BACKGROUND: Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma coagulation factor (F) compositions from 28 patients with ACS were obtained after onset of chest pain. Similar data were obtained from 25 age- and sex-matched patients with stable CAD. All individuals took aspirin. Patients on anticoagulant therapy were excluded. The groups were similar in demographic characteristics, comorbidities and concomitant treatment. Using each individual's coagulation protein composition, tissue factor (TF) initiated thrombin generation was assessed both computationally and empirically. TF pathway inhibitor (TFPI), antithrombin (AT), factor II (FII) and FVIII differed significantly (P < 0.01) between the groups, with levels of FII, FVIII and TFPI higher and AT lower in ACS patients. When thrombin generation profiles from individuals in each group were compared, simulated maximum thrombin levels (P < 0.01) and rates (P < 0.01) were 50% higher with ACS while the initiation phases of thrombin generation were shorter. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. The differences between the thrombin generation profiles for each population were primarily dependent upon the collective contribution of AT, FII and FVIII. CONCLUSION: Simulations of thrombin formation based on plasma composition can discriminate between acute and stable CAD.
BACKGROUND:Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD). METHODS AND RESULTS: Plasma coagulation factor (F) compositions from 28 patients with ACS were obtained after onset of chest pain. Similar data were obtained from 25 age- and sex-matched patients with stable CAD. All individuals took aspirin. Patients on anticoagulant therapy were excluded. The groups were similar in demographic characteristics, comorbidities and concomitant treatment. Using each individual's coagulation protein composition, tissue factor (TF) initiated thrombin generation was assessed both computationally and empirically. TF pathway inhibitor (TFPI), antithrombin (AT), factor II (FII) and FVIII differed significantly (P < 0.01) between the groups, with levels of FII, FVIII and TFPI higher and AT lower in ACS patients. When thrombin generation profiles from individuals in each group were compared, simulated maximum thrombin levels (P < 0.01) and rates (P < 0.01) were 50% higher with ACS while the initiation phases of thrombin generation were shorter. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. The differences between the thrombin generation profiles for each population were primarily dependent upon the collective contribution of AT, FII and FVIII. CONCLUSION: Simulations of thrombin formation based on plasma composition can discriminate between acute and stable CAD.
Authors: Nena Matijevic; Yao-Wei W Wang; Vadim Kostousov; Charles E Wade; K Vinod Vijayan; John B Holcomb Journal: Thromb Res Date: 2011-03-21 Impact factor: 3.944
Authors: Harold L Dauerman; Christine M DeStephan; Heidi Taatjes Sommer; Kathryn C Kurchena; Michael DeSarno; Erika G Mendoza; Amy Henderson; David J Schneider Journal: J Am Coll Cardiol Date: 2019-08-13 Impact factor: 24.094
Authors: Kathleen E Brummel-Ziedins; Matthew Gissel; Charles Francis; John Queenan; Kenneth G Mann Journal: Thromb Res Date: 2009-03-17 Impact factor: 3.944
Authors: K E Brummel-Ziedins; T Orfeo; F R Rosendaal; A Undas; G E Rivard; S Butenas; K G Mann Journal: J Thromb Haemost Date: 2009-07 Impact factor: 5.824