Abstract Number: PB0403
Meeting: ISTH 2020 Congress
Background: Collagen can trigger clot formation via activation of factor (F) XII and platelets to initiate coagulation and expose phosphatidylserine as a procoagulant surface, respectively. However, in the absence of FXII, collagen can still initiate coagulation.
Aims: To delineate the mechanism of coagulation initiation by platelet activation.
Methods: Thrombin generation (TG) triggered with collagen, the GPVI agonists collagen-related peptide (CRP) and convulxin, the α2β1 agonist GFOGER or tissue factor (TF) was measured in platelet-rich plasma (PRP) with or without FXII inhibitor (corn trypsin inhibitor, CTI) or active site-inhibited FVIIa (FVIIai) and in factor-deficient plasmas supplemented with washed platelets. In addition, FXa generation was measured in the presence of CRP or convulxin in a purified system consisting of FX, FVIII, washed platelets and a FXa fluorogenic substrate. Furthermore, in both assays, platelets were incubated with an inhibitory anti-human FIX antibody. Proteins from platelet lysates were analyzed by western blot and purified by immunoprecipitation.
Results: Both in the presence or abscence of CTI or FVIIai, collagen induced TG in PRP (Figure 1). Both GPVI agonists but not the α2β1 agonist could mimic the effect of collagen. In addition, collagen and CRP could trigger TG in FXII-, FXI-, or FVII-deficient plasma, but not FIX- or FVIII-deficient plasma, supplemented with washed platelets. Both GPVI agonists could significantly increase FXa generation in a purified system with FX, FVIII and washed platelets. Interestingly, both TG and FXa generation induced by GPVI agonists were dose-dependently inhibited by an anti-human FIX antibody (Figure 2). Furthermore, with western blot and immunoprecipitation, platelet lysates contained a protein recognized by anti-human FIX antibody, with a similar molecular weight as FIXa.
Conclusions: Platelet activation via GPVI (collagen, CPR and convulxin) could initiate TG via the release of a molecule similar to FIXa.
To cite this abstract in AMA style:Li L, Roest M, Meijers JCM, de Laat B, de Groot PG, Huskens D. Platelet Activation via GPVI Initiates FXII- and TF-independent Thrombin Generation [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-activation-via-gpvi-initiates-fxii-and-tf-independent-thrombin-generation/. Accessed October 1, 2023.
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