Effect of cyanate on red blood cell sickling

The possible use of cyanate as a therapeutic agent in the treatment of sickle cell disease was investigated, with a review of chemical, biological and recent clinical studies. The possibility that cyanate, which is in equilibrium with urea in solution, might also inhibit the sickling process, led to studies which showed that such was in fact the case. Isocyanic acid was found to react specifically with the NH ₂ terminal valine of the hemoglobin molecule, and the carbamylation reaction was irreversible. The carbamylation was found not detrimental to the activity of a number of important glycolytic enzymes although pyruvate kinase levels were somewhat depressed, and the oxygen affinity of the red cells was increased. Toxicological studies on animals with approximate dose levels of cyanate revealed no adverse effects. Ten patients with sickle cell disease were treated with oral cyanate, and the hematological indices of two patients are presented. There was a significant reduction in serum LDH and bilirubin levels. The ⁵¹Cr cell survival increased from 4.5 to 14 and from 10 to 15 days. There was a concomitant rise in hemoglobin and hematocrit values. No irreversible toxic side effects were observed. (Newman - Bridgeport, Conn.)