title: Comparison of hemorrhagic effect of heparin and human activated protein C with use of Thrombostat 4000.
abstract: The importance of bleeding as a complication of anticoagulant therapy is clearly recognized. We previously reported that amelioration of hemorrhage associated with disseminated intravascular coagulation by the human activated protein C (APC) was greater than that by heparin. In this study, we compared the bleeding complication of intravenously administered APC and heparin in rabbits, and also estimated primary hemostasis. When both anticoagulants were intravenously infused, the bleeding time from a punctured ear vein was prolonged dose-dependently. However, at doses which prolonged the activated partial thromboplastin time nearly equally, the prolongation of bleeding was greater in heparin-administered rabbits. Blood withdrawn from heparin-administered animals showed increases in in vitro bleeding parameters which correlated with the in vivo bleeding time. However, only small changes were observed in the blood withdrawn from APC-administered animals. Both drugs induced 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.
authors.affiliation: Pharmaceutical Development Research Laboratories, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Katsuura
authors.forename: H
authors.initials: H
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Kiyoki
authors.forename: A
authors.initials: A
authors.lastname: Funatsu
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000633:toxicity*; D001760:Bleeding Time; D001780:Blood Coagulation Tests / Q000295:instrumentation*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004789:Enzyme Activation; D005340:Fibrinogen / Q000032:analysis; D006400:Hematocrit; D006470:Hemorrhage / Q000139:chemically induced*; D006493:Heparin / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D010314:Partial Thromboplastin Time; D010976:Platelet Count / Q000187:drug effects; D011486:Protein C / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D011817:Rabbits
chemical_list: D000925:Anticoagulants; D011486:Protein C; D005340:Fibrinogen; D006493:Heparin