Relation between D-dimer level, venous valvular reflux and the development of post-thrombotic syndrome after deep vein thrombosis

Background: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. Objective: To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients. Methods: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24 months. D-dimer was measured at 4 months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12 months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. Results: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0 mu g L-1; P = 0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P = 0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P = 0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P = 0.01). Conclusion: D-dimer levels, measured 4 months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.