Macrocytic and Aplastic Anaemia for NEET PG Pathology: Vitamin B12, Folate, Pernicious Anaemia, Pancytopenia, Parvovirus B19

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🎯 Exam priority: Very high. Expect: hypersegmented neutrophils, pernicious anaemia with paraesthesia, MMA vs homocysteine, a vegan or metformin user with low B12, alcohol and folate, and pancytopenia with an empty marrow.

CBME mapping: PA 15.1–15.3, 17.1.

Megaloblastic Anaemia

Vitamin B12 versus folate deficiency, and non-megaloblastic macrocytosis. Drawn by TrackNation.

• Most often from B12 or folate deficiency. Ineffective haematopoiesis affects all cell lines, especially red cells.

• Smear: macro-ovalocytes, Howell-Jolly bodies, hypersegmented neutrophils, low reticulocytes. Neutrophil hypersegmentation is a sensitive, readily available test.

Vitamin B12

• Binds intrinsic factor from gastric parietal cells; absorbed in the terminal ileum. Liver stores last 3–5 years — so deficiency appears late in new vegans.

• Commonest cause: pernicious anaemia (autoantibodies impair intrinsic factor secretion), which can occur in young women. Other causes include vegans without supplements and drugs such as metformin.

• Labs: both methylmalonic acid and homocysteine are raised (only homocysteine in folate deficiency).

• Nerves: neurological signs (neuropathy, unsteady gait) are unique to B12 deficiency and can become permanent; paraesthesia may come before anaemia. Subacute combined degeneration affects mainly brain and spinal-cord white matter.

Folate and Other Macrocytosis

• Folate stores last only a few months. Causes: poor or restrictive diet, alcohol, anorexia, pregnancy and lactation, malabsorption (coeliac disease, tropical sprue, short bowel) and drugs (methotrexate, triamterene, trimethoprim).

• Maternal folate deficiency raises the risk of neural tube defects.

• Non-megaloblastic: round (not oval) macrocytes with target cells suggest liver disease; many reticulocytes also raise the MCV.

Aplastic Anaemia and Red-Cell Aplasia

• Diagnosis: peripheral pancytopenia plus a hypocellular marrow on biopsy. Marrow testing includes cytogenetics, and flow cytometry for PNH is part of the work-up.

• Causes: chemicals (benzene, arsenic), drugs (anticancer drugs, antibiotics, NSAIDs, antiseizure drugs and others), seronegative hepatitis, pregnancy, radiation, EBV and CMV, inherited marrow failure (Fanconi anaemia); about half are idiopathic.

• Spleen is not enlarged (unless from transfusion iron overload).

• Treatment: equine antithymocyte globulin plus cyclosporine, or bone marrow transplantation.

• Pure red-cell aplasia: parvovirus B19 binds the P antigen on red-cell precursors (dangerous in HIV or chronic haemolysis); also linked to thymoma.

Traps the Examiner Sets

• MMA raised = B12; homocysteine alone = folate.

• Neurological signs point to B12, not folate.

• Pancytopenia with splenomegaly is not typical aplastic anaemia.

• Aplastic crisis in a child with chronic haemolysis: think parvovirus B19.

Memory Hooks & Shortcuts

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

• 🧠 B12 = Both (MMA and homocysteine) — folate raises homocysteine only

• 🧠 B12 for Brain and Back (nerves) — neurology only in B12 deficiency

• 🧠 B12 lasts Years, folate lasts Months — stores

• 🧠 Pernicious = Parietal cells lose intrinsic factor — commonest B12 cause

• 🧠 Aplastic: Empty marrow, Empty blood, No spleen — pancytopenia, hypocellular marrow, no splenomegaly

• 🧠 Parvo Picks the P antigen — red-cell aplasia

Rapid-Revision Cards

• Megaloblastic smear

  Macro-ovalocytes, Howell-Jolly bodies, hypersegmented neutrophils, low retics.

• Megaloblastic cause

  B12 or folate; ineffective haematopoiesis, all lines.

• B12 absorption

  Intrinsic factor (parietal cells); terminal ileum.

• B12 stores

  3–5 years.

• Commonest B12 cause

  Pernicious anaemia (autoantibodies).

• Other B12 causes

  Vegan diet, metformin.

• MMA + homocysteine

  Both high in B12; only homocysteine in folate.

• B12 nerves

  Neuropathy, gait; unique to B12; can be permanent.

• SCD

  Brain and spinal-cord white matter.

• Folate stores

  A few months.

• Folate causes

  Diet, alcohol, pregnancy, coeliac, methotrexate/trimethoprim.

• Folate in pregnancy

  Deficiency → neural tube defects.

• Liver-disease macrocytes

  Round, with target cells.

• Aplastic anaemia

  Pancytopenia + hypocellular marrow.

• Aplastic causes

  Benzene, drugs, seronegative hepatitis, viruses, Fanconi.

• Aplastic spleen

  Not enlarged.

• Aplastic treatment

  ATG + cyclosporine, or BMT.

• Parvovirus B19

  P antigen; red-cell aplasia in chronic haemolysis/HIV.

• PRCA association

  Thymoma.

Sources

Facts in this article were checked against these documents.

• MSD Manual Professional: Megaloblastic Macrocytic Anemias; Vitamin B12 Deficiency; Folate Deficiency; Aplastic Anemia; Pure Red Blood Cell Aplasia; Evaluation of Anemia — Merck & Co. (MSD Manuals), reviewed 2025–2026 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 15, 17) — 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 55-year-old woman has macrocytic anaemia; the smear shows oval macrocytes and hypersegmented neutrophils. The process is

• (a) megaloblastic anaemia

• (b) thalassaemia trait

• (c) iron deficiency

• (d) anaemia of chronic disease

Q2. The commonest cause of vitamin B12 deficiency is

• (a) pernicious anaemia (autoantibodies impair intrinsic factor)

• (b) vegan diet

• (c) tapeworm

• (d) metformin

Q3. Vitamin B12 bound to intrinsic factor is absorbed in the

• (a) stomach

• (b) colon

• (c) terminal ileum

• (d) duodenum

Q4. A man who became vegan 1 year ago has a normal B12 level. Deficiency may take years because

• (a) B12 is not needed by adults

• (b) liver B12 stores last 3–5 years

• (c) plants contain enough B12

• (d) B12 is made in the colon and absorbed

Q5. A patient has macrocytic anaemia with raised serum methylmalonic acid and homocysteine. The deficiency is

• (a) iron

• (b) folate

• (c) vitamin C

• (d) vitamin B12

Q6. Raised homocysteine with normal methylmalonic acid in a macrocytic anaemia indicates

• (a) B12 deficiency

• (b) folate deficiency

• (c) iron deficiency

• (d) aplastic anaemia

Q7. A 60-year-old with megaloblastic anaemia has a peripheral neuropathy and an unsteady gait. These features point to

• (a) alcohol only

• (b) folate deficiency

• (c) vitamin B12 deficiency

• (d) iron deficiency

Q8. Subacute combined degeneration in B12 deficiency mainly affects

• (a) the retina

• (b) brain and spinal-cord white matter

• (c) the cerebellar cortex only

• (d) skeletal muscle

Q9. A diabetic on long-term metformin has a low B12. This is because

• (a) metformin is a recognised cause of B12 deficiency

• (b) metformin causes folate excess

• (c) it is unrelated

• (d) metformin raises B12

Q10. A man with heavy alcohol use and poor diet has macrocytic anaemia with normal B12. The likely deficiency is

• (a) B12

• (b) copper

• (c) iron

• (d) folate

Q11. Folate deficiency appears faster than B12 deficiency because

• (a) folate is stored for years

• (b) folate is not absorbed

• (c) folate needs intrinsic factor

• (d) liver folate stores last only a few months

Q12. Maternal folate deficiency increases the risk of

• (a) cleft lip only

• (b) neural tube defects

• (c) congenital heart block

• (d) hypospadias

Q13. A patient on long-term trimethoprim and methotrexate develops megaloblastic anaemia. The mechanism is

• (a) drug-induced folate deficiency

• (b) B12 malabsorption

• (c) iron loss

• (d) haemolysis

Q14. A woman with coeliac disease has macrocytic anaemia. A likely cause is

• (a) aplastic anaemia

• (b) lead poisoning

• (c) excess iron

• (d) folate malabsorption

Q15. A man with cirrhosis has a raised MCV; the smear shows round macrocytes and target cells. This is

• (a) non-megaloblastic macrocytosis of liver disease

• (b) pernicious anaemia

• (c) thalassaemia

• (d) folate deficiency

Q16. A young man has pancytopenia, recurrent infections and bleeding; marrow biopsy is markedly hypocellular. The diagnosis is

• (a) hypersplenism

• (b) aplastic anaemia

• (c) megaloblastic anaemia

• (d) leukaemia

Q17. A worker exposed for years to benzene develops pancytopenia. The likely diagnosis is

• (a) thalassaemia

• (b) aplastic anaemia

• (c) iron deficiency

• (d) B12 deficiency

Q18. Splenomegaly in a patient with suspected aplastic anaemia (never transfused) suggests

• (a) classic aplastic anaemia

• (b) good prognosis

• (c) iron deficiency

• (d) another diagnosis, because the spleen is not enlarged in aplastic anaemia

Q19. A teenager develops pancytopenia after a hepatitis that tested negative for all hepatitis viruses. The marrow is empty. This is

• (a) aplastic anaemia after seronegative hepatitis

• (b) hepatitis B

• (c) iron deficiency

• (d) megaloblastic anaemia

Q20. Which inherited disorder of marrow failure is a recognised cause of aplastic anaemia?

• (a) iron deficiency

• (b) thalassaemia trait

• (c) pernicious anaemia

• (d) Fanconi anaemia

Q21. Standard immunosuppressive treatment of aplastic anaemia is

• (a) iron and folate

• (b) vitamin B12 injections

• (c) equine antithymocyte globulin plus cyclosporine

• (d) splenectomy

Q22. A child with hereditary spherocytosis develops sudden severe anaemia with very low reticulocytes after a febrile illness. The virus is

• (a) influenza

• (b) CMV

• (c) parvovirus B19

• (d) EBV

Q23. Pure red-cell aplasia in an adult should prompt a search for

• (a) kidney stones

• (b) thymoma

• (c) gallstones

• (d) pancreatitis

Q24. In megaloblastic anaemia, ineffective haematopoiesis affects

• (a) no cells

• (b) only platelets

• (c) all cell lines, especially red cells

• (d) only neutrophils

Active Recall

From memory: describe the megaloblastic smear, compare B12 and folate deficiency (absorption, stores, causes, MMA and homocysteine, nerves), name the clue to non-megaloblastic macrocytosis, and give the diagnosis, causes and treatment of aplastic anaemia and the cause of pure red-cell aplasia.