Haemolysis

Causes

Genetic

  • Membrane: hereitary spherocyotosis or elliptocytosis
  • Haemoglobin: sickling disordes, thalassaemia
  • Enzyme defects: G6PD and pyruvate kinase deficiency

Acquired

  • Immune: isoimmune (heamolytic disease of newborn, blood transfusion reaction), autoimmune (warm or cold antibody mediated) or drug-induced
  • Non-immune: trauma (cardiac haemolysis, microangiopathic anaemia), infection (malaria, septicaemia), membrane disorders (paroxysmal nocturnal haemoglobinuria, liver disease)
  • Increased red cell breakdown? raised bilirubin (unconjugated), raised urinary urobilinogen, reduced haptoglobin (good marker of haemolysis)
  • Increased red cell production? reticulocytosis, polychromasia, macrocytosis, marrow hyperplasia
  • Extravascular haemolysis? splenic hypertrophy
  • Intravascular haemolysis? methaemalbuminaemia, free plasma haemoglobin, haemoglobinuria, low haptaglobin, haemosiderinuria.

History - family history, race, jaundice, haematuria, drugs, previous anaemia.

Examination - Jaundice, hepatosplenomegaly, leg ulcers (sickle cell disease)

Tests - FBC, reticulocytes, bilirubin, LDH, haptoglobin, urinary urobilinogen.

Blood film: polychromasia, macrocytosis, spherocytes, elliptocytes, fragmented cells or sickle cells. Nucleated red cells if severe.

Direct Coombs' test - +ve = immune cause

RBC lifespan - chromium labelling

Urinary haemosiderin = chronic intravascular haemolysis

Hb electrophoresis - Hb abnormalities

Causes of Haemolytic anaemia

  • Sickle-cell disease
  • Hereditary spherocytosis (Autosomal dominant inheritance, causes fragile rbc's and varibale haemolysis. Mild anaemia, splenomegaly, risk of gallstones. Diagnosis: osmotic fragility tests. Treatment: folate replacement, splenectomy if required)
  • Hereditary elliptocytosis (Autosomal dominant inheritance. variable haemolysis. Splenectomy may help)
  • Glucose-6-phosphate dehydrogenase deficiency (commonest enzyme defect. Sex linked inheritance. Neonatal jaundice, symptomless, normal Hb and blood films. Susceptible to oxidative crises precipitated by drugs (primaquine, sulfonamides, ciprofloxacin), broad bean Vicia fava (favism) or illness. Rapid anaemia and jaundice with Heinz bodies. Diagnosis: enzyme assay. Treatment: avoid precipitants)
  • Pyruvate kinase deficiency (autosomal recessive inheritance, homzygotes have neonatal jaundice, later - chronic haemolysis, splenomegaly and jaundice). Diagnosis: enzyme assay. Splenectomy may help.
  • Drug induced immune haemolysis (formation of new RBC membrane antigens (prolonged high doses of penicillin), immune complex formation (rare, many drugs), or autoantibodies to RBC (alpha-methyldopa, mefenamic acid, L-dopa) -rare, Coombs' +ve)
  • Autoimmune haemolytic anaemia(warm or cold antibodies. Primary or secondary - lymphoma, generalised autoimmune disease (SLE). Warm -chronic or acute anaemia, treat - steroids +/- splenectomy. Cold - chronic anaemia, worse in cold, Raynaud's or acrocyanosis, treat - keep warm. Chlorambucil.
  • Cardiac haemolysis (cell trauma in prosthetic aortic valve - may indicate malfunction)
  • Microangiopathic haemolytic anaemia (marked fragmentation +/- many spherocytes. Includes haemolytic-uraemic syndrome and Idiopathic Thrombocytopenic Purpura. Treat underlying disease, blood and FFP for support)
  • Paroxysmal nocturnal haemoglobinuria (pancytopenia, abdo pain or thrombosis +/- haemolysis. Diagnosis: Ham's test. Treatment: anticoagulation, blood product replacement, consider stem cell transplant.

Factors exacerbating haemolysis

  • infection
  • parvoviruses (cause cessation of marrow erythropoiesis)