In contrast to an obsolete notion that erythrocytes, or red blood cells
(RBCs), play a passive and minor role in hemostasis and thrombosis, over the
past decades there has been increasing evidence that RBCs have biologically and
clinically important functions in blood clotting and its disorders. This review
summarizes the main mechanisms that underlie the involvement of RBCs in
hemostasis and thrombosis in vivo, such as rheological effects on blood
viscosity and platelet margination, aggregation and deformability of RBCs;
direct adhesion and indirect biochemical interactions with endothelial cells and
platelets, etc. The ability of stored and pathologically altered RBCs to
generate thrombin through exposure of phosphatidylserine has been emphasized.
The procoagulant and prothrombotic potential of RBC-derived microparticles
transfused with stored RBCs or formed in various pathological conditions
associated with hemolysis has been described along with prothrombotic effects of
free hemoglobin and heme. Binding of fibrinogen or fibrin to RBCs may influence
their effects on fibrin network structure, clot mechanical properties, and
fibrinolytic resistance. Recent data on platelet-driven clot contraction show
that RBCs compressed by platelets pulling on fibrin form a tightly packed array
of polyhedral erythrocytes, or polyhedrocytes, which comprises a nearly
impermeable barrier important for hemostasis and wound healing. RBCs may perform
dual roles, both helping to stem bleeding but at the same time contributing to
thrombosis in a variety of ways.