EFFECT OF HEPARIN ON FIBRINOLYTIC-ACTIVITY AND PLATELET-FUNCTION IN-VIVO

Heparin, a polyanionic glycosaminoglycan, is used routinely before the induction of cardiopulmonary bypass. Earlier observations in our labo ratory suggested that the postoperative bleeding that occurs, despite neutralization of heparin with protamine, is secondary to hypothermia and dilutional anemia during bypass. An additional, potential mechanis m for excessive bleeding following cardiopulmonary bypass is that hepa rin activates the fibrinolytic system, which may, in turn, adversely a ffect hemostasis. To understand better the effects of heparin administ ration on the fibrinolytic system in vivo, we simulated the anticoagul ant regimen of cardiopulmonary bypass by administering increasing dose s of intravenous heparin to five adult baboons over 60 min. We measure d fibrinolytic parameters serially following heparinization and demons trated that heparin induces activation of the fibrinolytic system. We showed that the fibrinolytic system was activated in vivo as evidenced by an increase in plasmin activity and immunoreactive plasmin light c hain, as well as an increase in immunoreactive fibrinogen fragment E i n vitro. These results demonstrate that the fibrinolytic system is act ivated in vivo by the administration of heparin during cardiopulmonary bypass. These data suggest that, despite administration of a neutrali zing agent such as protamine, heparin may contribute to postoperative bleeding complications following cardiopulmonary bypass surgery owing principally to its longer lived effects on the fibrinolytic system.