Young Guy, Yonekawa Karyn E, Nakagawa Peggy A, Blain Rachelle C, Lovejoy Amy E, Nugent Diane J
Department of Hematology, Children's Hospital of Orange County, Orange, California, USA.
Blood Coagul Fibrinolysis. 2007 Sep;18(6):547-53. doi: 10.1097/MBC.0b013e328201c9a9.
Bleeding is the major adverse reaction to anticoagulants, leading to significant morbidity and even mortality. Protamine is a specific antidote for heparin yet is only partially effective for enoxaparin, and the activated factor X inhibitor fondaparinux and the direct thrombin inhibitors argatroban and bivalirudin lack specific antidotes. We evaluated the ability of recombinant activated factor VII (rFVIIa), a general hemostatic agent, to reverse the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin, as measured by thromboelastography. Whole-blood samples containing each test anticoagulant, with or without rFVIIa 1.5-4.5 microg/ml, were prepared ex vivo (n >or= 48, each anticoagulant) and analyzed by thromboelastography. The thromboelastography parameters of clot initiation, propagation, rigidity and elasticity were compared for the ex-vivo samples for each anticoagulant. The reversal ability of rFVIIa was also assessed using the standard clinical assay used to monitor each anticoagulant. Thromboelastography was performed on blood from eight stably anticoagulated patients, with and without exogenous rFVIIa. For each anticoagulant, rFVIIa significantly improved and, in some cases, completely normalized all thromboelastography parameters (P < 0.001). rFVIIa significantly (P < 0.01) decreased the activated partial thromboplastin time for argatroban-containing, bivalirudin-containing, or heparin-containing blood yet did not affect the anti-activated factor X levels for enoxaparin-containing or fondaparinux-containing blood. By thromboelastography, rFVIIa exerted generally similar reversal effects on the anticoagulated patient samples as on the ex-vivo samples. In conclusion, rFVIIa effectively reverses the anticoagulant effects of heparin, enoxaparin, fondaparinux, argatroban, and bivalirudin, and should be considered for patients with excessive bleeding associated with these anticoagulants.
出血是抗凝剂的主要不良反应,可导致显著的发病率甚至死亡率。鱼精蛋白是肝素的特效解毒剂,但对依诺肝素仅部分有效,而活化因子X抑制剂磺达肝癸钠以及直接凝血酶抑制剂阿加曲班和比伐卢定则缺乏特效解毒剂。我们评估了通用止血剂重组活化因子VII(rFVIIa)逆转肝素、依诺肝素、磺达肝癸钠、阿加曲班和比伐卢定抗凝作用的能力,通过血栓弹力图进行测定。将含有每种测试抗凝剂的全血样本在体外制备,添加或不添加1.5 - 4.5微克/毫升的rFVIIa(每种抗凝剂n≥48),并通过血栓弹力图进行分析。比较每种抗凝剂体外样本的血栓弹力图参数,包括凝血起始、传播、硬度和弹性。还使用用于监测每种抗凝剂的标准临床检测方法评估rFVIIa的逆转能力。对八名稳定抗凝患者的血液进行血栓弹力图检测,检测时添加或不添加外源性rFVIIa。对于每种抗凝剂,rFVIIa均显著改善,在某些情况下还使所有血栓弹力图参数完全恢复正常(P < 0.001)。rFVIIa显著(P < 0.01)缩短了含阿加曲班、含比伐卢定或含肝素血液的活化部分凝血活酶时间,但对含依诺肝素或含磺达肝癸钠血液的抗活化因子X水平无影响。通过血栓弹力图检测,rFVIIa对抗凝患者样本的逆转作用与对体外样本的作用总体相似。总之,rFVIIa可有效逆转肝素、依诺肝素、磺达肝癸钠、阿加曲班和比伐卢定的抗凝作用,对于因这些抗凝剂导致出血过多的患者应考虑使用。