Background: A single point mutation in the gene coding for coagulation factor V results in a form of factor Va that is resistant to degradation by activated protein C and leads to a relative hypercoagulable state. This mutation, factor V Leiden, is found in 4% to 6% of the U.S. population.
Purpose: To review clinical data on factor V Leiden mutation, with emphasis on prevalence of and risks for thromboembolism and implications for screening and management.
Data sources: A MEDLINE search of the English-language literature published between 1993 and April 1997 and an extensive bibliography review.
Study selection: Case-control and prospective cohort studies were reviewed if clinical features of thromboembolic disease associated with factor V Leiden mutation or resistance to activated protein C were presented. Original research articles were reviewed if they addressed the identification of the laboratory abnormality of activated protein C or factor V Leiden mutation. Case reports and case series were reviewed when no analytic data were available.
Data extraction: Review of the identified articles.
Data synthesis: Factor V Leiden mutation is associated with three- to sixfold increases in risks for primary and recurrent venous thromboembolism, especially in patients without transient risk factors, such as surgery or trauma. Risks for venous thromboembolism in genetically affected persons are substantially higher among patients with coexistent predispositions for thrombosis, such as advanced age, use of oral contraceptives, hyperhomocystinemia, and deficiencies of protein C and protein S. Factor V Leiden mutation does not seem to increase risks for arterial thrombosis. Whether patients with the mutation would benefit from more intense or prolonged anticoagulation is unknown.
Conclusions: The presence of factor V Leiden mutation predisposes patients to venous thromboembolism, but screening for this disorder is of uncertain utility. Decisions about whether to screen for the mutation will depend on the results of clinical trials designed to evaluate the benefit-to-risk ratio of long-term anticoagulation in the secondary prevention of venous thromboembolism in patients with resistance to activated protein C.
PIP: The factor V Leiden mutation, present in 4-6% of the US population, makes the activated form of factor V relatively resistant to degradation by activated protein C, in turn producing resistance to activated protein C. Clinical studies have suggested that factor V Leiden mutation increases the risk of venous thrombosis during pregnancy and in oral contraceptive (OC) users, but the benefit-to-risk ratio of screening for this mutation is unclear. This paper reviews English-language articles published in 1993-97 on resistance to activated protein C or the factor V Leiden mutation with regard to laboratory diagnosis, prevalence, risks for thromboembolic disease, screening, and management. Included were case-control studies, prospective cohort studies, and case reports. The literature suggests that factor V Leiden mutation is associated with 3- to 6-fold increases in risks for primary and recurrent venous thromboembolism. In genetically affected persons, this risk is substantially higher among those with co-existent predispositions for thrombosis, including advanced age, OC use, hyperhomocystinemia, and deficiencies of proteins C and S. Any decisions about screening for factor V Leiden must await clinical trials designed to evaluate the benefit-to-risk ratio of long-term anticoagulation in the secondary prevention of venous thromboembolism in patients with resistance to activated protein C.