulation pathways. It helps monitor Heparin's effectiveness.

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Prolonged APTT

A longer-than-normal APTT can indicate several issues, including Heparin therapy, deficiencies in specific clotting factors (VIII, IX, XI, XII), or the presence of Lupus anticoagulant.

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Clauss Fibrinogen Test

A test that measures the amount of fibrinogen in a blood sample. This protein is essential for forming blood clots, and its levels indicate clotting capacity.

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Fibrinogen Test Procedure

Plasma is diluted and incubated, then thrombin, calcium, and phospholipids are added. The time it takes for clotting is recorded and compared to a calibration curve to determine fibrinogen concentration.

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Thrombin Time (TT)

A test that measures the time it takes to convert fibrinogen to fibrin, the final step in clot formation. This helps assess the quality and speed of clot formation.

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Thrombin Time & Heparin Therapy

Thrombin time is often prolonged in patients on Heparin therapy. This is because Heparin directly inhibits thrombin's activity, preventing the formation of fibrin and slowing down the clotting process.

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Bleeding Time Test

A test that assesses platelet function and the integrity of the primary haemostatic process. It measures how long it takes for bleeding to stop after a small incision is made.

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Mixing Studies

Tests used to investigate the cause of a prolonged APTT by mixing patient plasma with normal plasma. If the mixing study corrects the APTT, it indicates a factor deficiency. If it does not, it suggests an inhibitor.

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Factor Assays

Tests that measure the levels of specific clotting factors in the blood. They help diagnose congenital or acquired factor deficiencies, distinguish between disorders, and monitor replacement therapy.

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Prophylactic Treatments for Haemophilia

Prophylactic treatments for haemophilia aim to prevent bleeding episodes and include plasma-derived clotting factors, recombinant clotting factors, and DDAVP (desmopressin).

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Prophylaxis Risks in Haemophilia

Prophylaxis for haemophilia carries risks such as increased inhibitor development and potential complications from portacath access, including infections and thrombosis.

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von Willebrand Disease (vWD)

vWD is an inherited bleeding disorder affecting about 1% of the population, causing mild to moderate bleeding due to abnormalities in the von Willebrand factor (vWF).

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vWF and Factor VIII Protection

von Willebrand factor (vWF) plays a crucial role in protecting Factor VIII (FVIII) from degradation, ensuring its availability for blood clotting.

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Platelet Disorders

Platelet disorders involve abnormal or excessive bleeding due to problems with platelets, affecting their numbers (quantitative) or function (qualitative).

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Autologous Transplant

A bone marrow transplant using the patient's own stem cells.

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Allogeneic Transplant

A bone marrow transplant using stem cells from a donor.

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What are the types of leukaemia?

  1. Acute Lymphoblastic Leukaemia (ALL)
  2. Acute Myeloid Leukaemia (AML)
  3. Chronic Lymphocytic Leukaemia (CLL)
  4. Chronic Myeloid Leukaemia (CML)
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Liver Disease & Clotting Factors

Liver disease can reduce the production of clotting factors, leading to a bleeding risk. The order of factor reduction is usually Factor VII, then II, X, I, and V.

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Liver Disease & Platelet Count

Liver disease can decrease platelet count due to reduced thrombopoietin production. Thrombopoietin is a hormone produced in the liver and kidneys that stimulates platelet production.

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Massive Haemorrhage Components Lost

During massive haemorrhage, vital components like red blood cells, platelets, coagulation factors, and important signaling molecules are lost.

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Consumptive Coagulation

Consumptive coagulation is the depletion of clotting factors and platelets due to continuous clot formation and breakdown, often seen in severe conditions like sepsis.

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Plasma Products Defrosting

Plasma products need to be defrosted at 37°C for a minimum of 30 minutes for proper use in medical procedures.

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FFP Source & Administration

FFP is derived from male donors only and is often administered in a 1:1 ratio with red blood cells.

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Cryoprecipitate Contents & Effect

Cryoprecipitate contains Factor VIII, von Willebrand Factor (vWF), fibrinogen, Factor XIII, and fibronectin. One adult therapeutic dose (ATD) increases fibrinogen by 1 g/L.

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Octaplas: Solvent Detergent-Treated Plasma

Octaplas is a specific type of Fresh Frozen Plasma (SD-FFP) treated with solvents and detergents for safety and specific uses.

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Disseminated Intravascular Coagulation (DIC)

DIC is a complicated condition where blood clots form inappropriately, depleting clotting factors and platelets, often leading to severe bleeding.

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DIC Main Consequences

DIC can lead to thrombocytopenia (low platelet count), bleeding, and damage to organs due to the widespread clotting and depletion of clotting factors.

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DIC Causes

DIC can be triggered by infections/sepsis, obstetric complications, malignancies (cancers), and extensive tissue damage.

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Haemostasis's main purpose

To stop bleeding while keeping blood flowing normally.

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Primary haemostasis: what's involved?

First response to injury. Involves blood vessels, platelets, and von Willebrand factor (vWF) to form a temporary platelet plug.

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Secondary haemostasis: what happens?

Coagulation factors come into play, creating fibrin strands to strengthen the clot.

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Fibrinolysis: its role

Dissolving the fibrin clot after healing to prevent blood vessel blockage.

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Blood vessel layers: what are they?

Three layers: intima, media, and adventitia. Each has a specific function.

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Intima layer: its function

Inner layer, smooth lining for blood flow, regulates blood clotting.

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Media layer: its function

Middle layer of smooth muscle, controls blood vessel size and pressure.

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Adventitia layer: its function

Outer layer, provides support and anchors the vessel to surrounding tissues.

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How do platelets contribute to haemostasis?

Platelets, small cell fragments, bind to the site of injury and form a plug to stop bleeding.

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What are the key steps of normal haemostasis?

  1. Primary haemostasis - Formation of a platelet plug.
  2. Secondary haemostasis - Strengthening the plug with fibrin strands.
  3. Fibrinolysis - Degrading the clot once healing is complete.
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What inhibits platelet function and acts as a vasodilator?

Prostacyclin and nitric oxide, released by endothelial cells.

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How does thrombomodulin contribute to anticoagulation?

Thrombomodulin binds to free thrombin, reducing clot formation by diverting it from the coagulation cascade.

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What is the function of protein C in anticoagulation?

Protein C inactivates factors Va (FVa) and VIIIa (FVIIIa) to slow down the clotting process.

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What does tissue factor do in procoagulation?

Tissue factor, expressed by cells of the adventitia, binds with factor VIIa (FVIIa) to initiate the coagulation cascade.

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How do thromboxane A2 and PAF (platelet-activating factor) contribute to procoagulation?

They activate platelets by interacting with von Willebrand factor (vWF) on the endothelial cell wall.

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How is fibrinolysis inhibited during procoagulation?

Fibrinolysis is inhibited by PAI-1 (plasminogen activator inhibitor), which prevents the breakdown of clots.

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Where is von Willebrand factor (vWF) produced?

vWF is produced in the Weibel-Palade bodies of endothelial cells, alpha-granules of platelets, and sub-endothelial connective tissue.

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What gene encodes von Willebrand factor (vWF) and where is it located?

The VWF gene, located on chromosome 12, encodes von Willebrand factor.

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What happens during vessel injury to promote haemostasis?

Exposed procoagulant material triggers a response, and endothelial-1 is released, causing vasoconstriction to reduce blood loss and promote platelet aggregation.

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What is platelet adhesion?

Platelets adhere to the exposed subendothelial matrix, either directly or indirectly via von Willebrand factor (vWF). Circulating vWF immobilizes to collagen, allowing platelets to attach to the exposed collagen.

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Common Pathway Convergence

Where the intrinsic and extrinsic pathways of the coagulation cascade join to create a fibrin clot.

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TF-FVIIa Complex Function

Activates factor X (FX), a key enzyme in the coagulation cascade.

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Factor Xa (FXa) in Extrinsic Pathway

FXa cleaves prothrombin (FII) to create thrombin, a vital component of clot formation.

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FXIIIa Role in Clot Formation

FXIIIa strengthens the fibrin clot by cross-linking fibrin fibers, creating a stable mesh.

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Amplification Stage of Coagulation

A small amount of thrombin generated activates factors V, VIII, and platelets, amplifying the clotting process.

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Factor IXa (FIXa) in Amplification

FIXa moves to activated platelets, aiding in the production of more thrombin.

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Propagation Stage of Coagulation

This stage involves the formation of factor VIIIa (FVIIIa) and the creation of the tenase complex (FIXa + FVIIIa + FX).

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Tenase Complex Function

A complex of FIXa + FVIIIa + FX, which is much more efficient than TF-FVIIa in activating FX.

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Prothrombinase Complex Components

FXa + FVa (co-factor) + phospholipids + Ca²⁺. This key complex converts prothrombin to thrombin.

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Thrombin's Key Roles in Coagulation

Thrombin plays multiple roles, including fibrinogen conversion, activation of factors, platelet activation, and protein C activation.

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Thrombin Converting Fibrinogen to Fibrin

Thrombin changes soluble fibrinogen into insoluble fibrin, forming the mesh of a blood clot.

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Iron Transport Across Membranes

Iron cannot freely cross cell membranes, requiring special transporters.

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Ferric to Ferrous Conversion

Duodenal cytochrome b (Dcytb) reduces ferric iron (Fe³⁺) to ferrous iron (Fe²⁺) for absorption.

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Ferrous Iron Transporter

Divalent metal transporter 1 (DMT1) allows ferrous iron (Fe²⁺) to enter enterocytes.

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Haem Iron Absorption

Haem iron is transported by the haem carrier protein 1 (HCP1).

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Iron Release from Haem

Haem oxygenase releases iron from the protoporphyrin ring in haem iron.

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Iron Transport Out of Enterocytes

Ferroportin transports iron from enterocytes across the basolateral membrane.

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Hephaestin's Role in Iron Absorption

Hephaestin oxidizes ferrous iron (Fe²⁺) to ferric iron (Fe³⁺) for binding to transferrin.

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Major Forms of Stored Iron

Ferritin and haemosiderin are the major forms of stored iron.

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Ferritin's Role

Ferritin stores iron and releases it in a controlled manner.

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Hepcidin's Role in Iron Regulation

Hepcidin is the master iron-regulating hormone, produced in the liver.

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B12 Deficiency Main Cause

The primary cause of B12 deficiency is poor absorption, which can be due to problems with intrinsic factor (IF), IF receptors, or autoimmune attacks targeting stomach cells.

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Folate Deficiency Main Causes

Folate deficiency can be caused by poor diet, pregnancy, long-term antibiotic use, drugs affecting folate metabolism, and chronic digestive issues like celiac disease or Crohn’s disease.

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Drugs and B12/Folate

Some drugs can interfere with nucleic acid synthesis, causing deficiencies in B12 and folate.

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B12 Treatment Options

Treatment for B12 deficiency often involves dietary changes and supplements. In cases of severe absorption issues, injections are preferred.

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Anaemia Overview

Anemia is a condition where red blood cells are either too few or have problems with function, leading to reduced oxygen carrying capability.

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Parenteral Iron Therapy

Iron is administered intravenously (IV) or intramuscularly (IM) for patients who can't tolerate or haven't responded to oral iron therapy.

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Risks of Parenteral Iron Therapy

This therapy comes with costs and potential side effects, including allergic reactions and iron overload.

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Myelodysplastic Syndrome (MDS)

A group of disorders where the bone marrow produces dysfunctional blood cells.

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Stromal Cells

Fibroblasts and endothelial cells that provide structural support and secrete growth factors.

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Hypoxia-Inducible Factor (HIF)

A transcription factor activated by hypoxia that stimulates EPO production.

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Thrombopoietin and Platelets

Thrombopoietin, a hormone produced by the liver and kidneys, stimulates platelet production. Liver disease can reduce thrombopoietin production, leading to lower platelet counts and increased bleeding risk.

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Massive Haemorrhage

Massive haemorrhage is a life-threatening condition involving significant blood loss over a short period, exceeding 50% of circulating volume within 3 hours or more than 150 mL/minute.

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Components Lost in Haemorrhage

During massive haemorrhage, the body loses essential components like red blood cells, platelets, clotting factors, and even cytokines and chemokines, further disrupting blood clotting and immune function.

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FFP Dose

The typical dose of Fresh Frozen Plasma (FFP) is 15 mL per kilogram of body weight.

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FFP Donors

Fresh Frozen Plasma (FFP) is typically sourced from male donors only.

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Cryoprecipitate Components

Cryoprecipitate contains vital clotting factors like Factor VIII, von Willebrand Factor (vWF), fibrinogen, Factor XIII, and fibronectin, making it useful for treating certain bleeding disorders.

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Cryoprecipitate Effect

One adult therapeutic dose (ATD) of cryoprecipitate can increase fibrinogen levels by 1 g/L, restoring proper blood clotting ability.

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DIC Consequences

DIC can have severe consequences, including thrombocytopenia (low platelet count), bleeding, and multiple organ damage due to tissue ischemia caused by microclots.

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Inhibitors in Coagulation

Inhibitors are antibodies that target and neutralize specific clotting factors, leading to coagulation dysfunction. They can occur naturally or develop as a response to treatment.

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Autoantibodies and Inhibitors

Autoantibodies are antibodies that mistakenly target the body's own proteins, including clotting factors. These inhibitors can cause bleeding problems.

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Haemophilia Categories

Haemophilia severity is categorized into mild, moderate, and severe based on the level of clotting factor deficiency, influencing the frequency and severity of bleeding episodes.

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Haemophilia Prophylaxis

Prophylactic treatments for haemophilia aim to prevent bleeding episodes by regularly supplying clotting factors.

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Prophylaxis Benefits

Prophylaxis for haemophilia is cost-effective and reduces the frequency of bleeding episodes compared to on-demand treatment.

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Prophylaxis Risks

Prophylaxis for haemophilia may increase the risk of inhibitor development and complications related to portacath access, such as infection or thrombosis.

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vWD Types

vWD is categorized into three types based on the underlying defect in vWF: Type 1 (reduced amount), Type 2 (defective function), and Type 3 (complete absence).

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vWF and Factor VIII

vWF protects Factor VIII from degradation, ensuring it can function properly in the clotting cascade.

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Thrombocytopenia Causes

Thrombocytopenia (low platelet count) can arise from increased platelet destruction or reduced platelet production.

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Prolonged APTT Causes

Prolonged APTT can result from various conditions, including Heparin therapy, factor deficiencies (VIII, IX, XI, XII), and Lupus anticoagulant.

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Clauss Fibrinogen Calibration

The Clauss fibrinogen test involves a calibration curve, created by diluting a reference plasma with known fibrinogen levels. Clotting times are plotted against fibrinogen concentrations, establishing a relationship.

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Thrombin Time Applications

Thrombin time is used to monitor fibrinolytic therapy, assess fibrin formation, and occasionally detect heparin therapy effects.

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Elevated D-dimer Indication

An elevated D-dimer level points towards increased coagulation activity and fibrinolysis, which could be due to conditions like DIC, thromboembolic diseases, or myocardial infarction.

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Mixing Studies in Coagulation

Mixing studies are used to investigate the cause of a prolonged APTT. Patient plasma is mixed with normal plasma, and the APTT is retested to see if the mixing corrects the clotting time.

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Factor Assays in Coagulation

Factor assays diagnose congenital or acquired factor deficiencies, distinguish between disorders, and monitor factor replacement therapy. They assess specific clotting factors, either in the intrinsic or extrinsic pathway.

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Factor Deficiency in Assay

If a patient is deficient in a specific clotting factor, their plasma cannot compensate for the absence of that factor in the factor-deficient plasma used in the assay, resulting in a prolonged clotting time.

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Ristocetin Cofactor Assay (vWF:RCo)

A common test used to measure vWF activity by assessing the patient's plasma's ability to agglutinate platelets in the presence of the antibiotic ristocetin.

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Primary vs Secondary Haemostatic Defects

Primary haemostatic defects involve issues with initial clotting steps involving platelets and blood vessels, resulting in small bruises, nosebleeds, and prolonged bleeding from cuts. Secondary defects affect the later stage involving clotting factors, leading to larger bruises, haematomas, and joint bleeds.

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Acquired Bleeding Disorders

These disorders are caused by factors other than inherited genes, such as vitamin K deficiency, liver disease, massive hemorrhage, DIC, or autoimmune antibodies.

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Inherited Bleeding Disorders

These disorders result from genetic defects, such as hemophilia, von Willebrand Disease (vWD), Bernard-Soulier Syndrome, and Glanzmann's Thrombasthenia.

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May-Grunwald Giemsa (MGG) Stain

The most common stain used in the UK for blood films, helps visualize blood cells and their components.

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Blood Film Preparation Steps

The process involves spreading a blood drop on a slide, air drying, fixing with methanol, and staining with MGG stain.

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Oil Immersion Microscopy

Examining blood smears at a high magnification of 100x, where red blood cells just touch but don't overlap.

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Hypochromia in Red Cells

Pale red blood cells with a decreased hemoglobin content, making their center look lighter.

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Polychromasia in Red Cells

Red blood cells appear bluish due to the presence of young red blood cells called reticulocytes.

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Normal Myeloid-to-Erythroid Ratio

The typical balance of myeloid cells to erythroid cells in bone marrow, usually a ratio of 3:1.

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Bone Marrow Components

Normal bone marrow consists of two main parts: cellular components (different cell types) and fat components.

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Normal Range for Myeloblasts

Myeloblasts, the earliest stage of white blood cells, have a normal range of 0-3% in bone marrow.

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Metamyelocytes

Immature neutrophils that are part of the granulocyte lineage in bone marrow.

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Neutrophils

The most abundant type of white blood cell, responsible for fighting bacterial infections by phagocytosis.

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Eosinophils

White blood cells involved in allergic reactions and parasitic infections.

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Basophils

White blood cells that release histamine, a chemical involved in inflammation and allergic responses.

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Lymphocytes

White blood cells involved in immune response, including T cells and B cells.

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Monocytes

Large white blood cells that mature into macrophages, which engulf and destroy pathogens.

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Plasma cells

White blood cells that produce antibodies, which are proteins that target specific antigens.

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Erythroblasts

Immature red blood cells that develop in the bone marrow.

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Bone Marrow Aspirate

A sample of fluid bone marrow extracted with a needle, used to analyze cell content and abnormalities.

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Bone Marrow Trephine Biopsy

A core sample of solid bone marrow tissue taken with a trephine needle, used to assess architecture and cell composition.

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Perls' Prussian Blue Stain

A stain that detects the presence of iron in bone marrow cells.

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Reticulin Stain

A staining method used to visualize the network of reticulin fibers in bone marrow, indicating fibrosis.

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Blood Film Preparation

The process of making a thin layer of blood on a glass slide for microscopic examination.

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May-Grunwald Giemsa Stain

The most common stain used in the UK to color blood cells for easier identification under a microscope.

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Smear Thickness

The thickness of a blood smear affects how well we can see cell details.

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Hypochromia

Red blood cells appearing paler than normal due to low hemoglobin content.

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Polychromasia

Red blood cells appearing bluish due to the presence of young red blood cells (reticulocytes).

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Myeloid-to-Erythroid Ratio

The ratio of myeloid cells (white blood cells) to erythroid cells (red blood cells) in bone marrow. A normal ratio is 3:1.

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Normal Bone Marrow Cell Types

Healthy bone marrow contains various cell types: myeloid, erythroid, lymphoid, and megakaryocytic cells.

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Myeloblast Percentage

The percentage of myeloblasts (immature white blood cells) in bone marrow is normally 0-3%.

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Normal Metamyelocyte Range

The normal range for metamyelocytes in a blood sample is 2-6%, with a mean of 4.1%.

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Normal Neutrophil Range

The normal range for neutrophils in a blood sample is 22-46%, with a mean of 32.1% in males and 37.4% in females.

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Normal Eosinophil Range

The normal range for eosinophils in a blood sample is 0.3-4%, with a mean of 2.2%.

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Normal Basophil Range

The normal range for basophils in a blood sample is 0-0.5%, with a mean of 0.1%.

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Normal Lymphocyte Range

The normal range for lymphocytes in a blood sample is 5-20%, with a mean of 13.1% in males and 16.1% in females.

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Normal Monocyte Range

The normal range for monocytes in a blood sample is 0-3%, with a mean of 1.3%.

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Normal Plasma Cell Range

The normal range for plasma cells in a blood sample is 0-3.5%, with a mean of 0.6%.

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Normal Erythroblast Range

The normal range for erythroblasts in a blood sample is 5-35%, with a mean of 28.1% in males and 22.5% in females.

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Bone Marrow Aspirate Purpose

A bone marrow aspirate is a sample of liquid bone marrow used to evaluate the cellular composition and identify any abnormalities.

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Bone Marrow Trephine Biopsy Purpose

A bone marrow trephine biopsy is a core sample of bone marrow tissue used to assess the overall architecture and cellularity of the marrow.

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Periodic Acid-Schiff (PAS) Stain

The PAS stain is used to identify glycogen and mucopolysaccharides in cells, these substances are important for cell function and structure.

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Sudan Black B Stain

The Sudan Black B stain specifically detects lipids and myeloblast granules in bone marrow cells, helping in diagnosing certain types of blood disorders.

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Study Notes

Haemostasis

  • Haemostasis's primary purpose is preventing and controlling bleeding while maintaining blood fluidity.
  • Haemostasis mechanisms maintain blood fluidity, stop bleeding, and remove clots after healing.
  • These mechanisms involve blood vessels, platelets, and coagulation factors.

Clotting Trilogy

  • The clotting trilogy comprises blood vessels, platelets, and coagulation factors.

Primary Haemostasis

  • The immediate response to vessel injury, involving platelet adhesion to form a plug.
  • Involves von Willebrand factor (vWF) for platelet adhesion to the damaged site.
  • vWF is produced in Weibel-Palade bodies, alpha granules, and subendothelial connective tissue.

Secondary Haemostasis

  • Coagulation factors interact to create fibrin strands, strengthening the primary platelet plug.
  • Fibrin reinforces and stabilizes the clot.

Fibrinolysis

  • The process of clot breakdown following healing.
  • Important for preventing vascular occlusion.

Blood Vessel Wall Layers

  • The intima (inner layer) is composed of endothelial cells.
  • The media (middle layer) is composed of smooth muscle cells regulating blood pressure.
  • The adventitia (outer layer) provides structural support and anchors the vessel.

Anticoagulation Factors

  • Prostacyclin and nitric oxide inhibit platelet function and act as vasodilators.
  • Thrombomodulin binds thrombin, reducing clot formation.
  • Heparin sulfate enhances antithrombin's action on coagulation factors.
  • Protein C inactivates factors Va and VIIIa.
  • Protein S acts as a co-factor for protein C.
  • Tissue plasminogen promotes clot lysis.

Procoagulation Factors

  • Endothelial cells release endothelin-1, a vasoconstrictor.
  • Tissue factor (TF) initiates the coagulation cascade by binding with factor VIIa (FVIIa).
  • Thromboxane A2 and PAF activate platelets.

Von Willebrand Factor (vWF)

  • A large multimeric glycoprotein (2050 amino acids) essential for hemostasis.
  • Encoded by the VWF gene on chromosome 12.
  • vWF facilitates platelet adhesion to exposed collagen.
  • vWF protects factor VIII (FVIII) from degradation.
  • Regulated by ADAMTS13.

Vessel Injury and Haemostasis

  • Vessel injury exposes procoagulant material, causing vasoconstriction and platelet aggregation.
  • vWF activates platelets and mediates their adhesion to sites of injury.

Platelet Response

  • Platelets are positioned to rapidly respond to vessel damage by flowing near the vessel walls.
  • Platelet adhesion involves binding to exposed subendothelial matrix, vWF, or collagen.
  • Platelets aggregate and recruit more platelets to the injured site.
  • Fibrinogen mediates platelet bridge formation in the platelet plug.

Coagulation Factors

  • Coagulation factors are serine proteases, inactive precursors (zymogens).
  • Activation occurs primarily at membrane surfaces with specific binding sites.
  • Factors interact in a cascade, leading to fibrin formation.
  • Intrinsic pathway uses plasma factors.
  • Extrinsic pathway uses tissue factor.
  • Common pathway combines intrinsic and extrinsic pathways to generate fibrin.
  • The tissue factor-factor VIIa complex activates factor X.

Coagulation Amplification and Propagation

  • Thrombin activates factors V, VIII, and platelets, amplifying coagulation.
  • The tenase complex (FIXa + FVIIIa + FX) significantly increases thrombin production.
  • The prothrombinase complex (FXa + FVa + phospholipids + Ca²⁺) cleaves prothrombin to form thrombin.

Thrombin Role

  • Thrombin crucial for fibrinogen to fibrin conversion and clot stabilization.
  • Thrombin activates platelets and other factors (factors V, VII, VIII, XI, XII, protein C, and TAFI).
  • Thrombin promotes tissue repair.

Fibrinogen

  • Synthesized by hepatocytes, stored in platelets' alpha granules.
  • Thrombin converts soluble fibrinogen to insoluble fibrin.

FXIIIa

  • Stabilizes fibrin by forming cross-links, strengthening the clot to prevent degradation.
  • FXIIIa interacts with α2-antiplasmin to inhibit plasmin's action.

Natural Coagulation Inhibitors

  • Antithrombin, protein C, and TFPI inhibit coagulation.
  • Antithrombin inhibits thrombin and factor Xa.
  • Protein C, with Protein S, inactivates Factors Va and VIIIa.
  • TFPI blocks the tissue factor-factor VIIa complex.

Megaloblastic Anaemias

  • Megaloblastic anemias are characterized by delayed nuclear maturation in erythroblasts due to defective DNA synthesis.
  • Common causes are vitamin B12 or folate deficiencies.

Vitamin B12 (Cobalamin)

  • B12 is essential for DNA synthesis and is found in animal products.
  • Vitamin B12 is stored in the liver (3-4 years supply).
  • Dietary deficiency usually not problematic due to body's sufficient stores.
  • B12 must bind to intrinsic factor (IF) for absorption.

Vitamin B12 Absorption

  • B12 is bound to dietary proteins.
  • Salivary glands secrete R-protein.
  • Stomach parietal cells secrete intrinsic factor (IF).
  • Pepsin breaks down dietary proteins.
  • Free B12 binds to R-protein in the stomach.
  • Pancreatic proteases digest R-protein, releasing B12.
  • B12 binds to intrinsic factor (IF).
  • B12-IF complex absorbed in the terminal ileum.
  • B12 passes into the portal blood and binds to transcobalamin for transport.

Folate

  • Humans cannot synthesize folate and need dietary intake.
  • Folate is stored in the liver.
  • Absorbed as methyl-THF in the small intestine.
  • Converted to folate polyglutamates within cells.
  • Folate deficiency develops faster than B12 deficiency due to its rapid turnover.

Folate and B12 Interaction

  • Vitamin B12 is needed for folate metabolism by the enzyme methionine synthetase.
  • Methionine synthetase converts methyl-THF to THF and methylates homocysteine to methionine.
  • Deficiency in either vitamin affects DNA synthesis.

Clinical Features of Anemia

  • Fatigue, shortness of breath, pallor, jaundice, glossitis, nervous system/psychiatric disturbances are characteristic symptoms.

Lab Findings in Megaloblastic Anemia

  • Macrocytosis (enlarged, often oval-shaped red blood cells).
  • Anisocytosis (variation in red blood cell size).
  • Hypersegmented neutrophils (6+ lobes).
  • Poikilocytosis (abnormal red blood cell shapes).
  • Howell-Jolly bodies (nuclear remnants).
  • Basophilic stippling (ribosomal RNA aggregation).
  • Elevated serum unconjugated bilirubin and lactate dehydrogenase.

Red Cell Folate

  • Low red cell folate reflects folate deficiency.
  • Low red cell folate can occur in B12 deficiency too.

Homocysteine and Methylmalonic Acid (MMA)

  • Increased serum homocysteine in B12 and folate deficiencies.
  • Increased serum MMA only in B12 deficiency.

Investigations

  • Clinical assessment of anaemia → blood tests → macrocytic on blood smear → serum B12 levels → MC V, serum folate levels → LDH/unconjugated bilirubin → MMA/homocysteine.

Causes of B12 and Folate Deficiencies

  • B12: Lack of absorption (Congenital IF lack, Autoimmune conditions, Transcobalamin deficiency).
  • Folate: Poor diet, pregnancy, chronic digestive disease.

Schilling Test

  • A test to diagnose B12 malabsorption from dietary issues.
  • Uses radiolabeled B12 to measure intestinal absorption.

B12 and Folate Treatment

  • Treat B12 deficiencies with supplements (oral or IM).
  • Folate deficiency treated with increased intake of folate-rich foods or supplements.

Anemia

  • A condition where there are insufficient red blood cells or abnormal function.
  • Defined by reduced oxygen-carrying capacity of blood.
  • Risk factors include age, female gender, premature birth, illness, and poor diet.
  • Different blood parameters of haemoglobin, vary by sex and pregnancy state.

Iron: Role in Haemostasis

  • Iron predominantly found in erythroid bone marrow and mature erythrocytes.
  • Iron supplied by reticuloendothelial macrophages for new red blood cell synthesis.
  • Transferrin carries iron.

Iron Absorption

  • Iron absorbed in the duodenal epithelium.
  • Divalent metal transporter 1 (DMT1) facilitates iron uptake.
  • Haem iron absorbed via haem carrier protein 1 (HCP1) and oxygenase-aided release of iron from protoporphyrin ring.
  • Ferroportin transports iron.
  • Hephaestin oxidizes iron, assisting in transferrin binding.

Iron Storage

  • Stored iron mainly in liver hepatocytes as ferritin and haemosiderin.
  • Ferritin stores and releases iron.
  • Haemosiderin, aggregates of iron, proteins, and lipids, releases iron slowly.

Hepcidin

  • The master iron-regulating hormone produced in the liver.
  • A negative regulator of iron transport.
  • Hepcidin binds to ferroportin on cell surfaces, leading to its degradation.
  • Factors influencing hepcidin synthesis: infections, hypoxia, inflammation

Iron Homeostasis

  • Iron overload can arise from increased absorption or multiple transfusions.
  • Iron deficiency stems from inadequate intake, impaired absorption, or increased loss.

Iron Deficiency Anaemia (IDA)

  • IDA characterized by small, pale red blood cells (microcytic, hypochromic).
  • IDA involves variation in red blood cell size (anisocytosis), and occasional target cells or poikilocytes.

Lab Results in IDA

  • Serum ferritin typically low in IDA.
  • Serum iron typically low in IDA.
  • Total iron-binding capacity (TIBC) usually high in IDA.
  • Transferrin saturation less than 20% indicative of iron deficiency.

Perls Stain and Zinc Protoporphyrin

  • Perls stain detects haemosiderin stores.
  • Zinc protoporphyrin (ZPP) levels increase in iron deficiency.

Treatment and Management of IDA

  • Common oral treatment is ferrous sulfate.
  • Alternatives include ferrous fumarate or ferrous gluconate.
  • Therapy typically for 3 months.
  • Parenteral iron for non-responsive cases.
  • Response indicators: reticulocyte and hemoglobin improvement along with iron replenishment (6 months).

Lab Investigation of Coagulation

  • Evaluate platelet function through assays and coagulation cascade through prothrombin time (PT), APTT, fibrinogen levels, thrombin time, and D-dimers.

Sample Collection and Coagulation Analysers

  • Sodium citrate prevents coagulation by removing calcium ions.
  • Samples centrifuged at high speed (3500 rpm for 5 minutes) to yield platelet-poor plasma (PPP).
  • Coagulation analysers employ optical or mechanical principles to measure clotting times.

Platelet Function Assays

  • Used to investigate platelet adhesion and aggregation.
  • ADP and EPI used in assays to stimulate platelet function.
  • Samples kept at room temperature, delivered by hand, processed within 4 hours.

Platelet Dysfunction

  • Platelet function assay results vary depending on the specific platelet disorder (e.g., vWD types).

Prothrombin Time (PT)

  • PT assesses the extrinsic and common pathways of coagulation.
  • Assesses Factor II, V, VII, and X.

INR (International Normalized Ratio)

  • INR derived from PT to monitor anticoagulant therapy (e.g., warfarin).

APTT (Activated Partial Thromboplastin Time)

  • APTT assesses intrinsic and common pathways of coagulation.
  • APTT particularly sensitive to factors VIII, IX, and XI deficiencies.

Clotting Screen Interpretation

  • Prolonged PT and APTT indicate common pathway issues.
  • Prolonged APTT, normal PT suggests intrinsic pathway issue.

Clauss Fibrinogen Test

  • Used to measure fibrinogen levels in plasma.
  • Uses thrombin to initiate fibrin formation.

Fibrinogen Testing

  • Measures fibrinogen using plasma dilutions.

Thrombin Time (TT)

  • TT measures fibrinogen conversion to fibrin.

Bleeding Disorders: Symptoms, Mechanisms, and Example Conditions

  • Symptoms include epistaxis, bruising, purpura, petechiae, menorrhagia, joint/muscle bleeds, and anaemia.
  • Primary haemostatic defects feature small bruises and easy bleeding from cuts.
  • Acquired bleeding disorders: Vitamin K deficiency, liver disease, DIC, and autoantibodies/inhibitors.

Vitamin K Deficiency

  • A fat-soluble vitamin found in green leafy vegetables and liver.
  • Causes: Fat malabsorption, liver disease, oral anticoagulants, antibiotics.
  • Crucial cofactor for gamma-carboxylation of clotting factors.
  • Deficiency leads to prolonged PT and APTT.

Vitamin K Cycle

  • Gamma-carboxylation is crucial for vitamin K-dependent proteins.
  • Calcium chelation enables binding to phospholipids.

Coagulation Cascade and Vitamin K

  • Crucial vitamin in activating Factors II, VII, IX X.
  • Activated factors require vitamin K.

Liver Disease and Coagulation

  • Liver produces factors I (Fibrinogen), II, V, VII, IX, X and part of VIII.
  • Liver disease impairs factor production, leading to prolonged PT and APTT, decreased platelet count.

Massive Haemorrhage

  • Significant blood loss (>50% circulating volume in 3 hours).
  • Consumptive coagulation due to depletion of clotting factors and platelets.

Platelet Transfusions

  • Indications include thrombocytopenia, platelet dysfunction.

Plasma Products

  • Fresh Frozen Plasma (FFP), Cryoprecipitate, Octaplas (SD-FFP) used in coagulation replacement therapy.

Disseminated Intravascular Coagulation (DIC)

  • Inappropriate intravascular fibrin deposition consumes clotting factors and platelets, leading to bleeding and organ damage.
  • Treatment focuses on the underlying cause and replacement therapy.

Autoantibodies/Inhibitors in Coagulation

  • Antibodies targeting clotting proteins, often found with autoimmune conditions.
  • Common targets include factors VIII and IX.
  • Antiphospholipid antibodies affect multiple coagulation proteins.

Haemophilia A and B

  • Both are X-linked bleeding disorders, representing deficiency in clotting Factor VIII (Haemophilia A) and IX (Haemophilia B) respectively.
  • Haemophilia inherited through the X chromosome.
  • Severity ranges from mild to severe cases in terms of Factor presence.

Haemophilia Treatment

  • Prophylaxis with plasma-derived or recombinant clotting factors.
  • Desmopressin (DDAVP) can increase factor VIII levels (in some mild cases)

von Willebrand Disease (vWD)

  • vWD is an inherited bleeding disorder with varying severity.
  • vWD caused by quantitative or qualitative deficiency of von Willebrand factor (vWF).
  • vWD classified into types 1, 2, and 3.

Platelet Disorders

  • Characterized by abnormal or excessive bleeding due to platelet abnormalities.
  • Quantitative defects (thrombocytopenia) or qualitative defects (platelet dysfunction).

Haemopoiesis

  • Haemopoiesis: Formation of blood cells in the bone marrow.
  • Adult haemopoiesis primarily in axial skeleton bone marrow.
  • HSCs (Haematopoietic Stem Cells).
  • Differentiation pathways: Myeloid (RBCs, platelets, myeloid WBCs) and Lymphoid (lymphocytes).
  • Stages of erythropoiesis, thrombopoiesis, granulopoiesis, monocytopoiesis, and lymphopoiesis.
  • Haemopoietic growth factors regulate these processes.

Haemopoiesis Regulation

  • Bone marrow microenvironment and cells (stromal, matrix) are crucial.
  • Regulation includes cytokines, EPO, TPO, adhesion molecules, and transcription factors like HIF.
  • Extra-medullary production possible due to bone marrow failure or high need.

Haemopoietic Disorders

  • Aplastic anemia, MDS, Polycythemia vera, Leukaemias.
  • Treatments range from EPO injections, TPO agonists, GCSF, Bone marrow transplant.

Cell Production Rates

  • High cell production rates of Red Blood cells (RBCs), White Blood cells (WBCs), and platelets in normal haematopoiesis.

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Description

This quiz covers the essential mechanisms of haemostasis, including primary and secondary haemostasis. Learn about the roles of blood vessels, platelets, coagulation factors, and the process of fibrinolysis in preventing and controlling bleeding. Test your knowledge on how these components work together to maintain blood fluidity and promote healing.

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