Red Blood Cells are Critical for Hemostasis and Thrombosis

Hemostasis in humans has traditionally been considered to be a function of platelets, coagulation, and the subendothelial matrix, but the role of red blood cells (RBCs) has been increasingly recognized. RBCs regulate hemostasis through biophysical and biochemical means. For the former, faster-moving RBCs in the center of vessels marginalize platelets and plasma to the vessel walls, where the platelets constantly probe the endothelial surface for injury. RBC counts also determine blood viscosity, which regulates the shear stress of laminar blood flow. For the latter, RBCs are the largest pool of adenosine triphosphate (ATP), which, upon release, is rapidly hydrolyzed to adenosine diphosphate (ADP). Both ATP and ADP activate platelets. Quantitative and qualitative abnormalities in RBCs have also been consistently identified as significant risk factors for arterial and venous thrombosis. Thrombosis is a major complication associated with diseases such as polycythemia vera, secondary erythrocytosis, and sickle cell anemia, all of which present with changes in numbers and physical properties of RBCs. Thrombosis is also common in conditions with significant hemolysis, such as paroxysmal nocturnal hemoglobinuria, severe infections, and when patients are on mechanical support. In this review, we discuss findings from clinical observations and mechanistic studies of how RBCs regulate hemostasis and contribute to thrombosis.