Microvascular flow behavior of red cells in sickle cell anemia

Abstract

Microcirculatory flow behavior of sickle (SS) blood is significantly influenced by a variety of cellular and vascular factors. In the oxy state, hemodynamic abnormalities of SS red cells are caused by an elevated mean corpuscular hemoglobin concentration (MCHC) and the presence of irreversibly sickled cells (ISC). Further, microvascular flow behavior of SS red cells is highly sensitive to the level of oxygen tension and the amount of intracellular hemoglobin S (HbS) polymer; the latter is dependent on the MCHC differences in heterogenous SS red cells. The HbS polymer characteristics of SS red cells, as determined by the rate and duration of deoxygenation, may also play an important role. The microvascular factors that are known to influence the flow behavior of SS red cells are the vascular topographical features, perfusion pressure, arteriovenous wall shear rate gradients, endothelial-derived substances (e.g., von WiIlebrand factor), and the vascular tone. In the ex vivo mesocecum microvasculature, infusion of SS red cells is followed by adhesion of these cells exclusively to the venular endothelium. The observed inverse correlation of SS cell adhesion with the venular diameter is in accordance with the arteriovenous wall shear rate profiles in the microcirculation. Thus, the narrow immediate postcapillary venules show the highest incidence of adhesion. In addition, random trapping of ISC may occur at arteriolar-capillary junctions. Microvascular obstruction can be caused by a combination of precapillary obstruction by ISC, adhesion in postcapillary venules, and secondary trapping of dense SS red cells (high MCHC), which may induce local hypoxia, increased polymerization of HbS, and rigidity of SS red cells. In the steady state, appropriate adjustments in the vascular tone may help dislodge such ensuing obstructive events.