Effects of inhibition of P2Y1 and P2Y12 on whole blood clotting, coagulum elasticity and fibrinolysis resistance studied with free oscillation rheometry

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Abstract

Introduction: In vivo, initial platelet activation is likely caused by platelet contacts with collagen in the subendothelium or from the small amounts of thrombin formed by the tissue factor/factor VIIa complex. Our aim was to study the coagulative role of ADP released by the platelets after activation with strong stimuli such as collagen and/or thrombin, and the relative importance of the platelet ADP receptors P2Y1 and P2Y12. Materials and methods: We used 10 Hz free oscillation rheometry to measure clotting time, clot elasticity and fibrinolysis resistance of non-anticoagulated whole blood. The platelets were activated with a collagen-related peptide (CRP), with the PAR1 thrombin receptor activating peptide TRAP-6 or by thrombin, the latter generated by small amounts of thromboplastin. To inhibit the platelet ADP receptors, we used the P2Y1 antagonist MRS2179 and the P2Y12 antagonist AR-C69931MX. Results: Both antagonists significantly retarded the clotting induced by CRP. The effects were most pronounced with AR-C69931MX. For TRAP-6, the same trend was seen, but the retardation was only significant with AR-C69931MX. Clotting induced by small amounts of thromboplastin was not affected by any ADP-receptor antagonist. Addition of both antagonists did not change the results as compared to samples with AR-C69931MX alone. Nor did the antagonists, one at a time or in concert, effect fibrinolysis or the elastic properties of the clot. Conclusion: We conclude that ADP-receptor inhibition prolongs the clotting time for whole blood activated by CRP, but that it does not affect the properties of the subsequently formed coagulum. © 2003 Elsevier Science Ltd. All rights reserved.

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Ramström, S., Rånby, M., & Lindahl, T. L. (2003). Effects of inhibition of P2Y1 and P2Y12 on whole blood clotting, coagulum elasticity and fibrinolysis resistance studied with free oscillation rheometry. Thrombosis Research, 109(5–6), 315–322. https://doi.org/10.1016/S0049-3848(03)00254-8

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