Functional enhancement of platelet activation and aggregation by erythrocytes: role of red cells in thrombosis

Platelets expose phosphatidylserine (PS), a component of the prothrombinase complex, on the outer surface of the plasma membrane when activated. [ref 1] The prothrombinase complex catalyzes the conversion of prothrombin to thrombin, and it has been demonstrated that an increase in PS exposure is correlated with an increase in thrombin generation by platelets. [refs 2,3] Similarly, erythrocyte (RBC) activation, or eryptosis, is also characterized by PS exposure on the plasma membrane. [ref 4] Although PS exposure on RBCs is considered a signal for splenic macrophage destruction, eryptosis may allow RBCs to contribute to thrombosis.[ref 4] The aims of this study were to determine whether the addition of RBCs to platelets increased functional platelet aggregation and coagulation properties. A ratio of 4 RBCs to 1 platelet (4:1) was evaluated for aggregation and coagulation compared to platelet control. Platelet aggregation and coagulation properties were evaluated with impedance aggregometry and thromboelastography, respectively. The 4:1 experimental group had significant increases in aggregation and coagulation relative to the platelet control. These results indicate that RBCs increase platelet aggregation and coagulation properties. This suggests that RBCs play a role in diseases traditionally thought of as associated solely via dysregulated platelet activation.