Haemolytic Anaemia

Related Subjects: |Microangiopathic Haemolytic anaemia |Haemolytic anaemia |Immune(Idiopathic) Thrombocytopenic Purpura (ITP) |Thrombotic Thrombocytopenic purpura (TTP) |Haemolytic Uraemic syndrome (HUS) |Thrombocytopenia |Disseminated Intravascular Coagulation (DIC)

📖 About

• Definition: A condition where red blood cells (RBCs) are destroyed faster than the bone marrow can replace them.
• Normal RBC lifespan is ~120 days; in haemolysis, this is shortened significantly ⏳.
• Excess RBC breakdown → anaemia 😓, ↑ bilirubin (jaundice 🟡), and compensatory reticulocytosis 🔄.

🧬 Causes

• Membrane Defects: Hereditary spherocytosis, hereditary elliptocytosis
• Metabolic Defects: G6PD deficiency, pyruvate kinase deficiency
• Haemoglobinopathies: Sickle cell anaemia, thalassaemia
• Immune: Autoimmune haemolytic anaemia (warm IgG 🔥, cold IgM ❄️), transfusion reactions, haemolytic disease of the newborn 👶
• Drugs: Penicillin 💊, quinine, methyldopa
• Others:
  • Microangiopathic haemolysis (TTP, HUS, DIC, PET)
  • Mechanical damage (prosthetic valves ⚙️)
  • Infections (e.g., malaria 🦟)
  • Paroxysmal nocturnal haemoglobinuria (PNH 🌙)

🧾 Congenital vs Acquired

⚡ Clinical Features

• Pallor, fatigue, dyspnoea 😮‍💨
• Jaundice (unconjugated bilirubin 🟡)
• Splenomegaly & hepatomegaly 🍷
• Gallstones (pigment stones due to chronic bilirubin excess 🪨)
• Leg ulcers (esp. in sickle cell 🦵)
• Dark urine (esp. intravascular haemolysis ⚫)

🔍 Comparison of Intravascular vs Extravascular Haemolysis

🧪 Investigations

• Basic tests: Hb (low 📉), reticulocyte count (raised 🔄), blood film (spherocytes 🔵, schistocytes ✂️, sickle cells 🌙, Heinz bodies 🟣)
• Biochemistry: ↑ LDH, ↑ unconjugated bilirubin, ↓ haptoglobin 🧪
• Urine: Haemoglobinuria ⚫, haemosiderinuria, ↑ urobilinogen 💧
• Direct Coombs (DAT): Positive in autoimmune haemolysis ✅
• Enzyme assays: G6PD, pyruvate kinase 🧬
• Haemoglobin analysis: Electrophoresis for thalassaemia/sickle cell 📈
• Special tests: Schumm’s test (methaemalbumin 🧪), ADAMTS13 (TTP) 🧫

💡 Teaching Pearls

• DAT is the single most important test for autoimmune haemolysis ✅.
• Spherocytes = hereditary spherocytosis OR warm AIHA 🔥 (DAT distinguishes).
• Dark urine in the morning is a classic clue for PNH 🌙.
• Heinz bodies are only seen with supravital staining 🔬.
• Chronic haemolysis → pigment gallstones 🪨 + folate deficiency 🌿.

Cases - Haemolytic Anaemia (10 Cases)

• Case 1 - Warm Autoimmune Haemolysis: A 55-year-old woman with rheumatoid arthritis presents with jaundice and dark urine. Hb 7.8 g/dL, reticulocytes high, Coombs test positive (IgG). Warm AIHA.
• Case 2 - Cold Agglutinin Disease: A 70-year-old man develops acrocyanosis and anaemia after a chest infection. Blood film shows agglutination, Coombs positive for C3d. Cold AIHA.
• Case 3 - Hereditary Spherocytosis: A 14-year-old boy with recurrent jaundice and gallstones. Blood film: spherocytes. Family history positive. Membrane defect haemolysis.
• Case 4 - G6PD Deficiency (Drug-Triggered): A 25-year-old African man develops jaundice and anaemia after co-trimoxazole. Film: bite cells, Heinz bodies. Enzyme defect haemolysis.
• Case 5 - Sickle Cell Anaemia (Haemolytic Crisis): A 20-year-old Afro-Caribbean man presents with pallor, jaundice, and pain crisis. Hb electrophoresis: HbS homozygosity. Haemoglobinopathy-related haemolysis.
• Case 6 - Thrombotic Thrombocytopenic Purpura (TTP): A 40-year-old woman with confusion, petechiae, renal impairment. Film: schistocytes. Platelets 30 ×10⁹/L. Microangiopathic haemolysis.
• Case 7 - Haemolysis on a Mechanical Heart Valve: A 68-year-old man with metallic aortic valve develops anaemia and jaundice. LDH high, haptoglobin undetectable. Film: fragmented red cells. Mechanical haemolysis.
• Case 8 - Paroxysmal Nocturnal Haemoglobinuria (PNH): A 35-year-old man has episodes of dark morning urine, pancytopenia, and venous thrombosis. Flow cytometry shows absent CD55/CD59. Complement-mediated haemolysis.
• Case 9 - Malaria (Infective Cause): A 30-year-old traveller returning from Nigeria has fever, anaemia, and jaundice. Blood film: ring forms of Plasmodium falciparum. Intravascular haemolysis due to malaria.
• Case 10 - Drug-Induced Non-Immune Haemolysis: A 50-year-old man treated with dapsone for dermatitis herpetiformis develops anaemia and reticulocytosis. Coombs test negative. Oxidative haemolysis from drug exposure.

Teaching Commentary 🩸

These ten cases cover the breadth of haemolytic anaemia. Always think: is the cause intrinsic to the RBC (membrane, enzyme, haemoglobin) or extrinsic (immune, infection, drugs, mechanical, complement, microangiopathy)? Clinical clues include jaundice, dark urine, and splenomegaly. Lab hallmarks are reticulocytosis, raised LDH, raised unconjugated bilirubin, low haptoglobin. The blood film is diagnostic gold: spherocytes (AIHA/HS), bite cells (G6PD), sickled cells, schistocytes (TTP/valve), malaria parasites. Management is highly cause-specific: immunosuppression in AIHA, avoidance of triggers in G6PD, hydroxyurea in sickle cell, plasma exchange in TTP, anticoagulation vigilance in PNH.