Erythropoietin levels in cobalamin deficiency: comparison of anemic and non-anemic, subtly deficient patients.
The major stimulus for erythropoietin secretion is the circulating hemoglobin level, but other poorly understood factors appear to influence the erythropoietin level as well. Therefore, the effect of cobalamin deficiency was studied in patients who were not anemic, even though many of them had macrocytosis or metabolic deficiency of the bone marrow cells. All 15 cobalamin-deficient patients without anemia had normal erythropoietin levels, including the 4 patients with macrocytosis and 3 in whom metabolic cobalamin deficiency of the marrow cells was documented with the deoxyuridine suppression test. Moreover, among 21 cobalamin-deficient patients with anemia, the 4 least anemic patients also had normal erythropoietin levels. The other 17 anemic patients had elevated erythropoietin levels. Erythropoietin levels correlated with the severity of the anemia (r = 0.423, p less than 0.05). However, wide individual variations were observed; 4 patients with hemoglobin levels of 37-43 g/l had erythropoietin levels ranging from 69 to 3300 units/l, for example. These observations support the hypothesis that the hemoglobin level is the major, but not the sole factor that determines erythropoietin levels. As long as it does not produce anemia, however, cobalamin deficiency does not raise erythropoietin levels even when it induces metabolic deficiency of the bone marrow and macrocytosis.