Factors that Predict Risk of Thrombosis in Relatives of Patients with Unprovoked Venous Thromboembolism

Abstract

Conclusion: Unprovoked venous thromboembolism (VTE) occurring at a young age is associated with increased risk of VTE in families of patients with VTE. Summary: About one-quarter of all VTE is idiopathic or “unprovoked.” One-third of these patients will have identified genetic predispositions to thrombosis. The factor V-Leiden and G20210A prothrombin gene mutations account for 90% of detected genetic abnormalities (Lancet 2003;138:19-25). If a genetic mutation is not identified in a patient with VTE, it is often assumed that relatives do not have increased risk of thrombosis. Such an assumption may not be true, however, because it is likely there are many causes of heredity thrombophilia that have yet to be discovered. The authors' primary hypothesis was at the risk of VTE would be similar in families of patients who had factor V-Leiden or the G20210A prothrombin gene mutation compared with relatives of patients with neither of these two abnormalities. The authors assumed that most patients with unprovoked VTE, who have negative tests for thrombophilia, do in fact have hereditary defects that have yet to be discovered and that these abnormalities would increase the risk of thrombosis in the patient's first-degree relatives. This was a cross-sectional study. Investigators were blinded to whether patients or their relatives had thrombophilia. The prevalence of previous venous VTE in 1916 first-degree relatives of 348 unselected patients with a first episode of unprovoked VTE was investigated. Patient characteristics and the presence of factor V-Leiden or the G20210A prothrombin gene mutation was assessed as predictors of VTE in the patient's first-degree relatives. The first-degree relatives had sustained 102 previous episodes of VTE (prevalence 5.3%). Patient thrombosis at a young age was the strongest predictor of VTE in relatives. There was an odds ratio (OR) of 3.27 (95% confidence interval [CI], 1.68-6.38) for younger patients (patients aged <45 when VTE occurred; lowest quartile) compared with older patients (patients aged >71; highest quartile). The presence of factor V-Leiden or G20210A prothrombin gene mutation was a weak independent predictor of VTE in relatives (adjusted OR, 1.48; 95% CI, 0.94-2.33). Comment: The data indicate that the age of patients with unprovoked VTE is probably the single best way to stratify the risk of VTE in those patients' families. Testing for factor V-Leiden or the G20210A prothrombin gene mutation in a patient with unprovoked VTE has limited ability to predict VTE in first-degree relatives. The data also provide indirect evidence that there are undiscovered hereditary thrombophilic abnormalities in many patients with unprovoked VTE.