Speaker
Description
Blood clots are deadly. Anticoagulants, which prevent pathological clotting, are therefore vital. Protein S (PS) is an important anticoagulant implicated in pathological bleeding and clotting. PS binds with two other coagulation proteins—TFPIα and factor V short—to form the protein S complex (PSC), which enhances anticoagulant function by incompletely understood means. To investigate, we start with an experimentally validated, ODE-based model of the blood coagulation biochemical reaction network in a blood vessel with flow and platelet deposition. We extend the model to include PSC and free PS (not a part of PSC) in the plasma, as well as free PS and TFPIα in platelets. We find that PSC accumulates on platelets far more than expected, and that determining the affinity for PSC binding with clotting factor Xa is necessary to understand PSC's anticoagulant properties. We show that deficiencies in PSC can rescue thrombin production in several bleeding disorders, including severe hemophilia A.
