Carbon Monoxide Production Associated with Ineffective Erythropoiesis*

Abstract

The rate of endogenous carbon monoxide production (˙Vco), determined by the closed rebreathing system technique, was elevated above the normal range in four of five patients studied with ineffective erythropoiesis (four patients with primary refractory anemia, one with thalassemia). The mean molar ratio of ˙Vco to ˙Vheme (rate of circulating heme catabolism, determined from ⁵¹Cr red cell survival curves) was 3.0 ± 0.6 (SE), indicating that most of the CO originated from sources other than circulating erythrocyte hemoglobin, in contrast to previous findings in patients with hemolytic anemia, where ˙Vco paralleled ˙Vheme closely. After administration of glycine-2-¹⁴C to these patients, endogenous CO was isolated by washout of body CO stores at high pO₂ or by reacting peripheral venous blood samples with ferricyanide. The CO was then oxidized to CO₂ by palladium chloride and trapped for counting in a liquid scintillation spectrometer. “Early labeled” peaks of ¹⁴CO were demonstrated which paralleled “early labeled” peaks of stercobilin and preceded maximal labeling of circulating heme. Production of “early labeled” ¹⁴CO in patients with ineffective erythropoiesis was greatly increased, up to 14 times that found in a normal subject. The increased ˙Vco and “early ¹⁴CO” production shown by these patients are presumably related mainly to heme catabolism in the marrow. The possibility exists that hepatic heme and porphyrin compounds may also contribute significantly to ˙Vco, as suggested by the finding of a high ˙Vco in an additional patient with porphyria cutanea tarda.