The polymerization of hemoglobin (Hb) S, which results in morphological sickling and increased rigidity of red cells, is critical but may not be the sole factor responsible for the initiation of a sickle (SS) cell vasoocclusive episode. The role of multiple factors' remains to be fully delineated, although both erythrocytic and vascular factors make significant contributions. Sickle cell anemia is characterized by abnormal rheological properties of red cells. Studies utilizing a variety of in vitro techniques (ektacytometry, micropipette, rheoscope, and nucleopore filtration) have indicated reduced red cell deformability as a major determinant of the rheological abnormalities, hernolysis, and reduced red cell life span in this disorder. Excellent reviews by LaCelle and Weed,'Mohandas et al.,'and Chien'have provided insight into the rheological behavior of sickle cells in vitro.

The total resistance to the flow of blood in a microvascular bed is determined both by intrinsic characteristics of blood (eg, red cell deformability, red cell aggregation, hematocrit) and by microvascular factors such as vessel wall features, vascular geometry (eg, vessel length, vessel diameter, branching patterns), intravascular pressure, and wall shear rate gradients. By the use of intravital microscopy of microvascular network flow, it has been possible to characterize hemodynamic behavior of sickle blood and its density-defined red cell classes, red cell-endothelial interaction and the probable mechanisms involved in the microvascular obstruction induced by sickle red cells.