Tissue-type plasminogen activator and fibrin monomers synergistically cause platelet dysfunction during retransfusion of shed blood after cardiopulmonary bypass.

Reduced hemostasis and bleeding tendency after cardiopulmonary bypass results from platelet dysfunction induced by the bypass procedure. The causes of this acquired platelet dysfunction are still subject to discussion, although, recently, greater emphasis has been placed on an overstimulated fibrinolytic system as a probable cause. In the first part of this study we assessed the effects of postoperative retransfusion of shed blood on blood loss to patients undergoing cardiopulmonary bypass. We observed that increasing concentrations of fibrinogen degradation products and tissue-type plasminogen activator stimulating activity in shed blood correlated significantly with a higher postoperative bleeding tendency (p < 0.05 for both). We further noted that retransfusion of shed blood increased the total postoperative blood loss by 43% (925 versus 1320 ml, p < 0.05). On the basis of these clinical observations, we hypothesized that the increased bleeding tendency was caused by fibrinolysis. In the second part of this study we collected evidence in support of this hypothesis by an in vitro study, in which we introduced similar (pro)fibrinolytic activity to platelet-rich plasma and measured the influence of this treatment on platelet function indicated by ristocetin agglutination. Tissue-type plasminogen activator and fibrin monomers (tissue-type plasminogen activator stimulator) together induced severe platelet damage, resulting in a decreased ristocetin agglutination response. Therefore, we propose a fibrinolysis-related mechanism for platelet dysfunction during cardiopulmonary bypass, dependent on fibrinolytic factors such as fibrin monomers, D-dimers, and tissue-type plasminogen activator.