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Haemolytic anaemia
Haemolysis is recognised by a foursome — high LDH, high unconjugated bilirubin, low haptoglobin and high reticulocytes — and then the direct Coombs test (DAT) divides it: positive = autoimmune; negative = membrane, enzyme, mechanical (schistocytes) or PNH.
Why it matters in the exam
The question presents weakness, jaundice and dark urine with anaemia and reticulocytosis, and asks for the type. A positive DAT with IgG and spherocytes = "warm" autoimmune haemolysis — linked to CLL, lupus and drugs — treated with steroids (and rituximab second line). A positive DAT with complement (C3) and an IgM antibody = "cold" — after Mycoplasma or EBV, or in lymphoma — where steroids do not work: avoid cold, and give rituximab or sutimlimab. In Israel and the Mediterranean, G6PD deficiency is common: sudden haemolysis after eating fava beans, an infection or an oxidant drug (primaquine, dapsone, sulfonamides, rasburicase), with "bite cells" and Heinz bodies.
An important trap: a G6PD activity test during acute haemolysis may come back normal, because the old deficient cells have already broken down — it is repeated after a few weeks. Hereditary spherocytosis presents with spherocytes and a negative DAT, a high MCHC, a large spleen and gallstones; splenectomy in the severe form. Schistocytes with low platelets point to TTP, HUS or DIC (see the thrombocytopenia chapter), and a leaking mechanical valve can cause mechanical haemolysis. PNH presents with haemolysis, thrombosis in unusual sites (hepatic veins) and cytopenia, and is diagnosed by flow cytometry (loss of CD55 and CD59). In chronic haemolysis folic acid is given.
Key points
- Haemolysis: high LDH and unconjugated bilirubin, low haptoglobin, high reticulocytes.
- DAT positive for IgG = warm (steroids); for C3 = cold (avoid cold, rituximab).
- G6PD deficiency: fava beans and oxidant drugs; test after a few weeks.
- Schistocytes = microangiopathy; PNH = thrombosis and flow cytometry.
- In chronic haemolysis — folic acid.
Summary table
| Type | Clues | Test | Treatment |
|---|---|---|---|
| Warm autoimmune | Spherocytes, CLL, lupus, drugs | DAT positive for IgG | Steroids; rituximab second line |
| Cold autoimmune | Mycoplasma, EBV, lymphoma, cyanosis in the cold | DAT positive for C3, IgM antibody | Avoid cold; rituximab or sutimlimab; not steroids |
| G6PD deficiency | Fava beans, infection, oxidant drug; bite cells | G6PD activity after a few weeks | Remove the trigger, transfuse as needed |
| Hereditary spherocytosis | Spherocytes, high MCHC, large spleen, gallstones | DAT negative, EMA test | Folic acid; splenectomy if severe |
| Microangiopathic | Schistocytes, low platelets | ADAMTS13, clotting tests | By cause (TTP, HUS, DIC) |
| PNH | Haemolysis, hepatic vein thrombosis, cytopenia | Flow cytometry: loss of CD55 and CD59 | Eculizumab or ravulizumab |
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Sources
- British Society for Haematology Guideline: The diagnosis and management of primary autoimmune haemolytic anaemia, 2017 — Warm and cold AIHA
- Harrison's Principles of Internal Medicine, 21st edition (2022) — Hemolytic Anemias and Anemia Due to Acute Blood Loss
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-02. The text may contain errors; when in doubt, check the source.