Carbamylation distributions in extracorporeal treatment of sickle cell anemia

The extracorporeal exposure of blood from patients with sickle cell anemia results in the binding of different amounts of cyanate to the hemoglobin of individual erythrocytes. This distribution pattern of carbamylated hemoglobin may affect the efficacy of treatment. A computer model has been developed to predict the carbamylation distribution attained in batch ex vivo exposures. In addition, an autoradiographic technique has been developed whereby the actual distribution pattern of carbamylated hemoglobin in small volumes of blood can be determined. Agreement was demonstrated between the computer model predictions and the actual distribution patterns. The model was applied to published results of extracorporeal treatments of sickle cell patients, and profiles of loading were compared. With the use of such approaches it will be possible to test the importance of the erythrocyte distribution of carbamylated hemoglobin on clinical effects and to design protocols to achieve an optimum distribution. The procedure may be adapted to the distribution of other therapeutic agents as they become available.