Delayed administration of tissue plasminogen activator reduces intra-abdominal abscess formation

Previous studies demonstrated that intraperitoneal fibrinolysis using tissue plasminogen activator (t-PA) prevented intraabdominal abscess formation in a rat fibrin clot infection model when administered simultaneously with the infecting inoculum. To more closely mimic the clinical setting, the efficacy of delayed administration of t-PA on intra-abdominal abscess formation was examined. A delay of 2, 6, and 18 hours had no effect on the rate of abscess formation but did reduce abscess size, indicating partial fibrinolysis. Since fibrin clots dehydrate in vivo, we hypothesized that a higher concentration of t-PA might be necessary to effect complete abscess resolution. High-dose t-PA (0.1 mg/mL) prevented abscess formation following a 6-hour delay and reduced mean weight following an 18-hour delay. Since heparin sodium may prevent new fibrin deposition and enhance t-PA activity, it was combined with t-PA to investigate potential synergistic effects. Despite adequate anticoagulation with heparin, no synergy with t-PA could be documented. In addition, the combination of antibiotics with t-PA did not affect its efficacy in vivo. We demonstrate that delayed administration of t-PA is effective in preventing abscess formation and may have implications for the clinical setting where initial surgical intervention is usually delayed.