Pathology
Macrocytic Anaemia
Macrocytic anaemia for MBBS and NEET-PG: vitamin B12 and folate metabolism, megaloblastic blood and marrow findings, pernicious anaemia and non-megaloblastic causes, mapped to NMC codes PA15.1 to PA15.4.
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Macrocytic Anaemia
Macrocytic anaemia for MBBS and NEET-PG: vitamin B12 and folate metabolism, megaloblastic blood and marrow findings, pernicious anaemia and non-megaloblastic causes, mapped to NMC codes PA15.1 to PA15.4.
This chapter covers the macrocytic anaemias, dominated by the megaloblastic anaemias of vitamin B12 and folate deficiency. It sets out B12 and folate metabolism, the causes and blood and marrow findings, the neurological features of B12 deficiency, and how to separate megaloblastic from non-megaloblastic macrocytosis.
High-yield: Macrocytic Anaemia
- Megaloblastic anaemia results from deficiency of vitamin B12 or folate, both needed for DNA synthesis.
- The blood film in megaloblastic anaemia shows oval macrocytes and hypersegmented neutrophils.
- The bone marrow in megaloblastic anaemia is hypercellular with megaloblasts showing nuclear-cytoplasmic asynchrony.
- Pernicious anaemia is autoimmune destruction of gastric parietal cells, causing loss of intrinsic factor and vitamin B12 malabsorption.
- Anti-parietal cell and anti-intrinsic factor antibodies support a diagnosis of pernicious anaemia.
- Vitamin B12 deficiency, unlike folate deficiency, causes subacute combined degeneration of the spinal cord.
- The Schilling test was historically used to identify the cause of vitamin B12 malabsorption.
- Folate deficiency develops within months because stores are small; vitamin B12 deficiency takes years because stores are large.
- Megaloblastic anaemia is often accompanied by mild leucopenia and thrombocytopenia, giving a pancytopenia.
- Raised serum lactate dehydrogenase and unconjugated bilirubin reflect ineffective erythropoiesis in megaloblastic anaemia.
- Non-megaloblastic macrocytosis occurs in liver disease, alcoholism, hypothyroidism and reticulocytosis, without hypersegmented neutrophils.
- Folate is essential in early pregnancy and its deficiency increases the risk of neural tube defects.
- Treating vitamin B12 deficiency with folate alone can worsen the neurological damage, so B12 must be corrected.
- Fish tapeworm infestation and vegan diets are recognised causes of vitamin B12 deficiency.
Megaloblastic versus non-megaloblastic macrocytosis
- **Megaloblastic:** B12 or folate deficiency; oval macrocytes and hypersegmented neutrophils.
- **Non-megaloblastic:** Liver disease, alcohol, hypothyroidism, reticulocytosis; no hypersegmentation.
- **B12 versus folate:** Only B12 deficiency causes subacute combined degeneration of the cord.
- **Store size:** Folate stores last months; B12 stores last years.
NMC competencies in this chapter
- **PA15.1:** Vitamin B12 and folate metabolism, absorption and causes of deficiency
- **PA15.2:** Differentiate megaloblastic from non-megaloblastic macrocytic anaemias
- **PA15.3:** Blood and bone marrow findings in megaloblastic anaemia
- **PA15.4:** Peripheral smear features and clinical correlation in macrocytic anaemias
Frequently Asked Questions
What is the blood film in megaloblastic anaemia?
Oval macrocytes and hypersegmented neutrophils, often with a mild reduction in white cells and platelets.
Why does vitamin B12 deficiency cause neurological signs?
Because B12 is needed for myelin, its deficiency causes subacute combined degeneration of the posterior and lateral columns of the spinal cord, which folate deficiency does not.
What is pernicious anaemia?
An autoimmune destruction of gastric parietal cells that removes intrinsic factor and prevents vitamin B12 absorption in the terminal ileum.
Why should folate not be given alone in B12 deficiency?
Because it can correct the anaemia while allowing the neurological damage of B12 deficiency to progress, so B12 must also be replaced.
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