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Decreased plasma sensitivity to activated protein C by oral contraceptives is associated with decreases in plasma glucosylceramide

Academic Article
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Overview

authors

  • Deguchi, H.
  • Bouma, B. N.
  • Middeldorp, S.
  • Lee, Y. M.
  • Griffin, John

publication date

  • 2005

journal

  • Journal of Thrombosis and Haemostasis  Journal

abstract

  • Oral contraceptive (OC) use increases venous thrombosis (VTE) risk and causes activated protein C (APC) resistance. Plasma glucosylceramide (GlcCer) deficiency is associated with VTE and GlcCer functions as an APC anticoagulant cofactor. Because estradiol decreases GlcCer in cultured cells, we hypothesized OC use would decrease plasma GlcCer and contribute to APC resistance. In a pilot study, seven female adults alternatively took second and third generation OCs and plasma samples were analyzed for GlcCer using high performance liquid chromatography and for APC sensitivity using modified prothrombin time assays. Second and third generation OC usage decreased the APC sensitivity ratio by 8.1% +/- 4.7% (P = 0.004) and 11.7% +/- 8.2% (P = 0.013) and plasma GlcCer levels by 10.1% +/- 6.8% (P = 0.008) and 11.0% +/- 5.1% (P = 0.002), respectively. The plasma GlcCer level correlated with the sensitivity of plasma to APC (P = 0.017, r = 0.51, n = 21 plasma samples). Thus, both second and third generation OC usage decreased plasma GlcCer which could cause a reduction in the plasma sensitivity to APC/protein S, thereby potentially increasing VTE risk.

subject areas

  • Activated Protein C Resistance
  • Chromatography, High Pressure Liquid
  • Contraceptives, Oral
  • Contraceptives, Oral, Combined
  • Desogestrel
  • Estradiol
  • Ethinyl Estradiol
  • Female
  • Glucosylceramides
  • Humans
  • Levonorgestrel
  • Pilot Projects
  • Protein C
  • Protein S
  • Prothrombin Time
  • Risk
  • Sensitivity and Specificity
  • Venous Thrombosis
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Research

keywords

  • APC resistance
  • activated protein C
  • glucosylceramide
  • oral contraceptive
  • venous thrombosis
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Identity

International Standard Serial Number (ISSN)

  • 1538-7933

Digital Object Identifier (DOI)

  • 10.1111/j.1538-7836.2005.01335.x

PubMed ID

  • 15869587
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Additional Document Info

start page

  • 935

end page

  • 938

volume

  • 3

issue

  • 5

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