Elevated levels of prothrombin activation fragment 1 + 2 in plasma from patients with heterozygous Arg506 to Gln mutation in the factor V gene (APC-resistance) and/or inherited protein S deficiency.

Inherited resistance to activated protein C (APC-resistance), caused by a point mutation in the factor V gene leading to replacement of Arg(R)506 with a Gln (Q), and inherited protein S deficiency are associated with functional impairment of the protein C anticoagulant system, yielding lifelong hypercoagulability and increased risk of thrombosis. APC-resistance is often an additional genetic risk factor in thrombosis-prone protein S deficient families. The plasma concentration of prothrombin fragment 1 + 2 (F1 + 2), which is a marker of hypercoagulable states, was measured in 205 members of 34 thrombosis-prone families harbouring the Arg506 to Gln mutation (APC-resistance) and/or inherited protein S deficiency. The plasma concentration of F1 + 2 was significantly higher both in 38 individuals carrying the FV:Q506 mutation in heterozygous state (1.7 +/- 0.7 nM; mean +/- SD) and in 48 protein S deficient cases (1.9 +/- 0.9 nm), than in 100 unaffected relatives (1.3 +/- 0.5 nM). Warfarin therapy decreased the F1 + 2 levels, even in those four patients who had combined defects (0.5 +/- 0.3 nM). Our results agree with the hypothesis that individuals with APC-resistance or protein S deficiency have an imbalance between pro- and anti-coagulant forces leading to increased thrombin generation and a hypercoagulable state.
AuthorsB Zöller, J Holm, P Svensson, B Dahlbäck
JournalThrombosis and haemostasis (Thromb Haemost) Vol. 75 Issue 2 Pg. 270-4 (Feb 1996) ISSN: 0340-6245 [Print] GERMANY
PMID8815575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Peptide Fragments
  • factor V Leiden
  • prothrombin fragment 1.2
  • Warfarin
  • Factor V
  • Prothrombin
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Child
  • Disease Susceptibility
  • Factor V (genetics)
  • Factor V Deficiency (blood, genetics)
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments (analysis)
  • Point Mutation
  • Protein S Deficiency (blood, genetics)
  • Prothrombin (analysis)
  • Thromboembolism (etiology, prevention & control)
  • Warfarin (therapeutic use)

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