Unmasking covert folate deficiency in iron--deficient subjects with neutrophil hypersegmentation: dU suppression tests on lymphocytes and bone marrow.

Abstract

Fifteen patients with apparently uncomplicated iron‐deficiency anaemia were studied to determine the presence of covert folate or vitamin B12 deficiency. None had morphologic or conventional biochemical evidence of folate or vitamin B12 deficiency on admission, except for neutrophil hypersegmentation in peripheral blood smears of 10 of the 15 patients, and giant metamyelocytes in some of the bone marrow aspirates.Although deoxyuridine (dU) suppression tests on pretreatment bone marrow were normal in all 15 patients, similar tests on pretreatment transformed lymphocytes were characteristic of folate deficiency in eight of 14 patients (57%), with poor transformation obscuring results in the fifteenth subject.After six patients were given 6 weeks of oral folate and iron therapy, the dU suppression test was repeated in the lymphocytes of two subjects who demonstrated folate deficiency in this test on admission. The test still showed folate deficiency, supporting our prior report that the test was useful as a marker of past folate deficiency despite intervening folate therapy.The nine remaining subjects received iron alone for 3–6 weeks, which produced no change in serum folate, red cell folate, or dU suppression tests in lymphocytes. In five of the nine subjects (56%), however, an abnormality characteristic of folate deficiency appeared for the first time in bone marrow dU suppression tests, with morphologic megaloblastosis developing frankly in four and equivocally in one. Four of these five subjects had a folate corrected defect in the lymphocyte dU suppression test before treatment, and the fifth was the subject in whom lymphocytes did not transform sufficiently to allow testing for the defect.These observations: 1. Suggest that when a patient with apparently uncomplicated iron deficiency has hypersegmentation of his granulocyte nuclei, underlying folate deficiency should be sought. It was found in nine of the 10 current such subjects. 2. Suggest that the most sensitive test to detect covert folate deficiency in contrary to the situation in severe uncomplicated deficiency of vitamin B12 or folate, in which hypersegmentation is striking and rapid scanning of a hundred neutrophils yields a minimum of five with more than five lobes.In uncomplicated iron deficiency, iron binding capacity is almost always elevated above 400 μg/dl. Such levels were seen in only four of our 15 patients, two without hypersegmentation and two with hypersegmentation. This may suggest that a patient population with relatively low total iron binding capacity, perhaps often in association with liver disease, is more likely to have covert folate deficiency with their iron deficiency.