Unprovoked recurrent venous thrombosis: prediction by D‐dimer and clinical risk factors

Background: The aim of the study was to determine the predictive value of D‐dimer measurement for unprovoked recurrent venous thrombosis and the influence of sex, age and type of first event (unprovoked or provoked). Methods: Prospective cohort study of 272 patients with a first episode of venous thrombosis that was unprovoked or provoked by a non‐surgical trigger. Findings: The cumulative rate of unprovoked recurrence in patients with a positive D‐dimer was 20% at 5 years [5.5/100 patient‐years, 95% confidence interval (CI) 3.7–7.8] and in patients with a negative D‐dimer 17% (4.1/100 patient‐years, 95% CI 2.3–6.9). The rates are not different (hazard ratio 1.3, 95% CI 0.7–2.5). After adjustment for clinical risk factors a positive D‐dimer result was significantly associated with an increased risk of unprovoked recurrent thrombosis (hazard ratio 2.0, 95% CI 1.01–3.9). The strongest indicator of risk of recurrence was male sex (hazard ratio 3.3 unadjusted and 2.9 after adjustment). The only determinant of D‐dimer in a linear regression model was age (P<0.001). Conclusions:The analysis indicates that clinical risk factors confound the association between D‐dimer and risk of recurrence and when adjusted for these confounders a positive D‐dimer result is significantly associated with unprovoked recurrence. The clinical utility of D‐dimer measurement in individual patients should be interpreted in conjunction with clinical risk factors.