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Flow-simulated thrombin generation profiles as a predictor of thrombotic risk among pre-menopausal women

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH12-02-0098
Issue: 2012: 108/2 (Aug) pp. 201-403
Pages: 258-265

Flow-simulated thrombin generation profiles as a predictor of thrombotic risk among pre-menopausal women

S. W. Jordan (1), M. A. Corriere (2, 3), C. Y. Vossen (4, 5), F. R. Rosendaal (4), E. L. Chaikof (1, 6, 7)

(1) Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA; (2) Division of Vascular Surgery, Emory University, Atlanta, Georgia, USA; (3) Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; (4) Departments of Clinical Epidemiology and Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, Netherlands; (5) Division of Biomedical Genetics, Department of Medical Genetics at the University Medical Center Utrecht, Utrecht, Netherlands; (6) Department of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA; (7) Wyss Institute of Biologically Inspired Engineering of Harvard University, Boston, Massachusetts, USA

Keywords

Computer Simulation, thrombosis, blood coagulation, thromboembolism

Summary

A large number of individuals are at risk for deep venous thrombosis (DVT) due to alterations in multiple coagulation factors and inhibitors secondary to malignancy, drug interactions, or other general medical conditions. Traditional metrics of haemostasis such as prothrombin time, partial thromboplastin time, and bleeding time, generally estimate anticoagulation status and bleeding risk rather than thrombosis risk. The objective of this study was to correlate a novel, systems-based metric of clotting potential to risk of DVT from a database derived from the Leiden Thrombophilia Study (LETS). We utilised a computational model of blood coagulation, which addresses the interplay between biochemical factors, blood flow, and physiologic surface initiation of coagulation, to calculate an individualised, systems-based metric of clotting potential, termed the flow-simulated thrombin generation (FSTG), for 210 pre-menopausal women in LETS. Both DVT and oral contraceptive (OC) use were associated with higher values of FSTG. We demonstrated a nearly three-fold increased risk of DVT for each standard deviation increase above the mean in FSTG determined under venous flow conditions, which remained highly predictive after adjustment for age and OC status (adjusted odds ratio 2.66; 95% confidence interval 1.69–4.19; p<0.0001). In conclusion, a systems-based screening approach that integrates biochemical factors and flow haemodynamics identifies small subgroups of patients at risk of thrombosis that may benefit from oral anticoagulants.

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