Department of Anesthesiology, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA 30322, USA.
Anesth Analg. 2010 Sep;111(3):601-8. doi: 10.1213/ANE.0b013e3181e9ed15. Epub 2010 Aug 4.
Protamine sulfate is the antidote for heparin, but in excess it exerts weak anticoagulation.
We evaluated the effects of increasing protamine concentrations (0 to 24 microg/mL) on prothrombin time and diluted Russell's viper venom time measurements on thrombin generation in platelet-poor and platelet-rich plasma after activation by tissue factor or actin, and on thromboelastometry in platelet-poor plasma and whole blood from 6 healthy volunteers. The reversibility of excess protamine (24 microg/mL) by recombinant factor VIIa or factor VIII/von Willebrand factor concentrate was also tested.
Protamine prolonged prothrombin time and Russell's viper venom time, concentration dependently. Protamine also increased lag time and decreased peak of thrombin generation in platelet-poor plasma after tissue factor and actin activation. In platelet-rich plasma with platelets at 50 to 200 x 10(3)/microL, protamine (24 microg/mL) prolonged the lag time, but had no effect on peak thrombin generation. The addition of factor VIII/von Willebrand factor (1.5-3.0 U/mL) to platelet-poor plasma with protamine (24 microg/mL) decreased lag time and increased peak thrombin generation with actin activation. A therapeutic concentration of recombinant factor VIIa (60 nM) only affected the lag time of thrombin generation triggered with actin. In agreement, protamine increased coagulation time evaluated by thromboelastometry significantly more in platelet-poor plasma than in whole blood.
We demonstrated that protamine affects the propagation of thrombin generation, which is partially reversed by platelets or increased factor VIII/von Willebrand factor concentrations. The present data suggest that excess protamine might potentially increase bleeding in the case of severe thrombocytopenia or low factor VIII.
硫酸鱼精蛋白是肝素的解毒剂，但过量时会产生较弱的抗凝作用。
我们评估了增加鱼精蛋白浓度（0 至 24μg/mL）对组织因子或肌动蛋白激活后血小板减少和富含血小板的血浆中凝血酶原时间和稀释的 Russell 蝰蛇毒时间测量以及对血小板减少和全血中凝血酶生成的影响。来自 6 名健康志愿者的血栓弹性测定法。还测试了过量鱼精蛋白（24μg/mL）通过重组因子 VIIa 或因子 VIII/血管性血友病因子浓缩物的逆转作用。
鱼精蛋白浓度依赖性地延长凝血酶原时间和 Russell 蝰蛇毒时间。鱼精蛋白还增加了组织因子和肌动蛋白激活后血小板减少的血浆中凝血酶生成的迟滞时间并降低了峰值。在血小板计数为 50 至 200×103/μL 的富含血小板的血浆中，鱼精蛋白（24μg/mL）延长了迟滞时间，但对峰值凝血酶生成没有影响。在含有鱼精蛋白（24μg/mL）的血小板减少的血浆中添加因子 VIII/血管性血友病因子（1.5-3.0U/mL）可缩短迟滞时间并增加肌动蛋白激活时的峰值凝血酶生成。治疗浓度的重组因子 VIIa（60nM）仅影响肌动蛋白触发的凝血酶生成的迟滞时间。一致地，鱼精蛋白明显更多地增加了血小板减少的血浆中血栓弹性测定法评估的凝血时间，而不是全血中的凝血时间。
我们证明鱼精蛋白影响凝血酶生成的传播，血小板或增加的因子 VIII/血管性血友病因子浓度部分逆转了该传播。目前的数据表明，在严重血小板减少症或因子 VIII 水平低的情况下，过量的鱼精蛋白可能会增加出血的风险。
