Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram.
Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram.
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DOI：
10.1160/th09-03-0180
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发表时间：
2009-11
影响因子：
6.7
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Machlus KR;Colby EA;Wu JR;Koch GG;Key NS;Wolberg AS
在流行病学研究中，促凝血剂水平的升高与体外凝血酶生成的增加和静脉血栓栓塞症(VTE)风险的增加相关。凝血酶生成试验越来越多地被用作高通量方法，以提供血浆样本中促凝血剂活性的全球测量。本研究的目的是区分检测条件[组织因子(TF)、血栓调节蛋白、血小板/脂类]和因子水平对凝血酶生成参数的影响，并确定检测因子水平升高的敏感性和特异性最高的条件和参数。用校准自动血栓造影术(CAT)检测经玉米胰酶抑制剂(CTI)处理的无血小板血浆(PFP)和富含血小板血浆(PRP)的凝血酶生成。使用观察值的对数进行统计分析，并进行说明试验和处理的方差分析。滞后时间(LT)、达峰时间(TTP)、峰值高度和内源性凝血酶潜力(ETP)对升高的因子XI、IX、VIII、X和凝血酶原的相对敏感度如下：PFP由1 pm Tf&Gt启动；PFP由5 pm Tf&Gt启动；PRP由1 pm Tf启动。在所有情况下，加入血栓调节蛋白延长了LT，降低了峰值和ETP；然而，加入血栓调节蛋白并不增加CAT检测单个促凝血因子水平升高的能力。总而言之，CAT条件不同地影响凝血酶生成对因子水平升高的敏感性。用1 PM Tf监测PFP开始凝血后的峰值高度和/或ETP，最有可能检测到由于促凝血因子水平增加而导致的高凝状态。
Elevated procoagulant levels have been correlated with increased thrombin generation in vitro and with increased venous thromboembolism (VTE) risk in epidemiological studies. Thrombin generation tests are increasingly being employed as a high throughput method to provide a global measure of procoagulant activity in plasma samples. The objective of this study was to distinguish the effects of assay conditions [tissue factor (TF), thrombomodulin, platelets/lipids] and factor levels on thrombin generation parameters, and determine the conditions and parameters with the highest sensitivity and specificity for detecting elevated factor levels. Thrombin generation was measured using calibrated automated thrombography (CAT) in corn trypsin inhibitor (CTI)-treated platelet-free plasma (PFP) and platelet-rich plasma (PRP). Statistical analysis was performed using logarithms of observed values with analysis of variance that accounted for experiment and treatment. The relative sensitivity of lag time (LT), time to peak (TTP), peak height and endogenous thrombin potential (ETP) to elevated factors XI, IX, VIII, X, and prothrombin was as follows: PFP initiated with 1 pM TF > PFP initiated with 5 pM TF > PRP initiated with 1 pM TF. For all conditions, inclusion of thrombomodulin prolonged the LT and decreased the peak and ETP; however, addition of thrombomodulin did not increase the ability of CAT to detect elevated levels of individual procoagulant factors. In conclusion, CAT conditions differentially affected the sensitivity of thrombin generation to elevated factor levels. Monitoring the peak height and/or ETP following initiation of clotting in PFP with 1 pM TF was most likely to detect hypercoagulability due to increased procoagulant factor levels.