The glycoprotein Ib-DC-V complex contributes to tissue factor-independent thrombin generation by recombinant factor Vila on the activated platelet surface. Commentaty

Several lines of evidence suggest that recombinant factor VΙΙa (rFVIΙa) is able to activate factor X on an activated platelet, in a tissue factor-independent manner. We hypothesized that, besides the anionic surface, a receptor on the activated platelet surface is involved in this process. Here, we showed that, in an ELISA setup, a purified extracellular fragment of GPIbα bound to immobilized rFVIIa. Surface plasmon resonance established a affinity constant (K d ) of approximately 20 nM for this interaction. In addition, CHO cells transfected with the GPIb-IX-V complex could adhere to immobilized rFVIIa, whereas wild-type CHO cells could not. Furthermore, platelets stimulated with a combination of collagen and thrombin adhered to immobilized rFVIIa under static conditions. Platelet adhesion was inhibited by treatment with O-sialoglycoprotein endopeptidase, which specifically cleaves GPIbα from the platelet surface. In addition, rFVΙΙa-mediated thrombin generation on the activated platelet surface was inhibited by cleaving GPIbα from its surface. In summary, 3 lines of evidence showed that rFVΙIa interacts with the GPΙb-ΙX-V complex, and this interaction enhanced tissue factor-independent thrombin generation mediated by rFVΙIa on the activated platelet surface. The rFVIIa-GPIbα interaction could contribute to cessation of bleeding after administration of rFVΙΙa to patients with bleeding disorders.