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Questions and Answers
What is the main diagnostic tool used to assess the risk of pulmonary embolism?
Which treatment is considered for long-term management of pulmonary embolism?
What type of bleeding is commonly associated with hemophilia A and B?
Which laboratory test would be prolonged in patients with Disseminated Intravascular Coagulation (DIC)?
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What is the underlying cause of Von Willebrand's Disease?
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Which of the following is a complication of Disseminated Intravascular Coagulation (DIC)?
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What is the common presentation of a patient with thrombus lodged in the lung artery?
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In which scenario would thrombolysis be indicated for pulmonary embolism?
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What is typically observed in the laboratory tests for Hemophilia A?
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What is a common underlying reason for thrombocytopenia?
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What is the term for the formation of blood cells in the bone marrow?
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Which condition is characterized by a reduction in all blood cell types due to bone marrow damage?
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What does a low reticulocyte count indicate in the context of anaemia?
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Which of the following is NOT an aetiology of Aplastic Anaemia?
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How does myelodysplastic syndrome typically present?
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Which component constitutes about 55% of blood?
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What is the main cause of pernicious anaemia?
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Which type of anaemia is characterized by a high mean corpuscular volume (MCV)?
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Which of the following is a common trigger for G6PD deficiency-related haemolysis?
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What type of anaemia is associated with congenital deletions in alpha or beta hemoglobin chains?
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In patients with sickle cell anaemia, what phenomenon is often seen due to RBC sickling?
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What is the function of vitamin B12 in the body?
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Which test is used to confirm B12 absorption deficiency?
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Which drug class is known to reduce folate absorption?
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What is the most common blood group in Australia?
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Which antibodies are present in the serum of an individual with type A blood?
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What type of blood group incompatibility is primarily associated with Rh D-negative mothers?
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What common complication can arise from acute haemolytic transfusion reactions?
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Which factor is NOT typically assessed in pre-transfusion testing?
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How does hydroxyurea function in the treatment of conditions like sickle cell disease?
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What cells are tested during the forward grouping procedure?
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During pregnancy, which antibodies can cross the placenta?
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What is the primary purpose of irradiating blood products?
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What risk factor is NOT part of Virchow's triad related to thrombus formation?
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What is the consequence of sensitization in Rh D-negative mothers?
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What is NOT a component of whole blood after centrifugation?
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What symptom is a common sign of haemolytic disease of the fetus and newborn (HDFN)?
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What is a key characteristic of fresh frozen plasma?
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Which of the following is a common clinical presentation of pulmonary embolism?
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What laboratory finding would you expect to be elevated in a patient with Disseminated Intravascular Coagulation (DIC)?
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What is a primary treatment option for managing severe Von Willebrand's Disease?
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In patients with hemophilia A, which of the following laboratory tests would likely show a prolonged result?
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Which condition is characterized by the activation of coagulation pathways leading to both thrombosis and bleeding?
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Which of the following is a recommended short-term treatment for patients diagnosed with a pulmonary embolism?
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What is the genetic nature of Von Willebrand's Disease?
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Which of the following could be considered a preventive measure against venous thromboembolism?
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What presentation is consistent with a diagnosis of Haemophilia A or B?
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What is the primary immunoglobulin type that constitutes antibodies formed in response to Rh D antigen?
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Which blood group is the least common in the Australian population?
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What laboratory test is used to identify antibodies present in serum?
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Which condition can occur due to ABO incompatibility during pregnancy?
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What is the common treatment strategy for preventing complications in Rh D-negative mothers?
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What is a possible consequence of acute haemolytic transfusion reactions due to transfusion of incompatible blood?
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Which platelet preparation method involves collecting platelets from a single donor?
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What is the anticipated effect on red blood cells after gamma-irradiation?
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What is the main function of hydroxyurea in treating certain blood conditions?
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Which form of blood product is specifically derived to provide clotting factors?
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In the context of blood transfusion, what does a positive crossmatch indicate?
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What is Virchow's triad primarily related to?
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What is the primary cause of apLASTic anaemia?
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Which of the following best describes myelodysplastic syndrome?
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What is a common presentation observed in pernicious anaemia?
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Which vitamin is essential for DNA synthesis and is often associated with neural tube defects if deficient during pregnancy?
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What characterizes the anaemia associated with G6PD deficiency?
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What distinguishes sideroblastic anaemia from other types of anaemias?
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Which clinical feature is commonly associated with thalassemia?
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What is the main treatment approach for patients with pernicious anaemia?
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In sickle cell anaemia, what is a common complication due to vaso-occlusive crises?
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Which symptom is least likely to be associated with iron deficiency anaemia?
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In patients with macrocytic anaemia, what is a likely cause of their condition?
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Which test is essential for diagnosing hemolytic anaemia?
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What condition is specifically characterized by the presence of megaloblastic red blood cells?
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What is a key feature of reticulocytosis in the context of haemolytic anaemia?
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Which statement correctly describes a presentation associated with a pulmonary embolism?
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What is a typical laboratory finding in patients suspected of having Disseminated Intravascular Coagulation (DIC)?
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In the management of acute pulmonary embolism, which treatment option is most commonly utilized?
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What is the primary genetic inheritance pattern of Von Willebrand’s disease?
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Which factor is NOT typically associated with increased platelet destruction in thrombocytopenia?
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What laboratory result would most likely indicate Hemophilia A?
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Which of the following is a common complication associated with Disseminated Intravascular Coagulation (DIC)?
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What is the major concern when managing severe cases of Von Willebrand's disease?
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In patients with both Haemophilia A and B, what symptom is more commonly observed?
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Which of the following conditions type is characterized by increased red blood cell destruction leading to elevated bilirubin levels?
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Which of the following treatments is specifically indicated for pernicious anemia to address long-term management?
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What is the hallmark blood film finding associated with beta-thalassemia major?
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Which of the following factors can contribute to macrocytic anemia due to vitamin B12 deficiency?
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Which autoimmune disease is associated with Aplastic Anemia due to intrinsic factors?
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Which test is used to differentiate between intrinsic factor deficiency and dietary B12 deficiency?
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Which of the following is a common characteristic of sideroblastic anemia?
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Which laboratory finding is typically observed in hemolytic anemias?
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What is the complication associated with sickle cell disease that affects the spleen?
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Which of these describes a clinical presentation common to folate-deficiency anemia?
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What symptom is usually observed in patients with aplastic anemia?
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In sickle cell anemia, which clinical outcome is primarily due to the sickling of red blood cells?
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Which of the following describes a common consequence of vitamin B12 deficiency?
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Which blood group incompatibility is most commonly associated with a type O mother and A/B child?
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What type of antibodies are formed in response to the Rh D antigen?
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What is the most appropriate blood product to prevent transfusion-associated graft-versus-host disease (TA-GVHD)?
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Which complication is usually observed due to acute hemolytic transfusion reactions?
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What is the primary risk factor contributing to the formation of a thrombus as per Virchow's triad?
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Which screening test is typically performed to assess antibodies in a patient's serum prior to transfusion?
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Which of the following components is NOT usually present in fresh frozen plasma?
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What is the recommended action for an unsensitized Rh D-negative mother at risk for Rh incompatibility?
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What type of blood product predominantly contains clotting factors and must be thawed before use?
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Which symptom is primarily associated with Haemolytic Disease of Fetus and Newborn (HDFN)?
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Which type of blood group inheritance is described as codominant?
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What laboratory finding is typically observed in a patient with Disseminated Intravascular Coagulation (DIC)?
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What is the incidence rate of Deep Vein Thrombosis (DVT) in adults?
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Study Notes
Haematopoiesis
- Production of blood cells
- Occurs in bone marrow (medullary haematopoiesis) and other tissues (extramedullary haematopoiesis)
- Produces 200 billion cells per day
Aplastic Anaemia
- Pancytopenia due to bone marrow damage
- Low reticulocyte count can indicate aplastic anaemia or renal impairment
- Aetiology: inherited (Fanconi anaemia, Dyskeratosis congenita, Schwachman-Diamond syndrome) or acquired (immune mediated, toxins, occupational and environmental factors, chemotherapy and radiation, infections)
- Diagnosis: bone marrow biopsy - reveals hardly any progenitors and mostly fat cells
Myelodysplastic Syndrome
- Clonal disorder of haematopoietic stem cells (HSC)
- Dysplastic HSC leads to peripheral pancytopenia
- Results in hypercellular or hypocellular bone marrow
- Can progress to acute myeloid leukaemia
Blood Components
- 55% plasma: albumin, globulins, immunoglobulins, fibrinogen
- 45% haematocrit (red blood cells)
Anaemia - Vitamin B12 Deficiency
- Vitamin B12 is stored in the liver and required for B9 functionality and nerve health
- Pathophysiology: usually due to malabsorption caused by pernicious anaemia, gastrectomy, or inflammatory bowel disease
- Presentation: anaemia, glossitis, neurological issues
- Diagnosis: autoantibody screen for intrinsic factor antibody, Schilling test to assess absorption of vitamin B12, elevated homocysteine levels
- Treatment: hydroxocobalamin (IM) injections
Anaemia - Folate Deficiency
- Folate is found in leafy green vegetables, yeast, liver and kidney
- Absorbed in the jejunum
- Function: DNA synthesis
- Aetiology: dietary deficiency (chronic alcoholics, elderly, overcooked vegetables), malabsorption, increased requirement (pregnancy, infancy, chronic haemolysis), drugs (phenytoin, methotrexate)
- Presentation: similar to Vitamin B12 deficiency but no neurological features
- Treatment: oral folic acid supplementation
Anaemia - Aetiology
- Mean corpuscular volume (MCV) indicates the size of red blood cells
- Normocytic anaemia: Acute blood loss, bone marrow failure, chronic disease, destruction (haemolytic anaemia)
- Microcytic anaemia: Thalassemia, anaemia of chronic disease, iron deficiency, lead poisoning, sideroblastic anaemia
- Macrocytic anaemia: Foetus (pregnancy), alcohol, thyroid (hypothyroidism), reticulocytosis, vitamin B12/folate deficiency, cirrhosis, drugs (phenytoin, metformin, methotrexate)
Anaemia - Haemolytic Anaemias
- Anaemia due to red blood cell breakdown
- Diagnosis: biochemical tests (increased LDH, increased bilirubin, decreased haptoglobin), blood film morphology (reticulocytosis), Coomb’s test (positive if red cells are covered with IgG or C3)
Anaemia - Haemolytic Anaemias - G6PD Deficiency
- X-linked deficiency in glucose-6-phosphate dehydrogenase (G6PD)
- G6PD maintains glutathione which mops up oxidative stress
- Red blood cells are more prone to oxidative stress leading to haemolysis
- Common in areas where malaria is prevalent
- Presentation: usually asymptomatic, dark red/black urine (haemoglobinuria), prolonged or severe neonatal jaundice
- Triggers: fava beans/broad beans, acute illness/infection, medications (oxidative drugs)
- Diagnosis: blood smear review, specific enzyme assay
- Treatment: avoid precipitants
Anaemia - Haemolytic Anaemias - Sideroblastic Anaemia
- Failure to produce haem
Anaemia - Haemolytic Anaemias - Thalassemia
- Congenital alpha or beta haemoglobin chain deletion
- Prevalent in Asians and Mediterraneans
- 3 syndromes: Thalassemia trait (asymptomatic, microcytosis), Thalassemia intermedia (intermittent haemolysis), Thalassemia major (two beta chains deleted - nucleated red cells, iron overload, lifelong transfusion dependence)
- Diagnosis: haemoglobin electrophoresis, blood film (microcytic hypochromic, target cells, anicytosis, poikilocytosis)
Anaemia - Haemolytic Anaemias - Sickle Cell Anaemia
- Red blood cells are shaped like a sickle
- Pathophysiology: autosomal recessive inheritance, missense mutation in the HBB gene causing a valine substitution at the 6th amino acid of beta-globin
- Repeated sickling of red blood cells leads to anaemia, spillage of haemoglobin (decreased haptoglobin, increased unconjugated bilirubin)
- Sickle shape can cause vaso-occlusion in bones (dactylitis, avascular necrosis), spleen (splenic infarct), brain (stroke), lungs (acute chest syndrome), and kidneys (haematuria/proteinuria)
- Diagnosis: newborn blood spot screen, blood smear, protein electrophoresis
- Management: oxygen and fluids, pain management (opioids), infection management (antiobiotics, prophylaxis), blood transfusion, bone marrow transplant, prevention strategies (penicillin and polysaccharide vaccine against Strep pneumoniae, hydroxyurea)
Blood Groups: ABO
- Most common blood group in Australia is O+
- Least common blood group is AB-
- Antigens: A and B
- Antibodies: present in plasma when antigen is not present on red blood cells
- ABO gene (chromosome 9) - codominant A/B, recessive O
- Exceptions: infants do not produce anti-A or anti-B antibodies until a few months old, during pregnancy maternal IgG antibodies can cross the placenta into fetal circulation
Blood Groups: Rh
- Rh positive or negative
- RHD gene on chromosome 1, dominant
- Antigen: D (mainly)
- Antibodies: IgG, not naturally present in serum, formed in response to exposure to RhD antigen
Blood Grouping Procedures
- Cell Typing (Forward grouping): determines ABO and Rh antigen on cells
- Serum Typing (Reverse Grouping): determines antibodies present in serum
Haemolytic Disease of Foetus & Newborn (HDFN)
- Symptoms: jaundice, kernicterus
- ABO incompatibility: occurs mainly in type O mothers with type A/B fetuses
- Rh Blood Group incompatibility: RhD-negative mother and RhD-positive child, most common cause of HDFN
- Prevention: give all unsensitised mothers anti-D immunoglobulin, use Rh(D) negative blood products in women of childbearing age
Blood Products
- Whole blood can be centrifuged into: red cells, fresh frozen plasma, platelets, cryoprecipitate
- Cellular products in Australia are leukoreduced to prevent HLA alloimmunization, transfusion transmitted CMV and febrile non-haemolytic transfusion reactions
- Irradiated blood products prevent transfusion associated graft-versus host disease (TA-GVHD)
Blood Transfusions
- Pre-transfusion testing: identify patient specimen, ABO RH(D) typing, antibody screen, crossmatch
- Considerations for transfusing blood: acute/chronic anaemia, alternatives, transfusion volume and rate
- Emergency release of blood: no specimen, current specimen
Blood Transfusion Reactions/Complications
- Acute Haemolytic Transfusion Reactions: usually due to ABO incompatibility, intravascular haemolysis, can be fatal
- Other complications: febrile non-haemolytic transfusion reactions, allergic reactions, transfusion associated graft-versus host disease (TA-GVHD)
Bleeding/Clotting Pathology
- Too much clotting: deep vein thrombosis (DVT), pulmonary embolism (PE)
- Too much bleeding: haemophilia A/B, disseminated intravascular coagulation (DIC), Von Willebrand’s disease
Deep Vein Thrombosis (DVT)
- Thrombus in deep veins, usually in lower limbs
- Incidence: 1/1000 adults
- Presentation: unilateral (can be bilateral) swelling/oedema, pain, redness/warmth
- Complications: pulmonary embolism
- Virchow’s Triad: Risk factors for DVT - surgery, cancer, COCP, pregnancy, genetic factors
- Diagnosis: Well’s score, D-dimer, Doppler ultrasound
- Management: anticoagulants, surgery, prevention
Pulmonary Embolism (PE)
- Thrombus lodged in artery of lung
- Incidence: 1/2000
- Presentation: dyspnoea, sudden, sharp chest pain, cough (blood/pink foamy mucus), tachycardia, tachypnoea, sweating, anxiety, syncope
- Diagnosis: modified Well’s score, D-dimer, imaging (CTPA, V/Q scan)
- Treatment: oxygen support, heparin/LMWH, thrombolysis, long-term warfarin
Haemophilia A and B
- X-linked recessive deficiency in clotting factors, often a new mutation
- Haemophilia A: factor 8 deficiency
- Haemophilia B: factor 9 deficiency
- Severity: mild, moderate, severe
- Presentation: deep haemorrhage, post-traumatic and post-operative bleeding, mucocutaneous bleeding
- Diagnosis: genetic tests, APTT, factor 8 levels, vWF levels
- Treatment: various therapies depending on severity
Disseminated Intravascular Coagulation (DIC)
- Acquired syndrome characterised by activation of coagulation pathways leading to excessive clotting and bleeding
- Diagnosis: prolonged APTT, INR, TT, increased D-dimer, decreased platelets, decreased fibrinogen
- Presentation: bleeding (epistaxis, gingival bleeding, GI bleeding, petechiae, ecchymosis, haematuria), oliguria, cough, dyspnoea, fever, hypoxia, hypotension, mental disorientation, delirium, coma
- Complications: life-threatening haemorrhage, acute renal failure, gangrene, loss of digits
- Treatment: address underlying disorder, replace plasma, platelets, and clotting factors
Von Willebrand’s Disease
- Common genetic disorder: 1% of the population
- Autosomal dominant
- Deficiency in Von Willebrand factor (vWF)
- Presentation: mild to moderate bleeding disorder
- Diagnosis: mildly prolonged APTT, vWF assays, decreased factor 8 levels
- Treatment: tranexamic acid, vasopressin analogues, concentrated forms of vWF
Thrombocytopenia
- Low platelets
- Aetiology: increased destruction (immune thrombocytopenic purpura), decreased production (bone marrow failure, medication induced), splenomegaly, dilution (blood transfusion)
- Presentation: bleeding (mucocutaneous, intracranial, gastrointestinal), petechiae, ecchymosis
- Diagnosis: complete blood count
Haematopoiesis
- Haematopoiesis is the process of blood cell production, with around 200 billion cells produced each day.
- Bone marrow is responsible for medullary haematopoiesis while other tissues contribute to extramedullary haematopoiesis.
Aplastic Anaemia
- Aplastic Anaemia (AA) is characterised by pancytopenia, a reduction in all blood cell types, due to bone marrow damage.
- Patients with AA will have a low reticulocyte count, which can also be caused by renal impairment.
- AA is distinguished by having neutropenia and thrombocytopenia in addition to low reticulocyte counts.
- AA can be inherited (Fanconi anaemia, Dyskeratosis congenita, Schwachman-Diamond syndrome) or acquired through immune-mediated responses, toxins, occupational/environmental exposure, chemotherapy/radiation, and infections (e.g., EBV).
- Bone marrow biopsy is used for diagnosis, showing hardly any progenitors and mostly fat.
Myelodysplastic Syndrome
- Myelodysplastic Syndrome is a group of clonal haematopoietic stem cell (HSC) disorders causing dysplastic HSC and peripheral pancytopenia.
- The bone marrow can be hypercellular or hypocellular.
- Myelodysplastic Syndrome can progress to acute myeloid leukaemia.
Blood Components
- Plasma, comprising 55% of blood, contains albumin, globulins including clotting factors and immunoglobulins, and fibrinogen.
- Haematocrit, containing red blood cells (RBC), makes up 45% of blood.
- Platelets (4-5%) are stored in the liver and function in coagulation.
Anaemia - Vitamin B12 Deficiency
- Vitamin B12 (Cobalamin) is essential for B9 function and nerve function.
-
Pathophysiology involves malabsorption due to:
- Pernicious anaemia with autoantibodies against intrinsic factor (IF) or parietal cells.
- Gastrectomy
- Inflammatory bowel disease
- Inadequate intake can also occur, particularly in vegans.
- Presentation includes anaemia, glossitis, and neurological issues such as peripheral neuropathy, numbness, and dementia.
- Diagnosis is confirmed through an autoantibody screen for intrinsic factor antibodies, a Schilling test measuring B12 absorption, and an elevated homocysteine level.
- Treatment involves hydroxocobalamin injections and lifelong therapy is required for pernicious anaemia.
- Folic acid alone should never be given to a B12 deprived patient as it will worsen the neurological deficit.
Anaemia - Folate Deficiency
- Folate (B9) is found in green leafy vegetables, yeast, liver, and kidney.
- Absorption occurs in the jejunum.
- Folate is essential for DNA synthesis.
-
Aetiology includes:
- Dietary deficiency in chronic alcoholics, the poor, and elderly, as well as overcooking vegetables.
- Malabsorption.
- Increased requirement during pregnancy, infancy, and chronic haemolysis.
- Reduced folate absorption caused by phenytoin.
- Folate antagonist drugs like methotrexate.
- Presentation is similar to B12 deficiency but lacks neurological features.
- Pregnancy-related folate deficiency can lead to neural tube defects.
- Treatment involves oral folic acid supplementation at 5mg/day.
- It's important to exclude B12 deficiency before treating folate deficiency.
Anaemia Aetiology
- Mean Corpuscular Volume (MCV) is normal (80) in normocytic anaemia.
- Microcytic anaemia is associated with Thalassemia, Anaemia of chronic disease, Iron deficiency, Lead poisoning, and Sideroblastic.
- Macrocytic anaemia includes Foetus (pregnancy), Alcohol, Thyroid (hypothyroidism), Reticulocytosis, B12/Folate (megaloblastic macrocytic) , Cirrhosis, and drugs (phenytoin, metformin, methotrexate).
Anaemia - Haemolytic Anaemias
- Haemolytic Anaemia is related to RBC breakdown.
-
Diagnosis involves:
- Biochemical tests showing increased LDH, increased bilirubin, and decreased haptoglobin.
- Blood film morphology revealing reticulocytosis.
- Coomb’s test to identify IgG or C3 covering red cells - agglutination indicates a positive test.
Anaemia - Haemolytic Anaemias - G6PD Deficiency
- G6PD Deficiency is an X-linked disorder affecting glucose-6-phosphate dehydrogenase, which maintains glutathione.
- Reduced glutathione levels lead to increased RBC sensitivity to oxidative stress and haemolysis.
- Common in regions with high malaria prevalence.
- Presentation is often asymptomatic, but can manifest as dark red/black urine (haemoglobinuria), prolonged/severe neonatal jaundice, and triggers like fava beans, acute illness/infection, and oxidative drugs.
- Diagnosis is made through smear review and enzyme assay.
- Treatment focuses on avoiding precipitants.
Anaemia - Haemolytic Anaemias - Sideroblastic Anaemia
- Sideroblastic Anaemia is characterized by failure to produce heme.
Anaemia - Haemolytic Anaemias - Thalassemia
- Thalassemia is a congenital disorder caused by alpha or beta Hb chain deletions, primarily affecting Asians and Mediterraneans.
-
Three syndromes:
- Thalassemia trait: Asymptomatic, microcytosis.
- Thalassemia intermedia: Intermittent haemolysis.
- Thalassemia major: Deletion of two beta chains leading to nucleated red cells, iron overload, and lifelong transfusion dependence.
- Diagnosis involves haemoglobin electrophoresis and blood film showing microcytic hypochromic cells, target cells, anicytosis (variation in size) and poikilocytosis (variation in shape).
Anaemia - Haemolytic Anaemias - Sickle Cell Anaemia
- Sickle Cell Anaemia is characterised by sickle-shaped red blood cells.
-
Pathophysiology:
- Autosomal recessive inheritance with a missense mutation in the HBB gene, replacing glutamic acid with valine at the 6th amino acid of beta-globin.
- Sickle haemoglobin consists of two alpha-globin chains and two mutated beta-globin chains.
- Repeated sickling weakens the RBC membrane, leading to anaemia, haemoglobin spillage causing decreased haptoglobin and increased unconjugated bilirubin, vaso-occlusion affecting bones (dactylitis, avascular necrosis), the spleen (splenic infarct), the brain (stroke), the lungs (acute chest syndrome), the kidneys (haematuria/proteinuria), and the penis (priapism).
- Diagnosis: Newborn blood spot screen, blood smear, and protein electrophoresis showing HbS (sickle haemoglobin).
- Management involves oxygen and fluids, pain control with opioids, infection management with antibiotics and prophylaxis, blood transfusions, and bone marrow transplant.
- Prevention in children includes penicillin and polysaccharide vaccine against Streptococcus pneumoniae and hydroxyurea to increase fetal haemoglobin.
Blood Groups - ABO
- The ABO blood group system classifies blood types based on the presence of A and B antigens on red blood cells (RBCs).
- Antibodies are present in the plasma when the corresponding antigens are not present on the RBCs.
- ABO blood type can be tested in serum.
- ABO gene on chromosome 9 is codominant for A/B and recessive for O.
- Babies do not produce anti-A or anti-B IgM antibodies until a few months old.
- Some maternal antibodies (IgG) can cross the placenta and enter the fetal circulation during pregnancy.
Blood Groups - Rh
- The Rh blood group system determines whether an individual is positive or negative.
- The RHD gene on chromosome 1 is dominant.
- Rh antigen D, primarily located on RBCs, is responsible for Rh-positivity.
- Antibodies are IgG, not naturally occurring in serum, and develop in response to exposure to Rh-positive cells, typically through transfusion or pregnancy.
Blood Grouping Procedures
- Cell Typing (Forward grouping) determines the presence of ABO and Rh antigens on red blood cells.
- Serum Typing (Reverse Grouping) identifies antibodies present in serum.
- Agglutination indicates a positive test for cell typing and a negative test for serum typing.
Haemolytic Disease of Foetus & Newborn (HDFN)
- Haemolytic Disease of Foetus & Newborn (HDFN) presents with jaundice and kernicterus (brain damage due to bilirubin accumulation).
- ABO incompatibility, mainly in type O mothers with A/B foetuses, contributes to HDFN.
- However, Rh blood group incompatibility is the major cause.
- RhD-negative mothers and RhD-positive children are at risk.
- Sensitisation occurs during the first pregnancy with small amounts of fetal blood entering the mother's circulation.
- Subsequent pregnancies with RhD-positive babies are affected.
- Prevention includes anti-D Ig administration to unsensitized mothers to remove fetal RBCs and using Rh(D) negative blood products in women of childbearing age.
Blood Products
- Whole blood can be separated into red blood cells (RBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate.
- RBCs are leukodepleted, stored at 4°C, and have a shelf life of 42 days.
- FFP contains all plasma components, thawed in 30 minutes, and stored in a -1Y freezer.
- Platelets are obtained from the buffy coat or apheresis, stored at room temperature, and have a 5-day shelf life.
- Cryoprecipitate is a cold precipitate of frozen plasma containing Factor VIII, XIII, vWF, and fibrinogen, stored in a -1Y freezer.
- All cellular blood products in Australia are leukoreduced to prevent HLA alloimmunization, transfusion-transmitted CMV, and febrile non-haemolytic transfusion reactions.
- Irradiation of blood products (gamma-irradiation) prevents **transfusion-associated graft-versus-host disease (TA-GVHD) **, which typically presents two weeks after transfusion with rash, pancytopenia, and abnormal liver function.
- Irradiation is indicated for immunosuppressed patients, especially those sharing HLA types.
- Irradiation shortens shelf life, with varying effects on different blood products.
Blood Transfusions
- Pre-transfusion testing includes identifying the patient, ABO/Rh typing of both donor and patient, antibody screen, and crossmatch for FFP and packed red cells.
- Blood transfusion is considered for acute/chronic anaemia, with alternatives evaluated as needed.
- Transfusion volume and speed are adjusted to increase Hb by 10g/L over 2-4 hours.
- Emergency release of blood is used when there's no available specimen, with O Rh(D) negative blood preferred for women of childbearing age and O Rh(D) positive for all others.
- ABO/Rh compatible blood is released if specimen is available with a 10-15 minute turnaround time.
- Immediate spin crossmatch compatible blood can also be released within 15-30 minutes.
- Patient identification is crucial at the time of transfusion.
Blood Transfusion Reactions/Complications
-
Complications include:
- Acute Haemolytic Transfusion Reactions, occurring in 1/50,000 transfusions, usually due to ABO incompatibility, causing intravascular haemolysis and cytokine release.
- Allergic reactions, which are usually mild but can be severe.
- Febrile non-haemolytic transfusion reactions.
- Transfusion-associated circulatory overload (TACO), associated with rapid transfusion.
- Transfusion-related acute lung injury (TRALI).
- Post-transfusion purpura (PTP).
- Transfusion of packed red cells increases the risk of spontaneous or post-traumatic bleeding compared to warfarin.
Bleeding/Clotting Pathology
- Thrombosis (excessive clotting) can lead to deep vein thrombosis (DVT) and pulmonary embolism (PE).
- Bleeding disorders include haemophilia A/B, disseminated intravascular coagulation (DIC), and Von Willebrand's disease.
Deep Vein Thrombosis (DVT)
- DVT affects large veins, usually in the lower limbs, causing partial or complete vein occlusion.
- Incidence is 1/1000 adults.
- Presentation includes unilateral swelling, pain, redness, and warmth.
- Complications include pulmonary embolism (PE).
- Diagnosis involves a Well's score, D-dimer to rule out DVT if negative, and a Doppler ultrasound.
- Management involves anticoagulants like apixaban, and potentially surgical interventions like percutaneous aspiration thrombectomy, vena cava filter, venous balloon dilatation, and stent placement.
- Prevention strategies include heparin post-surgery, warfarin, weight management, and compression stockings.
- Risk factors for DVT include Virchow's triad - surgery, cancer, COCP, and pregnancy – as well as genetic factors like factor V Leiden, protein C/S deficiency, and antithrombin deficiency.
Pulmonary Embolism (PE)
- PE occurs when a thrombus lodges in a pulmonary artery.
- Incidence is 1/2000.
- Presentation includes dyspnoea, sudden sharp chest pain aggravated with deep breathing or coughing, cough with blood or pink foamy mucus, tachycardia, tachypnoea, sweating, anxiety, and syncope.
- Diagnosis uses a modified Well's score for risk assessment, D-dimer to rule out PE if low, and imaging such as CTPA (gold standard) or V/Q scan (pregnancy).
- Treatment includes short-term oxygen therapy, heparin or LMWH, thrombolysis for massive PE, and long-term warfarin.
Haemophilia A and B
- Haemophilia A and B are X-linked recessive disorders, often arising from new mutations.
- Haemophilia A involves factor VIII deficiency.
- Haemophilia B (Christmas disease) affects factor IX.
- Diagnosis involves genetic tests, prolonged activated partial thromboplastin time (APTT), and decreased levels of the respective factor.
- vWF levels are normal in haemophilia.
- Severity is classified based on factor level, with 5% representing mild haemophilia.
- Presentation is similar for both types, including deep haemorrhage in muscles and joints, post-traumatic/post-operative bleeding, mucocutaneous bleeding (gums, nosebleeds), haematomas, and ecchymosis.
- Treatment varies based on severity and involves replacing the deficient factor.
Disseminated Intravascular Coagulation (DIC)
- DIC is an acquired syndrome characterized by activation of coagulation pathways, leading to increased clotting and bleeding.
- Activation of coagulation pathways depletes platelets and coagulation factors, contributing to the bleeding.
- Diagnosis is based on prolonged APTT, INR, and thrombin time (TT) in proportion to severity, increased D-dimer, normal or decreased platelet count, and decreased fibrinogen.
- Presentation includes bleeding (epistaxis, gingival bleeding, GI bleeding, petechiae, ecchymosis, haematuria), oliguria, cough, dyspnoea, fever, hypoxia, hypotension, and mental disorientation.
- Treatment focuses on treating the underlying disorder, replacing plasma, platelets, and clotting factors to control bleeding.
- Complications include life-threatening haemorrhage, acute renal failure, gangrene, and loss of digits.
Von Willebrand's Disease (vWD)
- vWD is a common genetic disorder affecting 1% of the population.
- Autosomal dominant inheritance leads to vWF deficiency.
- vWF is required for platelet adhesion and activation, and acts as a carrier for factor VIII, mimicking haemophilia A.
- Presentation includes mild to moderate bleeding.
- Diagnosis involves mildly prolonged APTT, vWD assays, and decreased factor VIII.
- Treatment is usually minimal, but can involve tranexamic acid for heavy periods, vasopressin analogue (DDAVP) for planned surgery, and infusions of concentrated vWF for severe vWD.
Thrombocytopenia
- Thrombocytopenia refers to low platelet counts.
- Mild levels are 100-150, moderate is 30-100, and severe is less than 30.
- Aetiology includes increased destruction, often immune-mediated as in immune thrombocytopenic purpura (ITP).
- Other causes include decreased production, consumption, and dilution.
- Presentation involves increased bleeding (petechiae, ecchymosis, epistaxis, gingival bleeding, menorrhagia).
- Treatment depends on the cause and severity, and may involve steroids, immunoglobulins, splenectomy, and platelet transfusions.
Haematopoiesis
- Production of blood cells in the bone marrow, called medullary haematopoiesis
- 200 billion cells are produced daily
- Production in other tissues is called extramedullary haematopoiesis
Aplastic Anaemia (AA)
- Reduction in all blood cells (pancytopenia) caused by damage to bone marrow
- Low reticulocyte count can indicate either AA or renal impairment (lack of EPO)
- AA presents with neutropenia and thrombocytopenia in addition to a low reticulocyte count
Aetiology
- Inherited (Fanconi anaemia, Dyskeratosis congenita, Schwachman-Diamond syndrome)
- Acquired (immune-mediated, toxins, occupational/environmental exposures, chemotherapy/radiation, infections (EBV))
Diagnosis
- Bone marrow biopsy is used to differentiate AA from other causes of pancytopenia, showing:
- Hardly any progenitors
- Mostly fat
Myelodysplastic Syndrome
- A clonal disorder affecting hematopoietic stem cells (HSCs)
- HSCs are dysplastic, resulting in peripheral pancytopenia
- Bone marrow may appear hypercellular or hypocellular
- Can progress to acute myeloid leukaemia
Blood Components
- 55% Plasma
- Plasma proteins:
- Albumin
- Globulins (clotting factors)
- Immunoglobulins
- Fibrinogen
- Plasma proteins:
- 45% Haematocrit (RBC)
Anaemia - Vitamin B12 deficiency
- Vitamin B12 is stored in the liver
- Functions:
- Required for B9 function
- Nerve function
- Usually due to malabsorption:
- Pernicious anaemia: autoantibodies against intrinsic factor (IF) or parietal cells
- Gastrectomy
- Inflammatory bowel disease
- Inadequate intake: vegan diet
Pathophysiology
- Deficiency leads to:
- Megaloblastic macrocytic anaemia
- Oval macrocytes
- Pancytopenia (severe cases)
- Poikilocytosis
Diagnosis
- Autoantibody screen
- Tests for intrinsic factor antibodies
- Schilling test
- Measures Vitamin B12 absorption with and without IF
- Elevated homocysteine
- Homocysteine needs Vitamin B12 as a cofactor
Treatment
- Hydroxocobalamin (IM)
- 1mg every alternate day for 2 weeks
- Follow up with 1mg every 2 months
- Lifelong therapy is required for pernicious anaemia
- Do not administer folic acid alone to patients with Vitamin B12 deficiency
- Folic acid will not correct the neurologic deficit
Presentation
- Anaemia
- Lethargy
- Pallor
- Glossitis
- Neurological issues
- Peripheral neuropathy
- Numbness
- Dementia
Anaemia - Folate Deficiency
- Folate is found in green leafy vegetables, yeast, liver, and kidney
- Absorbed in the jejunum
- Function: DNA synthesis
Aetiology
- Dietary deficiency
- Chronic alcoholics
- Poor and elderly
- Overcooked vegetables
- Malabsorption
- Increased requirement
- Pregnancy and infancy
- Chronic haemolysis
- Drugs:
- Phenytoin (reduces folate absorption)
- Methotrexate toxicity (folate antagonist)
Presentation
- Similar to B12 deficiency but without neurologic features
- Leads to neural tube defects in pregnancy
Treatment
- Oral folic acid supplementation
- 5mg/day
- Exclude Vitamin B12 deficiency
Anaemia Aetiology
Mean Corpuscular Volume (MCV)
- Normal = 80
Normocytic Anaemia (MCV normal)
- ABCD:
- Acute blood loss
- Bone marrow failure
- Chronic disease
- Destruction (haemolytic anaemia)
Microcytic Anaemia (MCV low)
- TAILS
- Thalassemia
- Anaemia of chronic disease
- Iron deficiency
- Lead poisoning
- Sideroblastic anaemia
Macrocytic Anaemia (MCV high)
- FATRBC
- Foetus (pregnancy)
- Alcohol
- Thyroid (hypothyroidism)
- Reticulocytosis
- B12/Folate*
- Cirrhosis
- Drugs (phenytoin, metformin, methotrexate)
- Megaloblastic macrocytic anaemia (B12/Folate deficiency)
Anaemia - Haemolytic Anaemias
- Anaemia due to red blood cell (RBC) breakdown
Diagnosis
- Biochemical tests:
- Increased LDH, bilirubin
- Decreased haptoglobin
- Blood film morphology
- Essential for diagnosis
- Reticulocytosis
- Coombs' test
- Detects IgG or C3 on red cells
- Positive result indicates agglutination
Anaemia - Haemolytic Anaemias - Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
- X-linked deficiency of G6PD
- G6PD maintains glutathione levels, which mops up oxidative stress
- Deficiency leads to increased RBC susceptibility to oxidative stress and haemolysis
- Common in regions with endemic malaria
Presentation
- Asymptomatic in most cases
- Dark red/black urine
- Prolonged or severe neonatal jaundice
- Triggers:
- Fava beans
- Acute illness/infection
- Medications (oxidative drugs)
Diagnosis
- Blood smear review
- Specific enzyme assay
Treatment
- Avoid precipitants
Anaemia - Haemolytic Anaemias - Sideroblastic Anaemia
- Failure to produce heme
Anaemia - Haemolytic Anaemias - Thalassemia
- Congenital deletion of alpha or beta haemoglobin chains
- Common in individuals of Asian and Mediterranean descent
Syndromes
- Thalassemia trait:
- Asymptomatic
- Microcytosis
- Thalassemia intermedia:
- Intermittent haemolysis
- Thalassemia major:
- 2 beta chains deleted
- Nucleated red cells
- Iron overload
- Lifelong transfusion dependence
Diagnosis
- Haemoglobin electrophoresis
- Blood film:
- Microcytic hypochromic
- Target cells
- Anicytosis
- Poikilocytosis
Anaemia - Haemolytic Anaemias - Sickle Cell Anaemia
- Red blood cells are shaped like a sickle due to a missense mutation in the HBB gene
Pathophysiology
- Autosomal recessive inheritance
- Missense mutation in the HBB gene
- 6th amino acid of beta-globin is valine, instead of glutamic acid
- Sickle haemoglobin: 2 alpha-globin + 2 mutated beta-globin
- Repeated sickling of RBCs weakens the membrane, leading to:
- Anaemia
- Haemoglobin spillage:
- Decreased haptoglobin (recycling)
- Increased unconjugated bilirubin (jaundice, gallstones)
- Sickle shape leads to vaso-occlusion, causing:
- Bones:
- Dactylitis (digit inflammation)
- Avascular necrosis
- Spleen:
- Splenic infarct
- Susceptibility to encapsulated bacteria
- Brain:
- Stroke
- Lungs:
- Acute chest syndrome
- Kidneys:
- Haematuria
- Proteinuria
- Penis:
- Priapism (painful prolonged erection)
- Bones:
Diagnosis
- Newborn blood spot screen
- Blood smear
- Protein electrophoresis for HbS
Management
- Oxygen and fluids
- Pain management (opioids)
- Infection:
- Antibiotics
- Prophylaxis
- Blood transfusion
- Bone marrow transplant
- Prevention:
- Children:
- Penicillin
- Polysaccharide vaccine against Streptococcus pneumoniae
- Hydroxyurea:
- Increases gamma-globin
- Increases fetal haemoglobin
- Children:
Blood Groups - ABO
- Most common in Australia: O+
- Least common: AB-
ABO Blood Types
- Antigens: A and B
- Antibodies:
- Present in plasma when the corresponding antigen is not on RBCs
- Can be tested for in serum
- IgM
- ABO gene (chromosome 9):
- Codominant A/B
- Recessive O
Exceptions
- Babies do not produce anti-A or anti-B (IgM) until several months old
- During pregnancy, some of the mother's antibodies (IgG) are transported across the placenta into fetal circulation
Blood Groups - Rh
- Rh positive or negative based on the presence or absence of the RhD antigen
- RHD gene on chromosome 1, dominant
- Antigen: D (mainly), confined to red blood cells (RBCs)
- Antibodies:
- IgG
- Do not occur naturally in serum
- Formed as an immune response to red cells carrying the antigen (usually due to transfusion or pregnancy)
Blood Grouping Procedures
1. Cell Typing (Forward Grouping)
- Determines ABO and Rh antigen on cells
- Donor cells are tested with anti-sera containing antibodies to ABO/Rh antigens
- Agglutination indicates a positive test result
2. Serum Typing (Reverse Grouping)
- Determines antibodies present in serum
- Donor serum is tested with cells of known blood groups
- Agglutination indicates a negative test result
Haemolytic Disease of Foetus & Newborn (HDFN)
- Symptoms: Jaundice and kernicterus
ABO incompatibility
- Most common in type O mothers with foetuses with type A/B blood
- 1% of type O mothers have high levels of IgG antibodies against A and B, which cross the placenta and cause haemolysis within the placenta
Rh blood group incompatibility
- Rh D-negative mother and Rh D-positive child
- Occurs when the mother is sensitized to the RhD antigen in previous pregnancies
- Sensitization requires a small amount of foetal blood to enter the mother’s circulation
- Affects subsequent pregnancies with RhD-positive babies
Prevention
- Administer anti-D immunoglobulin to all unsensitised mothers
- Anti-D immunoglobulin removes foetal RBCs leaked into the mother’s circulation
- Use Rh(D)-negative blood products in women of child-bearing age
Blood Products
-
Whole blood can be centrifuged into different components:
- Red cells:
- Packed red cells (Hct)
- Leukocyte-depleted
- Stored at 4°C
- Fresh frozen plasma:
- Contains all plasma components (including clotting factors)
- Thawed in 30 minutes
- Stored in a -1Y freezer
- Platelets:
- Buffy coat or apheresis
- Stored at room temperature
- Shelf life: 5 days
- Cryoprecipitate:
- Cold precipitate of frozen plasma
- Contains factor VIII, XIII, vWF, and fibrinogen
- Stored in a 1Y freezer
- Red cells:
-
All cellular products in Australia are leukoreduced to:
- Prevent:
- HLA alloimmunization
- Transfusion-transmitted CMV in at-risk patients
- Febrile non-haemolytic transfusion reactions
- Prevent:
-
Irradiated blood products are used to prevent transfusion-associated graft-versus host disease (TA-GVHD)
- Irradiated with gamma irradiation
- TA-GVHD presents 2 weeks after transfusion and is characterized by rash, pancytopenia, and abnormal liver function
- Indications:
- Immunosuppressed patients
- Shared HLA type
- Decreases shelf life
- Effects:
- Red cells: membrane damage, shortened survival
- Platelets: no clinically significant change (all platelet products are irradiated)
- Granulocytes: conflicting
Blood Transfusion
Pre-Transfusion Testing
- Identify patient specimen
- ABO and Rh(D) typing of donor and patient
- Antibody screen
- Tested against 3 screening cells with known RBC phenotype
- Positive test requires further investigation:
- Indirect antiglobulin test to identify free antibodies in patient plasma
- Gel/column format
- Crossmatch:
- Required for fresh frozen plasma and packed red cells
- Immediate spin or computer crossmatch if no clinically significant antibodies are present
- Faster, less reagent, more efficient
- Release of blood for transfusion
Transfusing Blood
- Consider:
- Acute/chronic anaemia
- Alternatives to transfusion
- Amount and speed of transfusion:
- 1 unit (240ml) given initially and reassessed
- Aim to raise Hb by 10g/L
- Transfuse over 2-4 hours
- Emergency release of blood:
- No specimen:
- O Rh(D) negative for women of child-bearing age
- O Rh(D) positive for all others
- Current specimen (ABO/Rh known):
- ABO Rh(D) compatible (10-15 minutes)
- Current specimen (immediate spin crossmatch compatible)
- Immediate spin crossmatch compatible (15-30 minutes)
- No specimen:
Blood Transfusion Reactions/Complications
- Complications
- Increased risk of spontaneous or post-traumatic bleeding compared to warfarin
Acute Haemolytic Transfusion Reactions
- 1/50,000 transfusions
- Usually due to ABO incompatibility
- Intravascular haemolysis:
- IgM antibodies present in blood activate complement, leading to cytokine release
- Symptoms:
- Fever
- Chills
- Back pain
- Hypotension
- Shock
- Haemoglobinuria
- Treatment:
- Stop transfusion
- Fluids
- Diuretics
- Blood products
Bleeding/Clotting Pathology
- Too much Clotting:
- Deep vein thrombosis (DVT)
- Pulmonary embolism (PE)
- Too much Bleeding:
- Haemophilia A/B
- Disseminated intravascular coagulation (DIC)
- Von Willebrand’s disease
Deep Vein Thrombosis (DVT)
- Thrombus in the body's large veins, usually in the lower limbs, leading to complete or partial occlusion of circulation in the vein
- Incidence: 1/1000 adults
- Presentation:
- Unilateral (can be bilateral) swelling/oedema
- Pain
- Redness and warmth
- Complications:
- Pulmonary embolism
Risk Factors
- Virchow's triad:
- Stasis
- Hypercoagulability
- Endothelial damage
- Other factors:
- Surgery
- Cancer
- COCP/Pregnancy
- Genetic:
- Factor V Leiden
- Protein C/S deficiency
- Antithrombin deficiency
Diagnosis
- Well's score - assess risk
- D-dimer - rules out DVT if result is negative
- Doppler ultrasound
Management
- Anticoagulants (apixaban)
- Surgical:
- Percutaneous aspiration thrombectomy
- Vena cava filter (for PE prevention)
- Venous balloon dilatation and stent
- Prevention:
- Heparin (for surgery)
- Warfarin
- Weight management
- Compression stockings
Pulmonary Embolism (PE)
- Thrombus lodged in an artery of the lung
- Incidence: 1/2000
- Presentation:
- Dyspnoea
- Sudden, sharp chest pain, aggravated by deep breathing or coughing
- Cough
- Blood or pink, foamy mucus
- Tachycardia
- Tachypnoea
- Sweating
- Anxiety
- Syncope
Diagnosis
- Modified Well's score
- D-dimer - rules out PE if result is low
- Imaging:
- CTPA (gold standard)
- V/Q Scan (used during pregnancy)
Treatment
- Short term:
- Oxygen support
- Heparin/LMWH
- Thrombolysis if massive
- Long term: warfarin
Haemophilia A and B
- X-linked recessive deficiency of clotting factors
- Often a new mutation
- Haemophilia A: factor VIII deficiency
- Haemophilia B (Christmas disease): factor IX deficiency
Diagnosis
- Genetic tests
- Prolonged activated partial thromboplastin time (aPTT)
- Decreased factor VIII (A) or factor IX (B)
- Normal von Willebrand factor
Severity
- Mild haemophilia: factor level is 5% or greater
Presentation
- Nearly identical for haemophilia A and B
- Deep haemorrhage: muscles, joints
- Post-traumatic and post-operative bleeding
- Mucocutaneous bleeding (gums, nosebleeds)
- Haematomas
- Ecchymosis
Treatment
- Genetic testing and aPPT are essential for diagnosis.
- Factor replacement therapy (e.g. recombinant factor VIII or IX) is the mainstay of treatment.
- Desmopressin (DDAVP) can be administered for milder cases to increase factor VIII levels.
- Prophylactic factor replacement regimens can help prevent bleeding episodes.
Disseminated Intravascular Coagulation (DIC)
- Acquired syndrome caracterized by:
- Activation of coagulation pathways
- Increased clotting
- Increased bleeding due to depletion of platelets and coagulation factors
- Intravascular thrombi
Diagnosis
- Prolonged aPTT, INR, TT (proportional to severity)
- Increased D-dimer
- Normal or decreased platelet count
- Decreased fibrinogen
Presentation
- Bleeding:
- Epistaxis
- Gingival bleeding
- GI bleeding
- Petechiae
- Ecchymosis
- Haematuria
- Oliguria
- Cough
- Dyspnoea
- Fever
- Hypoxia
- Hypotension
- Mental disorientation
- Delirium
- Coma
Treatment
- Treat the underlying disorder
- Replace plasma, platelets and clotting factors
Complications
- Life-threatening haemorrhage
- Acute renal failure
- Gangrene
- Loss of digits
Von Willebrand’s Disease
- Common genetic disorder
- 1% of the population
- Autosomal dominant inheritance
- Deficiency in von Willebrand factor (vWF)
- vWF is required for platelet adhesion/activation and is a carrier for factor VIII
- This can mimic haemophilia A
Presentation
- Mild-moderate bleeding disorder
Diagnosis
- Mildly prolonged aPPT
- vWF assays
- Decreased factor VIII
Treatment
- Usually minimal
- Heavy periods: tranexamic acid
- Planned surgery: vasopressin analogue (DDAVP)
- Severe vWD: infusions of concentrated forms of vWF purified from human plasma
Thrombocytopenia
- Low platelet count
- Mild: 100-150 x 10^9/L
- Moderate: 30-100 x 10^9/L
- Severe: <30 x 10^9/L
Aetiology
- Increased destruction:
- Immune thrombocytopenic purpura (ITP)
- Decreased production:
- Aplastic anaemia
- Myelodysplasia
- Leukaemia
- Sequestration:
- Hypersplenism
- Dilution
- Massive blood transfusion
Presentation
- Spontaneous bleeding:
- Petechiae
- Purpura
- Ecchymosis
- Mucosal bleeding:
- Epistaxis
- Gingival bleeding
- Gastrointestinal bleeding
- Menorrhagia
- Intracranial haemorrhage (severe cases)
Treatment
- Corticosteroids
- Immunosuppressants
- Splenectomy
- Platelet transfusion (severe cases)
- Treatment of the underlying cause
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