COMPARISON OF HEMORRHAGIC EFFECT OF HEPARIN AND HUMAN ACTIVATED PROTEIN-C WITH USE OF THROMBOSTAT-4000

The importance of bleeding as a complication of anticoagulant therapy is clearly recognized. We previously reported that amelioration of hem orrhage associated with disseminated intravascular coagulation by the human activated protein C (APC) was greater than that by heparin. In t his study, we compared the bleeding complication of intravenously admi nistered APC and heparin in rabbits, and also estimated primary hemost asis. When both anticoagulants were intravenously infused, the bleedin g time from a punctured ear vein was prolonged dose-dependently. Howev er, at doses which prolonged the activated partial thromboplastin time nearly equally, the prolongation of bleeding was greater in heparin-a dministered rabbits. Blood withdrawn from heparin-administered animals showed increases in in vitro bleeding parameters which correlated wit h the in vivo bleeding time. However, only small changes were observed in the blood withdrawn from APC-administered animals. Both drugs indu ced either no change or only a slight decrease in the platelet count, hematocrit and fibrinogen content. These observations suggest that APC may be a more useful anticoagulant than heparin since it causes less bleeding tendency.