title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Zöller
authors.forename: J
authors.initials: J
authors.lastname: Holm
authors.forename: P
authors.initials: P
authors.lastname: Svensson
authors.forename: B
authors.initials: B
authors.lastname: Dahlbäck
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D002648:Child; D004198:Disease Susceptibility; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000097:blood* / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D017354:Point Mutation; D018455:Protein S Deficiency / Q000097:blood* / Q000235:genetics; D011516:Prothrombin / Q000032:analysis*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C095381:factor V Leiden; C045879:prothrombin fragment 1.2; D014859:Warfarin; D005165:Factor V; D011516:Prothrombin