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Pregnancy‐associated changes in the hemostatic system in wild‐type and factor V Leiden mice
Author(s) -
TCHAIKOVSKI S. N.,
VAN VLIJMEN B. J. M.,
CLEUREN A. C. A.,
THOMASSEN M. C. L. G. D.,
TCHAIKOVSKI V.,
TANS G.,
ROSING J.
Publication year - 2009
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2008.03240.x
Subject(s) - protein c , pregnancy , medicine , tissue factor pathway inhibitor , endocrinology , protein s , antithrombin , activated protein c resistance , immunology , thrombosis , factor v leiden , venous thrombosis , biology , coagulation , tissue factor , heparin , genetics
Summary. Background: Pregnancy, oral contraceptive (OC) use and hormone replacement therapy (HRT) are established risk factors for venous thrombosis. Acquired resistance to activated protein C (APC) has been proposed to contribute to the increased thrombosis risk. Mouse models are often used for preclinical testing of newly developed hormone preparations. However, it is not known whether hormone‐induced APC resistance is also observed in laboratory animals. Objectives: To investigate whether hormonal changes modulate APC resistance in mice, we used pregnant mice as a model of hormone‐induced APC resistance. The effect of pregnancy on APC resistance was studied in wild‐type and factor (F)V Leiden mice. Methods: APC resistance was determined in mouse plasma using a thrombin generation‐based APC resistance test. APC resistance determinants, i.e. prothrombin, FV, FX, antithrombin and protein S levels, and of tissue factor pathway inhibitor (TFPI) activity were evaluated in plasma from non‐pregnant and pregnant mice. Results: In contrast to humans, pregnancy induced a decrease in APC resistance in wild‐type and in FV Leiden mice. Pregnant mice had higher levels of prothrombin, FV, FX, protein S and TFPI activity as compared with non‐pregnant mice. Conclusions: Pregnancy causes a decrease in APC resistance in mice, which can be explained by the elevation of protein S levels and increased TFPI activity in plasma. Our findings show species specificity in the effects of pregnancy on the major determinants of the protein C system and suggest that protein S and TFPI play an important role in the development of pregnancy‐induced APC resistance in humans.