d-Dimer Testing in Patients With a First Unprovoked Venous Thromboembolism

IN RESPONSE: We agree with Dr. Palareti's suggestion that exclusion of patients older than 75 years explains the fewer positive d-dimer results in our study than in the 2 earlier studies he mentions (1, 2). Dr. Palareti, however, does not report the proportion of patients younger than 76 years who had positive d-dimer results in their early studies, so this remains uncertain. The recent DULCIS study also had a higher proportion of patients with positive d-dimer results than our study (3). As Dr. Palareti notes, a higher proportion of positive d-dimer results was also present in DULCIS patients younger than 76 years. In patients younger than 70 years, DULCIS used lower d-dimer cutoffs to define a positive result than the level that corresponds to a positive Clearview Simplify d-dimer result in our study. Also in DULCIS, d-dimer levels were measured on 4 occasions after anticoagulation was stopped, compared with once in our study. These differences in testing resulted in twice as many patients having a positive d-dimer result and still receiving anticoagulant therapy as in our study. Dr. Palareti attributes the lower risk for recurrence in DULCIS patients who had negative d-dimer results to how testing was performed and interpreted. We suspect that this is not the most important reason for the lower reported risk for recurrence in DULCIS. We reported the risk for recurrent VTE separately for men and women with unprovoked VTE and for women with VTE associated with estrogen therapy. We did not enroll patients with VTE provoked by other reversible risk factors. DULCIS enrolled patients with unprovoked VTE, women with VTE associated with estrogen therapy, and patients with VTE provoked by other weak reversible risk factors. The risk for recurrence in the main DULCIS report (3) and in Dr. Palareti's letter is for all of these patients, rather than for those with unprovoked VTE. Consistent with other studies (4), DULCIS found that risk for recurrence in all patients with VTE provoked by a weak reversible risk factor was much lower than in DULCIS patients with unprovoked VTE (1.3% vs. 6.1% per patient-year; P= 0.036) (3). In fact, the risk for recurrence in the patients with unprovoked VTE in DULCIS (6.1% per patient-year for men and women combined) was similar to that in our patients with unprovoked VTE (9.7% and 5.4% per patient-year for men and women, respectively). Therefore, we suggest that that difference in the patient populations and reporting, as much as differences in how d-dimer testing was performed and interpreted, accounts for the apparently lower risk for recurrence in DULCIS.