title: Prothrombin G20210A carriers the genetic mutation and a history of venous thrombosis contributes to thrombin generation independently of factor II plasma levels.
abstract: BACKGROUND
  The prothrombin (PT) G20210A gene mutation is a common risk factor for venous thrombosis (VT), which is mainly mediated through an increase in factor II (FII) plasma levels. High FII plasma levels may act through an increase in endogenous thrombin potential (ETP) a key step in hemostasis and thrombosis. While FII may be the main contributor to ETP in PT G20210A carriers, the knowledge of other environmental or genetic factors influencing ETP may help to better identify those at risk of VT.
  
  
  OBJECTIVE
  ETP was determined in 472 non-carriers of PT G20210A (PT-) and in 325 unrelated carriers of PT G20210A (PT+) with (symptomatic n = 158) or without (asymptomatic, n = 167) a history of VT. All PT+ were heterozygous and free of other thrombophilic defects.
  
  
  RESULTS
  ETP was higher in asymptomatic PT+ than in PT- (2038 +/- 371 vs. 1616 +/- 267 nmol L(-1) min; P < 0.0001). ETP was significantly higher in symptomatic PT+ than in controls PT+ (2129 +/- 430 vs. 2038 +/- 371 nmol L(-1) min; P = 0.01). Multivariate analyses evidenced the importance of FII and fibrinogen plasma levels in determining ETP.
  
  
  CONCLUSIONS
  After taking these variables into account, a personal history of VT remained associated with ETP in PT+ carriers. Moreover, PTG20210A still contributes to ETP after consideration of FII levels.
  
  
  CONCLUSIONS
  In conclusion, the increase in ETP observed in carriers is not entirely explained by higher FII or fibrinogen plasma levels but also by the history of VT.
authors.affiliation: INSERM U626, Université de la Méditerranée, Marseille.
authors.forename: G
authors.initials: G
authors.lastname: Lavigne-Lissalde
authors.forename: C
authors.initials: C
authors.lastname: Sanchez
authors.forename: C
authors.initials: C
authors.lastname: Castelli
authors.forename: S
authors.initials: S
authors.lastname: Alonso
authors.forename: E
authors.initials: E
authors.lastname: Mazoyer
authors.forename: C
authors.initials: C
authors.lastname: Bal Dit Sollier
authors.forename: L
authors.initials: L
authors.lastname: Drouet
authors.forename: I
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: J C
authors.initials: JC
authors.lastname: Gris
authors.forename: M C
authors.initials: MC
authors.lastname: Alessi
authors.forename: P E
authors.initials: PE
authors.lastname: Morange
mesh_terms: D000328:Adult; D005260:Female; D006580:Genetic Carrier Screening; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism*; D013917:Thrombin / Q000096:biosynthesis*; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D011516:Prothrombin; D013917:Thrombin