Measurement of the carbamylation kinetics and antisickling mechanism in hemoglobin S blood.

The kinetics of HbS carbamylation in whole blood have been investigated under conditions anticipated in extracorporeal treatment systems. The reaction was well represented by a bimolecular, irreversible, second-order mechanism, and the overall carbamylation rate was enhanced by increasing the temperature and decreasing the pH and PO2. An expression was developed to predict the carbamylation rate for a range of experimental conditions. The relative amount of beta chain carbamylation was increased for those conditions under which the overall carbamylation rate was lowered, i.e., lower temperature, higher PO2, and higher pH. Morphological examination of cells with predominantly beta chain carbamylation showed that the antisickling effect, as measured by this technique, could be accounted for entirely by an increase in the oxygen affinity. Although this observation does not exclude an effect independent of change in the oxygen affinity of carbamylated hemoglobin, such an effect, if it occurs, is not detectable by this method. The results of this study were used to design a reaction vessel for an extracorporeal treatment system for sickle cell anemia patients.