Tolerance and threshold in the extrinsic coagulation system

Müller, Johannes; Brandt, Stefan; Mayerhofer, Katrin; Tjardes, Thorsten; Maegele, Marc

doi:10.1016/j.mbs.2007.07.007

Cited by 3 publications

(1 citation statement)

References 22 publications

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“…Although Beltrami and Jesty were able to demonstrate experimentally that thresholds indeed occur in enzyme systems with feedback and inhibition [46], existence of a threshold in a real blood clotting remained an unresolved experimental issue. One paper (once again, a theoretical one) even suggested that there is no threshold in coagulation in the absence of blood flow [47]. An experimental effort by our group in 1995 demonstrated calcium concentration threshold [48], but not the activation threshold.…”

Section: Clotting Initiation: Activation Threshold and Local Explosiomentioning

confidence: 99%

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Panteleev

Dashkevich

Ataullakhanov

2015

Thrombosis Research

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Section: Clotting Initiation: Activation Threshold and Local Explosiomentioning

confidence: 99%

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Panteleev

Dashkevich

Ataullakhanov

2015

Thrombosis Research

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The Blood Coagulation Cascade in a Perfusion Experiment: Example from the Pharmaceutical Industry

Efendiev

2012

International Series of Numerical Mathematics

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A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability

Chung¹,

Bakshi

Graaf

2023

Pharmaceutics

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Despite the numerous therapeutic options to treat bleeding or thrombosis, a comprehensive quantitative mechanistic understanding of the effects of these and potential novel therapies is lacking. Recently, the quality of quantitative systems pharmacology (QSP) models of the coagulation cascade has improved, simulating the interactions between proteases, cofactors, regulators, fibrin, and therapeutic responses under different clinical scenarios. We aim to review the literature on QSP models to assess the unique capabilities and reusability of these models. We systematically searched the literature and BioModels database reviewing systems biology (SB) and QSP models. The purpose and scope of most of these models are redundant with only two SB models serving as the basis for QSP models. Primarily three QSP models have a comprehensive scope and are systematically linked between SB and more recent QSP models. The biological scope of recent QSP models has expanded to enable simulations of previously unexplainable clotting events and the drug effects for treating bleeding or thrombosis. Overall, the field of coagulation appears to suffer from unclear connections between models and irreproducible code as previously reported. The reusability of future QSP models can improve by adopting model equations from validated QSP models, clearly documenting the purpose and modifications, and sharing reproducible code. The capabilities of future QSP models can improve from more rigorous validation by capturing a broader range of responses to therapies from individual patient measurements and integrating blood flow and platelet dynamics to closely represent in vivo bleeding or thrombosis risk.

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Tolerance and threshold in the extrinsic coagulation system

Cited by 3 publications

References 22 publications

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion

The Blood Coagulation Cascade in a Perfusion Experiment: Example from the Pharmaceutical Industry

A Review of Quantitative Systems Pharmacology Models of the Coagulation Cascade: Opportunities for Improved Usability

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