One potential mode of action of an antisickling drug would be an interaction with the hemoglobin molecule that would increase the hemoglobin's affinity for oxygen thereby reducing sickling. Zinc is known to bind to isolated hemoglobin and causes a 3-4 fold increase in oxygen affinity. Unfortunately, zinc cannot easily pass through the red blood cell membrane. However, we have shown that the chelator, ethyl maltol, can facilitate zinc uptake by red blood cells allowing an increase in the oxygen affinity in a dose. dependant fashion. We have examined the effects of incubation with increasing concentrations of zinc complex on deformability and hematological indices of sickle erythrocytes. The deformability was not affected at low concentrations yet MCHC was greatly decreased. A drop in the MCHC values is a definite advantage in influencing the kinetics of HbS polymerization. Data from this work are being compiled for publication. 2) As part of a long standing interest in the variability in sickle cell disease expression in human populations, we are currently collaborating with Dr. G. Rodgers and others at NIDDK in employing a computer based analysis of biochemical, hematological, and clinical data on some 140 non African sickle cell patients known to experience a milder form of anemia. Prediction of polymer fraction as a function of oxygen saturation in relation to disease severity will be established and compared to similar parameters of other, more severe sickle cell syndromes.
