Microangiopathic Hemolytic Anemia

Microangiopathic haemolytic anaemia (MAHA) is mechanical fragmentation of red cells in small vessels, with schistocytes and thrombocytopenia.

• Causes: thrombotic microangiopathies (TTP, HUS, complement mediated aHUS), DIC (sepsis, malignancy, obstetric), HELLP syndrome, malignant hypertension, scleroderma renal crisis, vasculitis, SLE, antiphospholipid syndrome, malignancy, drugs (gemcitabine, mitomycin, calcineurin inhibitors, quinine), transplant, HIV, mechanical valves.
• Hallmark: Coombs negative haemolysis, schistocytes, low platelets.
• Differentiation guides urgent therapy (TTP needs plasma exchange).

• Pallor, jaundice, petechiae, fever, neurological symptoms (confusion, seizures, focal deficits), renal failure, abdominal pain, hypertension.
• Features of the underlying cause: sepsis, pregnancy, malignancy, scleroderma.

• Blood film: schistocytes (over 1%), polychromasia; anaemia, thrombocytopenia, raised LDH and bilirubin, low haptoglobin, high reticulocytes, negative direct antiglobulin test.
• Coagulation screen: normal in TTP/HUS; prolonged PT/aPTT, low fibrinogen, raised D dimer in DIC.
• ADAMTS13 activity (below 10% in TTP) before plasma exchange; PLASMIC score; stool Shiga toxin PCR; complement (C3, C4, factor H, factor I, MCP, anti factor H antibodies).
• Creatinine, urinalysis, troponin (cardiac involvement), pregnancy test, ANA, antiphospholipid antibodies, HIV, blood cultures, malignancy search.

• Urgent identification of TTP: plasma exchange (1.0 to 1.5 plasma volumes daily) with methylprednisolone 1 g IV daily for 3 days, rituximab 375 mg/m2, caplacizumab 10 mg IV then 10 mg daily.
• Typical HUS: supportive care, dialysis, avoid antibiotics and antimotility drugs.
• aHUS: eculizumab 900 mg weekly for 4 doses then 1200 mg every 2 weeks, or ravulizumab.
• DIC: treat underlying cause, transfuse for bleeding.
• HELLP/pre-eclampsia: delivery, magnesium, blood pressure control.
• Malignant hypertension and scleroderma crisis: controlled blood pressure reduction, ACE inhibitor (captopril, enalapril).
• Drug induced: stop the drug.
• Avoid platelet transfusion in TTP unless life threatening bleeding.
• Folic acid 5 mg daily, thromboprophylaxis once platelets above 50 x 10^9/L.