Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram

Kellie R. Machlus; Emily A. Colby; Jogin R. Wu; Gary G. Koch; Nigel S. Key; Alisa S. Wolberg

doi:10.1160/TH09-03-0180

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 102(05): 936-944
DOI: 10.1160/TH09-03-0180

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Effects of tissue factor, thrombomodulin and elevated clotting factor levels on thrombin generation in the calibrated automated thrombogram

Kellie R. Machlus

¹Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

,

Emily A. Colby

²Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

,

Jogin R. Wu

³Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA

,

Gary G. Koch

²Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

,

Nigel S. Key

⁴Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

,

Alisa S. Wolberg

¹Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA

› Author Affiliations

Abstract

Summary

Elevated procoagulant levels have been correlated with increased thrombin generation in vitro and with increased venous thromboembolism (VTE) risk in epidemiological studies. hrombin 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 accounted for experiment and treatment. he 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.

Keywords

Thrombin - tissue factor - thrombomodulin - platelets - hypercoagulability - thrombosis

Full Text

References

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