Megaloblastic Anemia

Megaloblastic Anemia

Background Information

Megaloblastic anemia is an anemia that results from inhibition of DNA synthesis during RBC production. this impaired DNA synthesis results in the cell cycle unable to progress from the G2 growth stage to the mitosis (M) stage. Hence the RBCs This leads continue to undergo cell growth without division, resulting in RBCs being larger than normal (macrocytosis) --> increased MCV. 

Megaloblastic anemia has a rather slow onset, especially when compared to that of other anemia. Hypovitaminosis, specifically a deficiency of vitamin B₁₂ and/or folic acid leading to a malfunction in RBC DNA synthesis is often seen as the major etiology of megaloblastic anemia. However, Vitamin B₁₂ deficiency alone will not cause the syndrome in the presence of sufficient folate, for the mechanism is loss of B₁₂ dependent folate recycling, followed by folate-deficiency loss of nucleic acid synthesis, leading to defects in DNA synthesis. Fortunately, folic acid supplementation in the absence of vitamin B₁₂ prevents this type of anemia (although other vitamin B₁₂-specific pathologies continue). Additionally, copper deficiency resulting from zinc excess from unusually high oral consumption of zinc containing denture fixation creams has been found to be a cause.

Uncommonly, anti-metabolites such as some chemotherapeutic or antimicrobial agents (for example azathioprine or trimethoprim) that inhibit DNA production directly, can cause this condition too

Clinical Observations of PBFs

• Reduced RBC count and hemoglobin levels
• Increased MCV (>95 fl) due to macrocytes (larger sized biconcave round RBCs) and Ovalocytes (generally larger in size) seen and MCH (due to increase in hemoglobin concentration per cell)
• Normal MCHC (32–36 g/dL)
• The platelet count may be reduced.
• Hyper-segmented Neutrophils may be observed. This is thought to be due to decreased production of "new" neutrophils, hence a compensatory prolonged lifespan for circulating neutrophils, which increase numbers of nuclear segments with age.
• Increased RDW due to increased variation in RBC size (Anisocytosis)
• Poikilocytosis (abnormally shaped RBCs): Macrocytes, Ovalocytes

Diagnostic Strategy

Once macrocytosis is identified, the history and physical examination help narrow the differential diagnosis.

*MMA = methylmalonic acid