BACKGROUND/OBJECTIVE Intracranial bleeding (ICB) is a feared complication of systemic anticoagulation. Factor Xa inhibitors (FXaI) are used frequently due to their improved safety profile and predictable kinetics. Andexanet alfa was recently approved for emergent reversal of FXaI agents but was not compared formally to 4-Factor Prothrombin Complex Concentrates (4FPCC) which are the current standard of care in many centers. The objective of this study is to formally evaluate the hemostatic efficacy of 4FPCC in patients with FXaI-associated ICB. METHODS We performed a retrospective cohort study of patients receiving 4FPCC for the reversal of a FXaI in the setting of acute ICB. Hemostatic efficacy was adjudicated via evaluation of post-4FPCC CT scan using the criteria closely mirroring those outlined in Annexa-4 (excellent < 20% expansion, good > 20% but ≤ 35% expansion, poor > 35% expansion). Each image was reviewed by two neurointensivist attendings for grading. Mortality was assessed until date of discharge. Charts were screened for thrombotic events out to 30 days post-4FPCC administration. RESULTS A total of 59 patients were included in the final analysis. The mean age in years was 78.5 ± 10.9 and 56% were male. Apixaban was the most common FXaI prescribed at the time of presentation (67.8%). Most patients were on FXaI therapy for stroke prevention in the setting of atrial fibrillation (81.3%). Median Glasgow Coma Scale at presentation was 15(IQR 12-15), with the most frequently presenting ICB type being intracerebral hemorrhage (52.5%). The mean dose of 4FPCC prescribed was 46.6 (± 8.2) units/kg. Of those receiving 4FPCC for FXaI ICB, 88% were graded as having an excellent or good hemostatic outcome with excellent interrater reliability. Survival was high at 89.8%, and thrombotic events were seen in seven patients (11.9%). CONCLUSION 4FPCC appears to be an effective and safe option for FXaI-associated ICB with outcomes comparable to andexanet alfa. A formal prospective evaluation of this strategy versus andexanet alpha including cost analysis is warranted.

中文翻译：

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4 因子凝血酶原复合物浓缩物在因子 Xa 抑制剂相关颅内出血中的功效。

背景/目的 颅内出血 (ICB) 是全身抗凝治疗的可怕并发症。Xa 因子抑制剂 (FXaI) 因其改进的安全性和可预测的动力学而经常使用。Andexanet alfa 最近被批准用于 FXaI 药物的紧急逆转，但没有与 4 因子凝血酶原复合物浓缩物 (4FPCC) 进行正式比较，后者是许多中心目前的护理标准。本研究的目的是正式评估 4FPCC 对 FXaI 相关 ICB 患者的止血功效。方法 我们对接受 4FPCC 的患者在急性 ICB 的情况下逆转 FXaI 进行了一项回顾性队列研究。使用与 Annexa-4 中概述的标准非常接近的标准（优秀 < 20% 扩张，好 > 20% 但≤ 35% 膨胀，差 > 35% 膨胀）。每张图像都由两名神经重症监护医师审查以进行分级。直到出院日期评估死亡率。在 4FPCC 给药后 30 天内，针对血栓形成事件筛选图表。结果最终分析共纳入59例患者。平均年龄为 78.5 ± 10.9，56% 为男性。阿哌沙班是就诊时最常用的 FXaI (67.8%)。大多数患者在房颤情况下接受 FXaI 治疗以预防卒中（81.3%）。就诊时格拉斯哥昏迷量表的中位数为 15（IQR 12-15），最常见的 ICB 类型是脑内出血（52.5%）。规定的 4FPCC 平均剂量为 46.6 (± 8.2) 单位/公斤。在 FXaI ICB 接受 4FPCC 的人中，88% 的患者被评为具有优异或良好的止血结果，且具有优异的评分者间可靠性。存活率高达 89.8%，7 名患者（11.9%）发生血栓事件。结论 4FPCC 似乎是 FXaI 相关 ICB 的有效和安全选择，其结果与 andexanet alfa 相当。有必要对该策略与 andexanet alpha 进行正式的前瞻性评估，包括成本分析。