Document Detail

Pregnancy-associated changes in the hemostatic system in wild-type and factor V Leiden mice.
MedLine Citation:
PMID:  19036061     Owner:  NLM     Status:  MEDLINE    
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.
S N Tchaikovski; B J M van Vlijmen; A C A Cleuren; M C L G D Thomassen; V Tchaikovski; G Tans; J Rosing
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of thrombosis and haemostasis : JTH     Volume:  7     ISSN:  1538-7836     ISO Abbreviation:  J. Thromb. Haemost.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-13     Completed Date:  2009-05-15     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  101170508     Medline TA:  J Thromb Haemost     Country:  England    
Other Details:
Languages:  eng     Pagination:  312-8     Citation Subset:  IM    
Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands.
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MeSH Terms
Activated Protein C Resistance / diagnosis,  etiology*
Biological Markers / blood
Factor V*
Lipoproteins / blood*
Pregnancy Complications, Hematologic / blood
Protein S / analysis*
Species Specificity
Reg. No./Substance:
0/Biological Markers; 0/Lipoproteins; 0/Protein S; 0/factor V Leiden; 0/lipoprotein-associated coagulation inhibitor; 9001-24-5/Factor V

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