Clinical measurement of thrombin generation by calibrated automated thrombography requires contact factor inhibition

• Published in: Journal of thrombosis and haemostasis 2004-11, Vol.2 (11), p.1954-1959
• Main Authors: Luddington, R., Baglin, T.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Automation; Blood Coagulation Tests - instrumentation; Blood Coagulation Tests - methods; Blood Coagulation Tests - standards; Calibration; Clinical Laboratory Techniques; corn trypsin inhibitor, contact factor inhibition, thrombin generation, tissue factor; Hemophilia A - diagnosis; Humans; Middle Aged; Plant Proteins - pharmacology; Reproducibility of Results; Thrombin - biosynthesis; Thrombin - drug effects; Thrombophilia - diagnosis; Thromboplastin - pharmacology
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2004.00964.x

Background: Measurement of thrombin generation by calibrated automated thrombography (CAT) could fulfill the requirements of a global test of coagulability and is potentially applicable to routine clinical laboratory practice. The purpose of this study was to determine if corn trypsin inhibitor (CTI) could be used to abolish contact factor activation in this assay, thus allowing accurate measurement of low tissue factor (TF) concentration‐triggered thrombin generation on samples taken in a routine clinical setting. Methods: The endogenous thrombin potential (ETP) was measured by CAT. Results: The study demonstrated that addition of CTI after plasma separation is not sufficient and blood must be drawn into tubes containing CTI if in‐vitro contact factor‐activated thrombin generation is to be abolished. Contact factor‐activated thrombin generation is completely inhibited at a CTI concentration of 18.3 µg mL−1 whole blood. Increasing the CTI concentration above this level does not lead to suppression of the TF‐triggered ETP. At a TF concentration of 2 pmol, ETPs were significantly lower in the presence of CTI (P