Warm Autoimmune Hemolytic Anemia

Warm autoimmune haemolytic anaemia (wAIHA) is IgG (sometimes IgG plus complement) mediated red cell destruction at body temperature, mostly in the spleen.

• Incidence 1 to 3 per 100,000; two thirds of adult AIHA.
• Idiopathic (50%) or secondary: SLE, CLL, lymphoma, Evans syndrome, ulcerative colitis, common variable immunodeficiency, drugs, post transplant.
• Mechanism: phagocytosis of antibody coated cells by splenic macrophages, spherocytosis.
• Complications: severe anaemia, thrombosis (venous thromboembolism in 10 to 20%), infection from treatment, relapse.

• Fatigue, pallor, jaundice, dark urine, dyspnoea, splenomegaly.
• Rapid onset may cause angina, syncope, heart failure in the elderly.
• Features of the underlying disease.

• Anaemia with reticulocytosis, spherocytes, polychromasia, raised LDH, indirect bilirubin, low haptoglobin.
• Direct antiglobulin test positive for IgG (with or without C3d).
• Exclude secondary causes: ANA, anti dsDNA, immunoglobulins, lymphoma/CLL screen (CT, flow cytometry), HIV, hepatitis, viral serology, drug history.
• Platelet count (Evans syndrome), Donath Landsteiner test to exclude paroxysmal cold haemoglobinuria.
• Cross matching difficulties require alloantibody exclusion.

• First line: prednisolone 1 mg/kg/day (60 to 100 mg) until haemoglobin rises (usually 3 weeks), then taper over 3 to 6 months; response in 70 to 80%, but relapse in 50% on taper.
• Add rituximab 375 mg/m2 weekly for 4 doses (or 100 mg weekly x 4) at start or relapse; higher sustained remission.
• Second line: splenectomy (response 60 to 70%, vaccinate beforehand), azathioprine 100 to 150 mg daily, mycophenolate mofetil 1 g twice daily, ciclosporin, cyclophosphamide.
• Newer agents for refractory disease: fostamatinib 100 to 150 mg twice daily, parsaclisib, ibrutinib (some), IVIG 0.4 g/kg for 5 days (poor response), danazol.
• Transfuse only when necessary (give least incompatible units).
• Folic acid 5 mg daily; thromboprophylaxis (enoxaparin 40 mg daily) in hospitalised patients; Pneumocystis prophylaxis on prolonged steroids; bone protection.
• Treat secondary disease. Monitor reticulocytes, haemoglobin, LDH.