Abstract:
Thrombin generation (TG) and fibrin clot formation represent the central process of blood coagulation. Up to 95% of thrombin is considered to be generated after the clot is formed. However, this was not investigated in depth. In this study, we conducted a quantitative analysis of the Thrombin at Clot Time (TCT) parameter in 5758 simultaneously recorded TG and clot formation assays using frozen plasma samples from commercial sources under various conditions of activation. These samples were supplemented with clotting factor concentrates, procoagulant lipid vesicles and a fluorogenic substrate and triggered with tissue factor (TF). We found that TCT is often close to a 10% of thrombin peak height (TPH) yet it can be larger or smaller depending on whether the sample has low or high TPH value. In general, the samples with high TPH are associated with elevated TCT. TCT appeared more sensitive to some procoagulant phenotypes than other commonly used parameters such as clotting time, TPH or Thrombin Production Rate (TPR). In a minority of cases, TCT were not predicted from TG parameters. For example, elevated TCT (above 15% of TPH) was associated with either very low or very high TPR values. We conclude that clotting and TG assays may provide complementary information about the plasma sample, and that the TCT parameter may serve as an additional marker for the procoagulant potential in plasma sample.
摘要:
凝血酶生成(TG)和纤维蛋白凝块形成代表血液凝固的中心过程。高达95%的凝血酶被认为是在凝块形成后产生的。然而,没有深入调查。在这项研究中,我们使用来自商业来源的冷冻血浆样品在各种活化条件下对5758个同时记录的TG和凝块形成测定中的凝血酶在凝块时间(TCT)参数进行了定量分析.这些样品补充了凝血因子浓缩物,促凝血脂质囊泡和荧光底物,并由组织因子(TF)触发。我们发现TCT通常接近凝血酶峰高(TPH)的10%,但它可以更大或更小,这取决于样品是否具有低或高TPH值。总的来说,具有高TPH的样品与升高的TCT相关。TCT似乎对某些促凝血表型比其他常用参数更敏感,如凝血时间,TPH或凝血酶生产率(TPR)。在少数情况下,不能从TG参数预测TCT。例如,TCT升高(TPH的15%以上)与TPR值非常低或非常高相关.我们得出结论,凝血和TG测定可以提供有关血浆样品的补充信息,并且TCT参数可以用作血浆样品中促凝血电位的附加标记。