Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential

Rainer B. Zotz; Andrea Gerhardt; Cornelis Kluft; Rüdiger E. Scharf

doi:10.1160/TH04-06-0372

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(02): 306-310
DOI: 10.1160/TH04-06-0372

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Venous thromboembolism during pregnancy is not associated with persistent elevated activated protein C (APC) sensitivity ratio based on the endogenous thrombin potential

Authors

Rainer B. Zotz

¹Department of Haemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany
Andrea Gerhardt

¹Department of Haemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany
Cornelis Kluft

²Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands
Rüdiger E. Scharf

¹Department of Haemostasis and Transfusion Medicine, Heinrich Heine University Medical Center, Düsseldorf, Germany

Abstract

Summary

Women who are using oral contraceptives can acquire APC resistance, measured by the effect of APC on the endogenous thrombin potential (ETP). The objective of our study was to examine whether persistentAPC resistance determined with an ETP-based normalized APC sensitivity ratio (nAPCsr) is a risk marker for venous thromboembolism in women with pregnancy-associated thromboembolism. We determined the activities of antithrombin, protein C, protein S, and performed a genetic analysis of factor V Leiden G1691A, prothrombin mutation G20210A, and methylenetetrahydrofolate reductase mutation (MTHFR C677T) in 65 women with venous thromboembolism during pregnancy or the puerperium and in 114 normal women. A significantly (p<0.05) higher nAPCsr was present in normal women using hormones, in younger women (≤ 45 yrs), and in women with carrier status of factorV Leiden. In normal women without factor V Leiden a significant (p< 0.05) negative correlation of nAPCsr with age (r= –0.39),antithrombin activity (r= –0.38),protein S activity (r= –0,26),and a significant positive correlation with hormone intake (r= 0.36) was present. nAPCsr is influenced by several coagulation parameters, which are modified by the use of oral contraceptives. Consequently, a multivariate analysis of our data did not show a significant association of nAPCsr to venous thromboembolism, neither as a continuous variable (odds ratio 0.8, 95% CI 0.6–1.1, p=0.10) nor using a cutoff value (nAPCsr cut-off 3.1: odds ratio 1.2, 95% CI 0.3–5.3, p=0.77). Our study demonstrates that nAPCsr is not a risk marker for pregnancy-associated venous thromboembolism.

Keywords

Endogenous thrombin potential (ETP) - APC sensitivity ratio (nAPCsr) - venous thromboembolism - pregnancy

Full Text

References

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