Xin Kevin Z, Chang William C, Ovanesov Mikhail V
Office of Blood Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States of America.
Office of Blood Research and Review, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, United States of America.
Thromb Res. 2016 Apr;140:132-139. doi: 10.1016/j.thromres.2015.11.023. Epub 2015 Nov 19.
Fluorogenic thrombin generation (TG) assays and turbidity-based fibrin generation (FG)- and fibrinolysis (FL)-resistance assays have been sought to assess bleeding and clotting disorders. Theoretically, TG, FG and FL tests should provide overlapping information because thrombin is responsible for FG and induces protection from FL. The relationships between TG, FG and FL parameters remain poorly investigated, partly because existing experimental systems do not permit simultaneous detection of both TG and FG in the same sample of plasma, and are instead tested in separate experiments.
We evaluated the potential benefits of a combined TG/FG/FL assay by testing responses of normal plasma to a wide range of tissue factor (TF) and tissue plasminogen activator (tPA) concentrations. Correlations between multiple parameters extracted from the TG and FG/FL curves were also compared.
Rate of FG correlated well with TG peak height at all TF concentrations, but correlations between TG and FL parameters depended on the TF concentration. Without thrombomodulin, all FG/FL parameters at high TF could be predicted from TG parameters and no FL protection was observed. With thrombomodulin and high TF, TF-dependent FL protection did not correlate with TF-dependent TG. The fluorogenic thrombin substrate did not interfere with optical density readings, and meaningful tPA concentrations did not interfere with TG readings.
In normal plasma, TG, FG and FL parameters may provide interchangeable information. Evaluation of FL-resistance may provide additional data under special assay conditions, but the value of this information should be studied under disease conditions.
人们一直在寻求基于荧光的凝血酶生成（TG）测定法以及基于浊度的纤维蛋白生成（FG）和纤维蛋白溶解（FL）抗性测定法，以评估出血和凝血障碍。从理论上讲，TG、FG和FL测试应提供重叠的信息，因为凝血酶负责FG并诱导对FL的保护作用。TG、FG和FL参数之间的关系仍未得到充分研究，部分原因是现有的实验系统不允许在同一血浆样本中同时检测TG和FG，而是在单独的实验中进行测试。
我们通过测试正常血浆对广泛范围的组织因子（TF）和组织型纤溶酶原激活剂（tPA）浓度的反应，评估了TG/FG/FL联合测定法的潜在益处。还比较了从TG和FG/FL曲线提取的多个参数之间的相关性。
在所有TF浓度下，FG速率与TG峰值高度都具有良好的相关性，但TG和FL参数之间的相关性取决于TF浓度。在没有血栓调节蛋白的情况下，高TF时所有FG/FL参数都可以从TG参数预测出来，并且未观察到FL保护作用。在有血栓调节蛋白和高TF的情况下，TF依赖性FL保护与TF依赖性TG不相关。荧光凝血酶底物不干扰光密度读数，并且有意义的tPA浓度不干扰TG读数。
在正常血浆中，TG、FG和FL参数可能提供可互换的信息。在特殊的测定条件下，评估FL抗性可能会提供额外的数据，但应在疾病条件下研究该信息的价值。
