Elevated levels of FVIII:C within families are associated with an increased risk for venous and arterial thrombosis.
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.
Bank
I
I
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. I.Bank@amc.uva.nl
Libourel
E J
EJ
Middeldorp
S
S
Hamulyák
K
K
van Pampus
E C M
EC
Koopman
M M W
MM
Prins
M H
MH
van der Meer
J
J
Büller
H R
HR
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
C078147:F8 protein, human; D005169:Factor VIII