Mnemonic

Direct Antiglobulin Test

A memory aid for the Coombs tests and the causes of a positive result.

Expansion

Direct detects antibody on the cells, indirect detects antibody in the plasma

Expansion

  • Direct antiglobulin test (direct Coombs): detects antibody or complement already bound to the patient’s red cells. It answers “are these cells coated”
  • Indirect antiglobulin test: detects free antibody in the plasma, by incubating it with reagent red cells. Used for crossmatching and antenatal antibody screening

Causes of a positive direct test

  • Autoimmune haemolytic anaemia
    • Warm (IgG, extravascular, spleen): idiopathic, lymphoproliferative disease, lupus, drugs (methyldopa, penicillins), and it is the commonest type
    • Cold (IgM and complement, intravascular and hepatic): Mycoplasma, Epstein-Barr virus, lymphoma, cold agglutinin disease
  • Haemolytic disease of the newborn, from maternal alloantibody
  • Haemolytic transfusion reaction, and delayed reactions days later
  • Drug induced, by several mechanisms
  • Passenger lymphocyte syndrome after transplantation, and intravenous immunoglobulin
  • Healthy people: a weakly positive test occurs in around 1 in 10,000 donors, and more often in the elderly and in inpatients, so it is not synonymous with haemolysis

Confirming haemolysis requires the supporting evidence, whatever the Coombs result: raised reticulocytes, raised LDH, raised unconjugated bilirubin, low haptoglobin, and a film showing spherocytes in warm disease or agglutination in cold disease.

Coombs negative haemolysis does occur, in hereditary spherocytosis, G6PD deficiency, mechanical destruction, paroxysmal nocturnal haemoglobinuria and microangiopathy, so a negative test never excludes haemolysis.