Incidence of venous thromboembolism in asymptomatic family members who are carriers of factor V Leiden: a prospective cohort study

Abstract

In a prospective cohort study, we assessed the incidence of spontaneous and risk period-related venous thromboembolism (VTE) in asymptomatic family members of patients who experienced VTE and had the factor V Leiden mutation. In all, 561 family members of 131 probands were included, 313 of whom were carriers (299 heterozygous and 14 homozygous) and 248 of whom were noncarriers of the factor V Leiden mutation. Average follow-up was 4 years (range, 4 months-6 years). There were 1255 and 984 observation-years of follow-up in carriers and noncarriers, respectively. Eight episodes of VTE occurred in heterozygous carriers, resulting in an annual incidence of 0.67% (95% confidence interval [CI], 0.29-1.33). Two events occurred in the absence of associated risk factors, determining an annual incidence of spontaneous VTE of 0.17% (95% CI, 0.02-0.6). Only one VTE (risk period-related) occurred in noncarriers, with an annual incidence of 0.1% (95% CI, 0.003-0.56). Relative risk for VTE in heterozygous carriers compared with noncarriers of the factor V Leiden mutation was 6.6 (95% CI, 1.1-39.8). Risk periodrelated VTE occurred with an incidence of 18% and 5% per risk period in heterozygous carriers and in noncarriers, respectively. Thus, the low rate of VTE in asymptomatic family members carrying the mutation did not justify continuous anticoagulant prophylaxis. Screening families of symptomatic probands with the factor V Leiden mutation has the potential to identify those asymptomatic carriers who might benefit from thromboprophylaxis during risk periods. (Blood. 2002;99: 1938-1942 © 2002 by The American Society of Hematology IntroductionFactor V Leiden mutation (factor V Arg5063Gln) is the most common genetic defect associated with an increased risk for venous thromboembolism (VTE). [1][2][3] Its prevalence in the white population is approximately 5% and is as high as 20% to 40% in patients with documented VTE, depending on selection criteria. Case-control studies have shown that heterozygous carriers of this mutation exhibit a 3-to 7-fold increased risk for VTE than healthy controls. 1,[4][5][6] The association of factor V Leiden with other coagulation abnormalities predisposing to thrombosis, including deficiencies of antithrombin, protein C, protein S, hyperhomocystinemia, and the prothrombin variant G20210A may further increase such risk. [7][8][9][10] Most persons identified as carriers of the factor V Leiden mutation as a result of family studies, however, do not exhibit other associated coagulation defects.Benefits from an early identification of carriership status among asymptomatic subjects in terms of appropriate prophylactic measures should be balanced against the disadvantage of potential bleeding complications secondary to preventive treatment and the inconvenience of labeling otherwise healthy people as having a disease. Thus, valid estimates of the absolute risk for spontaneous and risk period-related VTE in asymptomatic family members who are carriers of the factor V Leiden mutation are crucial for clinic...

VTE, Thrombophilia, Antithrombotic Therapy, and Pregnancy

“…[241][242][243] Leiden mutation [224][225][226] ( Table 7 ). [219][220][221][222][223][224][225][226][227][228]231,232 These estimates are, however, imprecise, particularly for the less common thrombophilias (see wide CIs in Table 7 ).…”

Budd-Chiari Syndrome in a Patient with JAK2V617F and Factor V G1691A Mutations

“…Our patient has a history of previous use of oral contraceptives; moreover, the product of her last pregnancy was lost. Although some authors suggest that the Factor V Leiden mutation alone is not sufficient to cause BCS, it does represent a risk factor, with a relative risk of 11 (16) and of 6.6 for venous thromboembolism (17). It is recommended that relatives of these patients should avoid situations that confer a risk for hypercoagulable states and also engage in programmes of periodic medical evaluations.…”

The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study

“…[10][11][12][13] Thrombophilic adults carry a risk of venous thromboembolic events during circumstantial risk periods (such as major trauma or surgery, immobilization, For personal use only. on April 4, 2019. by guest www.bloodjournal.org From hormonal therapy, pregnancy, or puerperium), which is significantly higher than that observed in noncarriers.…”

“…In the large majority of available family studies of thrombophilic patients, members younger than 15 years were excluded from the evaluation. [10][11][12][13] As a consequence, it is unclear whether children who are family members of symptomatic probands with thrombophilia have, in turn, an increased risk of spontaneous or risk period-related VTE. Potential benefits coming from the early identification of congenital prothrombotic abnormalities in asymptomatic children depend on valid estimates of such a risk and on whether identified carriers might benefit from some form of thromboprophylaxis when exposed to triggering factors for VTE.…”