The significance of hypofibrinolysis for the risk of recurrence of venous thromboembolism. Duration of Anticoagulation (DURAC) Trial Study Group.
An impaired fibrinolytic function has been described in several case-control studies of patients with venous thromboembolism (VTE). In the present study the correlations between some fibrinolytic compounds and future recurrent VTE were investigated. Blood samples for analysis of tissue-type plasminogen activator (t-PA) antigen before and after 10 min of venous occlusion (V.O.) and plasminogen activator inhibitor type 1 (PAI-1) activity were taken at 6 months after the first episode of VTE or the first recurrent VTE in 784 and 207 patients, respectively, who were anticoagulated for 1.5 or 6 months (first VTE) and 6 months or indefinitely (first recurrence). During a follow-up of 3-6 years from the event which qualified for inclusion there have been 177 recurrences. All initial and recurrent events were verified with objective diagnostic methods. Using cut off points of 10.0 ng/ml for t-PA antigen before V.O. and 30 AU/ml for PAI-1 in samples taken at rest, there were more patients above those levels in the groups with than without further recurrence (t-PA antigen, 50% versus 36%, p = 0.001; PAI-1, 18% versus 12%, p = 0.045). In the 495 patients, who received oral anticoagulation for 6 months, t-PA antigen at rest discriminated better, with 59% versus 34% of patients above 10 ng/ml in the groups with and without recurrence, respectively (p < 0.001). The t-PA antigen levels after V.O. and the fibrinolytic capacity (t-PA antigen after V.O. minus t-PA antigen before V.O.) were distributed similarly in patients with and without new recurrences. There was a statistically significant positive correlation between age and t-PA antigen (p < 0.001), and by analysis of covariance the difference between the groups with and without further recurrence regarding t-PA antigen disappeared. In conclusion, increased levels of PAI-1 and t-PA antigen in VTE-patients correlate with development of recurrent VTE within the next 3-6 years, but the value of these components in predicting future events for the individual patients is limited.
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