Rivaroxaban Effects Illustrate the Underestimated Importance of Activated Platelets in Thrombin Generation Assessed by Calibrated Automated Thrombography
| Autor: | Marina Panova-Noeva, Philip Wenzel, Wolfram Ruf, Véronique Regnault, Stephanie Makhoul, Jeremy Lagrange |
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| Přispěvatelé: | REGNAULT, Véronique, University Medical Center [Mainz], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The Scripps Research Institute [La Jolla, San Diego] |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
medicine.drug_mechanism_of_action
[SDV]Life Sciences [q-bio] Factor Xa Inhibitor lcsh:Medicine 030204 cardiovascular system & hematology Pharmacology Article 03 medical and health sciences 0302 clinical medicine Tissue factor pathway inhibitor Thrombin 0502 economics and business medicine Platelet Platelet activation phospholipids Rivaroxaban business.industry factor Xa inhibitor lcsh:R 05 social sciences General Medicine thrombin [SDV] Life Sciences [q-bio] Coagulation Platelet-rich plasma platelets 050211 marketing business medicine.drug |
| Zdroj: | Journal of Clinical Medicine Journal of Clinical Medicine, 2019, 8 (11), pp.1990. ⟨10.3390/jcm8111990⟩ Volume 8 Issue 11 Journal of Clinical Medicine, Vol 8, Iss 11, p 1990 (2019) |
| ISSN: | 2077-0383 |
| DOI: | 10.3390/jcm8111990⟩ |
| Popis: | International audience; Background: The direct oral anticoagulant rivaroxaban inhibiting specifically activated factor X (FXa) causes delayed thrombin generation (TG) as measured by calibrated automated thrombography (CAT). The implications of these changes for assessing bleeding or residual prothrombotic risks of patients are unclear in the absence of a better understanding of the underlying mechanism. Methods: We compared platelet rich plasma (PRP) without or with prior collagen-induced platelet aggregation (agPRP) in the CAT assay to better characterize TG in the presence of rivaroxaban. Results: In the presence of rivaroxaban, TG curves in agPRP showed a distinct profile with a rapidly ascending phase followed with a protracted phase. Inhibition of tissue factor pathway inhibitor amplified the first phase of the curve which was also modulated by procoagulant phospholipids. Inhibition of FXIIa-dependent FXI activation revealed that aggregated platelets influenced the first phase by a combination of extrinsic and intrinsic coagulation pathway initiations. Thrombin-dependent amplification of TG (even prior collagen activation) was responsible for the second phase of the TG curve. Conclusions: AgPRP fully includes platelet ability to support TG and reveal distinct TG phases in the presence of direct FXa inhibitors highlighting its potential use in an anticoagulated setting. |
| Databáze: | OpenAIRE |
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