Master Haematology
for PLAB 1

Core Concepts

Haematology is the study of blood, blood-forming organs, and blood diseases. Blood consists of plasma and three main cellular components: red blood cells (RBCs), white blood cells (WBCs), and platelets. These cells are produced in the bone marrow from pluripotent haematopoietic stem cells.

• Red Blood Cells (Erythrocytes): Contain haemoglobin, essential for oxygen transport. Lifespan approx. 120 days.
  • **Anaemia:** Low haemoglobin/RBC count.
  • **Polycythaemia:** High RBC count.
• White Blood Cells (Leukocytes): Crucial for immunity. Types include neutrophils, lymphocytes, monocytes, eosinophils, basophils.
  • **Leukopenia:** Low WBC count (e.g., neutropenia).
  • **Leukocytosis:** High WBC count (e.g., neutrophilia).
  • **Leukaemia/Lymphoma:** Malignancies of WBCs.
• Platelets (Thrombocytes): Essential for haemostasis (clotting). Lifespan approx. 7-10 days.
  • **Thrombocytopenia:** Low platelet count, increasing bleeding risk.
  • **Thrombocytosis:** High platelet count, increasing thrombosis risk.
• Haemostasis & Coagulation: Complex process involving platelets (primary haemostasis) and coagulation factors (secondary haemostasis) to form a stable clot.
  • **Bleeding Disorders:** Deficiencies in platelets or coagulation factors (e.g., haemophilia, von Willebrand disease, ITP).
  • **Thrombophilia:** Tendency to form clots (e.g., Factor V Leiden, Antiphospholipid Syndrome).
• Blood Products: Whole blood is fractionated into components (Packed Red Blood Cells, Fresh Frozen Plasma, Platelets, Cryoprecipitate) for specific indications.

Clinical Presentation

• **Anaemia:** Fatigue, pallor, dyspnoea, palpitations, dizziness. Specific signs: koilonychia (iron deficiency), angular stomatitis (iron/B12), jaundice (haemolysis), neurological symptoms (B12 deficiency).
• **Bleeding Disorders:** Easy bruising, petechiae, purpura, epistaxis, menorrhagia, prolonged bleeding after injury/surgery, haemarthrosis (haemophilia).
• **Thrombotic Disorders:** Deep Vein Thrombosis (DVT - limb swelling, pain, warmth), Pulmonary Embolism (PE - dyspnoea, chest pain, haemoptysis).
• **Lymphoproliferative/Myeloproliferative Disorders (e.g., Leukaemia, Lymphoma):**
  • **General:** B symptoms (unexplained fever >38°C, drenching night sweats, unexplained weight loss >10% in 6 months).
  • **Local:** Lymphadenopathy (painless, rubbery), splenomegaly, hepatomegaly.
  • **Bone Marrow Failure:** Pancytopenia leading to anaemia symptoms, recurrent infections (neutropenia), bleeding (thrombocytopenia).
  • **Hyperviscosity (e.g., Polycythaemia):** Headache, blurred vision, plethora, pruritus (especially aquagenic), erythromelalgia.
• **Transfusion Reactions:** Fever, chills, urticaria, dyspnoea, hypotension (acute haemolytic reaction can be life-threatening).

Diagnosis (Gold Standard)

The Full Blood Count (FBC) with a peripheral blood film is the cornerstone of haematological diagnosis.

• **Anaemia:**
  • **Microcytic (MCV <80 fL):** Iron studies (Ferritin, Transferrin Saturation, TIBC) – Gold standard for Iron Deficiency Anaemia. Haemoglobin electrophoresis for thalassaemia.
  • **Normocytic (MCV 80-100 fL):** Reticulocyte count, renal function, inflammatory markers. Coombs test for autoimmune haemolytic anaemia.
  • **Macrocytic (MCV >100 fL):** Serum B12 and Folate levels.
• **Bleeding/Clotting Disorders:**
  • **Screening:** Prothrombin Time (PT), Activated Partial Thromboplastin Time (aPTT), Fibrinogen, Platelet count.
  • **Specific:** Factor assays (e.g., Factor VIII for Haemophilia A), von Willebrand factor antigen/activity.
  • **Thrombophilia Screen:** Factor V Leiden mutation, Prothrombin gene mutation, Antithrombin III, Protein C/S deficiencies, Antiphospholipid antibodies.
  • **DIC:** D-dimer, PT/aPTT, Fibrinogen, Platelet count.
• **Myeloproliferative/Lymphoproliferative Disorders:**
  • **Bone Marrow Aspiration & Trephine Biopsy:** Gold standard for diagnosing leukaemias, lymphomas, myelodysplastic syndromes, and aplastic anaemia. Provides morphology, cellularity, flow cytometry, cytogenetics, and molecular studies.
  • **Lymph Node Biopsy:** Excisional biopsy is gold standard for diagnosing lymphoma.
  • **Flow Cytometry:** Identifies cell lineage and abnormal populations (e.g., leukaemia, lymphoma).
  • **Molecular Genetics:** PCR for specific mutations (e.g., BCR-ABL for CML, JAK2 for Myeloproliferative Neoplasms).
• **Transfusion Medicine:** Blood Grouping and Cross-matching for safe transfusion.

Management (First Line)

• **Iron Deficiency Anaemia:** Oral ferrous sulphate, address underlying cause (e.g., diet, GI bleeding).
• **B12 Deficiency:** Intramuscular hydroxocobalamin, then oral/IM maintenance.
• **Folate Deficiency:** Oral folic acid.
• **Autoimmune Haemolytic Anaemia:** Corticosteroids (e.g., Prednisolone).
• **Deep Vein Thrombosis (DVT) / Pulmonary Embolism (PE):** Anticoagulation (e.g., LMWH followed by DOACs or Warfarin).
• **Haemophilia:** Factor replacement therapy (e.g., Factor VIII for Haemophilia A).
• **Immune Thrombocytopenia (ITP):** Corticosteroids, IV immunoglobulin (IVIG), splenectomy (refractory cases).
• **Acute Leukaemia (AML/ALL):** Intensive chemotherapy, supportive care (transfusions, antibiotics). Bone marrow transplant for eligible patients.
• **Chronic Myeloid Leukaemia (CML):** Tyrosine Kinase Inhibitors (TKIs, e.g., Imatinib).
• **Lymphoma (Hodgkin/Non-Hodgkin):** Chemotherapy (e.g., ABVD for Hodgkin's), radiotherapy, targeted therapy (e.g., Rituximab for CD20+ NHL). Watch and wait for indolent lymphomas.
• **Transfusion Reactions:** Stop transfusion immediately, maintain IV access, supportive care, send blood products/patient samples for investigation.