Calmette Leyla, Martin Anne-Céline, Le Bonniec Bernard, Zlotnik Diane, Gouin-Thibault Isabelle, Bachelot-Loza Christilla, Gaussem Pascale, Godier Anne
Faculté de Pharmacie, Inserm UMR-S1140, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
J Clin Pathol. 2017 Sep;70(9):733-739. doi: 10.1136/jclinpath-2016-204117. Epub 2017 Feb 3.
Management of ticagrelor-induced bleeding is challenging as platelet transfusion is ineffective. An effective strategy is needed. This study aimed to investigate the efficacy of four haemostatic drugs (HDs), namely recombinant activated factor VII (rFVIIa), fibrinogen concentrate (Fib), tranexamic acid (TXA) and factor XIII concentrate (FXIII) to improve the haemostatic capacity in the presence of ticagrelor.
Blood was spiked with ticagrelor then supplemented by either HD or control. Several assays were performed: ADP-induced platelet aggregation measured by impedance aggregometry, light transmission and two global assays, thrombolastography with the platelet mapping device (TEG-PM) and a platelet-dependent thrombin generation assay (TGA).
Ticagrelor inhibited ADP-induced platelet aggregation and decreased the clot strength maximum amplitude (MA) in TEG-PM. None of the HDs corrected these parameters. However, rFVIIa shortened the coagulation time R using TEG-PM and the time to peak prolonged by ticagrelor in TGA. Fib increased MA and FXIII decreased LY30. TXA had no effects.
Whereas none of the HDs corrected ticagrelor-induced platelet inhibition, rFVIIa shortened coagulation times, Fib increased clot firmness and FXIII decreased fibrinolysis. Consequently, they may bypass ticagrelor effects by acting on fibrin formation or fibrinolysis. Further studies are needed to confirm these data .
由于血小板输注无效，替格瑞洛所致出血的管理具有挑战性。需要一种有效的策略。本研究旨在调查四种止血药物（HDs），即重组活化因子VII（rFVIIa）、纤维蛋白原浓缩剂（Fib）、氨甲环酸（TXA）和因子XIII浓缩剂（FXIII）在替格瑞洛存在的情况下提高止血能力的疗效。
血液加入替格瑞洛，然后补充HD或对照。进行了多项检测：通过阻抗聚集法、光透射法以及两种整体检测方法，即使用血小板绘图装置的血栓弹力图（TEG-PM）和血小板依赖性凝血酶生成检测（TGA）来测量ADP诱导的血小板聚集。
替格瑞洛抑制ADP诱导的血小板聚集，并降低TEG-PM中的凝血块强度最大振幅（MA）。没有一种HD能纠正这些参数。然而，rFVIIa使用TEG-PM缩短了凝血时间R，并缩短了替格瑞洛在TGA中延长的达到峰值的时间。Fib增加了MA，FXIII降低了LY30。TXA没有效果。
虽然没有一种HD能纠正替格瑞洛诱导的血小板抑制，但rFVIIa缩短了凝血时间，Fib增加了凝血块硬度，FXIII降低了纤维蛋白溶解。因此，它们可能通过作用于纤维蛋白形成或纤维蛋白溶解来绕过替格瑞洛的作用。需要进一步研究来证实这些数据。
