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 thes e events has not been well characterized. Regression of DVT has been p resumed to result from activation of the endogenous fibrinolytic syste m. This study was performed to compare measurements of the enzymatic c omponents of the intrinsic fibrinolytic system (tissue plasminogen act ivator [tPA], plasminogen activator inhibitor [PAI-1]) with the observ ed morphologic changes in thrombosed venous segments using venous dupl ex ultrasound scanning (VDUS) at intervals after diagnosis of acute DV T. Methods: Nineteen patients with acute DVT underwent serial VDUS to assess regression of thrombus at intervals of 1 to 2 weeks, 3 to 6 wee ks, 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 femor al, superficial femoral, profunda femoris, popliteal, and tibial veins . Thrombus scores for the group at each interval were compared with ba seline 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 inhibito r PAI-1. Results: Thrombus regression was evident by VDUS at 1 to 2 we eks 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 acti vity 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 populat ion at baseline (23.1 +/- 1.8 AU/ml) but remained unchanged throughout the study period. Progression of thrombus was observed in three patie nts (15.8%). Patients who experienced propagation of thrombus did not have the increased tPA activity that appeared to mark activation of in trinsic fibrinolysis. Conclusions: Regression of acute DVT begins earl y and continues for at least 9 months. It is accompanied by significan t enhancement of the endogenous fibrinolysis, which appears to be prim arily mediated by increased tPA activity. Patients who have thrombus p ropagation in spite of standard antithrombotic therapy may have failur e of activation of endogenous fibrinolysis.