Factor XI Binding to Platelets

Abstract

Platelets are crucial in supporting coagulation reactions. The classical view is that platelets bind the vitamin K-dependent factors (VII, IX, X, II, protein C, S, and Z) via their gamma carboxyglutamic acid (gla) residues, and in this way localize coagulation factor complexes to the platelet membrane.1 For binding of gla-containing proteins to the platelet surface to occur, the platelet needs to be activated after which negatively charged phospholipids, including phosphatidylserine, are translocated from the inner to the outer leaflet of the platelet membrane. Exposure of negatively charged lipids enables a Ca2+-dependent interaction of gla-containing proteins with the negatively charged platelet membrane. See accompanying article on page 1602 In addition to the gla-containing coagulation factors, multiple coagulation factors lacking a gla-domain, including thrombin,2 factor XI(a),3 factor XII(a),4 and high-molecular-weight kininogen5 interact with platelets, and the interaction of all these proteins has been shown to be (in part) mediated by glycoprotein Ibα (GPIbα). Recent work has demonstrated that also some of the gla-containing coagulation factors, factor VII(a),6 factor IX(a),7 and both zymogen and activated protein C8 interact with GPIbα. These findings indicate that localization of coagulation factors to the platelet surface is much more complicated than anticipated by the model in which the interaction with negatively charged phospholipids was considered required and sufficient for gla-containing proteins to bind to platelets. Indeed, it has been demonstrated that the thrombin-generating capacity of activated platelets from different …