Simioni Paolo, Tormene Daniela, Prandoni Paolo, Zerbinati Patrizia, Gavasso Sabrina, Cefalo Philip, Girolami Antonio
Department of Medical and Surgical Sciences, Second Chair of Internal Medicine, University of Padua Medical School, Via Ospedale, 105 35128-Padua, Italy.
Blood. 2002 Mar 15;99(6):1938-42. doi: 10.1182/blood.v99.6.1938.
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 period-related 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.
在一项前瞻性队列研究中，我们评估了经历静脉血栓栓塞（VTE）且携带因子V莱顿突变的患者无症状家庭成员中自发性和与风险期相关的静脉血栓栓塞的发生率。总共纳入了131名先证者的561名家庭成员，其中313名是携带者（299名杂合子和14名纯合子），248名不是因子V莱顿突变的携带者。平均随访时间为4年（范围为4个月至6年）。携带者和非携带者的随访观察年数分别为1255年和984年。杂合子携带者发生了8次VTE事件，年发生率为0.67%（95%置信区间[CI]，0.29 - 1.33）。在无相关危险因素的情况下发生了2次事件，确定自发性VTE的年发生率为0.17%（95%CI，0.02 - 0.6）。非携带者仅发生1次VTE（与风险期相关），年发生率为0.1%（95%CI，0.003 - 0.56）。与因子V莱顿突变非携带者相比，杂合子携带者发生VTE的相对风险为6.6（95%CI，1.1 - 39.8）。杂合子携带者和非携带者在每个风险期与风险期相关的VTE发生率分别为18%和5%。因此，携带该突变的无症状家庭成员中VTE发生率较低，不支持持续进行抗凝预防。对有症状先证者且携带因子V莱顿突变的家庭进行筛查，有可能识别出那些在风险期可能从血栓预防中获益的无症状携带者。
