Role of Extracellular Hemoglobin in Thrombosis and Vascular Occlusion in Patients with Sickle Cell Anemia

Figure 2

The schematic diagram shows that upon activation of the vascular endothelium, ultralarge VWF is released and is cleaved by ADAMTS13 to smaller fragments that circulate in plasma as an inactive form. Under pathophysiological conditions such as SCA, excessive extracellular Hb blocks the cleavage of a subpopulation of VWF multimers. The uncleaved Hb-bound VWF multimers accumulate in plasma, which are hyperactive in binding to platelets or sickled/fragmented-RBCs to promote cell adhesion and events such as thrombosis and vascular occlusion.