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Thromb Haemost 2002; 88(01): 5-11
DOI: 10.1055/s-0037-1613145
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Schattauer GmbH

Effects of Hereditary and Acquired Risk Factors of Venous Thrombosis on a Thrombin Generation-Based APC Resistance Test

Joyce Curvers
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
M. Christella L. G. D. Thomassen
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
Janet Rimmer
2   Sheffield Hemophilia and Thrombosis Center, Royal Hallamshire Hospital, Sheffield, United Kingdom
,
Karly Hamulyak
3   Department of Haematology, University Hospital Maastricht, Maastricht University, Maastricht, Groningen, The Netherlands
,
Jan van der Meer
4   Division of Haemostasis, Thrombosis and Rheology, University Hospital Groningen, Groningen, The Netherlands
,
Guido Tans
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
,
F. Eric Preston
2   Sheffield Hemophilia and Thrombosis Center, Royal Hallamshire Hospital, Sheffield, United Kingdom
,
Jan Rosing
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received 14 November 2002

Accepted 02 March 2002

Publication Date:
09 December 2017 (online)

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Summary

Background

Several hereditary and acquired risk factors for venous thromboembolism (VTE) are associated with impaired down-regulation of thrombin formation via the protein C pathway. To identify individuals at risk, functional tests are needed that estimate the risk to develop venous thrombosis.

Method

We determined the effects of hereditary and acquired risk factors of venous thrombosis on an APC resistance test that quantifies the influence of APC on the time integral of thrombin formation (the endogenous thrombin potential, ETP) initiated in plasma via the extrinsic coagulation pathway. APC sensitivity ratios (APCsr) were determined in plasma from carriers of factor VLeiden (n = 56) or prothrombin G20210A (n = 18), of individuals deficient in antithrombin (n = 9), protein C (n = 7) or protein S (n = 14) and of women exposed to acquired risk factors such as hormone replacement therapy (n = 49), oral contraceptive use (n = 126) or pregnancy (n = 35). We also analysed combinations of risk factors (n = 60).

Results

The thrombin generation-based APC resistance test was sensitive for the factor VLeiden and prothrombin G20210A mutation, to protein S deficiency, hormone replacement therapy, oral contraceptive use and pregnancy. The assay was not influenced by antithrombin-or protein C deficiency. The presence of more than one risk factor of venous thrombosis resulted in more pronounced APC resistance. The APCsr of individuals with a single or combined risk factors of VTE correlated well with reported risk increases.

Interpretation

The thrombin generation-based APC resistance test identifies individuals at risk for venous thrombosis due to acquired risk factors and/or hereditary thrombophilic disorders that affect the protein C pathway.

Keywords

Hereditary APC resistance - acquired APC resistance - thrombin generation-based test
 

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