A Whole Blood Thrombin Generation Assay to Assess Hypercoagulability

新鲜全血的凝结是通过添加钙和组织因子来刺激的。对凝血样本进行凝血酶活性检测。测量的参数是凝血酶活性的最大浓度、达到峰值的时间和凝血酶活性的积分x时间。我们测试了红细胞压积、白细胞计数和血小板计数对这些参数的影响，发现所有类型的细胞都会影响凝血酶的生成。我们还发现，在检测系统中，各凝血因子和天然抑制物的浓度也会影响凝血酶的生成。 这项测试现在已经应用于一组接受大手术的晚期恶性肿瘤患者。对14名患者和14名年龄和性别匹配的对照组进行了研究。凝血酶生成在术前、术后均有明显变化。这个项目的收益过早地停止了，因为现在进行手术的外科医生更喜欢在手术前给予肝素预防。这个时间安排混淆了我们的测量结果。然而，已经完成了大量的测试，以寻找我们在手术前和手术后观察到的凝血酶生成变化的原因。

Clotting of fresh whole blood is stimulated by adding calcium and tissue factor. Subsamples of the clotting blood are assayed for thrombin activity. The measured parameters are the maximal concentration of thrombin activity, the time to peak activity, and the integral of thrombin activity x time. We have tested the effect of hematocrit, white cell count, and platelet count on these parameters and have found that all of the cell types influence thrombin generation. We have also found that the concentration of each coagulation factor and natural inhibitor also affects thrombin generation in the assay system. The test has now been applied in a group of patients with advanced malignancies who undergo major surgery. Fourteen patients and 14 age- and sex-matched controls have been studied. There were obvious changes in thrombin generation between the pre-operative and post-operative days. Accrual for this project was halted prematurely because the surgeons now performing the operations prefer to give heparin prophylaxis pre-operatively. This timing confounds our measurements. Nevertheless, a large battery of tests has been completed to search for an explanation for the changes we observed between pre- and post-operative thrombin generation.