Drug Induced Immune Hemolytic Anemia

Drug induced immune haemolytic anaemia (DIIHA) is red cell destruction mediated by drug dependent or drug independent antibodies.

• Incidence about 1 in 1 million per year.
• Mechanisms: drug dependent antibodies (ceftriaxone, piperacillin, cefotetan; immune complex type with intravascular haemolysis), hapten/drug adsorption (penicillin high dose), autoantibody induction (methyldopa, fludarabine, levodopa), nonimmunologic protein adsorption.
• Implicated drugs: cephalosporins (cefotetan, ceftriaxone), piperacillin, penicillin, quinine, NSAIDs (diclofenac), rifampicin, oxaliplatin, fludarabine, checkpoint inhibitors.
• Ceftriaxone can cause fulminant intravascular haemolysis in children, with mortality.

• Acute pallor, jaundice, dark urine, back pain, fever, hypotension, renal failure, DIC.
• Onset days to weeks after starting drug, or abrupt after re exposure.
• Chronic extravascular haemolysis with methyldopa.

• Haemolysis markers (raised LDH, bilirubin, low haptoglobin, haemoglobinuria), spherocytes.
• Direct antiglobulin test positive (IgG and/or C3); eluate negative in drug dependent type; drug dependent antibody tests in reference laboratory.
• Suspect when haemolysis starts after drug exposure and resolves on stopping.
• Exclude autoimmune haemolytic anaemia, TTP, PNH, G6PD deficiency.

• Stop the offending drug immediately; avoid rechallenge.
• Supportive care: fluids to maintain urine output, transfusion if severe (compatible units, cross matching may be difficult), folic acid 5 mg daily.
• Severe intravascular haemolysis: prednisolone 1 mg/kg, plasma exchange or exchange transfusion, treatment of renal failure and DIC.
• Autoantibody type (methyldopa): stop drug, recovery in weeks to months.
• Document allergy; inform transfusion service.
• Monitor haemoglobin, renal function.