Bonveda's Blog

The six or seven causes of a macrocytic anemia can be easily subdivided into those causes secondary to vitamin B12 or folate deficiency (pathologically termed “megaloblastic”) versus the other causes (nonmegaloblastic). Typically, the MCV is markedly increased in vitamin deficiency (>115 fL), whereas the macrocytosis of the non-vitamin-deficiency states (alcohol use, chronic liver disease, drugs, familial, hypothyroidism, MDS) typically is milder-in the 100- to 110-fL range.
The usual cause of folate deficiency is dietary. In the case of B12 decifiency, several causes can be remembered best by understanding the physiology of b12 metabolism. The initial step is the dietary intake of b12 thus, strict vegetarianism over a 10- to 15- year period can be a cause. The B12 then is liberated into a free form in the stomach by its acidic environment; hence, H2 blocker use can be a cause. The stomach also produces a protein called “intrinsic factor” which is responsible for the absorption of B12. Major loss of stomach tissue as in the case of a total or partial gastrectomy can be causative, as can be pernicious anemia, the specific autoimmune-mediated destruction of the intrinsic factorproducing parietal cells. Whereas B12 is liberated by the acidic environment in the stomach and the passes through the jejunum, futher release of its bound form by pancreatic enzymes occur;therefore, chronic pancreatic insufficiency can be a cause of deficiency. Also, bacterial overgrowth from blind loops or diverticula or fish tapeworm in the jejunum compete with the host for the B12. Absorption takes place in the presen of intrinsic factor in the terminal ileum. Malabsorption (That can also cause folate deficiency) can be from numerous causes such as Crohn disease, Whipple disease, tropical sprue, celiac disease, radiation ileitis, and infiltrative diseases such as lymphoma or scleroderma.
The non-vitamin-deficiency macrocytic anemias often are misdiagnosed initially as B12 or folate deficiency. A patient with a macrocytic anemia with a borderline low vitamin level may be started on folate or B12 injections without any further consideration for confirming the underlying cause of either folate or B12 deficiency. The clinician may observe after several months that the anemia is not responding to the vitamin supplementation.
Finally, certain drugs, particularly chemotherapy drugs and the antiretroviral drug, azidothymidine, can cause a macrocytic anemia, typically a macrocytosis without much of an anemia. Chemotherapy drugs can increase the MCV significantly in the range of B12 or folate deficiency. Two other drugs to mention under the heading of macrocytic anemia are phenytoin and sulfasalazine, which can intertere with folate absorption.