Megaloblastic anaemia


Megaloblastic anaemia

The megaloblastic anaemias are characterised by delayed maturation of the nucleus of red cells in the bone marrow due to defective synthesis of DNA. Red cells either die in the marrow (‘ineffective haematopoiesis’) or enter the bloodstream as enlarged, misshapen cells with a reduced survival time. In clinical practice megaloblastic anaemia is almost always caused by deficiency of vitamin B12 (cobalamin) or folate (pteroylmonoglutamate). It is one of the most common causes of a macrocytic anaemia.

Why does deficiency of vitamin B12 or folate lead to megaloblastic anaemia?

Key characteristics of these essential vitamins are summarised in Table 13.1.

Both folate and vitamin B12 are necessary for the synthesis of DNA (Fig 13.1). Folate is needed in its tetrahydrofolate form (FH4) as a cofactor in DNA synthesis. Deficiency of B12 leads to impaired conversion of homocysteine to methionine causing folate to be ‘trapped’ in the methyl form. The resultant deficiency in methylene FH4 deprives the cell of the coenzyme necessary for DNA formation.

All dividing cells in the body suffer from the impaired DNA synthesis of B12 and folate deficiency. However, the actively proliferating cells of the bone marrow are particularly affected. As RNA synthesis progresses unhindered in the cytoplasm, the erythroid cells develop nuclear–cytoplasmic imbalance with abundant basophilic cytoplasm and enlarged nuclei. The chromatin pattern in the nucleus is characteristically abnormal; one author has described it as resembling ‘fine scroll work’, another as ‘sliced salami’ (Fig 13.2). The slowed synthesis of DNA leads to prolonged cell cycling and the cells being discharged into the blood without the normal quota of divisions. Red cells are enlarged and egg-shaped and the neutrophils hypersegmented due to retention of surplus nuclear material (Fig 13.3).

Jun 12, 2016 | Posted by in HEMATOLOGY | Comments Off on Megaloblastic anaemia

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