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Measuring thrombin generation based sensitivity to activated protein C using an automated coagulometer (ACL 9000)
C Gardiner1, S J Machin, I J Mackie
1Department of Haematology, University College London, London, UK. chris.gardiner@uchevaluation.co.uk
International Journal of Laboratory Hematology
|July 31, 2008
Summary
A new automated test measures sensitivity to activated protein C (APC), a risk factor for thrombosis. This test, using thrombin generation, identifies individuals susceptible to blood clots.
Area of Science:
- Biochemistry
- Hematology
- Thrombosis Research
Background:
- Increased thrombin generation with activated protein C (APC) is a known thrombosis risk factor.
- Existing thrombin generation assays lack sensitivity to APC.
Purpose of the Study:
- To develop and validate an automated thrombin generation assay for measuring APC sensitivity.
- To establish normal reference ranges for the APC sensitivity test.
Main Methods:
- Developed an automated thrombin generation assay using a chromogenic substrate and specific reagents.
- Tested defibrinated plasma with and without APC (5 nm) using an automated coagulometer (ACL9000).
- Measured endogenous thrombin potential (ETP) with (ETP(+APC)) and without APC (ETP), expressed as a ratio.
Main Results:
- Established normal reference ranges for ETP (0.73-1.06) and ETP(+APC) (0.42-1.07) in 30 healthy subjects.
- Demonstrated that ETP(+APC) is sensitive to factor V Leiden, oral contraceptive use, low protein S, tissue factor pathway inhibitor, and elevated factor VIII.
- The developed assay provides a novel method for assessing APC sensitivity.
Conclusions:
- The automated APC sensitivity test is a viable tool for assessing thrombosis risk.
- This assay can identify individuals with genetic or acquired conditions affecting APC function.
- Further research can explore its clinical utility in managing thrombotic disorders.
