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Modeling thrombin generation: plasma composition based approach

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Abstract

Thrombin has multiple functions in blood coagulation and its regulation is central to maintaining the balance between hemorrhage and thrombosis. Empirical and computational methods that capture thrombin generation can provide advancements to current clinical screening of the hemostatic balance at the level of the individual. In any individual, procoagulant and anticoagulant factor levels together act to generate a unique coagulation phenotype (net balance) that is reflective of the sum of its developmental, environmental, genetic, nutritional and pharmacological influences. Defining such thrombin phenotypes may provide a means to track disease progression pre-crisis. In this review we briefly describe thrombin function, methods for assessing thrombin dynamics as a phenotypic marker, computationally derived thrombin phenotypes versus determined clinical phenotypes, the boundaries of normal range thrombin generation using plasma composition based approaches and the feasibility of these approaches for predicting risk.

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Acknowledgments

This review was supported by NIH HL46705 and by the Systems Biology program W911NF-10-1-0376. The authors would like to thank Drs. Bravo, Danforth, and Foley and M. Gissel for work on the mathematical models, and Drs. Baker, Bernstein, Francis, McLean, Neaton, Rivard, Rosendaal, Schneider, Tracy, and Undas for studies on their patient populations.

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Authors and Affiliations

  1. Department of Biochemistry, College of Medicine, University of Vermont, Burlington, VT, USA

    Kathleen E. Brummel-Ziedins, Stephen J. Everse, Kenneth G. Mann & Thomas Orfeo

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  1. Kathleen E. Brummel-Ziedins
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  2. Stephen J. Everse
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  3. Kenneth G. Mann
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  4. Thomas Orfeo
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Correspondence to Kathleen E. Brummel-Ziedins.

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Brummel-Ziedins, K.E., Everse, S.J., Mann, K.G. et al. Modeling thrombin generation: plasma composition based approach. J Thromb Thrombolysis 37, 32–44 (2014). https://doi.org/10.1007/s11239-013-1006-9

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