Haemolytic Anaemia

Haemolytic Anaemia

1. Overview

   • Definition
     • ↓ Haemoglobin → ↓ oxygen-carrying capacity
   • Major Causes of Anaemia
     • Increased RBC destruction (haemolysis)
     • Reduced RBC production
     • Blood loss
   • Normal RBC Lifecycle
     • 4. Haemoglobin recycled
     • 3. Removed by spleen/liver macrophages
     • 2. Circulate ~120 days
     • 1. Produced in bone marrow

2. Pathophysiology

   • Core Lab Changes
     • ↑ Bilirubin (RBC breakdown)
     • ↑ Reticulocytes (bone marrow response)
     • ↑ LDH (cell destruction marker)
     • ↓ Haemoglobin
     • ↓ Haptoglobin (binds free Hb)

3. Classification

   • By Site of Destruction
     • Intravascular Haemolysis
       • Causes
         • Complement activation
         • Mechanical damage
         • Severe infections
       • Lab Features
         • Haemoglobinaemia
         • Haemoglobinuria
         • ↓↓↓ Haptoglobin
         • ↑↑ LDH
         • Schistocytes (fragmented RBCs)
       • (Inside blood vessels)
     • Extravascular Haemolysis
       • (Spleen + liver)
       • Mechanism
         • Macrophage-mediated destruction
         • Most common type
       • Lab Features
         • ↑ Unconjugated bilirubin
         • ↓ Haptoglobin (milder)
         • Spherocytes
         • Splenomegaly
   • By Cause
     • Intrisic
       • RBC Defect
       • Usually Inherited
     • Extrinsic
       • External Factors
       • Mechanical
       • Immune
       • Infectious

4. Pathways

   • Intrinsic
     • Membrane Disorders
       • Examples
         • Hereditary spherocytosis
         • Hereditary elliptocytosis
       • Pathophysiology
         • Defects In
           • Spectrin
           • Ankyrin
         • Loss of membrane stability → shape change
       • Blood Film
         • Spherocytes (round, dense RBCs)
       • Diagnosis
         • EMA binding test
         • Osmotic fragility test
     • Enzyme Deficiencies
       • Examples:
         • G6PD deficiency
           • X-linked recessive
           • Triggered By:
             • Drugs
             • Infection
             • Fava Beans
           • Pathogenesis:
             • Oxidative stress → RBC damage → haemolysis
           • Blood Film:
             • Heinz Bodies
             • Bite Cells
         • Pyruvate kinase deficiency
     • Haemoglobinopathies
       • Sickle Cell Disease
         • Cause:
           • β-globin mutation → HbS formation
         • Mechanism:
           • HbS polymerises under low O₂
           • RBCs become sickle-shaped
         • Effects:
           • Vaso-occlusion (blocked vessels)
           • Haemolysis
       • Thalassaemia
         • Cause:
           • Reduced synthesis of globin chains
         • Key Concept:
           • Imbalance in globin chains → ineffective RBC production
         • Types:
           • Alpha (α)
           • Alpha (α)
   • Extrinsic
     • Infection-Related
       • Malaria
       • Viral Infections
       • Sepsis
     • Mechanical Haemolysis
       • Causes:
         • March haemoglobinuria
         • Severe burns
         • Prosthetic heart valves
     • Immune Causes:
       • Diagnosis:
         • Direct Antiglobulin (Coombs) Test
           • Detects antibodies/complement on RBCs
       • Autoimmune Haemolytic Anaemia (AIHA)
         • Mechanism:
           • Antibodies attack RBCs
         • Types:
           • Cold AIHA → IgM
           • Warm AIHA → IgG

5. Diagnoses

   • Full Blood Count
     • ↑ MCV (sometimes)
     • ↑ Reticulocytes
     • ↓ Haemoglobin
   • Blood Film
     • Schistocytes → intravascular
     • Spherocytes → extravascular
     • Bite cells → G6PD
   • Special Tests
     • Coombs test → immune cause
     • EMA / osmotic fragility → membrane disorders
     • PCR/genetic tests (advanced)
   • Biochemical Markers
     • ↑ LDH
     • ↑ Unconjugated bilirubin
     • ↓ Haptoglobin

6. Clinical Features

   • Fatigue
   • Jaundice (↑ bilirubin)
   • Dark urine
   • Splenomegaly
   • Pallor

7. Managment

   • General Principles:
     • Treat underlying cause
     • Support RBC levels
   • Specific Treatments:
     • Blood transfusion (severe cases)
     • Avoid triggers → G6PD
     • Steroids → AIHA
     • Splenectomy (selected cases)

8. Defined as premature destruction of red blood cells (RBCs)

9. RBC lifespan ↓ from ~120 days

10. Bone marrow compensates → ↑ erythropoiesis