Familial Elevated Factor VIII in Children With Symptomatic Venous Thrombosis and Post-Thrombotic Syndrome: Results of a Multicenter Study

• Published in: Arteriosclerosis, thrombosis, and vascular biology Vol. 26; no. 8; pp. 1901 - 1906
• Main Authors: Kreuz, Wolfhart, Stoll, Monika, Junker, Ralf, Heinecke, Achim, Schobess, Rosemarie, Kurnik, Karin, Kelsch, Reinhard, Nowak-Göttl, Ulrike
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.08.2006; Hagerstown, MD Lippincott
• Subjects: Adolescent; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Case-Control Studies; Child; Child, Preschool; Diseases of the cardiovascular system; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Factor VIII - genetics; Factor VIII - metabolism; Female; Genetic Predisposition to Disease; Humans; Infant; Infant, Newborn; Male; Medical sciences; Osmolar Concentration; Phenotype; Postphlebitic Syndrome - blood; Postphlebitic Syndrome - genetics; Prospective Studies; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Recurrence; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels; Venous Thrombosis - blood; Venous Thrombosis - genetics; Human; Vascular disease; Body mass index; recurrent thrombosis; Multicenter study; post-thrombotic syndrome; Atherosclerosis; Factor VIII; Cardiovascular disease; Venous thrombosis; factor VIII and children; Child
• ISSN: 1079-5642; 1524-4636; 1524-4636
• DOI: 10.1161/01.ATV.0000227510.36653.ed

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-offFVIII: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.