title: Thrombin generation in first-degree relatives of patients with venous thromboembolism who have factor V Leiden. A pilot study.
abstract: The thrombin generation test appears to be a highly sensitive and specific test in the detection of thrombophilia in patients with venous thromboembolism. We aimed to determine the accuracy of the thrombin generation test to detect factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden. Sixty-two first-degree relatives of 21 index cases were tested for factor V Leiden, the G20210A prothrombin gene mutation and thrombin generation. Information about oestrogen therapy and previous VTE was also collected. The normalized Thrombomodulin sensitivity ratio (n-TMsr) was defined as the ratio of endogenous thrombin potential determined in the presence and absence of thrombomodulin which was normalized against the same ratio determined in normal control plasma. The mean n-TMsr was 1.37 (+/- 0.33) in the 45 relatives with one or more prothrombotic state (factor V Leiden, G20210A prothrombin mutation, oestrogen therapy or hormonal therapy) and 1.02 (+/- 0.34) in the 17 relatives without prothrombotic state (p = 0.001). The positive predictive value was 90.3 (95%CI, 73.1-97.4). In relatives with an abnormal n-TMsr, the adjusted odds ratio for having a prothrombotic state was 8.3 (95%CI, 1.9-36.9) and the adjusted odds ratio for having the factor V Leiden was 14.3 (95%CI, 2.9-71.2). An abnormal thrombin generation test appears highly predictive for having factor V Leiden and/or other prothrombotic states in first-degree relatives of patients with venous thromboembolism and factor V Leiden.
authors.affiliation: G.E.T.B.O. (Groupe d'Etude de la Thrombose de Bretagne Occidentale), EA 3878, Department of Internal Medicine and Chest Diseases, University Hospital of Brest, Brest, France. francis.couturaud@chu-brest.fr
authors.forename: Francis
authors.initials: F
authors.lastname: Couturaud
authors.forename: Jérôme
authors.initials: J
authors.lastname: Duchemin
authors.forename: Christophe
authors.initials: C
authors.lastname: Leroyer
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Delahousse
authors.forename: Jean François
authors.initials: JF
authors.lastname: Abgrall
authors.forename: Dominique
authors.initials: D
authors.lastname: Mottier
mesh_terms: D000328:Adult; D000368:Aged; D001780:Blood Coagulation Tests / Q000379:methods*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010375:Pedigree; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D012307:Risk Factors; D013917:Thrombin / Q000378:metabolism*; D018180:Thrombomodulin / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D054556:Venous Thromboembolism / Q000097:blood / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics
chemical_list: D003278:Contraceptives, Oral, Hormonal; D018180:Thrombomodulin; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D013917:Thrombin