Fibrinolytic response to cardiopulmonary bypass. CPB increases t-PA antigen and activity in a time-dependent manner. The fibrinolytic response during CPB is heterogeneous, with t-PA levels varying as much as 250-fold. The mechanism of t-PA release during CPB is likely multifactorial. As outlined above, we and others have shown that CPB increases bradykinin, a potent stimulus to t-PA release. In addition, thrombin or complement generated during CPB may stimulate the release of t-PA from endothelium. In addition to the changes in t-PA concentrations during CPB, PAI-1 activity falls because of hemodilution and the rise in t-PA release which consumes active PAI-1. Plasmin generation increases over 100-fold while D-dimer generation increases 200-fold within 5 minutes of CPB initiation. For the remainder of the CPB, average plasmin and D-dimer levels remain 20-fold to 30-fold above baseline levels. The postoperative period is marked by a systemic inflammatory response caused by a combination of CPB and surgery producing an acute -phase response that results in increased PAI-1 production. PAI-1 levels begin to rise about 2 hours after surgery. Once CPB is over, PAI-1 levels continue to rise and peak during the first 12-36 hours postoperatively and return to normal by the second postoperative day. Thus, the fibrinolytic response to CPB is characterized by an initial hyperfibrinolytic phase that begins with a rapid rise in t-PA, plasmin, and D-dimer concentrations followed by a postoperative hypofibrinolytic phase associated with a rise in PAI-1 secretion and a fall in t-PA concentrations.