Early Heparin Administration Attenuates Tissue Factor-Mediated Thrombin Generation During Simulated Cardiopulmonary Bypass

Early Heparin Administration Attenuates Tissue Factor-Mediated Thrombin Generation During Simulated Cardiopulmonary Bypass
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DOI:
10.1111/jocs.12254
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发表时间:
2014-01-01
影响因子:
1.6
通讯作者:
Sakakibara, Yuzuru
Sakakibara, Yuzuru
中科院分区:
医学4区
文献类型:
--
作者:
Morizumi, Sei;Hiramatsu, Yuji;Sakakibara, Yuzuru

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BackgroundWe测试了这样一个假设,即在组织因子(TF)出现之前肝素给药会增加血浆TF途径抑制物(TFPI)并减弱TF介导的凝血酶生成,在模拟心肺转流(CPB)过程中,使用氧合器和滚子泵将人血再循环120分钟。检查了四组:对照组(肝素3.75U/mL,供体血,n=7)、rTF组(肝素+重组TF 1000 pg/mL,供体血,n=7)、TFPI加强组(肝素,预肝素化供体血,n=8)和rTF+TFPI加强组(肝素+rTF,预肝素化供体血,n=7)。在两个TFPI加强组中,在捐献前5分钟静脉内给予供体50 U/kg肝素以提高血浆TFPI水平。总血浆TFPI,凝血酶-抗凝血酶复合物,凝血酶原片段F1+2的水平进行了测量之前和CPB过程中。ResultsPreheparinization增加总血浆TFPI水平的一个因素为8.0。rTF的施用显著增强了F1+2的产生(p=0.0002)。在rTF+TFPI加强组中,肝素诱导的TFPI升高使凝血酶-抗凝血酶复合物和F1+2降低至对照水平(凝血酶-抗凝血酶复合物p=0.0158,p
BackgroundWe tested the hypothesis that heparin administration prior to the emergence of tissue factor (TF) would increase plasma TF pathway inhibitor (TFPI) and attenuate TF-mediated thrombin generation during simulated cardiopulmonary bypass (CPB).MethodsHuman blood was recirculated for 120minutes using an oxygenator and roller pump. Four groups were examined: control group (heparin 3.75U/mL, in donor blood, n=7), rTF group (heparin+recombinant TF 1000pg/mL, in donor blood, n=7), TFPI boost group (heparin, in preheparinized donor blood, n=8), and rTF+TFPI boost group (heparin+rTF, in preheparinized blood, n=7). In the two TFPI boost groups, 50U/kg of heparin was given to the donors intravenously five minutes before donation to boost plasma TFPI levels. Total plasma TFPI, thrombin-antithrombin complex, and prothrombin fragment F1+2 levels were measured before and during CPB.ResultsPreheparinization increased total plasma TFPI levels by a factor of 8.0. Administration of rTF significantly enhanced the generation of F1+2 (p=0.0002). The heparin-induced TFPI elevation reduced both thrombin-antithrombin complex and F1+2 to control levels in rTF+TFPI boost group (p=0.0158 for thrombin-antithrombin complex, p