Haemolytic Anaemia
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Direct answer
Suspect haemolysis whenever anaemia coexists with reticulocytosis, jaundice of the indirect type, and a preserved or rising LDH — then divide by site and by cause. Intravascular haemolysis releases haemoglobin into plasma (haemoglobinaemia, haemoglobinuria, haemosiderinuria, low haptoglobin), while extravascular haemolysis is splenic macrophage clearance of damaged cells, giving spherocytes or removal without free haemoglobin. Inherited causes are intracorpuscular: membrane defects (hereditary spherocytosis, spectrin-ankyrin), enzyme defects (G6PD deficiency, classically precipitated by primaquine, sulfa drugs, fava beans and infection), and haemoglobinopathies — sickle cell disease and thalassaemia, both highly prevalent in Indian central and tribal belts. Acquired causes are extracorpuscular: autoimmune haemolysis (warm IgG spherocytes with positive direct antiglobulin test, cold IgM agglutinin), microangiopathic fragmentation (schistocytes), malaria, and paroxysmal nocturnal haemoglobinuria, a complement-mediated clone deficient in CD55 and CD59 diagnosed by flow cytometry.
What you must remember
- Laboratory signature of haemolysis: reticulocytosis, indirect hyperbilirubinaemia, raised LDH, low haptoglobin, increased erythropoietin; intravascular adds haemoglobinaemia, haemoglobinuria (dipstick positive, red cells absent) and haemosiderinuria after days.
- Hereditary spherocytosis: autosomal dominant defect most often in ankyrin or spectrin; spherocytes with increased MCHC (the only anaemia with high MCHC), positive osmotic fragility and EMA-binding tests; aplastic crisis with parvovirus B19; treated by splenectomy with vaccination and penicillin prophylaxis, gallstones common.
- G6PD deficiency: X-linked, protects against falciparum malaria; oxidative stress produces Heinz bodies and bite cells on supravital staining; episodes are self-limited because old, enzyme-poor cells are destroyed first.
- Sickle cell disease in India: HbS beta 6 Glu-to-Val substitution; polymerises when deoxygenated; the Arab-Indian haplotype with high HbF produces a milder course than African haplotypes; tribal central India (Chhattisgarh, Madhya Pradesh, Maharashtra, Odisha) is the endemic zone, targeted by the National Sickle Cell Anaemia Elimination Mission launched in 2023 with 2047 as its elimination goal for the disease burden.
- Autoimmune haemolysis: warm antibody (IgG, 37 degrees, spherocytes, secondary to SLE, lymphoproliferative disease, drugs) versus cold agglutinin (IgM, complement, red cell agglutination on the film, Mycoplasma and infectious mononucleosis associations); direct antiglobulin test is the diagnostic anchor.
- Microangiopathic haemolysis: schistocytes, helmet cells, triangular cells — think TTP, HUS, DIC, malignant hypertension, mechanical valves; a smear without fragments argues strongly against TTP.
- Paroxysmal nocturnal haemoglobinuria: acquired PIGA mutation losing glycosyl-phosphatidylinositol anchors for CD55 and CD59; complement-mediated haemolysis with pancytopenia and hepatic vein thrombosis; flow cytometry on FLAER is the modern test; eculizumab blocks C5.
Where candidates slip
The DAT is misapplied more than any other test: hereditary spherocytosis has spherocytes but a negative DAT, and treating it as autoimmune haemolysis with steroids fails. Second slip — reading schistocytes as specific for DIC; fragments occur in TTP-HUS, malignant hypertension and valve haemolysis, so complete the picture with platelet count, INR and creatinine: platelets low with normal INR and creatinine high suggests HUS or TTP rather than DIC. Third, the G6PD assay timing trap: testing during acute haemolysis can return normal because the destroyed cells were the enzyme-deficient ones. Fourth, in sickle disease the reticulocyte count should be high; a normal or low reticulocyte count during a crisis drop means aplastic crisis (parvovirus B19) or splenic sequestration — an emergency distinction the exam loves.
Frequently asked questions
Which tests distinguish intravascular from extravascular haemolysis?
Intravascular haemolysis shows haemoglobinaemia, haemoglobinuria, haemosiderinuria and markedly low haptoglobin; extravascular haemolysis mainly raises indirect bilirubin and LDH with splenomegaly.
Why does hereditary spherocytosis raise MCHC?
Loss of membrane surface area concentrates haemoglobin in a smaller spherocyte, making high MCHC the only anaemia in which it is elevated — a favourite exam fact.
What precipitates haemolysis in G6PD deficiency?
Oxidative stress from primaquine and related antimalarials, sulphonamides, dapsone, fava beans, naphthalene and infections, producing Heinz bodies and bite cells.
How is paroxysmal nocturnal haemoglobinuria diagnosed?
Flow cytometry showing loss of CD55 and CD59 (or FLAER binding) on granulocytes and monocytes, reflecting the PIGA mutation abolishing glycosyl-phosphatidylinositol anchors.
Which haemoglobin is protective in Indian sickle cell disease?
Fetal haemoglobin HbF, high on the Arab-Indian haplotype, dilutes HbS polymerisation and produces the milder Indian phenotype seen in the central tribal belt.