Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor.
Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor.
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体外灌注期间的内源性抗凝：肝素样抑制剂的产生。
DOI：
10.1152/ajpheart.1980.239.6.h742
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
Hinshaw,LB
中科院分区：
文献类型：
--
作者：
Murphy,TL;Walker,FJ;Taylor3rd,FB;Beller-Todd,B;Archer,LT;Sofer,SS;Hinshaw,LB
进行了研究，以确定血流动力学稳定的麻醉犬在我们的动静脉体外循环系统中灌注（未添加肝素）时出现的凝血缺陷。45分钟后，犬的全血凝血时间（WBCT）超过24小时。ADP诱导的血小板聚集和因子V、VIII和X水平分别下降75.8%、33.5%和46.8%。尽管纤维蛋白原降解产物增加，但纤维蛋白原水平或血小板计数无显著变化。凝血酶和凝血因子Xa凝血的血浆的抑制剂出现，是“肝素样”，因为它刺激灭活因子Xa的抗凝血酶III（ATIII），但不是由O-甲基异脲氨改性的ATIII。凝血酶抑制ATIII也受到刺激。该缓蚀剂对热稳定，能被硫酸钡吸附，并能被鱼精蛋白中和。将硫酸鱼精蛋白输注到两只灌注犬中，中和了抑制剂，并使WBCT从大于24 h降至小于对照。6只犬产生了相当于0.98至6.15 U/ml肝素的抑制剂水平。结扎肝动脉的5只内脏切除犬的血浆抑制剂峰值水平为3.2 +/- 1.0 U/ml。因此，内源性肝素样抑制剂是我们的灌注系统诱导的抗凝状态的主要贡献者，并且可能具有肝外起源。
Studies were done to define the coagulation defect that develops in hemodynamically stable anesthetized dogs perfused on our arteriovenous extracorporeal system without added heparin. After 45 min, the dogs developed whole blood clotting times (WBCT) greater than 24 h. There was an associated decrease in ADP-induced platelet aggregation and a drop in factor V, VIII, and X levels of 75.8, 33.5, and 46.8%, respectively. Despite an increase in fibrinogen degradation products, there was no significant change in fibrinogen level or platelet count. An inhibitor of thrombin and factor Xa clotting of plasma appeared that was "heparinlike", because it stimulated the inactivation of factor Xa by antithrombin III (ATIII) but not by O-methyl isoureamodified ATIII. Thrombin inhibition by ATIII was also stimulated. The inhibitor was heat stable, adsorbed by BaSO4, and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs neutralized the inhibitor and brought the WBCT from greater than 24 h to less than control. Six dogs developed inhibitor levels equivalent to 0.98 to 6.15 U/ml heparin. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma inhibitor levels of 3.2 +/- 1.0 U/ml. Thus, the endogenous heparinlike inhibitor is a major contributor to the anticoagulated state induced with our perfusion system and may have an extrahepatic origin.