title: Influence of factor VIII/von Willebrand complex on the activated protein C-resistance phenotype and on the risk for venous thromboembolism in heterozygous carriers of the factor V Leiden mutation.
abstract: High factor VIII plasma levels have been shown to represent a common increased risk for venous thromboembolism (VTE) and may cause an activated protein C (APC) resistance in the absence of the factor V Leiden mutation, but there are no studies specifically aimed to establish if high factor VIII and von Willebrand factor (vWF) concentrations may influence the APC sensitivity ratio (APC-SR) and increase the risk for VTE in the presence of the factor V Leiden mutation. For this purpose, we performed a retrospective case-control study to investigate the influence of the procoagulant factor VIII (VIII:C) and the antigen of vWF (vWF:Ag) on the normalized APC-SR (n-APC-SR) and on the risk for VTE, in two selected groups of 30 symptomatic (Group I) and 32 asymptomatic (Group II) related heterozygotes for the factor V Leiden mutation. Differences between the two groups (Group I versus Group II) were: n-APC-SR, 0.57+/-0.06 versus 0.63+/-0.08, P = 0.001; factor VIII:C, 1.49+/-0.42 versus 1.13+/-0.28 IU/ml, P<0.001; vWF:Ag, 1.46+/-0.53 versus 1.26+/-0.32 IU/ml, NS. As a whole (Group I + Group II), Pearson correlation coefficients were: n-APC-SR versus factor VIII:C, r = -0.410, P = 0.001; n-APC-SR versus vWF:Ag, r = -0.309, P = 0.01; factor VIII:C versus vWF:Ag, r = +0.640, P<0.0001. The relative risk for VTE in individuals with the factor VIII:C concentration > 1.5 IU/ml was 2.5 (95% confidence interval 1.6-3.9). We concluded that high factor VIII:C levels, probably in the effect of vWF, play a determinant role in worsening the APC-resistance phenotype and represent a common additional risk factor for VTE in heterozygous carriers of the factor V Leiden mutation.
authors.affiliation: Dipartimento di Medicina Interna, University of Bari School of Medicine, Italy. v.demitrio@hemoph.uniba.it
authors.forename: V
authors.initials: V
authors.lastname: De Mitrio
authors.forename: R
authors.initials: R
authors.lastname: Marino
authors.forename: F A
authors.initials: FA
authors.lastname: Scaraggi
authors.forename: L
authors.initials: L
authors.lastname: Di Bari
authors.forename: F
authors.initials: F
authors.lastname: Giannoccaro
authors.forename: M
authors.initials: M
authors.lastname: Petronelli
authors.forename: P
authors.initials: P
authors.lastname: Ranieri
authors.forename: N
authors.initials: N
authors.lastname: Tannoia
authors.forename: O
authors.initials: O
authors.lastname: Schiraldi
mesh_terms: D000328:Adult; D005165:Factor V / Q000235:genetics*; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011486:Protein C / Q000378:metabolism*; D012306:Risk; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D011486:Protein C; C095381:factor V Leiden; D014841:von Willebrand Factor; D005165:Factor V; D005169:Factor VIII