Haemolysis

Premature red cell destruction, can result in anaemia

Aetiology

Immune

  • Autoimmune
    • Warm (IgG) - idiopathic (most common), autoimmune disorders (SLE), lymphoproliferative disorders (CLL), drugs (penicillins etc), infections
    • Cold (IgM) - idiopathic, infections (EBV, mycoplasma), lymphoproliferative disorders
  • Alloimmune
    • Haemolytic transfusion reaction
      • Immediate (IgM) predominantly intravascular
      • Delayed (IgG) predominantly extravascular
    • Haemolytic disease of the newborn (Rh D, ABO incompatibility, others e.g. anti-Kell)

Mechanical red cell destruction

  • Disseminated intravascular coagulation
  • Haemolytic uraemia syndrome e.g. E. coli O157
  • TTP
  • Leaking heart valve
  • Infections e.g. malaria
  • Burns related haemolysis

Membrane defects

  • Liver disease (Zieve’s syndrome)
  • Vitamin E deficiency
  • Paroxysmal noctural haemoglobinuria
  • Hereditary spherocytosis

Abnormal red cell metabolism

  • Failure to cope with oxidant stress (G6PD deficiency)
  • Failure to generate ATP

Abnormal haemoglobin

  • Sickle cell disease

Pathophysiology

Why are red cells particularly susceptible to damage?

  • Biconcave shape
  • Limited metabolic reserve, rely exclusively on glucose metabolism for energy (no mitochondria)
  • Can’t generate new proteins once in circulation (no nucleus)

Compensated haemolysis

  • Increased red cell destruction compensated by increased red cell production - Hb is maintained

Haemolytic anaemia (decompensated hamolysis)

  • Increased rate of red cell destruction exceeding bone marrow capacity for red cell production - Hb falls

Consequences of haemolysis

  • Reticulocytosis by bone marrow
  • Bone marrow erythroid hyperplasia
  • Excess red cell breakdown products e.g. billirubin (clinical features differ by aetiology and site of red cell breakdown)

Classification

Extravascular haemolysis
  • Red cells are taken up by reticuloendothelial system (predominantly spleen and liver)
  • More common
  • Hyperplasia at site of destruction (splenomegaly +/- hepatomegaly)
  • Release of protoporphyrin - unconjugated bilrubinaemia (jandice, gallstones), urobilinogenuria
  • Products are normal products but generated in excess
Intravascular haemolysis
  • Red cells destroyed within the circulation spilling their contents
  • Haemoglobinaemia (free Hb in circulation)
  • Methaemalbuminaemia
  • Haemoglobinuria - pink urine, turns black on standing
  • Haemosiderinuria
  • Products are abnormal - may be life threatening
  • Causes:
    • ABO incompatible blood transfusion
    • G6PD deficiency
    • Severe falciparum malaria
    • PNH, PCH (vary rare)

Clinical presentation

  • Depends on underlying cause and whether the haemolysis is compensated

Investigations

  • Confirm haemolytic state - FBC (+ blood film), reticulocyte count, serum unconjugated bilirubin, serum hepatoglobins, urinary urobilinogen
  • History and examination - family history, organomegaly
  • Blood film
    • Membrane damage → spherocytes
    • Mechanical damage → red cell fragments
    • Oxidative damage due to G6PD deficiency → Heinz bodies
    • Others e.g. HbS
  • Specialist investigations e.g. direct Coombs’ test (identifies antibody and complement bound to own red cells)

Management

  • Depends on underlying cause