Deciphering the coagulation profile through the dynamics of thrombin activity

Moniek De Maat,Marisa Ninivaggi,Qiuting Yan,Bas De Laat,Romy M W De Laat-Kremers

doi:10.1038/s41598-020-69415-y

Moniek De Maat, Marisa Ninivaggi + Show 3 more

Open Access

https://doi.org/10.1038/s41598-020-69415-y

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Abstract

Thrombosis has proven to be extremely difficult to predict. Measuring the generation of thrombin is a very sensitive method to detect changes in the hemostatic system. We developed a method based on the generation of thrombin to further fingerprint hemostasis, which we have named thrombin dynamics. Via this method we are able to exactly measure the prothrombin conversion and thrombin inactivation, and any change in the coagulation cascade will be reflected in these two processes. In the current study we analyzed the importance of the members of the prothrombin complex on the dynamics of thrombin activation and inactivation. We show that prothrombin conversion is predominantly influenced by factor X and antithrombin, which will provide essential insights in complex thrombosis-related diseases, such as liver cirrhosis and kidney failure.

Highlights

Thrombin inactivation parameters, which makes it difficult to interpret the assays results clinically when a study is performed in a clinical setting
We investigated the effect of individual coagulation factors mostly belonging to the prothrombinase complex on the dynamics of thrombin activity using thrombin generation, prothrombin conversion and thrombin inactivation as read out
We investigated the effect of four major coagulation factors on five thrombin dynamics parameters (PCtot, PCmax, T-AT, T-α2M, and TDC)

Summary

Introduction

Thrombin inactivation parameters, which makes it difficult to interpret the assays results clinically when a study is performed in a clinical setting. In the case of in silico experimentation on clinical data, reference values are an important tool to define what is considered normal and what is not. Thrombin is the last enzyme of the coagulation cascade which converts fibrinogen into fibrin thereby changing the liquid blood into a solid compound. Any change in the coagulation factors will have an effect on the generation and activity of thrombin. We investigated the effect of individual coagulation factors mostly belonging to the prothrombinase complex on the dynamics of thrombin activity using thrombin generation, prothrombin conversion and thrombin inactivation as read out

Methods

Results

Conclusion