Chapter 100. Megaloblastic Anemias (Part 14)

Serum Folate This is also measured by an ELISA technique. In most laboratories, the normal range is from 11 nmol/L (2.0 µg/L) to ~82 nmol/L (15 µg/L). The serum folate level is low in all folate-deficient patients. It also reflects recent diet. Because of this, serum folate may be low before there is hematologic or biochemical evidence of deficiency. Serum folate rises in severe cobalamin deficiency because of the block in conversion of MTHF to THF inside cells; raised levels have also been reported in the intestinal stagnant loop syndrome, due to absorption of bacterially synthesized folate.Red Cell FolateThe...
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Chapter 100. Megaloblastic Anemias (Part 14) Chapter 100. Megaloblastic Anemias (Part 14) Serum Folate This is also measured by an ELISA technique. In most laboratories, thenormal range is from 11 nmol/L (2.0 µg/L) to ~82 nmol/L (15 µg/L). The serumfolate level is low in all folate-deficient patients. It also reflects recent diet.Because of this, serum folate may be low before there is hematologic orbiochemical evidence of deficiency. Serum folate rises in severe cobalamindeficiency because of the block in conversion of MTHF to THF inside cells; raisedlevels have also been reported in the intestinal stagnant loop syndrome, due toabsorption of bacterially synthesized folate. Red Cell Folate The red cell folate assay is a valuable test of body folate stores. It is lessaffected than the serum assay by recent diet and traces of hemolysis. In normaladults, concentrations range 880–3520 µmol/L (160–640 µg/L) of packed redcells. Subnormal levels occur in patients with megaloblastic anemia due to folatedeficiency but also in nearly two-thirds of patients with severe cobalamindeficiency. False-normal results may occur if the folate-deficient patient hasreceived a recent blood transfusion or if the patient has a raised reticulocyte count. Megaloblastic Anemia: Treatment It is usually possible to establish which of the two deficiencies, folate orcobalamin, is the cause of the anemia and to treat only with the appropriatevitamin. In patients who enter hospital severely ill, however, it may be necessaryto treat with both vitamins in large doses once blood samples have been taken forcobalamin and folate assays and a bone marrow biopsy has been performed (ifdeemed necessary). Transfusion is usually unnecessary and inadvisable. If it isessential, packed red cells should be given slowly, one or two units only, with theusual treatment for heart failure if present. Potassium supplements have beenrecommended to obviate the danger of the hypokalemia that has been recorded insome patients during the initial hematologic response. Occasionally, an excessiverise in platelets occurs after 1–2 weeks of therapy. Antiplatelet therapy, e.g.,aspirin should be considered if the platelet count rises to >800 x 10 9/L. Treatment of Cobalamin Deficiency It is usually necessary to treat patients who have developed cobalamindeficiency with lifelong regular cobalamin injections. In the UK, the form used ishydroxocobalamin; in the United States, cyanocobalamin. In a few instances, theunderlying cause of cobalamin deficiency can be permanently corrected, e.g., thefish tapeworm, tropical sprue, or an intestinal stagnant loop that is amenable tosurgery. The indications for starting cobalamin therapy are a well-documentedmegaloblastic anemia or other hematologic abnormalities or neuropathy due to thedeficiency. Patients with borderline serum cobalamin levels but no hematologic orother abnormality should be followed, e.g., at yearly intervals to make sure thatthe cobalamin deficiency does not progress. If malabsorption of cobalamin or risesin serum MMA levels have also been demonstrated, however, they should also begiven regular maintenance cobalamin therapy. Cobalamin should be givenroutinely to all patients who have had a total gastrectomy or ileal resection.Patients who have undergone gastric reduction for control of obesity or who arereceiving long-term treatment with proton pump inhibitors should be screenedand, if necessary, given cobalamin replacement. Replenishment of body stores should be complete with six 1000-µg IMinjections of hydroxocobalamin given at 3- to 7-day intervals. More frequent dosesare usually used in patients with cobalamin neuropathy, but there is no evidencethat these produce a better response. For maintenance therapy, 1000 µghydroxocobalamin IM once every 3 months is satisfactory. Because of the poorerretention of cyanocobalamin, protocols generally use higher and more frequentdoses, e.g., 1000 µg IM, monthly, for maintenance treatment. Toxic reactions are extremely rare and are usually due to contamination inits preparation rather than to cobalamin itself. Because a small fraction ofcobalamin can be absorbed passively through mucous membranes even when thereis complete failure of physiological IF-dependent absorption, large daily oraldoses (1000–2000 µg) of cyanocobalamin can be used in PA for replacement andmaintenance of normal cobalamin status. Sublingual therapy has also beenproposed for those in whom injections are difficult because of a bleeding tendencyand may not tolerate oral therapy. If oral therapy is used, it is important to monitorcompliance, particularly with elderly, forgetful patients. Treatment ...