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Circulating activated protein C in subjects with heterozygous GIn506-factor V

Academic Article
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Overview

authors

  • Petaja, J.
  • Hakala, L.
  • Rasi, V.
  • Griffin, John

publication date

  • January 1998

journal

  • Haemostasis  Journal

abstract

  • Congenital resistance to activated protein C due to a point mutation in the factor V gene (Gln506-FV) is the most common genetic risk factor for familial venous thrombosis. Considering the central role of activated protein C as a physiological anticoagulant, the question of why the thrombotic risk associated with Gln506-FV was not more pronounced was asked. We hypothesized that in Gln506-FV heterozygotes, enhanced thrombin formation might preferentially activate protein C and thereby constitute a compensatory antithrombotic effect. We compared the circulatory level of activated protein C in twelve heterozygous carriers of Gln506-FV mutation with that in eighteen noncarriers in same families, and used prothrombin fragment 1+2 as a measure of thrombin generation. The circulating level of activated protein C was higher but not significantly different in heterozygotes compared with normal relatives. Activated protein C levels correlated strongly and positively with protein C antigen levels in both carriers (Spearman R 0.684, p < 0.05) and controls (Spearman R 0.642, p < 0.01). Correlation between activated protein C and prothrombin fragment 1+2 levels was of borderline significance (Spearman R 0.354, p = 0.055). In the current study, thrombin formation assessed by prothrombin fragment 1+2 levels was not significantly enhanced in subjects with heterozygous Gln506-FV compared with family members without the mutation. In conclusion, enhanced thrombin formation is not present in all healthy Gln506-FV heterozygotes in basal conditions. It seems that enhanced protein C activation by thrombin does not constitute a compensatory anticoagulant feedback loop in heterozygous carriers of Gln506-FV. However, the positive correlation between prothrombin fragment 1+2 and activated protein C suggests that, in healthy subjects and in basal conditions, thrombin upregulates the anticoagulant protein C pathway. Thus, it is questionable whether prothrombin fragment 1+2 can directly be used as an indicator of a hypercoagulable state.

subject areas

  • Adolescent
  • Adult
  • Aged
  • Enzyme Activation
  • Factor V
  • Female
  • Genetic Carrier Screening
  • Glutamine
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Protein C
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Research

keywords

  • activated protein C
  • activated protein C resistance
  • factor V
  • factor V Leiden
  • prothrombin fragment 1+2
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Identity

International Standard Serial Number (ISSN)

  • 0301-0147

PubMed ID

  • 9885368
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Additional Document Info

start page

  • 31

end page

  • 36

volume

  • 28

issue

  • 1

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