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Analysis of thrombin generation in plasma

H Kessels¹, G Willems, H C Hemker

¹Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.

Computers in Biology and Medicine

|July 1, 1994

Summary

This study introduces a mathematical method to accurately measure free thrombin generation in plasma. The thrombin potential, derived from this method, offers valuable insights into coagulation system status for clinical applications.

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Area of Science:

Biochemistry
Hematology
Medical Diagnostics

Background:

Thrombin is a key enzyme in hemostasis, crucial for evaluating coagulation.
Measuring thrombin generation is vital for assessing the coagulation system's state.
Existing methods can be confounded by thrombin-inhibitor complexes, affecting accuracy.

Purpose of the Study:

To develop a mathematical procedure to isolate the free thrombin signal from plasma measurements.
To introduce the 'thrombin potential' as a condensed parameter for thrombin generation.
To enable accurate calculation of thrombin production and assess clinical applicability of thrombin generation tests.

Main Methods:

Utilized oligopeptide chromogenic substrates to measure thrombin activity in plasma.
Developed a mathematical model to differentiate free thrombin signal from thrombin-alpha 2-macroglobulin complex signals.
Applied continuous registration of chromogenic substrate conversion during plasma coagulation.

Main Results:

Successfully extracted the signal attributed solely to free thrombin.
Defined the time integral of free thrombin as the 'thrombin potential'.
Demonstrated a method for calculating thrombin production, accounting for inhibitor consumption.

Conclusions:

The developed mathematical procedure accurately quantifies free thrombin generation.
The thrombin potential provides a robust parameter for assessing coagulation.
Continuous measurement and analysis of thrombin generation show significant clinical potential.

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