Megaloblastic anemia
| Megaloblastic anemia | |
|---|---|
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| Peripheral blood smear showing hypersegmented neutrophils, characteristic of megaloblastic anemia. | |
| Classification and external resources | |
| Specialty | Hematology |
| ICD-10 | D51.1, D52.0, D53.1 |
| ICD-9-CM | 281 |
| DiseasesDB | 29507 |
| MedlinePlus | 000567 |
| eMedicine | med/1420 ped/2575 |
| MeSH | D000749 |
Megaloblastic anemia (or megaloblastic anaemia) is an anemia (of macrocytic classification) that results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the G2 growth stage to the mitosis (M) stage. This leads to continuing cell growth without division, which presents as macrocytosis. Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemias. The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically a deficiency of vitamin B12 and/or folic acid. Vitamin B12 deficiency alone will not cause the syndrome in the presence of sufficient folate, as the mechanism is loss of B12 dependent folate recycling, followed by folate-deficiency loss of nucleic acid synthesis (specifically thymine), leading to defects in DNA synthesis. Folic acid supplementation in the absence of vitamin B12 prevents this type of anemia (although other vitamin B12-specific pathologies may be present). Loss of micronutrients may also be a cause. Copper deficiency resulting from an excess of zinc from unusually high oral consumption of zinc-containing denture-fixation creams has been found to be a cause.
Megaloblastic anemia not due to hypovitaminosis may be caused by antimetabolites that poison DNA production directly, such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim).
The pathological state of megaloblastosis is characterized by many large immature and dysfunctional red blood cells (megaloblasts) in the bone marrow and also by hypersegmented neutrophils (those exhibiting five or more nuclear lobes ("segments"), with up to four lobes being normal). These hypersegmented neutrophils are found in the "peripheral blood" (i.e., a diagnostic smear of a blood-sample taken from the circulation).
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