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

Abstract

Summary. Factor V Leiden and the G20210A mutation in the prothrombin gene are the most frequent abnormalities associated with venous thromboembolism. It is unknown whether the risks due to the presence of either mutation are of the same magnitude. We compared the prevalence and incidence rate of venous thromboembolism in relatives with either mutation or both. The finding of different rates might influence the strategies for primary prevention of thrombosis in carriers of these mutations. The study population included 1076 relatives of probands with the prothrombin gene mutation, factor V Leiden or both who underwent screening for inherited thrombophilia and were found to be carriers of single mutations or double mutations or who were non-carriers. The prevalence of venous thromboembolism was 5´7% in relatives with the prothrombin gene mutation, 7´8% in those with factor V Leiden, 17´1% in those with both mutations and 2´5% in non-carriers. Annual incidences of thrombosis were 0´13% [95% confidence interval (CI) 0´06±0´24], 0´19% (0´13±0´25), 0´42% (0´15±0´83) and 0´066% (0´03±0´11), respectively, and the relative risk of thrombosis was two times higher in carriers of the prothrombin gene mutation, three times higher in those with factor V Leiden and six times higher in double carriers than in non-carriers. The incidence of venous thromboembolism in carriers of the prothrombin gene mutation is slightly lower than that observed in carriers of factor V Leiden, whereas in carriers of both mutations it is two or three times higher. These findings suggest that lifelong primary anticoagulant prophylaxis of venous thromboembolism is not needed in asymptomatic carriers of single or double mutations. Anticoagulant prophylaxis seems to be indicated only when transient risk factors for thrombosis coexist with mutations.

Factor V Leiden, prothrombin G20210A substitution and hormone therapy: indications for molecular screening

“…Heterozygous carriers constitute approximately 2% of the general Caucasian population, and reach 20% in the population with recurrent or familial thrombotic events (47,48). Heterozygous subjects for the G20210A mutation carry an estimated two-to five-fold increased risk of venous thrombosis without other concomitant risk factors, and a more than additive synergistic risk of VTE when other thrombophilic risk factors, particularly factor V Leiden, are simultaneously present (47)(48)(49). The risk of VTE is remarkably increased in women heterozygous for prothrombin G20210A polymorphism who are taking OC (37)(38)(39)(50)(51)(52).…”

The G20210A prothrombin gene mutation: is there room for screening families?

“…Although several case‐control and family studies suggest that prothrombin gene mutation G20210A (PT G20210A) is associated with an increased risk of venous thrombosis [1–5], the clinical relevance of the identification of heterozygous carriers of this mutation in daily practice is still under discussion. The benefits coming from an early identification of a carriership status among asymptomatic subjects in terms of appropriate prophylaxis measures should be balanced against the costs involved and the inconvenience of labeling otherwise healthy people as having ‘a disease’.…”

The incidence of venous thromboembolism in carriers of antithrombin, protein C or protein S deficiency associated with the HR2 haplotype of factor V: a family cohort study

“…Because of the high prevalence of these two genetic polymorphisms, the gene‐to‐gene and gene‐to‐environment interaction is likely to play a major role in the development of thromboembolic complications. Several case–control and family studies have indeed shown a higher thrombotic risk in carriers of both defects than in carriers of a single polymorphism [1–6].…”