Kortchinsky T, Vigué B, Samama C M
Centre chirurgical Marie-Lannelongue, réanimation adulte, 92350 Le Plessis-Robinson, France.
Ann Fr Anesth Reanim. 2013 Jan;32(1):37-49. doi: 10.1016/j.annfar.2012.10.034. Epub 2012 Dec 27.
Even with unfractionated heparin or derivates, the reversal of pharmacologic anticoagulation is crucial in anticoagulated patients developing a life-threatening bleeding or scheduled for an emergency procedure. The antagonisation of unfractionated heparin is well codified: each milligram of protamine sulfate antagonizes 100 IU of heparin. Measurement of thrombin time reflects the anti-IIa effect of heparin and has to be monitored immediately and 1hour after the injection of protamine. The required dose of protamine sulfate depends on dosage and time of LMWH administration, although no clinical study supports these data. To date, there is no effective antidote for new anticoagulants (fondaparinux and other pentasaccharides, direct thrombin inhibitors, direct anti-Xa inhibitors). Some preliminary studies suggest the effectiveness of recombinant activated factor VII for pentasaccharides and activated or not Prothrombin Complex Concentrates and recombinant activated factor VII for oral anti-Xa and anti-IIa agents. Therefore, while the characteristics of these new anticoagulants could increase the comfort and improve the compliance, their development needs to ascertain the lack of increase in bleeding complications and the need for a safe and effective antidote.
即使使用普通肝素或其衍生物,对于发生危及生命的出血或计划进行急诊手术的抗凝患者,逆转药物性抗凝作用至关重要。普通肝素的拮抗方法已明确规范:每毫克硫酸鱼精蛋白可拮抗100国际单位的肝素。凝血酶时间的测定反映了肝素的抗IIa作用,必须在注射鱼精蛋白后立即及1小时后进行监测。硫酸鱼精蛋白的所需剂量取决于低分子肝素的给药剂量和时间,尽管尚无临床研究支持这些数据。迄今为止,新型抗凝剂(磺达肝癸钠和其他五糖、直接凝血酶抑制剂、直接抗Xa抑制剂)尚无有效的解毒剂。一些初步研究表明,重组活化因子VII对五糖有效,活化或未活化的凝血酶原复合物浓缩物以及重组活化因子VII对口服抗Xa和抗IIa药物有效。因此,虽然这些新型抗凝剂的特性可能会提高舒适度并改善依从性,但其研发需要确定出血并发症是否不会增加以及是否需要一种安全有效的解毒剂。