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Resistance to activated protein C is a risk factor for pregnancy-related venous thrombosis in the absence of the F5 rs6025 (factor V Leiden) polymorphism.

Abstract
Resistance to activated protein C (aPC) is most commonly due to the F5 rs6025 (factor V Leiden) polymorphism, which increases the risk of venous thrombosis. In the present population-based study of 313 cases and 353 controls, we investigated whether reduced sensitivity to aPC was associated with a history of pregnancy-related venous thrombosis. Calibrated automated thrombography was used to determine the sensitivity to aPC, and normalized aPC sensitivity ratio (n-aPC-sr) was calculated. Pregnant women and women using oral contraceptives and/or anticoagulants were excluded due to the effect on the n-aPC-sr. In women without the F5 rs6025 polymorphism, free tissue factor pathway inhibitor (TFPI), free protein S and protein C activity were associated with n-aPC-sr. Unadjusted odds ratio for venous thrombosis for women with n-aPC-sr in the 4th quartile as compared with n-aPC-sr below the 4th quartile was 2·4 (95% confidence interval 1·7-3·6). Adjusting for free protein S, free TFPI and age did not influence the odds ratios. Also in carriers of the F5 rs6025 polymorphism the risk for venous thrombosis was increased for women with higher n-aPC-sr. Our findings substantiate the importance of the aPC resistant phenotype as a risk factor for pregnancy-related venous thrombosis.
AuthorsAstrid Bergrem, Anders Erik Astrup Dahm, Anne Flem Jacobsen, Marie-Christine Mowinckel, Leiv Sandvik, Per Morten Sandset
JournalBritish journal of haematology (Br J Haematol) Vol. 154 Issue 2 Pg. 241-7 (Jul 2011) ISSN: 1365-2141 [Electronic] England
PMID21564075 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
Copyright© 2011 Blackwell Publishing Ltd.
Chemical References
  • Protein C
  • factor V Leiden
  • Factor V
Topics
  • Activated Protein C Resistance (complications, genetics)
  • Adult
  • Case-Control Studies
  • Factor V (genetics)
  • Female
  • Humans
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Pregnancy
  • Pregnancy Complications, Cardiovascular (genetics)
  • Pregnancy Complications, Hematologic (genetics)
  • Protein C (physiology)
  • Risk Factors
  • Venous Thrombosis (etiology, genetics)
  • Young Adult

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