Sartori Maria Teresa, Prandoni Paolo
a Clinical Medicine I, Department of Medicine , University of Padua , Padua , Italy.
Expert Rev Hematol. 2016 Jan;9(1):37-50. doi: 10.1586/17474086.2016.1112733. Epub 2015 Nov 17.
Since affecting hemostasis, all the anticoagulant drugs carry a risk of bleeding. Minor bleeds may be managed without the need to reverse the anticoagulant effect, which is instead a key step to ensure efficacious hemostasis in major and life-threatening bleeding. Drug withdrawal applies to all anticoagulants. Unfractionated heparin can be neutralized by protamine, which may partly neutralize low-molecular-weight heparins. There is no antidote for fondaparinux, and recombinant factor VIIa (rFVIIa) may be considered for critical bleeding. For vitamin K antagonists-induced major bleeding, rapid reversal with prothrombin complex concentrates (PCC) or plasma and intravenous vitamin K to confer lasting correction are recommended. PCC, activated PCC and rFVIIa are suggested for major bleeding related to new direct oral anticoagulants (DOAC), despite proper studies are lacking. Premarketing studies are ongoing on new antidotes (idarucizumab, andexanet, aripazine), which appear to be suitable for the treatment of DOAC-induced life-threatening hemorrhage.
由于影响止血,所有抗凝药物都有出血风险。轻微出血无需逆转抗凝作用即可处理,而逆转抗凝作用是确保严重及危及生命的大出血时有效止血的关键步骤。停用药物适用于所有抗凝剂。普通肝素可用鱼精蛋白中和,鱼精蛋白也可部分中和低分子肝素。磺达肝癸钠没有解毒剂,对于严重出血可考虑使用重组凝血因子VIIa(rFVIIa)。对于维生素K拮抗剂引起的严重出血,建议用凝血酶原复合物浓缩剂(PCC)或血浆快速逆转,并静脉注射维生素K以实现持久纠正。尽管缺乏充分研究,但对于新型直接口服抗凝剂(DOAC)相关的严重出血,建议使用PCC、活化PCC和rFVIIa。针对新型解毒剂(艾达司珠单抗、andexanet、阿利哌嗪)的上市前研究正在进行,这些解毒剂似乎适用于治疗DOAC引起的危及生命的出血。