Steppich B, Dobler F, Brendel L C, Hessling G, Braun S L, Steinsiek A L, Deisenhofer I, Hyseni A, Roest M, Ott I
Deutsches Herzzentrum der Technischen Universität München, Lazarettstr 36, 80636, Munich, Germany.
Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.
J Thromb Thrombolysis. 2017 May;43(4):490-497. doi: 10.1007/s11239-017-1495-z.
Rivaroxaban and Apixaban, increasingly used for stroke prevention in non-valvular atrial fibrillation (AF), might impact platelet reactivity directly or indirectly. By inhibition of Factor Xa (FXa) they preclude not only generation of relevant thrombin amounts but also block signalling of FXa via protease activated receptors. However, weather FXa-inhibition affects platelet haemostasis remains incompletely known. One hundred and twenty-eight patients with AF on chronic anticoagulation with either Rivaroxaban or Apixaban for at least 4 weeks were included in the study. In a time course group (25 on Rivaroxaban, 13 on Apixaban) venous blood samples were taken before NOAC medication intake in the morning as well as 2 and 6 h afterwards. In 90 patients (Rivaroxaban n = 73, Apixaban n = 17) blood samples were drawn during left atrial RFA procedures before as well as 10 and 60 min after the first heparin application (RFA group). Platelet reactivity analyzed by whole blood aggregometry (Multiplate Analyzer, Roche) in response to ADP, Collagen, TRAP and ASPI (arachidonic acid) was not altered by Rivaroxaban or Apixaban neither in the time course nor in the RFA group. Moreover, soluble P-selectin, Thrombospondin, von Willebrand Factor and beta thromboglobulin plasma levels, measured by ELISA, showed no statistically significant changes in both clinical settings for either FXa-inhibitor. The present study fails to demonstrate any significant changes on platelet reactivity in patients with AF under chronic Rivaroxaban or Apixaban medication, neither for trough or peak levels nor in case of a haemostatic activation in vivo as depicted by RFA procedures.
利伐沙班和阿哌沙班越来越多地用于非瓣膜性心房颤动（AF）的卒中预防，它们可能直接或间接影响血小板反应性。通过抑制凝血因子Xa（FXa），它们不仅可防止产生相关量的凝血酶，还可阻断FXa通过蛋白酶激活受体的信号传导。然而，FXa抑制是否影响血小板止血尚不完全清楚。本研究纳入了128例接受利伐沙班或阿哌沙班长期抗凝治疗至少4周的AF患者。在一个时间进程组（25例使用利伐沙班，13例使用阿哌沙班）中，于早晨服用非维生素K拮抗剂（NOAC）药物前以及服药后2小时和6小时采集静脉血样本。在90例患者（利伐沙班组n = 73，阿哌沙班组n = 17）中，于左心房射频消融（RFA）手术期间，在首次应用肝素前以及应用后10分钟和60分钟采集血样（RFA组）。通过全血凝集测定法（罗氏多电极血小板功能分析仪）分析血小板对二磷酸腺苷（ADP）、胶原、凝血酶受体激活肽（TRAP）和花生四烯酸（ASPI）的反应性，结果显示在时间进程组和RFA组中，利伐沙班或阿哌沙班均未改变血小板反应性。此外，通过酶联免疫吸附测定法（ELISA）测量的可溶性P-选择素、血小板反应蛋白、血管性血友病因子和β-血小板球蛋白血浆水平，在两种临床情况下，两种FXa抑制剂均未显示出统计学上的显著变化。本研究未能证明长期服用利伐沙班或阿哌沙班的AF患者的血小板反应性有任何显著变化，无论是谷值或峰值水平，还是在RFA手术所描述的体内止血激活情况下。
