Objective: To evaluate the role of factor (F) VIII in children with non-cancer related venous thrombosis (DVT), post-thrombotic syndrome (PTS) or recurrent DVT.
Methods and results: FVIII levels were measured in White patients and age- and gender-matched healthy controls. Heritability of factor VIII was estimated in 99 pedigrees by the variance component method implemented in SOLAR. The group of 103 patients showed higher median values of FVIII than 206 controls [FVIII:Ag, 115 versus 96 IU/dL, P<0.0001; FVIII:C, 119 versus 106 IU/dL, P=0.0009], and had a significantly increased odds ratio (OR) for fibrinogen-adjusted elevated FVIII levels [FVIII >90th percentile versus values below the cut-off: FVIII:Ag, OR 4.3, 95% confidence interval (CI) 1.5 to 12.1; FVIII:C, OR 5.5, CI 2.03 to 15.06]. PTS occurred in 19 of 59 children and persisted in 5 individuals. Recurrent DVT was seen in 8 patients. The heritable(h2)/household(c2) components were calculated for FVIII:Ag levels (h2, 0.48+/-0.15, P=0.0008; c2, 0.21), and FVIII:C (h2, 0.61+/-0.15, P<0.0001; c2, 0.41). When incorporating h2 and c2 in the estimate, the phenotypic variance for FVIII:Ag levels is predominantly explained by h2, whereas c2 stayed significant in the model for FVIII:C (P=0.00002).
Conclusions: Elevated FVIII levels increase the DVT-risk in children.