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

Summary.  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 μg 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.