Regression of proximal deep venous thrombosis is associated with fibrinolytic enhancement

Purpose: Recanalization after acute lower limb deep venous thrombosis (DVT) is well documented, but the precise mechanism and timing of these events has not been well characterized. Regression of DVT has been presumed to result from activation of the endogenous fibrinolytic system. This study was performed to compare measurements of the enzymatic components of the intrinsic fibrinolytic system (tissue plasminogen activator [tPA], plasminogen activator inhibitor [PAI-1]) with the observed morphologic changes in thrombosed venous segments using venous duplex ultrasound scanning (VDUS) at intervals after diagnosis of acute DVT. Methods: Nineteen patients with acute DVT underwent serial VDUS to assess regression of thrombus at intervals of 1 to 2 weeks, 3 to 6 weeks, 8 to 12 weeks, and 24 to 36 weeks. The extent of thrombus in each limb was quantitated at each interval by VDUS of the residual thrombus present in each of five major axial venous segments: the common femoral, superficial femoral, profunda femoris, popliteal, and tibial veins. Thrombus scores for the group at each interval were compared with baseline scores at diagnosis to calculate the percent residual thrombus. Endogenous fibrinolytic activity was determined at the same intervals by serologic assay of the biologic activities of tPA and its inhibitor PAI-1. Results: Thrombus regression was evident by VDUS at 1 to 2 weeks and progressed such that only 26% of residual thrombus remained at 24 to 36 weeks. Complete resolution of thrombus occurred in 10 of 18 patients (56%) who completed the 9-month study. Baseline mean tPA activity was 0.60 +/- 0.07 IU/ml and increased to 1.31 +/- 0.26 IU/ml at 1 to 2 weeks (p = 0.014). tPA activity remained significantly elevated through the 8 to 12 week interval and returned to baseline at 24 to 36 weeks. PAI-1 activity was elevated relative to an age-matched population at baseline (23.1 +/- 1.8 AU/ml) but remained unchanged throughout the study period. Progression of thrombus was observed in three patients (15.8%). Patients who experienced propagation of thrombus did not have the increased tPA activity that appeared to mark activation of intrinsic fibrinolysis. Conclusions: Regression of acute DVT begins early and continues for at least 9 months. It is accompanied by significant enhancement of the endogenous fibrinolysis, which appears to be primarily mediated by increased tPA activity. Patients who have thrombus propagation in spite of standard antithrombotic therapy may have failure of activation of endogenous fibrinolysis.