Abstract Number: PB0862
Meeting: ISTH 2022 Congress
Background: In a platelet-rich environment, coagulation can be activated by collagen via a FXIIa dependent pathway and via a platelet activation dependent pathway.
Aims: To delineate the platelet-derived trigger that initiates coagulation after platelet activation by collagen.
Methods: Thrombin generation (TG) initiated with collagen, with Glycoprotein VI (GPVI) specific agonists (collagen-related peptide, CRP-XL, or convulxin) or an α2β1 specific agonist (GFOGER) was measured in PRP and PPP. Inhibitors of FXIIa (corn trypsin inhibitor, CTI) and active-site inactivated FVIIa or anti-FVII antibodies were used to establish the mechanism of initiation. To determine the platelet-derived trigger of coagulation, the activation of isolated coagulation factors by activated washed platelets, and the inhibition of this activation by specific antibodies was studied. Also, TG in factor-depleted plasmas reconstituted with activated washed platelets was investigated.
Results: Stimulation of PRP with collagen initiated TG, even in the presence of FXIIa- and FVIIa- inhibitors. GPVI agonists, but not α2β1 agonists, initiated TG in PRP but not in PPP (Fig. 1). GPVI agonists could also initiate fibrin formation in PRP. Stimulation of platelets via GPVI, initiated TG in FVII- and FXII-depleted plasma but failed to initiate TG in FVIII or FIX depleted plasma. Addition of CRP-XL to washed platelets in buffer with FX and FVIII resulted in FX activation. FX activation was abolished in the presence of an inhibiting anti-FIX antibody, suggesting CRP-XL stimulated platelets release FIXa. Furthermore, addition of FVIII to FIX-deficient plasma restored TG induced by GPVI activated platelets, and was inhibited by an anti-FIX Ab.
Conclusion(s): Stimulation of platelets via GPVI initiated TG independent of the conventional FXII activation or tissue factor pathways. Our study provides new evidence that platelet activation by GPVI can initiate TG via platelet-derived FIX(a) activity.
To cite this abstract in AMA style:Li L, Roest M, Meijers J, de Laat B, Urbanus R, de Groot P, Huskens D. Platelet activation via glycoprotein VI initiates thrombin generation: a potential role for platelet-derived factor IX? [abstract]. https://abstracts.isth.org/abstract/platelet-activation-via-glycoprotein-vi-initiates-thrombin-generation-a-potential-role-for-platelet-derived-factor-ix/. Accessed February 21, 2024.
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