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

High factor WI plasma levels have been shown to represent a common increase d risk for venous thromboembolism (VTE) and may cause an activated protein C (APC) resistance in the absence of the factor V Leiden mutation, but ther e are no studies specifically aimed to establish if high factor VIII and vo n 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-cont rol study to investigate the influence of the procoagulant factor VIII (WI: 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 m utation. 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 ve rsus 1.26 +/- 0.32 IU/ml, NS. As a whole (Group I + Group II), Pearson corr elation 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 vW F: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 interva l 1.6-3.9). We concluded that high factor VIII:C levels, probably in the ef fect of vWF, play a determinant role in worsening the APC-resistance phenot ype and represent a common additional risk factor for VTE in heterozygous c arriers of the factor V Leiden mutation. (C) 1999 Lippincott Williams & Wil kins.