Middeldorp S, Henkens C M, Koopman M M, van Pampus E C, Hamulyák K, van der Meer J, Prins M H, Büller H R
Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Ann Intern Med. 1998 Jan 1;128(1):15-20. doi: 10.7326/0003-4819-128-1-199801010-00003.
The factor V Leiden mutation is a genetic defect associated with an increased incidence of venous thromboembolism. When the incidence of venous thromboembolism in relatives of patients known to have the mutation outweighs the disadvantages of prophylactic strategies, family screening may be necessary.
To determine the incidence of venous thromboembolism in first-degree relatives of symptomatic carriers of the factor V Leiden mutation.
Retrospective blinded study.
University hospitals.
437 first-degree relatives of 112 heterozygous propositi and 30 relatives of 6 homozygous propositi.
Before DNA testing, information on previous venous thromboembolism and concomitant risk factors was obtained. Relatives with and without the FV: Q506 mutation were compared.
The annual incidence of thromboembolism in relatives of heterozygous propositi was 0.45% (95% CI, 0.28% to 0.61%) in those with the mutation and 0.10% (CI, 0.02% to 0.19%) in those without the mutation (relative risk, 4.2 [CI, 1.8 to 9.9]). Among carriers, the incidence increased from 0.25% (CI, 0.12% to 0.49%) in the 15- to 30-year-old age group to 1.1% (CI, 0.24% to 3.33%) in persons older than 60 years of age. Half of the episodes of venous thromboembolism occurred spontaneously, 20% were related to surgery, and 30% were associated with pregnancy or use of oral contraceptives.
The observed low annual risk for venous thromboembolism in persons carrying the factor V Leiden mutation does not seem to outweigh the risks for bleeding associated with coumarin prophylaxis or justify discouragement of the use of oral contraceptives. A general policy of screening the families of all patients with the factor V Leiden mutation does not seem to be indicated. The observations in this moderate-size, retrospective study need to be confirmed by prospective follow-up studies.
凝血因子V莱顿突变是一种与静脉血栓栓塞发生率增加相关的基因缺陷。当已知有该突变的患者亲属中静脉血栓栓塞的发生率超过预防策略的弊端时，可能需要进行家族筛查。
确定凝血因子V莱顿突变症状携带者的一级亲属中静脉血栓栓塞的发生率。
回顾性盲法研究。
大学医院。
112名杂合子先证者的437名一级亲属和6名纯合子先证者的30名亲属。
在进行DNA检测之前，获取有关既往静脉血栓栓塞和伴随危险因素的信息。对有和没有FV:Q506突变的亲属进行比较。
杂合子先证者亲属中，有突变者的血栓栓塞年发生率为0.45%（95%CI，0.28%至0.61%），无突变者为0.10%（CI，0.02%至0.19%）（相对危险度，4.2[CI，1.8至9.9]）。在携带者中，发生率从15至30岁年龄组的0.25%（CI，0.12%至0.49%）增加到60岁以上人群的1.1%（CI，0.24%至3.33%）。一半的静脉血栓栓塞事件为自发发生，20%与手术有关，30%与妊娠或口服避孕药的使用有关。
凝血因子V莱顿突变携带者中观察到的静脉血栓栓塞年风险较低，似乎并未超过香豆素预防相关的出血风险，也不足以成为不鼓励使用口服避孕药的理由。对所有凝血因子V莱顿突变患者的家族进行筛查的总体政策似乎并不合适。这项中等规模的回顾性研究中的观察结果需要前瞻性随访研究加以证实。
