Hospital Course

The next morning the patient felt stronger. A second CBC showed hemoglobin, 8.9 gm/dL;

MCV, 95 µm3; RDW, 24.2%; white blood cell count, 3,800/mm3; and platelet count, 39,000/ mm3. Platelet transfusion was considered but deferred because the patient showed no signs of bleeding. Marked anisocytosis and occasional hypersegmented neutrophils

were noted on the blood smear. The bone marrow biopsy was canceled. After blood was drawn for tests, the patient was given a subcutaneous injection of vitamin B12 (100 µg), oral folic acid (1 mg), and oral ferrous sulfate (325 mg). The neurologic examination

showed diminished vibratory sense in the toes but was otherwise normal. The Mini-Mental Status Examination score was 27/30. The dietary history was found to be adequate. Pretreatment blood test results were vitamin B12, 96 ng/L (normal, 200-900); folate, 20.2 µg/L (normal, 5-20); total homocysteine, 38.9 µmol/L (normal, 5-14); methylmalonic acid, 1,850 nmol/L (normal, 90-280); ferritin, 800 µg/L (normal, 15-300); iron, 196 µg/dL (normal, 60-160); iron-binding capacity, 258 µg/dL (normal, 250-350); lactate dehydrogenase, 2,250 U/L (normal, 50-150); and reticulocyte count, 44,000/mm3 (normal, 25,000-75,000). The patient was given a second injection of vitamin B12 (100 µg) and discharged. She was to receive weekly injections of vitamin B12 (1,000 µg) for the next month, then monthly thereafter.
The changes in the CBC were entirely-predictably- due to the transfusion of three units of packed red cells. The hemoglobin level rose about 3 gm/dL, to 8.9 gm/dL. The MCV dropped to 95 µm3, because the large cells were diluted with normal-sized cells. The RDW, an indicator of anisocytosis, rose because the addition of normal blood cells increased the distribution of cell size.

In retrospect, the decrease in the platelet count was not surprising either. When patients with megaloblastic anemia receive a transfusion of red blood cells, the platelet count, for unknown reasons, decreases by about 50%. If the pretransfusion platelet count is low-say, 30,000/mm3-the decrease could result in serious bleeding. This is yet another reason to avoid transfusion unless absolutely necessary. In this case, the blood smear examination established the diagnosis of megaloblastic anemia and confirmed that the transfusion had been unnecessary.

Once megaloblastic anemia has been diagnosed, the next step is to determine whether it is caused by a deficiency of vitamin B12 or folate. Hence the importance of a neurologic examination, an evaluation of mental function, and a dietary history. In general, neurologic abnormalities do not occur in adult patients with folate deficiency (although they may result from coexisting conditions such as alcoholism). They do occur in about 50% of patients with vitamin B12 deficiency. Often the neurologic sequelae of B12 deficiency are more serious than the hematologic abnormalities.

The anemia can always be reversed by treatment, whereas neurologic abnormalities may or may not be. In this case, the mildly diminished vibratory sense in the toes suggested B12 deficiency. The Mini-Mental Status Examination score was normal for a person her age; however, this is a fairly crude test. The patient's unremarkable dietary history argued against folate deficiency, which, unlike B12 deficiency, typically results from inadequate intake.

The patient's physician gave her both B12 and folate. She also received iron, even though there were no signs of iron deficiency. Some physicians apparently give iron to all anemic patients whether they need it or not.

Immediate treatment with both B12 and folate is justifiable as long as the regimen is corrected as soon as blood test results identify the specific deficiency. The blood count will not begin to increase until after several days of vitamin therapy. If the hemoglobin level truly needs to be increased immediately, transfusion alone will suffice. Also, blood test results are equivocal on occasion. If the patient has not been treated, additional testing may resolve the uncertainty. But if the patient has already received vitamin therapy, the physician may be faced with a diagnostic dilemma. In this case, the test results clearly demonstrated vitamin B12 deficiency. The high folate level is typical of B12 deficiency. The physician also ordered measurement of homocysteine and methylmalonic acid levels. Although serum levels of both often are misleadingly high in patients with renal insufficiency, they are sensitive markers of B12 deficiency. However, homocysteine levels increase by similar amounts in patients with folate deficiency and other conditions. Measurement of the two metabolites is increasingly popular, since they can be useful in establishing the diagnosis when the clinical presentation or other laboratory results are equivocal. This is especially true in the early stages of vitamin B12 deficiency, when patients may have minimal or no anemia and borderline B12 levels. The homocysteine and methylmalonic acid readings in this patient are typical for B12 deficiency and would have confirmed the diagnosis had it been in doubt. In this case, however, the diagnosis was not in doubt: the B12 and folate levels were classic for B12 deficiency, and the patient's clinical presentation and other blood study results fit the diagnosis perfectly. Measuring homocysteine and methylmalonic acid levels was overkill.