Kelchtermans Hilde, Pelkmans Leonie, Bouwhuis Anne, Schurgers Evelien, Lindhout Theo, Huskens Dana, Miszta Adam, Hemker H Coenraad, Lancé Marcus D, de Laat Bas
Hilde Kelchtermans, Oxfordlaan 70, Maastricht 6229EV, The Netherlands, Tel.: +31 43 388 58 94, Fax: +31 43 388 45 70, E-mail:
Thromb Haemost. 2016 Jul 4;116(1):134-45. doi: 10.1160/TH15-10-0801. Epub 2016 Apr 14.
Assays based on the formation of thrombin and fibrin are frequently used, and results are considered exchangeable in research/clinical settings. However, thrombin generation and fibrin formation do not always go hand in hand and flow profoundly influences thrombus formation. We describe the technical/clinical evaluation of an assay to simultaneously measure thrombin generation and fibrin formation under conditions of flow. Introduction of a fluorometer into a 'cone and base principle'-based rheometer allowed the measurement of thrombin generation (using a thrombin-sensitive substrate) and fibrin formation (changes in viscosity), while applying a linear shear flow. Increasing shear rates inversely related with thrombin generation and fibrin formation. Increasing fibrinogen concentrations in defibrinated plasma resulted in increased thrombin generation and fibrin formation. In pre-operative samples of 70 patients undergoing cardiothoracic surgery, fibrin formation and thrombin generation parameters correlated with fibrinogen content, rotational thromboelastometry (ROTEM) and whole blood Calibrated Automated Thrombinography (CAT) parameters, respectively. Upon dividing patients into two groups based on the median clot strength, a significant difference in perioperative/total blood loss was established. In conclusion, we clinically evaluated a method capable of simultaneously measuring thrombin generation and fibrin formation in plasma/whole blood under continuous flow, rendering our method one step closer to physiology. Importantly, our test proved to be indicative for the amount of blood loss during/after cardiothoracic surgery.
基于凝血酶和纤维蛋白形成的检测方法经常被使用，并且在研究/临床环境中结果被认为是可互换的。然而，凝血酶生成和纤维蛋白形成并不总是同步进行，而且血流对血栓形成有深远影响。我们描述了一种在血流条件下同时测量凝血酶生成和纤维蛋白形成的检测方法的技术/临床评估。将荧光计引入基于“圆锥和基座原理”的流变仪中，能够在施加线性剪切流的同时测量凝血酶生成（使用凝血酶敏感底物）和纤维蛋白形成（粘度变化）。剪切速率增加与凝血酶生成和纤维蛋白形成呈负相关。去纤维蛋白血浆中纤维蛋白原浓度增加导致凝血酶生成和纤维蛋白形成增加。在70例接受心胸外科手术患者的术前样本中，纤维蛋白形成和凝血酶生成参数分别与纤维蛋白原含量、旋转血栓弹力图（ROTEM）和全血校准自动凝血酶生成检测（CAT）参数相关。根据中位凝血强度将患者分为两组后，围手术期/总失血量存在显著差异。总之，我们在临床上评估了一种能够在连续血流条件下同时测量血浆/全血中凝血酶生成和纤维蛋白形成的方法，使我们的方法更接近生理状态。重要的是，我们的检测被证明可指示心胸外科手术期间/术后的失血量。
