A Critical Review of the Evidence Supporting a Relationship Between Impaired Fibrinolytic Activity and Venous Thromboembolism

We critically evaluated the evidence for an association between venous thromboembolism and impaired fibrinolytic activity, as determined by global tests of fibrinolytic activity or specific tests for tissue plasminogen activator and plasminogen activator inhibitor. A computer-assisted and manual search was performed to retrieve all articles that reported on fibrinolytic activity and venous thromboembolism. The strength of the evidence for an association was assessed by analysis of the design of individual studies with special attention directed to choice of controls and methods of diagnosis of venous thromboembolism. It is concluded that for patients with symptomatic thrombosis the published evidence does not prove an association between impaired fibrinolytic activity and increased risk of thrombosis. In contrast, for postoperative thrombosis there is good evidence for an association between impaired fibrinolytic activity measured either preoperatively or postoperatively and increased risk of postoperative thrombosis. Whether this association is causal or coincidental is unclear, since randomized clinical trials that used interventions to enhance fibrinolytic activity produced inconsistent results.