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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:1901.)
© 2006 American Heart Association, Inc.

Thrombosis

Familial Elevated Factor VIII in Children With Symptomatic Venous Thrombosis and Post-Thrombotic Syndrome

Results of a Multicenter Study

Wolfhart Kreuz; Monika Stoll; Ralf Junker; Achim Heinecke; Rosemarie Schobess; Karin Kurnik; Reinhard Kelsch; Ulrike Nowak-Göttl

From the Department of Paediatric Haematology, Oncology, and Haemostaseology (W.K.), University Children’s Hospital, Frankfurt/Main; the Leibniz Institute for Arteriosclerosis Research, Department of Genetic Epidemiology (M.S.), University of Münster; the Institute of Clinical Chemistry and Laboratory Medicine (R.J.), University of Münster; the Coordination Centre for Clinical Trials (A.H.), University Hospital, Münster; the Department of Paediatrics (R.S.), University Children’s Hospital, Halle; the Department of Paediatrics (K.K.), University Children’s Hospital, Munich; the Department of Blood Transfusion Medicine (R.K.), University of Münster; and the Department of Paediatric Haematology/Oncology (U.N.-G.), University Children’s Hospital, Münster, Germany.

Correspondence to U. Nowak-Göttl, University Children’s Hospital, Paediatric Haematology and Oncology, Albert-Schweitzer-Str. 33, 48149 Münster, Germany. E-mail leagottl{at}uni-muenster.de

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.

Case–control study measuring FVIII in children experiencing DVT. FVIII values were elevated in patients. The odds ratio for FVIII above the 90th percentile was increased in DVT patients. The heritable(h2)/household(c2) components were calculated for FVIII:Ag levels (h2, 0.48±0.15; c2, 0.21), and FVIII:C (h2, 0.61±0.15; c2, 0.41).

Key Words: factor VIII and children • body mass index • venous thrombosis • post-thrombotic syndrome • recurrent thrombosis

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