Megaloblastic
Macrocytic AnemiaThis 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).
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