Background: Since the approval of the oral factor Xa (FXa) inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCC) in these patients based upon research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCC for FXa inhibitor-related ICH in a large, multicenter cohort of patients. Methods: This was a multicenter, retrospective, observational cohort study of patients with apixaban or rivaroxaban-related ICH who received PCC between January 1, 2015 and March 1, 2019. The study had two primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days following PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least one follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis based upon the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions and thrombotic event occurrence during multiple pre-defined periods. Results: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8%; 95% confidence interval 77.9 - 85.2). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days following PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0% and the median intensive care unit and hospital length of stay were 2.0 and 6.0 days, respectively. Conclusions: Administration of PCC after apixaban and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCC in patients with FXa inhibitor-related ICH are needed.

中文翻译：

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Xa因子抑制剂相关的颅内出血：多中心观察人群接受凝血酶原复合物的结果集中。

背景：自从批准口服Xa因子（FXa）抑制剂以来，人们一直担心颅内出血（ICH）后中和其抗凝作用的能力。根据包括有限数量的ICH患者在内的研究，多项指南建议在这些患者中使用凝血酶原复合浓缩物（PCC）。鉴于此，我们旨在评估PCC在大型多中心患者队列中与FXa抑制剂相关的ICH的安全性和有效性。方法：这是一项多中心，回顾性，队列研究，研究对象为2015年1月1日至2019年3月1日接受PCC的阿哌沙班或利伐沙班相关的ICH患者。该研究分为两个主要分析组：安全性和止血功效。安全性分析评估了所有符合入院标准的患者发生血栓事件的情况，这些事件在出院时或PCC给药后30天进行了检查。评估了在PCC给药后24小时内至少有一张随访图像的脑内，蛛网膜下腔或硬脑膜下出血的患者的止血效果。根据改良的Sarode标准，主要疗效结果是止血效果优异或良好的患者百分比。次要结果包括评估多个预定义期间的住院死亡率，住院时间，输液相关反应和血栓事件的发生。结果：共纳入663例患者，并对其安全性结果进行了评估。其中，433名患者符合止血功效评估标准。我们在354例患者中观察到了优异或良好的止血效果（81.8％； 95％置信区间77.9-85.2）。25名患者（3.8％）发生了26例血栓事件，其中22例发生在PCC给药后的前14天。一名患者有输液相关反应的记录。对于全部患者，住院死亡率为19.0％，中位重症监护病房和住院天数分别为2.0天和6.0天。结论：在阿哌沙班和利伐沙班相关的ICH后给予PCC具有较高的优良或良好止血率（81.8％），而血栓形成率为3.8％。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。25名患者（3.8％）发生了26例血栓事件，其中22例发生在PCC给药后的前14天。一名患者有输液相关反应的记录。对于全部患者，住院死亡率为19.0％，中位重症监护病房和住院天数分别为2.0天和6.0天。结论：在阿哌沙班和利伐沙班相关的ICH后给予PCC具有较高的优良或良好止血率（81.8％），而血栓形成率为3.8％。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。25名患者（3.8％）发生了26例血栓事件，其中22例发生在PCC给药后的前14天。一名患者有输液相关反应的记录。对于全部患者，住院死亡率为19.0％，中位重症监护病房和住院天数分别为2.0天和6.0天。结论：在阿哌沙班和利伐沙班相关的ICH后给予PCC具有较高的优良或良好止血率（81.8％），而血栓形成率为3.8％。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。一名患者有输液相关反应的记录。对于全部患者，住院死亡率为19.0％，中位重症监护病房和住院天数分别为2.0天和6.0天。结论：在阿哌沙班和利伐沙班相关的ICH后给予PCC具有较高的优良或良好止血率（81.8％），而血栓形成率为3.8％。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。一名患者有输液相关反应的记录。对于全部患者，住院死亡率为19.0％，中位重症监护病房和住院天数分别为2.0天和6.0天。结论：在阿哌沙班和利伐沙班相关的ICH后给予PCC具有较高的优良或良好止血率（81.8％），而血栓形成率为3.8％。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。8％的血栓形成率。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。8％的血栓形成率。需要评估FXa抑制剂相关ICH患者PCC临床疗效的随机对照试验。