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

Source: https://tracknation.in/story/macrocytic-and-aplastic-anaemia-for-neet-pg-pathology-vitamin-b12-folate-pernicious-anaemia-pancytopenia-parvovirus-b19 (TrackNation — free UPSC notes with PYQs)

> NEET PG Pathology: megaloblastic anaemia from B12 or folate deficiency (absorption, stores, smear, MMA and homocysteine, subacute combined degeneration), non-megaloblastic macrocytosis, aplastic anaemia (causes, hypocellular marrow, treatment) and pure red-cell aplasia, with a diagram, hooks, vignette MCQs and cards.

## Start Here

🎯 **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

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

- B12 or folate; ineffective haematopoiesis, all lines.

- Intrinsic factor (parietal cells); terminal ileum.

- 3–5 years.

- Pernicious anaemia (autoantibodies).

- Vegan diet, metformin.

- Both high in B12; only homocysteine in folate.

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

- Brain and spinal-cord white matter.

- A few months.

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

- Deficiency → neural tube defects.

- Round, with target cells.

- Pancytopenia + hypocellular marrow.

- Benzene, drugs, seronegative hepatitis, viruses, Fanconi.

- Not enlarged.

- ATG + cyclosporine, or BMT.

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

- 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

**Answer: (a)** — Macro-ovalocytes, Howell-Jolly bodies, hypersegmented neutrophils, low reticulocytes.

**Q2.** The commonest cause of vitamin B12 deficiency is

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

- (b) vegan diet

- (c) tapeworm

- (d) metformin

**Answer: (a)** — MSD.

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

- (a) stomach

- (b) colon

- (c) terminal ileum

- (d) duodenum

**Answer: (c)** — Intrinsic factor comes from gastric parietal cells.

**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

**Answer: (b)** — MSD.

**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

**Answer: (d)** — Only homocysteine is raised in folate deficiency.

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

- (a) B12 deficiency

- (b) folate deficiency

- (c) iron deficiency

- (d) aplastic anaemia

**Answer: (b)** — MSD.

**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

**Answer: (c)** — Neurological manifestations are unique to B12 deficiency and can be permanent.

**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

**Answer: (b)** — MSD.

**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

**Answer: (a)** — MSD lists metformin among causes.

**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

**Answer: (d)** — Folate stores last only months; alcohol and poor diet are causes.

**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

**Answer: (d)** — MSD.

**Q12.** Maternal folate deficiency increases the risk of

- (a) cleft lip only

- (b) neural tube defects

- (c) congenital heart block

- (d) hypospadias

**Answer: (b)** — MSD.

**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

**Answer: (a)** — MSD lists methotrexate, triamterene, trimethoprim.

**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

**Answer: (d)** — Coeliac disease, tropical sprue and short bowel cause folate deficiency.

**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

**Answer: (a)** — Round rather than oval macrocytes suggest liver disease.

**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

**Answer: (b)** — Pancytopenia plus hypocellular marrow.

**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

**Answer: (b)** — Benzene and inorganic arsenic are recognised causes.

**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

**Answer: (d)** — Splenomegaly is absent unless from transfusion haemosiderosis.

**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

**Answer: (a)** — MSD lists seronegative hepatitis as a cause.

**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

**Answer: (d)** — Inherited marrow failure syndromes cause aplastic 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

**Answer: (c)** — Or bone marrow transplantation.

**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

**Answer: (c)** — Parvovirus B19 binds the P antigen on erythroid precursors; dangerous in chronic haemolysis.

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

- (a) kidney stones

- (b) thymoma

- (c) gallstones

- (d) pancreatitis

**Answer: (b)** — MSD lists thymomas among causes.

**Q24.** In megaloblastic anaemia, ineffective haematopoiesis affects

- (a) no cells

- (b) only platelets

- (c) all cell lines, especially red cells

- (d) only neutrophils

**Answer: (c)** — Hence pancytopenia can occur.

### 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.