Figure 3.

Potential contributions of sickle RBCs to venous thrombosis in SCD. Increased ROS levels in sickle RBCs impair membrane structure and function, leading to membrane integrity loss and reduced deformability, thus negatively modulating sickle RBC quality. This leads to a reduced flow of sickle RBC through the microcirculation. Venous thrombi form slowly in the presence of low flow or stasis and they are rich in both RBCs and fibrin. In the vasculature, sickle RBCs aggregate into stacked rouleaux structures, increasing blood viscosity. These sickle RBCs also adhere to the endothelium and participate in thrombin generation within thrombi. Once incorporated into the venous thrombus, sickle RBCs increase clot size and reduce both clot permeability and susceptibility to lysis. In SCD, sickle RBCs and sickle RBC-derived micro-particles also adhere to the vessel wall or extracellular matrix; activate endothelial cells, platelets, and other blood cells; and enhance local thrombin generation during thrombosis.