Haemolytic Anaemia
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Direct answer
Haemolytic anaemia results from premature red cell destruction, classified as corpuscular — inherited membrane, enzyme or haemoglobin defects — or extracorpuscular — immune, microangiopathic, infectious or drug injury, and as extravascular (splenic) or intravascular (circulatory). The laboratory signature is high reticulocytes with high LDH, high indirect bilirubin and low haptoglobin; intravascular haemolysis adds haemoglobinaemia, haemoglobinuria and haemosiderinuria. FMGE staples are hereditary spherocytosis, G6PD deficiency, sickle disease, autoimmune haemolysis and paroxysmal nocturnal haemoglobinuria.
What you must remember
- General: anaemia, indirect jaundice, splenomegaly and pigment gallstones; chronic haemolysis expands marrow (frontal bossing); LDH up, haptoglobin down in all haemolysis.
- Hereditary spherocytosis: autosomal dominant spectrin or ankyrin defect; spherocytes, increased osmotic fragility, Coombs negative; splenectomy controls anaemia after pneumococcal, meningococcal and Hib vaccination; parvovirus B19 causes aplastic crisis.
- G6PD deficiency: X-linked, commonest red cell enzymopathy; Heinz bodies and bite cells after fava beans, primaquine, dapsone, sulphonamides or infection; African variants milder than Mediterranean.
- Sickle disease: Glu-to-Val at beta position 6 (HbS) polymerising on deoxygenation; vaso-occlusive crises, infant dactylitis, autosplenectomy with Howell-Jolly bodies and Salmonella osteomyelitis, acute chest syndrome and stroke; hydroxycarbamide raises HbF; electrophoresis diagnoses.
- Autoimmune haemolytic anaemia: warm IgG type with spherocytes and positive warm Coombs test, complicating SLE, CLL or methyldopa; cold IgM type after mycoplasma or infectious mononucleosis, with acrocyanosis.
- Paroxysmal nocturnal haemoglobinuria: acquired loss of GPI anchors (CD55, CD59) causing complement lysis; intravascular haemolysis, pancytopenia and hepatic vein thrombosis; flow cytometry diagnoses, eculizumab treats.
Common confusion
Warm autoimmune disease and hereditary spherocytosis both show spherocytes, but the direct antiglobulin test is positive in immune disease and negative in hereditary spherocytosis. Intravascular markers — haemoglobinuria, haemoglobinaemia, haemosiderinuria — indicate PNH, mismatched transfusion or G6PD attacks, whereas splenomegaly and jaundice dominate extravascular states. Remember Salmonella as the classical osteomyelitis organism after autosplenectomy.
Exam-focused takeaway
FMGE gives a smear or trigger vignette: bite cells after dapsone (G6PD), a child with pigmented stones posted for splenectomy (spherocytosis), dark morning urine (PNH), painful swollen hands in an infant (sickle dactylitis). Coombs test interpretation and pre-splenectomy vaccines are near-certain marks.
Frequently asked questions
Which tests confirm haemolysis?
Reticulocytosis out of proportion to anaemia, high LDH, high indirect bilirubin and low haptoglobin; urine haemosiderin and plasma free haemoglobin indicate an intravascular component.
What screens for hereditary spherocytosis?
The osmotic fragility test — spherocytes lyse in mildly hypotonic saline — with a negative direct antiglobulin test excluding immune spherocytes. EMA binding or protein studies confirm.
Why is G6PD deficiency episodic?
The pentose-phosphate pathway cannot maintain reduced glutathione, so only oxidant stress — fava beans, certain drugs or infection — damages cells. Old cells are lost first, limiting each attack.
Which organism causes osteomyelitis in sickle disease?
Salmonella classically, because autosplenectomy impairs clearance of encapsulated organisms. Vaccination and penicillin prophylaxis protect early childhood.
What causes paroxysmal nocturnal haemoglobinuria?
An acquired PIGA mutation abolishes CD55 and CD59 anchors, so complement lyses red cells. It presents with haemoglobinuria, pancytopenia and thrombosis, treated with eculizumab.
How is warm autoimmune haemolysis treated?
Corticosteroids first-line, IVIG for rapid control, rituximab or splenectomy for relapse, always treating the underlying cause such as lymphoma or the offending drug.