Erythrocyte function and marrow regulation in hemoglobin Bethesda (beta-145 histidine).

Hemoglobin Bethesda (beta145 histidine) is one of the two mutants known to affect the penultimate hemoglobin tyrosines. The result of this substitution is extreme disorganization of the oxygenation function of the molecule. Red cells containing 45% Hb Bethesda and 55% Hb A have increased oxygen affinity but, paradoxically, a normal Bohr effect. As is usually seen with other hemoglobins with increased oxygen affinity, Hb Bethesda clinically is manifest in heterozygotes by erythrocytosis. Red cell production in affected individuals is erythropoietin dependent. The reciprocal interdependence of oxygen delivery and effective erythropoiesis was documented by alterations in erythropoietin excretion, quantitative iron kinetics, and reticulocyte production in response to phlebotomy-induced reduction in the oxygen-carrying capacity.