title: Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis.
abstract: Elevated levels of coagulation factor VIII:C (FVIII:C) are associated with an increased risk for venous and arterial thromboembolism. Whether relatives of patients with elevated levels of FVIII:C are also at increased risk for thrombotic disease is unknown. The objective was to determine the annual incidences of both venous and arterial thrombotic events in first-degree relatives of patients with elevated levels of FVIII:C and venous thromboembolism (VTE) or premature atherosclerosis. A retrospective study with 584 first-degree relatives of 177 patients with elevated levels of FVIII:C was performed. The level of FVIII:C was determined and relatives with elevated and normal levels of FVIII:C were compared. Of the participants, 40% had elevated levels of FVIII:C. The annual incidence of a first episode of VTE was 0.34% and 0.13% in relatives with elevated levels of FVIII:C and those with normal levels, respectively [OR 3.7 (95% CI 1.9-7.5)]. The absolute annual incidence in the youngest age group with elevated levels of FVIII:C was 0.16% (0.05-0.37) and gradually increased to 0.99% (0.40-2.04) in those older than 60 years of age, although the odds ratios were not statistically significant. The annual incidences of a first arterial thrombotic event were 0.29% and 0.14% in relatives with and without elevated levels of FVIII:C, respectively [OR 3.1 (1.4-6.6)]. In particular the risks for a first myocardial infarction [OR 4.3 (1.0-18.1); P =0.046] and a first peripheral arterial thrombosis [OR 8.6 (1.6-47.6)] were increased. Within families of patients with elevated levels of FVIII:C and VTE or premature atherosclerosis, 40% of their first-degree relatives has elevated levels of FVIII:C as well, and they are at increased risk for both VTE and arterial thrombosis as compared with their relatives with normal levels.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. I.Bank@amc.uva.nl
authors.forename: I
authors.initials: I
authors.lastname: Bank
authors.forename: E J
authors.initials: EJ
authors.lastname: Libourel
authors.forename: S
authors.initials: S
authors.lastname: Middeldorp
authors.forename: K
authors.initials: K
authors.lastname: Hamulyák
authors.forename: E C M
authors.initials: EC
authors.lastname: van Pampus
authors.forename: M M W
authors.initials: MM
authors.lastname: Koopman
authors.forename: M H
authors.initials: MH
authors.lastname: Prins
authors.forename: J
authors.initials: J
authors.lastname: van der Meer
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D001161:Arteriosclerosis; D005169:Factor VIII / Q000096:biosynthesis*; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000150:complications; D016017:Odds Ratio; D011247:Pregnancy; D012189:Retrospective Studies; D012306:Risk; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology; D020246:Venous Thrombosis / Q000097:blood* / Q000209:etiology
chemical_list: C078147:F8 protein, human; D005169:Factor VIII