Haemostasis and Blood Vessels

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Questions and Answers

What is the primary role of primary haemostasis?

Vasoconstriction of blood vessels

Formation of fibrin strands

Interaction between blood vessels, platelets, and vWF (correct)

Degradation of the fibrin clot

Which mechanism is responsible for the removal of blood clots following wound healing?

Vascular tone regulation

Secondary haemostasis

Primary haemostasis

Fibrinolysis (correct)

What role does thrombomodulin play in haemostasis?

Inhibits platelet function

Activates platelets

Binds free thrombin (correct)

Promotes vessel constriction

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

Media Signup and view all the answers

What does the presence of von Willebrand factor facilitate?

Adhesion of platelets to vascular injury sites Signup and view all the answers

What is a crucial function of protein C in the coagulation process?

Inactivates FVa and FVIIa Signup and view all the answers

Which substance acts as a potent vasoconstrictor released by endothelial cells?

Endothelin-1 Signup and view all the answers

What is the function of tissue plasminogen in the clotting process?

Promotes clot lysis Signup and view all the answers

What is the initial role of vWF in platelet adhesion?

Binding to the GPIb receptor complex on platelets Signup and view all the answers

What triggers the extrinsic coagulation pathway?

Release of tissue factor due to endothelial injury Signup and view all the answers

Which of the following best describes the propagation stage of coagulation?

Formation of the FXa + FVa prothrombinase complex Signup and view all the answers

How does thrombin contribute to the coagulation process?

Cleaving fibrinogen to form fibrin Signup and view all the answers

What is the role of FXIIIa in fibrin formation?

Catalyzing the cross-linking of fibrin strands Signup and view all the answers

Which factor acts as a cofactor for the activation of FXA?

FV Signup and view all the answers

What is the function of antithrombin in coagulation?

Inhibiting thrombin and FXa Signup and view all the answers

How does the intrinsic pathway initiate the coagulation cascade?

Through the activation of plasma factors and enzymes Signup and view all the answers

What effect does thrombin have on platelets during coagulation?

It activates them through protease-activated receptors. Signup and view all the answers

What causes platelets to roll along the exposed collagen after initial adhesion?

High shear stress from blood flow Signup and view all the answers

Which condition is commonly caused by intrinsic factor deficiency leading to B12 malabsorption?

Pernicious anemia Signup and view all the answers

What is the primary method for assessing B12 absorption abnormalities?

Schilling test Signup and view all the answers

Which of the following is NOT a cause of folate deficiency?

Chronic renal failure Signup and view all the answers

What does the presence of radiolabeled B12 in the urine indicate after administering an oral dose?

Dietary problem Signup and view all the answers

What is the primary storage site for iron in the body?

Liver hepatocytes Signup and view all the answers

Which vitamin is required for the reduction of ferric iron (Fe3+) to ferrous iron (Fe2+) in the intestine?

Vitamin C Signup and view all the answers

What is a primary risk factor for developing anemia?

Being female Signup and view all the answers

How is iron primarily delivered to developing erythroid precursors?

By transferrin Signup and view all the answers

What is the effect of intrinsic factor on B12 absorption?

Facilitates intestinal absorption of B12 Signup and view all the answers

Which of the following conditions can lead to reduced red blood cell survival?

Sickle cell disease Signup and view all the answers

What is the primary storage site for vitamin B12 in the body?

Liver Signup and view all the answers

Which process must occur for vitamin B12 to be properly absorbed in the intestines?

Attachment to intrinsic factor Signup and view all the answers

What condition is associated with macrocytic anemia and hypersegmented neutrophils?

Megoblastic anemia Signup and view all the answers

What clinical feature is NOT typically associated with anemia?

Increased energy levels Signup and view all the answers

Which enzyme is vitamin B12 a co-factor for in its biochemical role?

Methionine synthetase Signup and view all the answers

What is the effect of vitamin B12 deficiency on homocysteine levels?

Increased levels Signup and view all the answers

What is a hallmark feature of megoblastic anemia seen in blood smears?

Hypersegmented neutrophils Signup and view all the answers

What type of anemia develops more quickly due to a faster turnover rate of cells?

Folate deficiency anemia Signup and view all the answers

What amino acid's methylation process is affected by vitamin B12 deficiency?

Methionine Signup and view all the answers

Which laboratory finding is typically normal in cases of folate deficiency?

Serum iron Signup and view all the answers

What dietary source is primarily responsible for providing vitamin B12 to humans?

Animal products Signup and view all the answers

What is the consequence of a deficiency in transcobalamin?

Anemia despite adequate vitamin B12 intake Signup and view all the answers

How do folate deficiency and vitamin B12 deficiency differ in terms of red blood cell folate levels?

Both are low Signup and view all the answers

What is the primary treatment approach for von Willebrand disease?

Desmopressin Signup and view all the answers

Which of the following statements about hemophilia genes is true?

Over 2000 mutations have been detected in the F8 gene. Signup and view all the answers

What characterizes von Willebrand disease type 3?

Total deficiency of von Willebrand factor Signup and view all the answers

What is a possible risk associated with the use of portacath access in hemophilia treatment?

Increased risk of infection and thrombosis Signup and view all the answers

Which symptom is most commonly associated with von Willebrand disease?

Excessive bruising Signup and view all the answers

Which protein is primarily responsible for transporting iron across the enterocyte basolateral membrane?

Ferroportin Signup and view all the answers

What is the primary storage form of iron in the body?

Ferritin Signup and view all the answers

How does Hepcidin affect iron metabolism?

It degrades ferroportin, reducing iron export. Signup and view all the answers

What changes in red blood cells are typical of iron deficiency anemia?

Microcytic hypochromic cells Signup and view all the answers

What laboratory method is commonly used to measure serum ferritin levels?

ELISA Signup and view all the answers

Which test is useful for assessing iron deficiency through transferrin saturation?

Total iron binding capacity Signup and view all the answers

What characteristic finds in a peripheral blood smear indicates a response to therapy in iron deficiency anemia?

Dimorphic blood film Signup and view all the answers

Which factor can falsely elevate serum iron levels?

Hemolysis during specimen collection Signup and view all the answers

Which of the following is NOT a reason for increased iron absorption leading to iron overload?

Chronic blood loss Signup and view all the answers

In the case of lead poisoning, which metabolite is produced instead of iron protoporphyrin?

Zinc protoporphyrin Signup and view all the answers

What is an important consideration when collecting samples for coagulation testing?

Sodium citrate must be added to prevent clotting. Signup and view all the answers

What technique is utilized to measure clotting times using optical methods?

Light absorbance transmission Signup and view all the answers

Which of the following factors can indicate a prolonged clotting time in diagnostic testing?

Platelet adhesion defect Signup and view all the answers

Which study is performed to assess deficiencies in platelet function?

Platelet function assays Signup and view all the answers

What factors can prolong prothrombin time (PT)?

Deficiency of Factor VII Signup and view all the answers

Which of the following conditions is primarily monitored using the International Normalized Ratio (INR)?

Warfarin therapy Signup and view all the answers

What does a prolonged activated partial thromboplastin time (APTT) indicate?

Deficiency in intrinsic pathway factors Signup and view all the answers

Which test evaluates the conversion of fibrinogen to fibrin?

Thrombin Time Signup and view all the answers

What can cause elevated D-dimer levels?

Thromboembolic diseases Signup and view all the answers

In mixing studies, what indicates the presence of a factor deficiency?

No correction in APTT after mixing Signup and view all the answers

What is a characteristic of Glanzmann thrombasthenia?

Normal platelet morphology Signup and view all the answers

What does the Clauss fibrinogen test measure?

Concentration of fibrinogen Signup and view all the answers

What can result from the use of direct anticoagulants?

Need for INR testing Signup and view all the answers

Which condition is associated with the highest risk of bleeding during anticoagulant therapy?

INR = 5.0 or greater Signup and view all the answers

What does a normal PT with an abnormal APTT suggest?

Intrinsic pathway defect Signup and view all the answers

Which of the following is true about inhibitors in coagulation?

Can develop during recombinant factor replacement therapy Signup and view all the answers

What is the method by which vWF antigen is quantitatively determined?

ELISA or automation techniques Signup and view all the answers

Which of the following symptoms is commonly associated with bleeding disorders?

Epistaxis Signup and view all the answers

In cases of vitamin K deficiency, which of the following factors is primarily affected?

Factor II Signup and view all the answers

What is the primary effect of disseminated intravascular coagulation (DIC) on coagulation factors?

Widespread consumption of factors Signup and view all the answers

Which of the following is a common cause of vitamin K deficiency?

Malabsorption of fat soluble vitamins Signup and view all the answers

Which bleeding disorder is characterized by large bruises at unusual sites?

Secondary haemostatic defects Signup and view all the answers

Which of the following is an inherited bleeding disorder?

Glanzmann's thrombasthenia Signup and view all the answers

What is the main purpose of platelet transfusions?

To treat or prevent bleeding in thrombocytopenia Signup and view all the answers

How is fresh frozen plasma (FFP) stored when not in use?

At -20 degrees Celsius Signup and view all the answers

In liver disease, which coagulation factor is typically the first to reduce?

Factor VII Signup and view all the answers

What does gamma carboxylation of glutamic acid facilitate in vitamin K dependent proteins?

Strong chelation of calcium Signup and view all the answers

Which treatment is more likely to be fatal in DIC cases?

Bleeding Signup and view all the answers

Which of the following is a characteristic of acquired bleeding disorders?

Caused by vitamin K deficiency or liver disease Signup and view all the answers

What happens to coagulation factors during massive hemorrhage?

Loss of platelets and coagulation factors Signup and view all the answers

What type of antibodies may develop in patients with certain bleeding disorders?

Antibodies that neutralize clotting proteins Signup and view all the answers

Study Notes

Haemostasis

Haemostasis is the body's normal response to prevent bleeding.
Crucial functions include maintaining blood fluidity, limiting bleeding after injury, and removing clots after healing.
The clotting trilogy involves blood vessels, platelets, and coagulation factors.
Primary haemostasis involves blood vessels, platelets, and von Willebrand factor (vWF) to form a primary haemostatic plug.
Secondary haemostasis involves coagulation factors to strengthen the clot with fibrin strands.
Fibrinolysis degrades the fibrin clot after wound healing to prevent blockage.

Blood Vessel Wall

The blood vessel wall consists of three layers: intima, media, and adventitia.
The intima is the inner layer with endothelial cells.
The media is the smooth muscle layer that regulates vascular tone.
The adventitia is the outer layer of collagen and fibroblasts that anchors and protects the vessel.

Anticoagulant Properties

Prostacyclin and nitric oxide inhibit platelet function and dilate vessels.
Thrombomodulin binds thrombin, preventing clotting factor activation.
Heparin sulphate and endothelial protein C activate protein C, a natural anticoagulant.
Protein C inactivates factors V and VIIa.
Heparin sulphate enhances antithrombin's inhibition of coagulation factors.
Protein S is a cofactor for protein C, binding to activated platelets.
Tissue plasminogen activator promotes clot lysis.

Procoagulant Properties

Endothelial cells release endothelial-1, a vasoconstrictor.
Adventitia cells express tissue factor, vital for initiating the coagulation cascade via FVIIa.
Thromboxane A2 and PAF activate platelets via vWF on the endothelial cell wall.
Plasminogen activator inhibitor (PAI-1) inhibits fibrinolysis.

Von Willebrand Factor (vWF)

vWF is a large glycoprotein produced by endothelial cells and platelets.
It's crucial for platelet adhesion to sites of vascular injury.
vWF is regulated and cleaved by ADAMTS13.
It carries ABO antigens and increases FVIIa plasma half-life.

Vessel Injury

Exposed procoagulant material triggers haemostasis.
Endothelial-1 causes vasoconstriction, reducing blood loss and promoting platelet aggregation.
Exposed vWF recruits circulating platelets via GPIb receptors.
Platelets, located at the edge of vessels, quickly respond to damage.

Platelets

Platelet adhesion occurs to the subendothelial matrix (directly or via vWF).
Platelet rolling occurs due to blood flow, facilitating further vWF-GPIb interactions.
Platelet activation recruits more platelets to the injury site.
Platelet plug formation occurs via fibrinogen bridging activated platelets.

Secondary Haemostasis

The platelet plug alone is insufficient for complete haemostasis.
Secondary haemostasis, involving coagulation, is initiated concurrently with primary haemostasis.
This process converts soluble fibrinogen into insoluble fibrin.

Coagulation Factors

Coagulation factors interact in a complex system through enzyme activation.
Coagulation factors are serine proteases.
Some require cofactors for optimal activation.
Activation generally happens at membrane surfaces due to factor and precursor binding to phospholipids, calcium, or receptors.
This localisation directs the haemostasis response.

Coagulation Cascade

Inactive zymogens are sequentially activated to active enzymes.
The intrinsic pathway uses plasma-based factors.
The extrinsic pathway requires a tissue factor initiator and plasma-based factors.
Both pathways converge to generate the fibrin clot.

Extrinsic Pathway

Tissue factor, exposed by endothelial injury, binds FVII, activating it.
The TF-FVIIa complex activates FX.
FXa forms the prothrombinase complex with FVa, phospholipids, and calcium, which converts prothrombin (FII) to thrombin.
FXIIIa cross-links fibrin for a stronger mesh.

Amplification Stage

Thrombin generation initiates amplification.
Thrombin activates factors V, VIII, and platelets.
FVa is a cofactor for FXa.
FIXa binds the activated platelet surface.
Increased thrombin availability is achieved at the activated platelet surface.

Propagation Stage

FVIIIa is formed during the amplification stage.
FIXa and FVIIIa form the tenase complex with FX.
This tenase complex is more efficient than the TF-FVIIa complex, activating more thrombin.

Thrombin Role

Thrombin cleaves fibrinogen to fibrin.
Thrombin activates factors V, VIII, IX, XI, and XII, platelets, protein C, and thrombin-activatable fibrinolysis inhibitor (TAFI).
Thrombin produces chemokines to attract WBCs to the injury site.
Thrombin promotes tissue repair.

Fibrin Formation

Thrombin converts soluble fibrinogen to insoluble fibrin.
Fibrin is reinforced by FXIIIa, which forms cross-links.
FXIIIa also binds a2-antiplasmin to inhibit plasmin degradation of the clot.

Natural Inhibitors

Natural inhibitors prevent inappropriate clotting cascade activation.
These include antithrombin (inhibits several serine proteases, enhanced by heparin sulphate), protein C (inactivates factors V and VIIIa, requiring protein S as a cofactor), and tissue factor pathway inhibitor (TFPI).
Antithrombin, protein C, and Protein S, and TFPI are vital in preventing inappropriate clotting.

Megaloblastic Anaemias

Megaloblastic anemias arise from delayed erythroblast nucleus maturation relative to cytoplasm, resulting in asynchronous maturation.
Deficiencies in vitamin B12 or folate, or abnormalities in their metabolism are common causes.

Vitamin B12

Vitamin B12 (cobalamin) is obtained from animal products, stored primarily in the liver.
The body can store enough B12 for 3-4 years, making short-term deficiencies less critical.
B12 absorption requires intrinsic factor, produced by parietal cells in the stomach.
B12-intrinsic factor complex is absorbed in the terminal ileum. The complex is then bound to transcobalamin and absorbed, delivering B12 to bone marrow.

Folate

Folate is needed for DNA synthesis and must be preformed in the diet.
Folates are absorbed as methyltetrahydrofolate in the upper small intestine.
Folate reserves are smaller than B12, due to rapid cell turnover.

Folate and B12 Interaction

B12 is a co-factor for methionine synthetase, needed to convert methyl-tetrahydrofolate to tetrahydrofolate (THF).
This reaction also converts homocysteine to methionine.
Folate deficiency also affects DNA synthesis.

Clinical Features of Anemia

Weakness, shortness of breath, pallor, jaundice, glossitis, nervous system disturbances, psychiatric disturbances.

Lab Findings

Macrocytosis (ovalocytes), anisocytosis, hypersegmented neutrophils, Howell-Jolly bodies, basophilic stippling, increased serum bilirubin and lactate dehydrogenase.
Serum iron and ferritin are generally normal in megaloblastic anemias. B12 deficiency often shows lower serum B12 levels but not always.
Red cell folate helps diagnose folate deficiency, but B12 deficiency can also cause this test to be falsely low.
Serum homocysteine is elevated in both folate and B12 deficiencies, while methylmalonic acid (MMA) is elevated only in B12 deficiency.

Causes of Deficiencies

B12 deficiency causes include intrinsic factor deficiency (pernicious anemia), transcobalamin deficiency, and malabsorption.
Folate deficiency causes include poor intake of folate-rich foods, pregnancy, some medications.

Schilling Test (Obsolete)

The Schilling test, used to diagnose B12 malabsorption, uses radiolabeled B12.
This test is now less common due to difficulty in obtaining isotopes.

Anemia

Anemia is a reduction in red blood cell count or function, leading to reduced oxygen-carrying capacity.
It is defined by low haemoglobin levels.

Iron Role in Haemostasis and Anemia

Iron is essential for red blood cell synthesis.
Transferrin transports iron.
Iron is stored primarily in the liver as ferritin and hemosiderin.

Iron Absorption

Iron is absorbed by enterocytes in the duodenum.
Ferric iron (Fe3+) is reduced to ferrous iron (Fe2+) before absorption.
Haem iron is absorbed more readily than non-haem iron.
Hephaestin oxidises ferrous iron to ferric iron.

Iron Deficiency Anemia

Patients often have microcytic, hypochromic red blood cells.
Lab results often show low serum ferritin, low serum iron, and high total iron-binding capacity.
Transferrin saturation is usually low.

Lab Investigation of Coagulation

Primary haemostasis tests involve platelet function.
Secondary haemostasis tests include PT, APTT, fibrinogen, TT, and d-dimers.
Investigations include mixing studies, factor assays, and inhibitor assays. Sampling is crucial for accurate testing.

Bleeding Disorders

Acquired disorders include vitamin K deficiency, liver disease, massive hemorrhage, DIC, and autoantibodies.
Inherited disorders include hemophilia, vWD, Bernard-Soulier syndrome, and Glanzmann thrombasthenia.
Vitamin K deficiency affects factors II, VII, IX, X, protein C, and protein S.
Liver disease impacts clotting factor production.
Massive hemorrhage can cause consumptive coagulopathies.
DIC causes a consumptive coagulopathy.
Autoantibodies/inhibitors can target clotting factors.

Hemophilia

Hemophilia is an X-linked bleeding disorder.
Hemophilia A involves factor VIII deficiency, and Hemophilia B involves factor IX deficiency.
Treatment involves prophylaxis with plasma-derived or recombinant clotting factors.

Von Willebrand Disease

von Willebrand disease is an inherited bleeding disorder with variable severity.
Types include type 1 (partial quantitative deficiency), type 2 (qualitative dysfunction), and type 3 (total deficiency) of vWF.
Treatment includes desmopressin, vWF/factor VIII concentrates, antifibrinolytics, and topical agents.

Platelet Disorders

Platelet disorders include thrombocytopenia (reduced platelet count) and defective platelet function.
Treatment can include platelet transfusions.

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Explore the essential mechanisms of haemostasis, including the roles of blood vessels, platelets, and coagulation factors in preventing bleeding. This quiz covers primary and secondary haemostasis as well as the structure of blood vessel walls and the anticoagulant properties that regulate clot formation.