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Determinants of the APTT- and ETP-based APC sensitivity tests
M C H de Visser1, A van Hylckama Vlieg, G Tans
1Department of Hematology, Hemostasis and Thrombosis Research Center, Leiden University Medical Center, Leiden, The Netherlands. M.C.H.deVisser@lumc.nl
Journal of Thrombosis and Haemostasis : JTH
|June 28, 2005
Summary
Activated protein C (APC) resistance, a risk factor for venous thrombosis, is influenced by clotting factor levels. The APTT-based test is mainly affected by Factor VIII and Factor II, while the ETP-based test is influenced by free protein S and TFPI.
Area of Science:
- Hematology
- Thrombosis Research
- Coagulation Science
Background:
- Reduced sensitivity to activated protein C (APC) increases venous thrombosis risk, independent of Factor V Leiden mutation.
- Two APC sensitivity tests, one based on activated partial thromboplastin time (APTT) and another on endogenous thrombin potential (ETP), quantify APC resistance.
Purpose of the Study:
- To identify the determinants of APC sensitivity tests in a control group.
- To investigate the influence of various coagulation factors and oral contraceptive use on APC sensitivity.
Main Methods:
- Multiple linear regression analysis was used to assess the relationship between APC sensitivity test results and levels of coagulation factors.
- Normalized APC-SR(APTT) and APC-SR(ETP) were dependent variables, with coagulation factors and inhibitors as independent variables.
Main Results:
- Factor VIII and Factor II levels were major determinants for the APTT-based APC sensitivity test.
- Free protein S and free tissue factor pathway inhibitor (TFPI) levels were the primary influences on the ETP-based APC sensitivity test.
- FXa formation plays a significant role in both tests, mediating the effects of FVIII and TFPI.
Conclusions:
- The determinants of APC sensitivity tests differ, with FVIII and FII for APTT-based, and free protein S and free TFPI for ETP-based tests.
- Oral contraceptive use significantly impacts the ETP-based test, suggesting mechanisms beyond the investigated coagulation factor levels.
- The molecular basis of acquired APC resistance associated with oral contraceptive use requires further investigation.