Hemoglobin S gelation and sickle cell disease

Abstract

The purpose of this article is to review recent developments in the relation between hemoglobin S gelation and sickle cell disease. We first present our current understanding of the major features of the gelation process. Since gelation is a physical rather than a chemical process, its description necessarily requires more physical detail than that of most biological processes. From these studies we are able to develop a more rigorous and comprehensive description of the relation between gelation and the pathophysiology than has been possible up to now. By combining the gelation studies with work on the rheology of sickle cells and blood flow in the microvasculature, a clearer picture emerges of the outstanding issues in understanding the mechanism of vaso-occlusion in patients and the resulting cardiovascular response. Finally we discuss the variation in clinical severity and analyze the problem of inhibiting gelation in patients. Throughout this discussion we shall see that the kinetics of gelation is a dominant factor in understanding gelation both in vitro and in vivo, and it will become clear that discussions of the pathophysiology that do not include a kinetic analysis are inadequate.