TY - JOUR
T1 - Platelet Activation via Glycoprotein VI Initiates Thrombin Generation
T2 - A Potential Role for Platelet-Derived Factor IX?
AU - Li, Li
AU - Roest, Mark
AU - Meijers, Joost C. M.
AU - de Laat, Bas
AU - Urbanus, Rolf T.
AU - de Groot, Philip G.
AU - Huskens, Dana
N1 - Funding Information: Li Li is supported by a scholarship (No. 201706230245) from the China Scholarship Council. Publisher Copyright: © 2022 Georg Thieme Verlag. All rights reserved.
PY - 2022/8/28
Y1 - 2022/8/28
N2 - Collagen triggers coagulation via activation of factor (F) XII. In a platelet-rich environment, collagen can also trigger coagulation independently of FXII. We studied a novel mechanism of coagulation initiation via collagen-dependent platelet activation using thrombin generation (TG) in platelet-rich plasma. Collagen-induced coagulation is minimally affected by active-site inactivated FVIIa, anti-FVII antibodies, or FXIIa inhibition (corn trypsin inhibitor). Activation of platelets via specific glycoprotein (GP) VI agonists initiates TG, FX activation, and fibrin formation. To determine the platelet-derived trigger of coagulation, we systematically reconstituted factor-deficient plasmas with washed platelets. TG triggered by GPVI-activated platelets was significantly affected in FIX- and FVIII-deficient plasma but not in FVII- and FXII-deficient plasma. In a purified system composed of FX and FVIII, we observed that absence of FIX was compensated by GPVI-activated platelets, which could be inhibited by an anti-FIX antibody, suggesting FIXa activity from activated platelets. Furthermore, with the addition of FVIII in FIX-deficient plasma, TG induced by GPVI-activated platelets was restored, and was inhibited by the anti-FIX antibody. In conclusion, GPVI-activated platelets initiate TG, probably via platelet-derived FIXa activity.
AB - Collagen triggers coagulation via activation of factor (F) XII. In a platelet-rich environment, collagen can also trigger coagulation independently of FXII. We studied a novel mechanism of coagulation initiation via collagen-dependent platelet activation using thrombin generation (TG) in platelet-rich plasma. Collagen-induced coagulation is minimally affected by active-site inactivated FVIIa, anti-FVII antibodies, or FXIIa inhibition (corn trypsin inhibitor). Activation of platelets via specific glycoprotein (GP) VI agonists initiates TG, FX activation, and fibrin formation. To determine the platelet-derived trigger of coagulation, we systematically reconstituted factor-deficient plasmas with washed platelets. TG triggered by GPVI-activated platelets was significantly affected in FIX- and FVIII-deficient plasma but not in FVII- and FXII-deficient plasma. In a purified system composed of FX and FVIII, we observed that absence of FIX was compensated by GPVI-activated platelets, which could be inhibited by an anti-FIX antibody, suggesting FIXa activity from activated platelets. Furthermore, with the addition of FVIII in FIX-deficient plasma, TG induced by GPVI-activated platelets was restored, and was inhibited by the anti-FIX antibody. In conclusion, GPVI-activated platelets initiate TG, probably via platelet-derived FIXa activity.
KW - activated platelets
KW - coagulation
KW - coagulation factors
KW - collagen receptor
UR - http://www.scopus.com/inward/record.url?scp=85129814632&partnerID=8YFLogxK
U2 - https://doi.org/10.1055/s-0042-1744379
DO - https://doi.org/10.1055/s-0042-1744379
M3 - Article
C2 - 35512832
SN - 0340-6245
VL - 122
SP - 1502
EP - 1512
JO - Thrombosis and haemostasis
JF - Thrombosis and haemostasis
IS - 9
ER -