title: High factor VIII levels contribute to the thrombotic risk in families with factor V Leiden.
abstract: Factor V Leiden (FVL)-carrying relatives of selected patients with venous thromboembolism (VTE) have much higher venous thrombotic risks than FVL-carrying relatives of unselected consecutive patients with VTE. To find an explanation for this, we explored other risk factors of VTE, in particular the presence of high factor VIII levels, in a retrospective follow-up study. We assessed levels of factor VIII, factor IX, fibrinogen, protein C, protein S, antithrombin, the presence of prothrombin 20210A, and the occurrence of VTE in 61 first-degree relatives of 12 selected thrombophilic families harbouring FVL, and 183 first-degree relatives of 47 unselected families of FVL carriers with a first VTE. In all families, FVL appeared to be an independent risk factor for VTE. Higher thrombosis incidence rates were found in carriers of both FVL and high factor VIII levels (> or = 150 IU/dl), while high levels of factor VIII appeared to be an independent thrombotic risk factor only in selected thrombophilic families. The fraction of individuals with more than one prothrombotic coagulation disorder was 10% higher in selected families. These results and the higher thrombotic risks we found in the thrombophilic families favour the hypothesis that other unknown co-existing genetic defects contribute to thrombophilia.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Lensen
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
authors.forename: J P
authors.initials: JP
authors.lastname: Vandenbroucke
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005165:Factor V; D005169:Factor VIII; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics / Q000401:mortality
chemical_list: C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII