Red blood cells in thrombosis

Abstract

Red blood cells (RBCs) have historically been considered passive bystanders in thrombosis. However, clinical and epidemiological studies have associated quantitative and qualitative abnormalities in RBCs, including altered hematocrit, sickle cell disease, thalassemia, hemolytic anemias, and malaria, with both arterial and venous thrombosis. A growing body of mechanistic studies suggests that RBCs can promote thrombus formation and enhance thrombus stability. These findings suggest that RBCs may contribute to thrombosis pathophysiology and reveal potential strategies for therapeutically targeting RBCs to reduce thrombosis.

Figure 1.

Potential contributions of normal and abnormal RBCs to arterial and venous thrombosis/thromboembolism. (A) Arterial thrombi arise in vessels with high shear rates, which promotes the rapid formation of platelet-rich thrombi. During arterial thrombosis, RBCs promote platelet margination, increase platelet-thrombus interactions, and enhance platelet adhesion and activation. Although RBCs increase blood viscosity, this effect is lessened in arteries by high shear-induced shape change. (B) Venous thrombi form slowly in stasis or low flow (frequently in venous valve pockets) and are RBC and fibrin rich. In veins, RBC aggregation into stacked rouleaux structures increases blood viscosity. RBCs can also directly or indirectly adhere to the vessel wall and may contribute to thrombin generation within thrombi. Once incorporated into venous thrombi, RBCs increase thrombus size and reduce thrombus permeability and susceptibility to lysis. In disease states, abnormal RBCs and RBC-derived microvesicles may also adhere to the endothelium or extracellular matrix, activate platelets and other cells, and enhance local thrombin generation during thrombosis.