Y2S2 P1 Haematology Physiology
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Y2S2 P1 Haematology Physiology

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Questions and Answers

What is the main diagnostic tool used to assess the risk of pulmonary embolism?

  • CTPA scan
  • Echocardiogram
  • Modified Well's score (correct)
  • D-dimer test

    • Which treatment is considered for long-term management of pulmonary embolism?

  • Heparin
  • Thrombolysis
  • Warfarin (correct)
  • Oxygen support

    • What type of bleeding is commonly associated with hemophilia A and B?

  • Ocular bleeding
  • GI bleeding
  • Intracranial bleeding
  • Nosebleeds (correct)

    • Which laboratory test would be prolonged in patients with Disseminated Intravascular Coagulation (DIC)?

    <p>PT</p> Signup and view all the answers

    What is the underlying cause of Von Willebrand's Disease?

    <p>Deficiency of Von Willebrand factor</p> Signup and view all the answers

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

    <p>Life-threatening hemorrhage</p> Signup and view all the answers

    What is the common presentation of a patient with thrombus lodged in the lung artery?

    <p>Dyspnoea and chest pain</p> Signup and view all the answers

    In which scenario would thrombolysis be indicated for pulmonary embolism?

    <p>If the PE is massive</p> Signup and view all the answers

    What is typically observed in the laboratory tests for Hemophilia A?

    <p>Prolonged APTT</p> Signup and view all the answers

    What is a common underlying reason for thrombocytopenia?

    <p>Increased platelet destruction</p> Signup and view all the answers

    What is the term for the formation of blood cells in the bone marrow?

    <p>Medullary haematopoiesis</p> Signup and view all the answers

    Which condition is characterized by a reduction in all blood cell types due to bone marrow damage?

    <p>Aplastic Anaemia</p> Signup and view all the answers

    What does a low reticulocyte count indicate in the context of anaemia?

    <p>Bone marrow damage</p> Signup and view all the answers

    Which of the following is NOT an aetiology of Aplastic Anaemia?

    <p>Chronic kidney disease</p> Signup and view all the answers

    How does myelodysplastic syndrome typically present?

    <p>Peripheral pancytopenia</p> Signup and view all the answers

    Which component constitutes about 55% of blood?

    <p>Plasma</p> Signup and view all the answers

    What is the main cause of pernicious anaemia?

    <p>Autoantibody production against intrinsic factor</p> Signup and view all the answers

    Which type of anaemia is characterized by a high mean corpuscular volume (MCV)?

    <p>Macrocytic anaemia</p> Signup and view all the answers

    Which of the following is a common trigger for G6PD deficiency-related haemolysis?

    <p>Fava beans</p> Signup and view all the answers

    What type of anaemia is associated with congenital deletions in alpha or beta hemoglobin chains?

    <p>Thalassemia</p> Signup and view all the answers

    In patients with sickle cell anaemia, what phenomenon is often seen due to RBC sickling?

    <p>Splenic infarction</p> Signup and view all the answers

    What is the function of vitamin B12 in the body?

    <p>DNA synthesis</p> Signup and view all the answers

    Which test is used to confirm B12 absorption deficiency?

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

    Which drug class is known to reduce folate absorption?

    <p>Anticonvulsants</p> Signup and view all the answers

    What is the most common blood group in Australia?

    <p>O+</p> Signup and view all the answers

    Which antibodies are present in the serum of an individual with type A blood?

    <p>Anti-B</p> Signup and view all the answers

    What type of blood group incompatibility is primarily associated with Rh D-negative mothers?

    <p>Rh D incompatibility</p> Signup and view all the answers

    What common complication can arise from acute haemolytic transfusion reactions?

    <p>Intravascular haemolysis</p> Signup and view all the answers

    Which factor is NOT typically assessed in pre-transfusion testing?

    <p>Blood pressure</p> Signup and view all the answers

    How does hydroxyurea function in the treatment of conditions like sickle cell disease?

    <p>Increases fetal haemoglobin</p> Signup and view all the answers

    What cells are tested during the forward grouping procedure?

    <p>Donor cells</p> Signup and view all the answers

    During pregnancy, which antibodies can cross the placenta?

    <p>IgG</p> Signup and view all the answers

    What is the primary purpose of irradiating blood products?

    <p>To prevent transfusion associated graft-versus host disease</p> Signup and view all the answers

    What risk factor is NOT part of Virchow's triad related to thrombus formation?

    <p>Infection</p> Signup and view all the answers

    What is the consequence of sensitization in Rh D-negative mothers?

    <p>Risk of complications in subsequent pregnancies</p> Signup and view all the answers

    What is NOT a component of whole blood after centrifugation?

    <p>Red cells</p> Signup and view all the answers

    What symptom is a common sign of haemolytic disease of the fetus and newborn (HDFN)?

    <p>Jaundice</p> Signup and view all the answers

    What is a key characteristic of fresh frozen plasma?

    <p>Can be thawed in 30 minutes</p> Signup and view all the answers

    Which of the following is a common clinical presentation of pulmonary embolism?

    <p>Sudden sharp chest pain aggravated by deep breathing</p> Signup and view all the answers

    What laboratory finding would you expect to be elevated in a patient with Disseminated Intravascular Coagulation (DIC)?

    <p>D-dimer</p> Signup and view all the answers

    What is a primary treatment option for managing severe Von Willebrand's Disease?

    <p>Infusions of concentrated vWF</p> Signup and view all the answers

    In patients with hemophilia A, which of the following laboratory tests would likely show a prolonged result?

    <p>APTT (Activated Partial Thromboplastin Time)</p> Signup and view all the answers

    Which condition is characterized by the activation of coagulation pathways leading to both thrombosis and bleeding?

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

    Which of the following is a recommended short-term treatment for patients diagnosed with a pulmonary embolism?

    <p>Oxygen support</p> Signup and view all the answers

    What is the genetic nature of Von Willebrand's Disease?

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

    Which of the following could be considered a preventive measure against venous thromboembolism?

    <p>Compression stockings</p> Signup and view all the answers

    What presentation is consistent with a diagnosis of Haemophilia A or B?

    <p>Increased bruising and joint bleeds</p> Signup and view all the answers

    What is the primary immunoglobulin type that constitutes antibodies formed in response to Rh D antigen?

    <p>IgG</p> Signup and view all the answers

    Which blood group is the least common in the Australian population?

    <p>AB-</p> Signup and view all the answers

    What laboratory test is used to identify antibodies present in serum?

    <p>Serum typing</p> Signup and view all the answers

    Which condition can occur due to ABO incompatibility during pregnancy?

    <p>Haemolytic Disease of the Foetus and Newborn (HDFN)</p> Signup and view all the answers

    What is the common treatment strategy for preventing complications in Rh D-negative mothers?

    <p>Administration of anti-D Ig</p> Signup and view all the answers

    What is a possible consequence of acute haemolytic transfusion reactions due to transfusion of incompatible blood?

    <p>Cytokine storm</p> Signup and view all the answers

    Which platelet preparation method involves collecting platelets from a single donor?

    <p>Apheresis</p> Signup and view all the answers

    What is the anticipated effect on red blood cells after gamma-irradiation?

    <p>Decreased shelf life</p> Signup and view all the answers

    What is the main function of hydroxyurea in treating certain blood conditions?

    <p>Increase gamma-globin levels</p> Signup and view all the answers

    Which form of blood product is specifically derived to provide clotting factors?

    <p>Cryoprecipitate</p> Signup and view all the answers

    In the context of blood transfusion, what does a positive crossmatch indicate?

    <p>Incompatibility between serum and red cells</p> Signup and view all the answers

    What is Virchow's triad primarily related to?

    <p>Risk factors for clot formation</p> Signup and view all the answers

    What is the primary cause of apLASTic anaemia?

    <p>Inherited genetic mutations</p> Signup and view all the answers

    Which of the following best describes myelodysplastic syndrome?

    <p>Bone marrow damage leading to peripheral pancytopenia</p> Signup and view all the answers

    What is a common presentation observed in pernicious anaemia?

    <p>Lethargy and glossitis</p> Signup and view all the answers

    Which vitamin is essential for DNA synthesis and is often associated with neural tube defects if deficient during pregnancy?

    <p>Folate (B9)</p> Signup and view all the answers

    What characterizes the anaemia associated with G6PD deficiency?

    <p>Hemolytic with dark urine and bilirubin increase</p> Signup and view all the answers

    What distinguishes sideroblastic anaemia from other types of anaemias?

    <p>Increased iron levels but ineffective erythropoiesis</p> Signup and view all the answers

    Which clinical feature is commonly associated with thalassemia?

    <p>Target cells and microcytic hypochromic red blood cells</p> Signup and view all the answers

    What is the main treatment approach for patients with pernicious anaemia?

    <p>Hydroxocobalamin injections</p> Signup and view all the answers

    In sickle cell anaemia, what is a common complication due to vaso-occlusive crises?

    <p>Spleen infarct leading to infection risks</p> Signup and view all the answers

    Which symptom is least likely to be associated with iron deficiency anaemia?

    <p>Neurological deficits</p> Signup and view all the answers

    In patients with macrocytic anaemia, what is a likely cause of their condition?

    <p>Folate deficiency due to dietary insufficiency</p> Signup and view all the answers

    Which test is essential for diagnosing hemolytic anaemia?

    <p>Coomb’s test</p> Signup and view all the answers

    What condition is specifically characterized by the presence of megaloblastic red blood cells?

    <p>Pernicious anaemia</p> Signup and view all the answers

    What is a key feature of reticulocytosis in the context of haemolytic anaemia?

    <p>Increased demand for erythropoiesis</p> Signup and view all the answers

    Which statement correctly describes a presentation associated with a pulmonary embolism?

    <p>Sudden sharp chest pain worsened by deep breathing</p> Signup and view all the answers

    What is a typical laboratory finding in patients suspected of having Disseminated Intravascular Coagulation (DIC)?

    <p>Decreased fibrinogen levels</p> Signup and view all the answers

    In the management of acute pulmonary embolism, which treatment option is most commonly utilized?

    <p>Apixaban anticoagulant therapy</p> Signup and view all the answers

    What is the primary genetic inheritance pattern of Von Willebrand’s disease?

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

    Which factor is NOT typically associated with increased platelet destruction in thrombocytopenia?

    <p>Increased platelet production</p> Signup and view all the answers

    What laboratory result would most likely indicate Hemophilia A?

    <p>Prolonged APTT with normal factor 9</p> Signup and view all the answers

    Which of the following is a common complication associated with Disseminated Intravascular Coagulation (DIC)?

    <p>Acute renal failure</p> Signup and view all the answers

    What is the major concern when managing severe cases of Von Willebrand's disease?

    <p>Severe hemorrhage during surgery</p> Signup and view all the answers

    In patients with both Haemophilia A and B, what symptom is more commonly observed?

    <p>Bleeding in mucocutaneous areas</p> Signup and view all the answers

    Which of the following conditions type is characterized by increased red blood cell destruction leading to elevated bilirubin levels?

    <p>Hemolytic anemia</p> Signup and view all the answers

    Which of the following treatments is specifically indicated for pernicious anemia to address long-term management?

    <p>Hydroxocobalamin injections</p> Signup and view all the answers

    What is the hallmark blood film finding associated with beta-thalassemia major?

    <p>Target cells</p> Signup and view all the answers

    Which of the following factors can contribute to macrocytic anemia due to vitamin B12 deficiency?

    <p>Use of methotrexate</p> Signup and view all the answers

    Which autoimmune disease is associated with Aplastic Anemia due to intrinsic factors?

    <p>Pernicious anemia</p> Signup and view all the answers

    Which test is used to differentiate between intrinsic factor deficiency and dietary B12 deficiency?

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

    Which of the following is a common characteristic of sideroblastic anemia?

    <p>Failure to produce heme</p> Signup and view all the answers

    Which laboratory finding is typically observed in hemolytic anemias?

    <p>Increased lactate dehydrogenase (LDH)</p> Signup and view all the answers

    What is the complication associated with sickle cell disease that affects the spleen?

    <p>Splenic infarction</p> Signup and view all the answers

    Which of these describes a clinical presentation common to folate-deficiency anemia?

    <p>Macrocytic red blood cells</p> Signup and view all the answers

    What symptom is usually observed in patients with aplastic anemia?

    <p>Pancytopenia</p> Signup and view all the answers

    In sickle cell anemia, which clinical outcome is primarily due to the sickling of red blood cells?

    <p>Splenic sequestration crisis</p> Signup and view all the answers

    Which of the following describes a common consequence of vitamin B12 deficiency?

    <p>Peripheral neuropathy</p> Signup and view all the answers

    Which blood group incompatibility is most commonly associated with a type O mother and A/B child?

    <p>ABO incompatibility</p> Signup and view all the answers

    What type of antibodies are formed in response to the Rh D antigen?

    <p>IgG</p> Signup and view all the answers

    What is the most appropriate blood product to prevent transfusion-associated graft-versus-host disease (TA-GVHD)?

    <p>Irradiated blood products</p> Signup and view all the answers

    Which complication is usually observed due to acute hemolytic transfusion reactions?

    <p>Intravascular hemolysis</p> Signup and view all the answers

    What is the primary risk factor contributing to the formation of a thrombus as per Virchow's triad?

    <p>Allergen exposure</p> Signup and view all the answers

    Which screening test is typically performed to assess antibodies in a patient's serum prior to transfusion?

    <p>Indirect antiglobulin test</p> Signup and view all the answers

    Which of the following components is NOT usually present in fresh frozen plasma?

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

    What is the recommended action for an unsensitized Rh D-negative mother at risk for Rh incompatibility?

    <p>Give anti-D Ig</p> Signup and view all the answers

    What type of blood product predominantly contains clotting factors and must be thawed before use?

    <p>Fresh frozen plasma</p> Signup and view all the answers

    Which symptom is primarily associated with Haemolytic Disease of Fetus and Newborn (HDFN)?

    <p>Jaundice</p> Signup and view all the answers

    Which type of blood group inheritance is described as codominant?

    <p>A and B blood types</p> Signup and view all the answers

    What laboratory finding is typically observed in a patient with Disseminated Intravascular Coagulation (DIC)?

    <p>Prolonged PT and aPTT</p> Signup and view all the answers

    What is the incidence rate of Deep Vein Thrombosis (DVT) in adults?

    <p>1/1000</p> Signup and view all the answers

    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
    • 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)

    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

    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

    • All cellular products in Australia are leukoreduced to:

      • Prevent:
        • HLA alloimmunization
        • Transfusion-transmitted CMV in at-risk patients
        • Febrile non-haemolytic transfusion reactions

    • 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)

    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

    1. Well's score - assess risk
    2. D-dimer - rules out DVT if result is negative
    3. 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

    1. Modified Well's score
    2. D-dimer - rules out PE if result is low
    3. 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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