Megaloblastic macrocytic anemia

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[edit] Megaloblastic macrocytic anemia

This is a common anemia and is due to either vitamin B12 deficiency or due to folate deficiency. Either of this vitamin deficiency leads to a defect in DNA synthesis of the precursors of red blood cells, but the RNA synthesis continues so that the end result are megaloblasts in the bone marrow that will also appear in the blood. With special staining they can be visualized in a blood smear.

This anemia takes a long time to develop and may not be symptomatic until it is fairly severe. With vitamin B12 deficiency there are neurological symptoms like numbness of the hands, forgetfulness from dementia or subacute combined degeneration in the more severe cases. With folate deficiency the symptoms are glossitis (inflammation of the tongue) and diarrhea. With folate deficiency the face looks wasted due to frontal muscle atrophy.

Diagnosis

When megaloblastic anemia is suspected, the indices of the CBC blood test show a macrocytic anemia. A blood smear shows the megaloblastic cells typical for megaloblastic macrocytic anemia. There are a number of other parameters in the blood smear that a trained hematologist will detect (anisocytosis, poikilocytosis and macroovalocytosis). Also the distribution width of the size of the RBC’s is high. There are so-called Howell-Jolly bodies in many red blood cells that is a leftover of the cell nucleus of the more immature red blood cell. The reticulocyte count is low as in all hypoproliferative anemias. Because of the change in metabolism with vitamin B12 and folate deficiency there are changes also in the white blood cell line. There is hyper-segmentation of the granulocytes (the pus cells that fight infection). At the later stages there can be neutropenia (=low white blood cell count) and also thrombocytopenia (=low platelet count). At this point the physician still does not know whether the megaloblastic anemia is due to vitamin B12 or folate deficiency. Blood tests are done for folate and vitamin B12 levels. With folate deficiency vitamin B12 deficiency must be sorted out first in order to avoid further progression of any neurological deficit in association with B12 deficiency. If serum concentration of folate is less than 3 micrograms per liter, folate deficiency needs to be treated. If intake of folate has recently changed, a more appropriate measurement of tissue levels of folate is the RBC folate level. A level of 140 micrograms per liter (or less than 305 nanomols per liter) would indicate a true folate deficiency. In difficult to diagnose cases blood methylmalonic acid levels can be determined, which are normal in folate deficiency, but are high in the case of B12 deficiency.

Treatment

Before treatment is given the physician needs to rule out other underlying causes. For instance folate deficiency develops in alcoholism. The patient may have underlying celiac disease or take medication that interferes with folate absorption (e.g. metformin, phenytoin, sulfasalazine etc.). With B12 deficiency there maybe an undetected fish tapeworm that consumes all the dietary B12 vitamins or the patient may have a chronic gastric inflammation with intrinsic factor deficiency (pernicious anemia). Small bowel disorders, gall bladder problems and pancreas disorders can also be associated with vitamin B12 deficiency. Any underlying disorder needs to be addressed. Usually 1000 to 2000 microgram tablets of vitamin B12 to be taken orally are given daily. Even when an intrinsic factor deficiency is present, there is enough absorption of vitamin B12 (in the past it was thought that vitamin B12 had to be injected). In more severe vitamin B12 deficiencies it is still true that the intramuscular route is preferred with 1 milligram of vitamin B12 intramuscularly one to four times per week until the megaloblastic anemia is corrected. A maintenance program once per month by injection can follow. Unfortunately in elderly patients cognition that was lost will not be regained, but further deterioration will be halted. In the case of folate deficiency, 400 to 1000 micrograms per day are given by mouth until blood tests normalize. The daily maintenance dose is 400 micrograms per day. For pregnant women the maintenance dose of folate is 600 micrograms per day (daily RDA). If there was a history of a neural tube defect in a child before, the recommended dose is higher (1000 to 5000 micrograms per day).

Home page

Anemia Overview

Anemia from deficient red blood cell production

References:

1. Merck Manual (Home edition): Anemia

2. Noble: Textbook of Primary Care Medicine, 3rd ed., Mosby Inc. 2001

3. Goldman: Cecil Medicine, 23rd ed., Saunders 2007: Chapter 162 – APPROACH TO THE ANEMIAS