Division of Hematology and Thromboembolism, Department of Medicine, and.
Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
Blood Adv. 2019 Jan 22;3(2):158-167. doi: 10.1182/bloodadvances.2018024133.
A targeted antidote for reversal of direct factor Xa (FXa) inhibitors is now available for clinical use in the United States, but it is costly and has limited availability. In a systematic review, we evaluated the safety and effectiveness of 4-factor prothrombin complex concentrate (4F-PCC) as an alternative for managing direct FXa inhibitor-related major bleeding. A systematic literature search was conducted using Medline, Embase, and the Cochrane Register of Controlled Trials up to September 2018. No comparative studies were found. Ten case series with 340 patients who received PCC for direct FXa inhibitor-related major bleeding were included. The pooled proportion of patients with effective management of major bleeding was 0.69 (95% confidence interval [CI], 0.61-0.76) in 2 studies using the International Society on Thrombosis and Haemostasis (ISTH) criteria and 0.77 (95% CI, 0.63-0.92) in 8 studies that did not use the ISTH criteria; all-cause mortality was 0.16 (95% CI, 0.07-0.26), and thromboembolism rate was 0.04 (95% CI, 0.01-0.08). On the basis of evidence with very low certainty from single-arm case series, it is difficult to determine whether 4F-PCC in addition to cessation of direct oral FXa inhibitor is more effective than cessation of direct oral FXa inhibitor alone in patients with direct FXa inhibitor-related major bleeding.
一种针对直接因子 Xa（FXa）抑制剂逆转的靶向解毒剂现已可在美国临床应用，但价格昂贵且供应有限。在一项系统评价中，我们评估了 4 因子凝血酶原复合物浓缩物（4F-PCC）作为管理直接 FXa 抑制剂相关大出血的替代方法的安全性和有效性。使用 Medline、Embase 和 Cochrane 对照试验登记处进行了系统文献检索，检索截至 2018 年 9 月。未发现比较研究。纳入了 10 项包含 340 例因直接 FXa 抑制剂相关大出血而接受 PCC 治疗的病例系列研究。2 项使用国际血栓形成与止血学会（ISTH）标准的研究中，大出血有效管理的患者比例为 0.69（95%置信区间[CI]，0.61-0.76），8 项未使用 ISTH 标准的研究中为 0.77（95%CI，0.63-0.92）；全因死亡率为 0.16（95%CI，0.07-0.26），血栓栓塞发生率为 0.04（95%CI，0.01-0.08）。基于单臂病例系列研究的极低确定性证据，很难确定在直接 FXa 抑制剂相关大出血患者中，除了停止直接口服 FXa 抑制剂之外，4F-PCC 是否比单独停止直接口服 FXa 抑制剂更有效。
