Kellie R. Machlus1; Emily A. Colby2; Jogin R. Wu3; Gary G. Koch2; Nigel S. Key4; Alisa S. Wolberg1
1Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 2Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA; 3Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA; 4Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
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 plateletrich plasma (PRP). Statistical analysis was performed using logarithms of observed values with analysis of variance that ac- counted 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.
thrombosis, Platelets, Tissue factor, thrombin, hypercoagulability, thrombomodulin
Mariann Gyöngyösi 1, Christoph Strehblow 1, Wolfgang Sperker 1, Akos Hevesi 2, Rita Garamvölgyi 2, Zsolt Petrási 2, Noemi Pavo 1, Péter Ferdinandy 3, Csaba Csonka 3, Tamás Csont 3, Christer Sylvén 4, Paul J. Declerck 5, Imre Pavo Jr 1, Johann Wo
Thromb Haemost 2006 96 2: 202-209
H. Lee (1), S. A. Sturgeon (1), S. P. Jackson (1), J. R. Hamilton (1)
Thromb Haemost 2012 107 2: 328-337
Ok-Nam Bae*1, Young-Dae Kim*1, Kyung-Min Lim1,2, Ji-Yoon Noh1, Seung-Min Chung1, Keunyoung Kim1, Suyoung Hong1, Sue Shin3, Jong-Hyun Yoon3, Jin-Ho Chung1
Thromb Haemost 2008 100 1: 52-59
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