Department of Clinical Pharmacy, UCSF Medical Center, San Francisco, USA.
J Thromb Thrombolysis. 2023 Jan;55(1):149-155. doi: 10.1007/s11239-022-02715-4. Epub 2022 Nov 10.
Background: Mortality of oral anticoagulation-associated ICH is around 60%, with oral anticoagulation increasing the risk of ICH seven to ten-fold compared to no anticoagulation. Current guidelines recommend DOACs (direct oral anticoagulants) as first-line therapy in the treatment of VTE (Venous Thromboembolism) due to their more favorable safety profile. There are two agents available for DOAC reversal, Coagulation Factor Xa (recombinant), inactivated-zhzo (andexanet alfa, Andexxa®) and 4-factor prothrombin complex concentrate (4FPCC). There is little data comparing the two agents in real-life clinical settings.
The primary objective of this study was to determine if there was a difference in hemostatic efficacy of andexanet alfa and 4FPCC in patients with a factor Xa inhibitor-related intracranial hemorrhage.
This was a retrospective, single-center study conducted in adult patients admitted at a quaternary academic medical center from September 2017 to March 2021. Adults with a diagnosis of intracranial hemorrhage (ICH) were included if they received either 4FPCC or andexanet alfa for reversal of apixaban or rivaroxaban. In addition to hemostatic efficacy per imaging, we assessed disposition location, cerebral performance score, blood product consumption, and the development of a new thrombus.
A total of 46 patients were included in this study, 15 received 4FPCC (32%) and 31 received andexanet alfa (68%). There was no difference in the proportion of patients with excellent (4FPCC 9 [60%] vs. andexanet alfa 16 [51.6%], p = 0.61), good (4FPCC 2 [13.3%] vs. andexanet alfa 7 [22.6%]), or poor (4FPCC 1 [6.7%] vs. andexanet alfa 5 [16.1%]) hemostasis after administration of each agent. There were no significant differences in any secondary outcomes.
Our study found no difference in hemostatic efficacy between andexanet alfa and 4FPCC. At this time, clinicians should choose an agent based on individual patient presentation and resource availability. Further research will help clarify the role of each agent in the management of DOAC-related intracranial hemorrhage.
口服抗凝相关脑出血的死亡率约为 60%，与未抗凝相比，口服抗凝可使脑出血的风险增加 7 至 10 倍。目前的指南建议 DOAC（直接口服抗凝剂）作为静脉血栓栓塞症（VTE）治疗的一线治疗药物，因为它们具有更有利的安全性。有两种因子 Xa （重组）、失活-zhzo（andexanet alfa，Andexxa®）和 4 因子凝血酶原复合物浓缩物（4FPCC）可用作 DOAC 的逆转剂。在真实临床环境中比较这两种药物的数据很少。
本研究的主要目的是确定 factor Xa 抑制剂相关颅内出血患者使用 andexanet alfa 和 4FPCC 的止血效果是否存在差异。
这是一项回顾性、单中心研究，在 2017 年 9 月至 2021 年 3 月期间在一家四级学术医疗中心收治的成年患者中进行。如果颅内出血（ICH）患者接受了 4FPCC 或 andexanet alfa 以逆转 apixaban 或 rivaroxaban，则将其纳入研究。除了影像学检查的止血效果外，我们还评估了患者的处置位置、脑功能评分、血液制品的消耗情况以及新血栓的形成情况。
本研究共纳入 46 例患者，其中 15 例接受 4FPCC（32%），31 例接受 andexanet alfa（68%）。接受两种药物治疗的患者中，止血效果极好（4FPCC 9 例[60%] vs. andexanet alfa 16 例[51.6%]，p=0.61）、良好（4FPCC 2 例[13.3%] vs. andexanet alfa 7 例[22.6%]）或差（4FPCC 1 例[6.7%] vs. andexanet alfa 5 例[16.1%]）的比例无差异。任何次要结局均无显著差异。
我们的研究发现 andexanet alfa 和 4FPCC 之间的止血效果无差异。目前，临床医生应根据患者的个体表现和资源可用性选择药物。进一步的研究将有助于阐明每种药物在 DOAC 相关颅内出血管理中的作用。
