Haemolytic Anaemias for NEET PG Pathology: Sickle Cell (ICMR), Thalassaemia, Spherocytosis, G6PD, Autoimmune Haemolysis, PNH

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🎯 Exam priority: Very high. Expect: the haemolysis panel, a child with a sickle crisis, thalassaemia major with Hb F, spherocytes with negative Coombs, bite cells after a drug, warm IgG vs cold IgM, and PNH with odd-site clots.

CBME mapping: PA 16.1–16.3. Indian protocol: ICMR Sickle Cell Disease workflow (July 2020).

Recognising Haemolysis

Haemolysis labs and red-cell shapes linked to the likely disorder. Drawn by TrackNation.

• Suspect haemolysis in anaemia with reticulocytosis. Test indirect bilirubin, LDH and haptoglobin (low in intravascular haemolysis); unconjugated jaundice appears when bilirubin production exceeds the liver's capacity.

• Mechanical intravascular causes: thrombotic microangiopathies, prosthetic heart valves, march haemoglobinuria — giving schistocytes.

Sickle Cell Disease (ICMR)

• Molecule: valine replaces glutamic acid at position 6 of the beta chain; deoxygenated HbS polymerises.

• India: autosomal recessive; about 88% of homozygous cases in Asia are Indian (ICMR). Crises are precipitated by fever, strenuous exercise, dehydration, drenching in rain, surgery and infection.

• Spleen: repeated infarcts shrink it (autosplenectomy) → pneumococcal and Salmonella infections (including osteomyelitis). ICMR: penicillin prophylaxis until 5 years; pneumococcal vaccine.

• Diagnosis: solubility test, HPLC or electrophoresis. ICMR screens all pregnant women with a CBC in the first trimester; if the mother is a carrier, testing the father is mandatory. Carriers usually need no treatment.

• Hydroxyurea reduces crises and acute chest syndrome.

Thalassaemias

• Beta-thalassaemia major: Hb F up to 90%, Hb A2 > 3%; smear shows target cells, small pale cells, nucleated red cells and basophilic stippling; skull shows a widened diploic space and sun-ray trabeculae; iron overload in the liver. Treatment: transfusion, chelation, splenectomy, stem cell transplant.

• Alpha-thalassaemia with no alpha genes is lethal in utero (hydrops fetalis): haemoglobin without alpha chains cannot carry oxygen.

Membrane, Enzyme, Immune and PNH

• Hereditary spherocytosis: autosomal dominant (spectrin, ankyrin, band 3, protein 4.2); anaemia, jaundice, splenomegaly, pigment gallstones; raised MCHC; increased osmotic fragility, reduced EMA binding and a negative Coombs test.

• G6PD deficiency: X-linked; haemolysis after illness or oxidant drugs (e.g. salicylates, sulfonamides); bite cells and Heinz bodies; the assay can be falsely normal during the crisis (reticulocytes are G6PD-rich).

• Autoimmune: diagnosed by the direct Coombs test. Warm type is mostly IgG (linked to SLE, lymphoma, CLL; microspherocytes); cold agglutinin disease is IgM (after Mycoplasma pneumonia or infectious mononucleosis). Paroxysmal cold haemoglobinuria = Donath-Landsteiner.

• PNH: acquired PIGA mutation → loss of GPI-anchored CD55 and CD59 → complement-mediated intravascular haemolysis and thrombosis at unusual sites (portal vein, cerebral sinuses). Diagnosed by flow cytometry.

Traps the Examiner Sets

• Spherocytes + negative Coombs = hereditary spherocytosis; positive Coombs = warm AIHA.

• G6PD assay may read normal during haemolysis — repeat later.

• Warm = IgG, cold = IgM.

• Sickle cell adults have small spleens; children with HS have big ones.

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 Sickle: Six, Valine Victory over Glutamate — β6 Glu→Val

• 🧠 HS: Spheres, Spleen, Stones, Sensitive to salt (osmotic fragility) — hereditary spherocytosis

• 🧠 G6PD: Bites and Heinz after Oxidants — bite cells, Heinz bodies

• 🧠 Warm = G (IgG), cold = M (IgM): 'Warm Gs, Cold Ms' — AIHA antibodies

• 🧠 PNH: PIGA Pulls the anchor (CD55, CD59) — GPI anchor loss

• 🧠 Thal major: F for Fetal, up to 90 — Hb F

Rapid-Revision Cards

• Haemolysis panel

  Retics ↑, indirect bilirubin ↑, LDH ↑, haptoglobin ↓.

• Beta-thalassaemia major

  Hb F up to 90%, Hb A2 > 3%; target cells; widened diploic space, sun-ray skull.

• Alpha-thalassaemia, all 4 genes deleted

  Hydrops fetalis — lethal in utero.

• Intravascular causes

  TMA, prosthetic valve, march haemoglobinuria; PNH.

• HbS

  Glu→Val at β6; polymerises when deoxygenated.

• SCD in India (ICMR)

  AR; ~88% of Asian homozygous cases are Indian.

• Sickle crisis triggers

  Fever, exercise, dehydration, rain, surgery, infection.

• Sickle spleen

  Autosplenectomy; pneumococcus, Salmonella osteomyelitis.

• ICMR prophylaxis

  Penicillin till 5 y; pneumococcal vaccine.

• ICMR antenatal

  CBC in 1st trimester; carrier mother → test father.

• Hydroxyurea

  Fewer crises and acute chest syndrome.

• Thal major

  Hb F up to 90%, A2 > 3%; target cells; sun-ray skull.

• Hydrops fetalis

  No alpha genes; lethal in utero.

• HS

  AD; spherocytes, MCHC ↑, osmotic fragility ↑, EMA ↓, Coombs −.

• G6PD

  X-linked; oxidant drugs; bite cells, Heinz bodies.

• G6PD test pitfall

  False normal during crisis.

• Warm AIHA

  IgG; SLE, lymphoma, CLL; Coombs +.

• Cold agglutinin

  IgM; Mycoplasma, EBV.

• PCH

  Donath-Landsteiner.

• PNH

  PIGA; CD55/59 lost; odd-site clots; flow cytometry.

• Schistocytes

  Helmets, triangles; MAHA.

Sources

Facts in this article were checked against these documents.

• Standard Treatment Workflow: Sickle Cell Disease — Indian Council of Medical Research / Department of Health Research, MoHFW, July 2020

• MSD Manual Professional: Overview of Hemolytic Anemia; Sickle Cell Disease; Thalassemias; Hereditary Spherocytosis and Elliptocytosis; G6PD Deficiency; Autoimmune Hemolytic Anemia; Paroxysmal Nocturnal Hemoglobinuria; Microangiopathic Hemolytic Anemia — Merck & Co. (MSD Manuals), reviewed 2025–2026 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 16) — National Medical Commission, 2024

Test Yourself: Practice Questions

Twenty-four questions in NEET PG style, most of them clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. A jaundiced woman has anaemia with reticulocytosis. To confirm haemolysis, the first panel is

• (a) indirect bilirubin, LDH and haptoglobin

• (b) ferritin and TIBC

• (c) bone marrow biopsy

• (d) B12 and folate

Q2. In intravascular haemolysis, plasma haptoglobin

• (a) rises

• (b) doubles

• (c) falls

• (d) is unchanged

Q3. In haemoglobin S, the change in the beta chain is

• (a) lysine replacing glutamic acid

• (b) deletion of the beta gene

• (c) valine replacing glutamic acid at position 6

• (d) an extra alpha chain

Q4. A boy with sickle cell disease develops a painful crisis. Which of these does the ICMR sickle cell workflow list as a crisis trigger?

• (a) getting drenched in rain

• (b) taking folic acid

• (c) drinking plenty of water

• (d) routine vaccination

Q5. An adult with sickle cell disease has a small, shrunken spleen on ultrasound. This is due to

• (a) repeated infarction and fibrosis (autosplenectomy)

• (b) splenic sequestration

• (c) lymphoma

• (d) thalassaemia

Q6. A child with sickle cell disease has fever and bone pain; blood culture grows Salmonella. The predisposition is

• (a) functional asplenia (pneumococcal and Salmonella infections)

• (b) B12 deficiency

• (c) hydroxyurea

• (d) iron overload

Q7. Per ICMR, a newborn with HbSS should receive

• (a) iron supplements

• (b) no prophylaxis

• (c) penicillin prophylaxis up to 5 years, plus pneumococcal vaccine

• (d) hydroxyurea from birth

Q8. A pregnant woman is found to be a sickle cell carrier. ICMR's next step is

• (a) start hydroxyurea

• (b) no further action

• (c) terminate the pregnancy

• (d) test the father (mandatory)

Q9. A drug shown to reduce sickle crises and acute chest syndrome is

• (a) hydroxyurea

• (b) folic acid alone

• (c) aspirin

• (d) iron

Q10. A child with severe anaemia from infancy has Hb F of 85%, Hb A2 4% and target cells. The diagnosis is

• (a) sickle cell trait

• (b) hereditary spherocytosis

• (c) beta-thalassaemia major

• (d) iron deficiency

Q11. A skull X-ray of a transfusion-dependent child shows a widened diploic space and 'sun-ray' trabeculae. The cause is

• (a) rickets

• (b) marrow expansion in thalassaemia major

• (c) multiple myeloma

• (d) hyperparathyroidism

Q12. A fetus with deletion of all four alpha-globin genes develops

• (a) mild anaemia

• (b) hydrops fetalis (lethal in utero)

• (c) sickle crises

• (d) no disease

Q13. A 12-year-old with jaundice, splenomegaly and gallstones has spherocytes, raised MCHC and a negative direct Coombs test. The diagnosis is

• (a) hereditary spherocytosis

• (b) warm autoimmune haemolysis

• (c) thalassaemia

• (d) G6PD deficiency

Q14. Hereditary spherocytosis is usually inherited as

• (a) mitochondrial

• (b) autosomal recessive always

• (c) autosomal dominant (spectrin, ankyrin, band 3, protein 4.2)

• (d) X-linked recessive

Q15. A modern flow-cytometric test supporting hereditary spherocytosis is

• (a) reduced eosin-5-maleimide (EMA) binding

• (b) Ham test

• (c) CD55/CD59 loss

• (d) Hb electrophoresis

Q16. A young man develops acute haemolysis after taking a sulfonamide; the smear shows bite cells. The diagnosis is

• (a) PNH

• (b) G6PD deficiency

• (c) sickle cell disease

• (d) hereditary spherocytosis

Q17. During that acute haemolytic episode, his G6PD assay is normal. The reason is

• (a) reticulocytes are rich in G6PD, giving a false normal

• (b) he does not have G6PD deficiency

• (c) the drug raised G6PD

• (d) lab error always

Q18. Heinz bodies in G6PD deficiency are

• (a) denatured haemoglobin seen only with special stains

• (b) iron granules

• (c) nuclear remnants

• (d) parasites

Q19. A woman with SLE has haemolytic anaemia with microspherocytes. The test that establishes the diagnosis is

• (a) osmotic fragility

• (b) Hb electrophoresis

• (c) direct antiglobulin (Coombs) test

• (d) G6PD assay

Q20. Two weeks after Mycoplasma pneumonia, a student has haemolysis worse in the cold. The antibody is

• (a) IgM (cold agglutinin)

• (b) IgG (warm)

• (c) IgE

• (d) IgA

Q21. Most autoantibodies in warm autoimmune haemolytic anaemia are

• (a) IgE

• (b) IgG

• (c) IgM

• (d) IgA

Q22. A man with haemolysis and dark urine develops a portal vein thrombosis. Flow cytometry shows loss of CD55 and CD59. The diagnosis is

• (a) sickle cell disease

• (b) G6PD deficiency

• (c) warm AIHA

• (d) paroxysmal nocturnal haemoglobinuria

Q23. PNH results from

• (a) an inherited spectrin defect

• (b) an X-linked enzyme defect

• (c) an acquired PIGA mutation in haematopoietic stem cells

• (d) an autoantibody

Q24. A patient with a prosthetic heart valve has anaemia; the smear shows helmet cells and triangles. These are

• (a) spherocytes

• (b) schistocytes from mechanical haemolysis

• (c) target cells

• (d) bite cells

Active Recall

From memory: list the haemolysis lab panel; explain sickle cell disease (mutation, triggers, spleen, ICMR prophylaxis and antenatal testing); describe thalassaemia major and hydrops fetalis; and distinguish hereditary spherocytosis, G6PD deficiency, warm and cold autoimmune haemolysis, PNH and microangiopathic haemolysis.