Haematology Questions PDF

Haematology Resources to Check out Hanyi’s Haematology Notion notes Lots and lots of blood films Hematopoiesis Video (Armando is an actual legend go watch this) Blood Typing 1. ABO Blood groups & RHD 2. Coomb’s Test & Blood Grouping ABO Blood Groups...

Haematology Resources to Check out Hanyi’s Haematology Notion notes Lots and lots of blood films Hematopoiesis Video (Armando is an actual legend go watch this) Blood Typing 1. ABO Blood groups & RHD 2. Coomb’s Test & Blood Grouping ABO Blood Groups General Principles Blood types are named according to the antigen on the RBC If a RBC has the antigen, the plasma won’t have the antibody Universal blood donor: O- Universal plasma donor: AB+ RhD Rhesus D = blood group protein attached to red cells Everyone is either Rh+ or Rh- Rh- individuals will not produce antibodies unless previously exposed to Rh+ RBCs Haemolytic Disease of the Newborn (HDN) HDN Continued... HDN usually occurs in the 2nd pregnancy due to previous exposure Responsible agent: IgG antibodies (past exam question) Treatment Administer RhD immunoglobulin in Rh- pregnant women This helps mop up any foetal RBCs - prevents maternal antibody production Coomb’s Test Agglutination = Positive Test DIRECT ANTIGLOBULIN TEST/COOMB’S TEST INDIRECT ANTIGLOBULIN TEST/COOMB’S TEST Detects antibodies on the surface of RBCs eg, Detects antibodies in the serum Autoimmune haemolysis Pretransfusion testing Drug induced haemolysis Prenatal antibody screen (HDN) Alloimmune haemolysis Eg. HDN. alloimmune haemolytic transfusion reaction Determining Blood Groups CELL TYPING Determines the ABO antigen present on the red cells. Patient's RBCs mixed with known antibodies Agglutination = Positive Determining Blood Groups SERUM TESTING Determines the ABO antibodies present in the patient serum Patient's serum mixed with known RBCs Agglutination = Positive Note: Consider transfusions when Hb < 70 Transfusions gone wrong 😨 Common complications that can arise include: Acute haemolytic transfusion reaction (within 24 hours) Delayed haemolytic transfusion reaction (days - months) Graft vs Host Disease (donor cells/organ attacks host - often see it in immunosuppressed hosts)  1. Microcytic Anaemia 2. Normocytic 3. Macrocytic 4. Some bad jokes  ANAEMIA Deficiency of red blood cells or haemoglobin in the blood Fatigue, shortness of breath, pallor, palpitation, sore tongue, arrhythmia Microcytic Normocytic Macrocytic Decreased Hb production Impaired blood cell production Increased Haemolysis T Thalassaemia reticulocytes Hereditary, autoimmune, Faulty Hb synthesis Megaloblastic Macronormoblastic infection, adverse reaction to drugs A Anaemia of chronic disease B12 deficiency Alcohol Acute blood loss I Less common, slow Iron deficiency onset, neural degeneration Liver disease L Lead poisoning Normal/decreased Bone marrow disease reticulocytes Folate deficiency S Sideroblastic Hypothyroidism Unable to use iron effectively to Anaemia of chronic disease More common nutritional make Hb deficiency, weeks onset, may be drug related Kidney failure Megaloblastic Presentation: Iron deficiency Numbness/tingling Balance/gait Presentation: Confusion Cold feet/hands Diarrhoea nausea Hair loss Haemolysis Brittle nails Bloods: high reticulocytes, low Unusual cravings haptoglobin, high lactate dehydrogenase See “Anaemia -S&S/Causes/Treatments” Notes ANAEMIA Microcytic Iron deficiency Decreased Hb production Presentation: Cold feet/hands T Thalassaemia Hair loss Faulty Hb synthesis Brittle nails Unusual cravings A Anaemia of chronic disease I Iron deficiency L Lead poisoning S Sideroblastic Unable to use iron effectively to make Hb Thalassaemia Common where malaria is endemic Various types and severity depending on genetic mutation More uniform in cell size and shape, much lower Hb compared to MCV Alpha: common in Asia, Africa Beta: more severe, Mediterranean See “Anaemia -S&S/Causes/Treatments” Notes  ANAEMIA Normocytic Increased Haemolysis reticulocytes Acute blood loss Normal/decreased Bone marrow disease reticulocytes Anaemia of chronic disease Kidney failure Haemolysis Bloods: may have high reticulocytes, low haptoglobin, high lactate dehydrogenase Causes: Metabolic abnormalities e.g. G6DP deficiency Haemoglobin abnormalities e.g. sickle cell, thalassaemia Membrane abnormalities e.g. hereditary spherocytosis Immune-mediated Mechanical Drugs See “Anaemia -S&S/Causes/Treatments” Notes ANAEMIA Macrocytic Impaired blood cell production Megaloblastic Presentation: Megaloblastic Macronormoblastic Numbness/tingling Balance/gait Confusion B12 deficiency Alcohol Diarrhoea nausea Less common, slow onset, neural degeneration Liver disease Folate deficiency Hypothyroidism More common nutritional deficiency, weeks onset, may be drug related Pernicious anaemia Intrinsic factor produced in the stomach is needed to absorb Vitamin B12 A lack of IF most commonly occurs due to an autoimmune against intrinsic factor and parietal cells See “Anaemia -S&S/Causes/Treatments” Notes Coagulation 1. Haemostasis 2. Coagulation pathway 3. Related pharmacology 4. Unhelpful movie references HAEMOSTASIS 1. Injury 2. Local smooth muscle contraction 3. Platelet adhesion/activation/aggregation 4. Secondary - Coagulation: fibrinogen to fibrin A B Negative feedback, degrade Va and VIIIa Tiny quantities of thrombin amplify activation of other clotting factors and Hereditary thrombophilia conditions co-factors Defect/deficiency of anticoagulant proteins Antithrombin III Protein C Hereditary haemophilia conditions Protein S Haemophilia A: Deficiency of VIII Genetic mutation increased tendency Haemophilia B: Deficiency of IX towards thrombosis Factor V Leiden (APC resistance) Elevated clotting factors Anticoagulants Enoxaparin LMWH Longer t1/2 Subcutaneous Potentiates How to memorise this? antithrombin action on X Common Factors of 10 in descending order Factor Xa inhibitor 10, 5, 2, 1 Apixaban Rivaroxaban Extrinsic 7issue factor Intrinsic Heparin K K K Antithrombin III binds to Count down from 12 and skip 10 (since it’s heparin common) IV/subcutaneous 12, 11, 9, 8 Emergency reversal - protamine sulphate Vitamin K-dependent factors Warfarin K Ok in pregnancy Oral, onset Australian TV channels (2, 7, 9, 10) delayed Vitamin K antagonist Dabigatran Maintain w/ INR DOAC, no INR, (variable, ~2-3.5) similar efficacy to Teratogenic warfarin Bind reversibly to thrombin Anticoagulants How to memorise this? Common Factors of 10 in descending order 10, 5, 2, 1 Extrinsic 7issue factor Intrinsic Count down from 12 and skip 10 (since it’s common) 12, 11, 9, 8 Vitamin K-dependent factors Australian TV channels (2, 7, 9, 10) Coagulation studies APTT: intrinsic + common TT: common PT: extrinsic + common What is INR? International normalised ratio, derived from PT, standardises testing. What is a mixing test? To determine the cause of a prolonged PT/APTT, the patient’s plasma is mixed with control plasma. Correction with mixing -- suggests a factor deficiency Non-correction with mixing -- suggests the presence of an inhibitor Virchow’s triad A 65 year old patient has had a hip replacement two days ago. She smokes, has hypertension and a BMI of 30. She had breast cancer at Deep Vein Thrombosis 45. In relation to Virchow’s triad, what are some possible risk factors When a clot forms in a vein, commonly in the lower extremities for developing a deep vein thrombosis? and pelvis Pulmonary embolism Occlusion of the pulmonary artery inn the lung, typically by a thrombus (DVT) from the leg or pelvis Antiplatelets Abciximab Glycoprotein Von Willebrand factor IIb/IIIa receptor Synthesised by endothelial cells antagonist lining the surface of blood vessels Some secreted into blood/subendothelial matrix/stored Clopidogrel in cytoplasmic granules Inhibit ADP induced Sites for binding collagen - when activation of platelets by bound, vWF activated, binds to inhibiting ADP binding to surface receptors the P2Y12 receptor Aspirin A carrier for Factor VIII Irreversibly inhibit COX, ○ Deficiency may lead to decrease thromboxane so mildly prolonged APTT, decrease platelet with INR and platelet aggregation normal, usually autosomal dominant, minimal treatment Fibrinolysis and fibrinolytics/anti-fibrinolytics Tranexamic acid Used to treat heavy bleeding, short term Disseminated intravascular coagulation (DIC) Precipitating events: infection, trauma, cancer etc. Excess clotting - ischaemia, organ damage Alteplase Which uses up platelets and Recombinant human tPa, used clotting factors in acute STEMI, Excess bleeding - shock, life-threatening PE hypotension Haematological 1. Hematopoiesis Malignancies 2. Leukemias 3. Lymphomas 4. Myeloid Diseases LEARN WHAT CELLS LOOK LIKE WHAT PLS You’re pretty much guaranteed to get a question asking you to identify the type of blood cell So pls learn it Hematopoiesis Quick Overview 1. Leukemias: Too many WBCs 2. Lymphomas: Too many lymphocytes 3. Multiple Myeloma: Too many B cells 4. Essential Thrombocytosis: Too many platelets 5. Polycythemia Rubra Vera: Too many RBCs 6. Primary Myelofibrosis: Fibrosis of BM - affects everything  Leukemias vs Lymphomas Leukemias Lymphomas Arises from bone marrow Arises from lymph nodes Affects immature WBCs Affects mature lymphocytes Note: Leukemias can metastasise to lymph nodes, but are still considered leukemias due to its SOURCE Leukemias Leukemias: Unregulated proliferation of immature/non-functional leukocytes in the bone marrow (undifferentiated) Build up of these immature leukocytes crowd out the normal cells, resulting in decreased amounts of functional cells - this is known as crowding, and is more often seen in acute leukemias Acute leukemias = more aggressive but often curable Chronic leukemias = often asymptomatic, rarely curable Clinical manifestations Anemia: Syncope, angina, dyspnoea, fatigue (SADF) Thrombocytopenia: Increased bleeding & bruising Leukopenia: Increased infections Systemic: Weight loss, fever, night sweats, loss of appetite Organs: Hepatosplenomegaly, bone pain +/- lymphadenopathy Leukemias - 4 types Acute Myeloid Leukemia (AML) Chronic Myeloid Leukemia (CML) Acute Lymphoid Leukemia (ALL) Chronic Lymphoid Leukemia (CLL) Auer Rods Smudge Cells = AML = CLL Lymphomas Lymphomas: Non-functional lymphocytes accumulating in the lymph nodes (these cells don’t produce antibodies) Two types 1. Hodgkin’s Lymphoma - contains Reed-sternberg cells (Owl eyes) 2. Non-Hodgkin’s Lymphoma - doesn’t contain reed-sternberg cells Hodgkin’s Lymphoma typically has a better prognosis Clinical manifestations B symptoms: Fever, night sweats & weight loss Also tend to see lymphadenopathy Myeloid 1. Polycythemia Rubra Vera 2. Essential Thrombocytosis Diseases 3. Primary Myelofibrosis 4. Multiple Myeloma 5. Myelodysplastic Syndrome Polycythemia Rubra Vera Too many RBCs being produced Management 95% association with a JAK2 mutation Phlebotomy (until Hct ≤ 0.45) Signs & Symptoms Prophylaxis aspirin Thrombotic events Cytoreductive therapy (eg. hydroxyurea, ruxolitinib) Bleeding (intracranial & gastrointestinal) Pruritis after a hot shower Erythromelalgia Diagnosis Increased RBCs - High Hb, Hct or RBC mass BM biopsy with trileage growth JAK 2 mutation Decreased EPO levels (minor criterion) Essential Thrombocytosis Overproduction of platelets 50% of patients have a JAK2 mutation (can also be caused by CALR or MPL mutations) Clinical features Thrombotic events Spontaneous abortion Acute gouty arthritis Headaches Treatment: Low dose aspirin & hydroxyurea Primary Myelofibrosis Fibrosis of the bone marrow as a result of a myeloproliferative neoplasm 50% association with JAK2 mutation Will present with hepatosplenomegaly (extramedullary haematopoesis) Hyperproliferative stage (increased WBC/platelets) → pancytopenic stage Blood film: Teardrop cells (cells have to squeeze out of the fibrotic BM) Bone marrow biopsy: Dry aspiration (punctio sicca) Treatment: Stem cell transplantation (younger patients), or supportive treatment Multiple Myeloma Uncontrolled proliferation of plasma cells producing monoclonal immunoglobulins Signs & Symptoms (CRAB) Hypercalcaemia Renal Failure Anaemia Bony lesions Blood film: Rouleaux bodies (‘Rouleaux bodies roll together’) Bone Marrow: Clusters of plasma cells Urine Test: Bence Jones proteins (produced by neoplastic cells) Myelodysplastic Syndrome Malfunctioning stem cells → ineffective maturation of all cell lineages → cytopenia of multiple cell lines Usually idiopathic etiology, affects elderly patients Blood film: Refractory anemia ○ Doesn’t respond to usual therapy such as iron/folate/B12 Hyposegmented nuclei Large agranular platelets Bone Marrow: Hypercellular & dysplastic Treatment: Possible allogeneic stem cell transplantation, but generally supportive Eg. Blood transfusions, granulocyte colony stimulating factor