Master Haematology
for MRCP Part 1
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Core Concepts
Haematology encompasses the study of blood, blood-forming organs, and blood diseases. Key areas include haemopoiesis (formation of blood cellular components), disorders of red blood cells (anaemias, polycythaemia), white blood cells (leukaemias, lymphomas, myeloproliferative neoplasms, immune deficiencies), platelets (thrombocytopenia, thrombocytosis), and coagulation (bleeding and thrombotic disorders).
- Haemopoiesis: All blood cells originate from a multipotent stem cell in the bone marrow, differentiating into myeloid (RBCs, platelets, granulocytes, monocytes) and lymphoid (T cells, B cells, NK cells) lineages.
- Anaemia Classification: Based on Mean Corpuscular Volume (MCV):
- Microcytic (<80 fL): Iron deficiency, Thalassaemia, Sideroblastic anaemia, Anaemia of chronic disease (sometimes).
- Normocytic (80-100 fL): Anaemia of chronic disease, Renal disease, Acute blood loss, Haemolysis, Aplastic anaemia, Bone marrow infiltration.
- Macrocytic (>100 fL): Megaloblastic (B12/Folate deficiency) vs. Non-megaloblastic (Alcohol, Liver disease, Hypothyroidism, Myelodysplasia, Reticulocytosis).
- Bleeding Disorders: Platelet defects (quantitative/qualitative) lead to mucocutaneous bleeding; coagulation factor defects lead to deep tissue/joint bleeding.
- Thrombophilia: Increased risk of thrombosis. Inherited (Factor V Leiden, Prothrombin gene mutation, Antithrombin, Protein C/S deficiencies) vs. Acquired (Antiphospholipid syndrome, malignancy, OCP, pregnancy, surgery).
- Haematological Malignancies: Leukaemias (acute vs chronic, myeloid vs lymphoid), Lymphomas (Hodgkin vs Non-Hodgkin), Myeloma, Myeloproliferative Neoplasms (MPNs: CML, PV, ET, Myelofibrosis), Myelodysplastic Syndromes (MDS).
- Transfusion Medicine: ABO/Rh compatibility, indications for blood products (RBCs, platelets, FFP, cryoprecipitate), and transfusion reactions.
Clinical Presentation
- Anaemia: Fatigue, pallor, dyspnoea, dizziness. Specific signs: Koilonychia (iron def), angular stomatitis (iron/B12/folate def), glossitis (iron/B12/folate def), jaundice (haemolysis), leg ulcers (sickle cell, thalassaemia).
- Bleeding: Petechiae, purpura, ecchymoses (bruising), epistaxis (nosebleeds), menorrhagia, gum bleeding. Deep haematomas and haemarthrosis (joint bleeding) suggest factor deficiency.
- Thrombosis: Deep Vein Thrombosis (DVT - unilateral leg swelling, pain, erythema), Pulmonary Embolism (PE - sudden dyspnoea, pleuritic chest pain, haemoptysis).
- Lymphadenopathy: Enlarged lymph nodes (localised vs generalised, painful vs painless).
- Splenomegaly/Hepatomegaly: Enlarged spleen/liver, often associated with haemolytic anaemias, infections, or haematological malignancies.
- "B" Symptoms: Unexplained fever (>38°C), drenching night sweats, unexplained weight loss (>10% in 6 months) – common in lymphomas, leukaemias.
- Infections: Recurrent or severe infections due to neutropenia (e.g., leukaemia, aplastic anaemia) or hypogammaglobulinaemia (e.g., CLL, myeloma).
- Bone Pain: Severe, localised bone pain, especially in multiple myeloma.
Diagnosis (Gold Standard)
The Full Blood Count (FBC) and blood film are the cornerstones of haematological diagnosis.
- Anaemias:
- Iron Deficiency: Low ferritin (best single test), low serum iron, high TIBC, low transferrin saturation.
- B12/Folate Deficiency: Low serum B12/folate, raised homocysteine (both), raised methylmalonic acid (B12 only).
- Haemolysis: Reticulocytosis, raised LDH, low haptoglobin, raised unconjugated bilirubin. Direct Antiglobulin Test (DAT/Coombs) for immune haemolysis.
- Thalassaemia: Haemoglobin electrophoresis, genetic testing.
- Aplastic Anaemia: Bone marrow biopsy (hypocellular marrow with fatty replacement).
- Bleeding Disorders:
- Platelet Disorders: FBC (platelet count), platelet function tests (if qualitative defect suspected).
- Coagulation Disorders: Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), Thrombin Time (TT), Fibrinogen, specific factor assays. Von Willebrand screen.
- Thrombophilia: Thrombophilia screen (Factor V Leiden mutation, Prothrombin gene mutation, Antithrombin III, Protein C, Protein S levels, Lupus Anticoagulant, Anticardiolipin antibodies).
- Malignancies:
- Leukaemias: FBC, blood film, bone marrow aspirate/biopsy, flow cytometry, cytogenetics/FISH.
- Lymphomas: Excisional lymph node biopsy (for histology, immunohistochemistry, flow cytometry). Staging with CT/PET scans.
- Myeloma: Serum and urine protein electrophoresis (monoclonal paraprotein), free light chains, bone marrow biopsy, skeletal survey/MRI.
Management (First Line)
- Anaemias: Treat underlying cause.
- Iron Deficiency: Oral iron supplementation (ferrous sulfate). IV iron if malabsorption or intolerance.
- B12/Folate Deficiency: Oral folate. IM B12 (lifelong in pernicious anaemia).
- Haemolytic Anaemia: Steroids for autoimmune haemolysis. Transfusions for severe anaemia.
- Bleeding Disorders:
- Thrombocytopenia: Platelet transfusions if severe bleeding or prophylaxis for invasive procedures. Treat underlying cause (e.g., steroids for ITP).
- Coagulation Factor Deficiencies: Replace deficient factor (e.g., Factor VIII concentrate for Haemophilia A), desmopressin (minor Haemophilia A, vWD). FFP for multiple factor deficiencies.
- Thrombosis: Anticoagulation (heparin, LMWH, warfarin, DOACs). Duration depends on cause (e.g., 3-6 months for provoked DVT/PE, lifelong for unprovoked or recurrent). Thrombolysis for massive PE or limb-threatening DVT.
- Haematological Malignancies: Highly disease-specific.
- Leukaemias/Lymphomas/Myeloma: Chemotherapy, immunotherapy, targeted therapy (e.g., imatinib for CML, rituximab for CD20+ lymphomas), radiotherapy, stem cell transplantation. Supportive care (transfusions, G-CSF for neutropenia, infection prophylaxis).
- Transfusion Reactions: Stop transfusion immediately. Maintain IV access, supportive care (fluids, adrenaline for anaphylaxis, furosemide for overload). Investigate reaction.
Exam Red Flags
- Microcytic anaemia with normal iron studies: Think Thalassaemia.
- Normocytic anaemia with reticulocytosis: Haemolysis or acute blood loss.
- Macrocytic anaemia with neurological symptoms: B12 deficiency (subacute combined degeneration of the cord).
- Isolated prolonged aPTT, normal PT: Haemophilia A/B, von Willebrand Disease (severe), Lupus Anticoagulant.
- Isolated prolonged PT, normal aPTT: Factor VII deficiency, early warfarin use.
- Prolonged PT and aPTT: Liver disease, DIC, severe common pathway factor deficiencies, supratherapeutic warfarin.
- Pancytopenia with 'dry tap' bone marrow aspirate: Myelofibrosis (confirm with trephine biopsy showing fibrosis).
- Painful bones, renal failure, hypercalcaemia, anaemia, raised ESR: Multiple Myeloma (CRAB features).
- Splenomegaly + high WCC with left shift (myelocytes, metamyelocytes): Chronic Myeloid Leukaemia (CML) – confirm with Philadelphia chromosome (BCR-ABL).
- Thrombocytopenia + Microangiopathic Haemolytic Anaemia (MAHA) + Renal failure + Neurological symptoms: Thrombotic Thrombocytopenic Purpura (TTP) / Haemolytic Uraemic Syndrome (HUS).
- Paroxysmal Nocturnal Haemoglobinuria (PNH): Haemolytic anaemia, pancytopenia, thrombosis in unusual sites. Diagnosed by flow cytometry (absence of CD55/CD59).
- Transfusion-related Acute Lung Injury (TRALI): Acute respiratory distress within 6 hours of transfusion; leading cause of transfusion-related mortality.
Sample Practice Questions
A 45-year-old female presents with a 6-month history of fatigue, exertional dyspnoea, and menorrhagia. Her haemoglobin is 8.5 g/dL, MCV 72 fL, MCH 24 pg. Serum ferritin is 8 ng/mL (normal range 15-150 ng/mL), and transferrin saturation is 10%. Peripheral blood film shows microcytic hypochromic red cells with anisocytosis and poikilocytosis. What is the most appropriate initial management step for this patient?
A 72-year-old woman with a history of hypertension and osteoarthritis presents with a 6-month history of progressive fatigue, pallor, and dyspnoea on exertion. She denies any blood loss, dietary changes, or recent infections. Her haemoglobin is 6.8 g/dL, MCV 108 fL, WCC 3.5 x 10^9/L, platelets 110 x 10^9/L. Peripheral blood film shows macro-ovalocytes and hypersegmented neutrophils. Her serum B12 level is normal, and folate is within the lower normal range. What is the most appropriate next investigation?
A 55-year-old woman with known alcoholic liver disease presents with severe epistaxis and easy bruising. Her current medications include omeprazole. Laboratory tests show: haemoglobin 10.2 g/dL, white cell count 6.5 x 10^9/L, platelets 45 x 10^9/L. Her prothrombin time (PT) is 25 seconds (normal 11-13 seconds) and activated partial thromboplastin time (APTT) is 40 seconds (normal 28-35 seconds). Which of the following is the most appropriate initial treatment to manage her bleeding?
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