Venous Thrombotic Risk in Family Members of Unselected Individuals with Factor V Leiden

Abstract

SummaryThe factor V Leiden mutation (FVL) leads to a seven-fold increased risk of venous thromboembolism (VTE). In thrombophilic families, 25% of carriers have experienced thrombosis before the age of 40 years. Aim of our study was to assess the association of FVL with VTE in first-degree family members of unselected symptomatic and asymptomatic carriers of FVL.We tested 197 relatives of consecutive thrombosis patients with FVL and 36 relatives of asymptomatic carriers on the presence of FVL and the occurrence of VTE.The incidence of VTE in relatives with FVL of symptomatic carriers was 0.34%/year. This was similar to the incidence in relatives with FVL of asymptomatic carriers. Kaplan Meier analysis in relatives of symptomatic propositi showed that at the age of 58 years, thrombosisfree survival was reduced to 75% in carriers and 93% in non-carriers (P < 0.05). Carriers of FVL had a three times higher thrombotic risk than non-carriers. In combination with environmental risk factors, FVL clearly adds to the risk of VTE. The thrombotic incidence rate in these unselected relatives with FVL, however, is considerably lower than was seen in carriers of thrombophilic families (1.7%/year). Therefore, special care should be paid to individuals with a positive family history of venous thrombosis while exposed to these risk factors.

The risk of venous thromboembolism in family members with mutations in the genes of factor V or prothrombin or both

“…However, when the analysis was limited to the 273 kindreds whose proband had a first episode of venous thromboembolism, excluding those presenting with SVT or arterial thrombosis, the results did not substantially change. This finding is in agreement with a recent observation on a similar annual incidence of venous thromboembolism in carriers of factor V Leiden belonging to families whose probands had venous thromboembolism or were asymptomatic (Lensen et al, 2000).…”

Factor V Leiden thrombophilia

“…The absolute incidence of VTE ranged from 0.19%/year to 0.49%/year, compared with 0.05%/year to 0.10%/year in individuals without the mutation. 37,63,182,183 VTE occurred in 7-12% of relatives with Factor V Leiden heterozygosity, compared with 2-3% of relatives without the mutation, consistent with other estimates that the lifetime risk for thrombosis is approximately 10%. Multiple prospective cohort studies found a similar low incidence of VTE in asymptomatic Factor V Leiden heterozygotes, in the range of 0.1%/year-0.67%/year.…”

“…35 The lifetime risk of VTE is higher (25-40%) in heterozygotes from thrombophilic families. 36,37 Heterozygosity for Factor V Leiden is not associated with an increase in mortality or reduction in normal life expectancy. 38,39 …”

“…At least 50% of thrombotic episodes in individuals with Factor V Leiden are provoked by additional predisposing factors. 37 In a large cohort of symptomatic Factor V Leiden homozygotes, the initial VTE was associated with circumstantial risk factors in 81% of women and 29% of men. Oral contraceptives and pregnancy were the most common predisposing factors in symptomatic women.…”

“…In a study of unselected families with Factor V Leiden, surgery was a common predisposing factor for VTE in relatives with the mutation. 37 Several studies suggested the mutation was associated with a 5-fold increased risk of symptomatic VTE after orthopedic and other surgery. 41,146,147 Factor V Leiden heterozygotes undergoing surgery had an approximately 13-fold higher risk for upper extremity DVT than controls with neither risk factor.…”