Gitel S N, Stephenson R C, Wessler S
Proc Natl Acad Sci U S A. 1977 Jul;74(7):3028-32. doi: 10.1073/pnas.74.7.3028.
The thrombogenicity of three highly purified proteases (thrombin, activated Factor X, and activated Factor IX) was determined quantitatively in an animal model. The minimal amounts required to produce a standard score 4 thrombus were 1.1 nmol for thrombin, 0.12 nmol for activated Factor X, and 0.018 nmol for activated Factor IX. After the administration of heparin at 5, 10, and 20 units/kg in rabbits, the thrombogenicity of each of these proteases decreased progressively. The heparin-induced inhibition of thrombosis decreased in the order, activated Factor IX > activated Factor X > thrombin at each heparin concentration. These differences were statistically significant. These in vivo data provide support for the following hypotheses originally developed from in vitro experiments: (i) activation of the blood coagulation system, which proceeds through a cascade mechanism, incorporates biochemical amplification; (ii) the inhibition of activated Factor IX by antithrombin III in the presence of heparin is an important reaction in the prevention of thrombosis; (iii) less heparin is required to inhibit thrombosis prior to thrombin generation than afterward; (iv) an increase in the reactivity of antithrombin III reflects a decreased tendency to thrombosis while a decrease in this reactivity reflects an increased tendency to thrombosis.
在动物模型中对三种高度纯化的蛋白酶（凝血酶、活化的因子X和活化的因子IX）的血栓形成性进行了定量测定。产生标准4分血栓所需的最小量，凝血酶为1.1纳摩尔，活化的因子X为0.12纳摩尔，活化的因子IX为0.018纳摩尔。在兔中以5、10和20单位/千克给予肝素后，这些蛋白酶各自的血栓形成性逐渐降低。在每个肝素浓度下，肝素诱导的血栓形成抑制作用按活化的因子IX>活化的因子X>凝血酶的顺序降低。这些差异具有统计学意义。这些体内数据为最初从体外实验得出的以下假设提供了支持：（i）通过级联机制进行的血液凝固系统激活包含生化放大作用；（ii）在肝素存在下抗凝血酶III对活化的因子IX的抑制是预防血栓形成的重要反应；（iii）在凝血酶生成之前抑制血栓形成所需的肝素比之后少；（iv）抗凝血酶III反应性的增加反映血栓形成倾向降低，而这种反应性的降低反映血栓形成倾向增加。
