Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism
Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism
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DOI：
10.1111/jth.13475
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发表时间：
2016-11-01
影响因子：
10.4
通讯作者：
Cohen, H.
中科院分区：
文献类型：
--
作者：
Arachchillage, D. R. J.;Mackie, I. J.;Cohen, H.
背景：补体激活可能在血栓性抗磷脂综合征（APS）的发病机制中起主要作用。凝血蛋白酶如因子Xa可激活补体蛋白。目的：在既往有静脉血栓栓塞（VTE）的APS患者中，确定与华法林相比，直接Xa因子抑制剂利伐沙班是否限制补体激活。研究方法：在RAPS（利伐沙班治疗抗磷脂综合征）试验中，共有111例既往VTE的APS患者接受华法林治疗，目标INR 2.5，在基线和随机化后第42天采集血样。五十六例患者继续服用华法林，55例患者改用利伐沙班。还研究了55名正常对照（NC）。评估补体激活标志物（C3 a、C5 a、末端补体复合物[SC 5 b-9]和Bb片段）。结果：无论使用何种抗凝剂，APS患者在两个时间点的补体激活标志物均显著高于NC。两组患者在基线时或第42天仍接受华法林治疗的患者之间无差异。在随机分配至利伐沙班的55名患者中，C3 a、C5 a和SC 5 b-9在第42天较低（中位数（ng mL（-1））[置信区间] 64 [29-125] vs. 83 [35-147]，9 [2-15] vs. 12 [4-18]和171 [56-245] vs. 201 [66-350]，但Bb片段的水平不变。利伐沙班水平与补体激活标志物之间无相关性。结论：既往接受华法林治疗的VTE的APS患者表现出补体激活增加，这可能通过经典途径发生，并通过利伐沙班给药降低。因此，利伐沙班可能通过限制补体激活，在该患者组中为其抗凝作用提供额外的获益。
Background: Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims: To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods: A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results: APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL(-1)) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions: APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration. Rivaroxaban may therefore potentially provide an additional benefit to its anticoagulant effect in this patient group by limiting complement activation.