Purpose: Current anticoagulation guidelines suggest that the length of anticoagulation (AC) for unprovoked venous thromboembolism (VTE) should be determined by an individual risk assessment, balancing bleeding risk due to AC with the risk of VTE recurrence. Among individuals who are heterozygous for the factor V Leiden (FVL) mutation, however, not only is VTE risk greater, but the risk for bleeding is lower, suggesting standard recommendations may not apply and longer term AC be considered.
Methods: We constructed a Markov model to compare lifetime anticoagulation vs. shorter durations in 20-year-old FVL patients with an unprovoked VTE. Risks of major, minor, and fatal bleeding with and without AC, VTE morbidity and mortality, and quality of life utilities were obtained from the literature. We used sensitivity analyses to determine model parameter values favoring lifelong AC in FVL patients. Outcomes are in quality adjusted life years (QALYs), discounted at 3%/yr.
Results: In general population groups (where VTE relative risk and odds ratio for AC-related bleeding are 1.0), the short-term AC strategy has 0.17 QALYs more than lifetime AC. In FVL patients, lifetime AC was favored if their VTE relative risk was > 1.1 or if their bleeding odds ratio was <0.85. A 2-way sensitivity analysis shows the effects of varying those parameters (Figure). Results were relatively insensitive to variation of other parameter values.
Conclusion: Lifelong anticoagulation may result in greater benefit than risk in individuals with FVL and previous idiopathic VTE; however, further research better documenting FVL-specific bleeding risk and recurrent VTE risk is needed.
