Department of Pharmacy (N.G.P.), Rush University Medical Center, Chicago, IL.
Department of Pharmacy, University of Kentucky Healthcare, Lexington (A.M.C.).
Circulation. 2020 May 26;141(21):1681-1689. doi: 10.1161/CIRCULATIONAHA.120.045769. Epub 2020 Apr 8.
Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients.
This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 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 after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 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 on the basis of 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 predefined periods.
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% CI, 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 after 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 lengths of stay were 2.0 and 6.0 days, respectively.
Administration of PCCs 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 PCCs in patients with factor Xa inhibitor-related ICH are needed.
自批准口服因子 Xa 抑制剂以来，人们一直担心在颅内出血（ICH）后能否中和其抗凝作用。多项指南建议在这些患者中使用凝血酶原复合物浓缩物（PCC），这是基于包括少数 ICH 患者在内的研究得出的。有鉴于此，我们旨在评估 PCC 在接受阿哌沙班或利伐沙班治疗的 ICH 患者中的安全性和疗效，这些患者来自一个大型多中心队列。
这是一项多中心、回顾性、观察性队列研究，纳入了 2015 年 1 月 1 日至 2019 年 3 月 1 日期间接受 PCC 治疗的与阿哌沙班或利伐沙班相关的 ICH 患者。该研究有 2 个主要分析组：安全性和止血疗效。安全性分析评估了所有符合血栓事件发生标准的患者，这些患者在出院或 PCC 给药后 30 天进行了截尾。在接受 PCC 治疗后 24 小时内至少有 1 次随访图像的颅内、蛛网膜下腔或脑硬膜下出血患者被评估止血疗效。主要疗效终点是根据改良 Sarode 标准评估的止血效果良好或优秀的患者比例。次要结局包括评估住院死亡率、住院时间、输注相关反应以及多个预设时间段内血栓事件的发生。
共纳入 663 例患者进行安全性评估。其中，433 例患者符合止血疗效评估标准。我们观察到 354 例患者（81.8%[95%CI，77.9-85.2]）止血效果良好或优秀。25 例（3.8%）患者共发生 26 例血栓事件，其中 22 例发生在 PCC 给药后 14 天内。1 例患者有输注相关反应的记录。对于整个患者队列，住院死亡率为 19.0%，重症监护病房和住院中位数分别为 2.0 天和 6.0 天。
阿哌沙班和利伐沙班相关 ICH 后给予 PCC 可达到较高的止血效果良好或优秀率（81.8%），血栓形成率为 3.8%。需要进行随机对照试验来评估 PCC 在因子 Xa 抑制剂相关 ICH 患者中的临床疗效。
