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.
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.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
[Show abstract][Hide abstract] ABSTRACT: Venous thromboembolism (VTE) is a leading cause of maternal mortality and morbidity during pregnancy in developed countries. The incidence of VTE per pregnancy-year increases about 4-fold during pregnancy and at least 14-fold during the puerperium. Risk factors include a personal history of VTE, presence of inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilisation, overweight, varicose veins, some haematological diseases and inflammatory disorders. VTE is considered potentially preventable with the prophylactic administration of anticoagulants, but there are no high quality randomized clinical trials that compared different strategies of thromboprophylaxis in pregnant women. Balancing the absolute risk of VTE against the risks of exposure to anticoagulants, this review provides advice regarding which women may benefit from thromboprophylaxis during and after pregnancy.
Thrombosis Research 02/2012; 129(6):673-80. DOI:10.1016/j.thromres.2012.01.017 · 2.45 Impact Factor
"This mutation paved the way for the concept of VTE as a complex disease (Rosendaal, 1999). Indeed, penetrance is low, with only 10% of F5 R506Q heterozygotes and 80% of homozygotes developing thrombosis in their lifetime, with varying severity among affected individuals (Middeldorp et al, 1998). "
[Show abstract][Hide abstract] ABSTRACT: Venous thromboembolism (VTE) is a frequent disease that has a major genetic component of risk. However, known identified genetic risk factors account for <30% of idiopathic (without any environmental origin) VTE cases. This article aims to review the lessons learnt during recent decades in the field of the genetics of VTE, describe the present state-of-art methods and discuss promising themes for finding new susceptibility loci.
British Journal of Haematology 11/2009; 148(4):495-506. DOI:10.1111/j.1365-2141.2009.07975.x · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Many inherited thrombophilias have been detected and the pathophysiologic insight has increased tremendously during the last decades. Despite, however, the overwhelming observational evidence on the association between inherited thrombophilia and several women's health issues, including VTE, thus far the implications for clinical practice are uncertain. Although there is firm epidemiologic evidence that is helpful in counseling women who have inherited thrombophilia to prevent a first or recurrent VTE, the uncertainty is particularly present for women who have other pregnancy complications, such as recurrent pregnancy loss and pre-eclampsia. For this group, well-designed placebo-controlled trials to assess the harm-benefit ratio are urgently needed.
Obstetrics and Gynecology Clinics of North America 10/2006; 33(3):357-74. DOI:10.1016/j.ogc.2006.05.011 · 1.38 Impact Factor