PAI-1 and t-PA/PAI-1 Complex Potential Markers of Fibrinolytic Bleeding After Cardiac Surgery Employing Cardiopulmonary Bypass

Agnese Ozolina; Eva Strike; Inta Jaunalksne; Angelika Krumina; Lars J Bjertnaes; Indulis Vanags


BMC Anesthesiol. 2012;12(27) 

In This Article


Increased per – and postoperative bleeding remains to be a serious problem in cardiac surgery. Alterations in hemostasis per - and postoperatively may have a diversity of etiologies. These include the surgery per se as well as effects of the cardiopulmonary bypass (CPB) on the coagulation and the inflammation cascades, and their cross-reactions with the fibrinolytic – and the kinin-kallikrein systems.[1–3] During the last few years, increasing attention has been paid to reports demonstrating the influence of the fibrinolytic system on increased bleeding, particularly after cardiac surgery employing CPB.[1,4–6]

Plasminogen, alpha-2 antiplasmin, tissue plasminogen activator (t-PA) and urinary type plasminogen activator are the main fibrinolytic components of plasma. The generation of plasmin is mainly regulated by processes involving t-PA and its counterpart plasminogen activator inhibitor type – 1 (PAI-1), which blocks the conversion of plasminogen to plasmin, thus inhibiting fibrinolysis.[7,8] PAI-1 is a serine protease, which is synthesized in platelets as well as in endothelium and adipose tissues.[9] PAI-1 binds rapidly with a ratio of 1:1 to t-PA forming a stable t-PA/PAI-1 complex, which is cleared from the circulation by macrophages in the liver. The rate of formation of the t-PA/PAI-1 complex depends on the plasma concentrations of the two proteins: the higher the concentrations of t-PA and PAI-1, the more complex will be formed in the circulation.[10]

Cardiac surgery employing CPB is associated with increased fibrinolytic activity and enhanced concentrations of PAI-1 and D-dimer as compared to off-pump surgery.[11–13] However, inter-individual variations in PAI-1 and t-PA/PAI-1 complex formation are relatively large. After normal primary hemostasis, low PAI-1 and low t-PA/PAI-1 complex plasma concentrations, may result in hyperfibrinolytic hemorrhage.[8] This implies that clots are primarily formed, but fibrinolysis occurs readily since the half-life of PAI-1 is short and the process might lead to relative lack of inhibitor to abate the plasmin activity.

We hypothesize that control of the fibrinolytic system pre – and postoperatively strengthen the possibilities of predicting enhanced bleeding after cardiac surgery. Therefore, our aim was to assess fibrinolytic activity pre- and postoperatively in patients undergoing cardiac surgery with the use of CPB.