Department of Critical Care Medicine, Mercy Hospital St. Louis, 615 S. New Ballas Road, St. Louis, MO, 63303, USA.
St. Louis College of Pharmacy, St. Louis, USA.
Neurocrit Care. 2021 Feb;34(1):112-120. doi: 10.1007/s12028-020-00968-6.
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.
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.
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%).
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.
背景/目的：颅内出血（intracranial bleeding，ICB）是全身性抗凝治疗的一种严重并发症。由于其安全性更好且药代动力学更可预测，因子 Xa 抑制剂（factor Xa inhibitor，FXaI）的应用越来越广泛。andexanet alfa 最近被批准用于紧急逆转 FXaI 药物，但尚未与目前许多中心的标准治疗方法 4 因子凝血酶原复合物浓缩物（4-factor prothrombin complex concentrate，4FPCC）进行正式比较。本研究的目的是正式评估 4FPCC 在 FXaI 相关 ICB 患者中的止血疗效。
我们对接受 4FPCC 逆转急性 ICB 时 FXaI 治疗的患者进行了回顾性队列研究。通过评估 4FPCC 后 CT 扫描，根据与 Annexa-4 中概述的标准非常相似的标准来判断止血疗效（优秀 < 20% 扩大，良好 > 20% 但 ≤ 35% 扩大，差 > 35% 扩大）。每位患者的图像均由两位神经科主治医生进行分级。评估至出院时的死亡率。在 4FPCC 给药后 30 天内筛查血栓形成事件。
最终共有 59 例患者纳入最终分析。患者的平均年龄为 78.5 ± 10.9 岁，56%为男性。阿哌沙班是当时最常开的 FXaI（67.8%）。大多数患者因心房颤动（81.3%）进行卒中预防而接受 FXaI 治疗。就诊时的中位格拉斯哥昏迷量表评分为 15（IQR 12-15），最常见的 ICB 类型为脑出血（52.5%）。4FPCC 的平均剂量为 46.6（± 8.2）单位/kg。在因 FXaI ICB 接受 4FPCC 治疗的患者中，88%的患者被评为止血效果优秀或良好，具有较高的可靠性。生存率为 89.8%，7 例患者（11.9%）发生血栓形成事件。
4FPCC 似乎是 FXaI 相关 ICB 的有效且安全的选择，其疗效与 andexanet alfa 相当。有必要对这种策略与 andexanet alpha 进行正式的前瞻性评估，包括成本分析。
