Megaloblastic
Macrocytic AnemiaThis is a common anemia and is due to either vitamin
B12 deficiency or due to folate deficiency, which leads to megaloblasts in the
bone marrow. When B12 deficiency is present, it is also known as pernicious anemia.
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 where intrinsic factor is missing (pernicious anemia). Intrinsic
factor is produced in the stomach wall and needed for absorption of vitamin B12
in the small bowel. 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).
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