Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model.

The in vivo antithrombotic properties of human plasma activated protein C (APC), a natural anticoagulant enzyme, were investigated in a baboon model of thrombus formation on prosthetic vascular grafts. Infusion of 0.25 to 1.1 mg/kg/h purified, human, APC inhibited blood clotting, as measured by the activated partial thromboplastin time (APTT), and reduced vascular graft platelet deposition by 40% to 70%, as determined by the real-time scintillation camera imaging of 111In-labeled platelet deposition. APC infusion also preserved graft patency. Hemostatic plug formation remained normal, as measured by the template bleeding times. These results suggest that APC administration may produce immediate antithrombotic effects under arterial flow conditions.

[1]  B. Lämmle,et al.  Immunoblotting studies of the molecular forms of protein C in plasma. , 1988, Thrombosis research.

[2]  C. Mitchell,et al.  A fatal thrombotic disorder associated with an acquired inhibitor of protein C. , 1987, The New England journal of medicine.

[3]  S. Hanson,et al.  Baboon Models of Acute Arterial Thrombosis , 1987, Thrombosis and Haemostasis.

[4]  A. Chang,et al.  Protein C prevents the coagulopathic and lethal effects of Escherichia coli infusion in the baboon. , 1987, The Journal of clinical investigation.

[5]  R. Schaub,et al.  Human protein C induces anticoagulation and increased fibrinolytic activity in the cat. , 1986, Thrombosis research.

[6]  G. Blaskó,et al.  Functional deficiency of protein C and skin necrosis in multiple myeloma. , 1986, Thrombosis research.

[7]  S. Hanson,et al.  Platelet Interactions with Dacron Vascular Grafts: A Model of Acute Thrombosis in Baboons , 1985, Arteriosclerosis.

[8]  S. Hanson,et al.  Studies of Suloctidil in Experimental Thrombosis in Baboons , 1985, Thrombosis and Haemostasis.

[9]  C. Esmon,et al.  Recurrent venous thromboembolism in patients with a partial deficiency of protein S. , 1984, The New England journal of medicine.

[10]  L. Harker,et al.  Thrombin stimulates tissue plasminogen activator release from cultured human endothelial cells. , 1984, The Journal of clinical investigation.

[11]  M. Colucci,et al.  Influence of protein C activation on blood coagulation and fibrinolysis in squirrel monkeys. , 1984, The Journal of clinical investigation.

[12]  S. Rapaport,et al.  Homozygous protein C deficiency manifested by massive venous thrombosis in the newborn. , 1984, The New England journal of medicine.

[13]  J. Griffin,et al.  Plasma protein S deficiency in familial thrombotic disease. , 1984, Blood.

[14]  J. Katz,et al.  INHERITED PROTEIN C DEFICIENCY AND COUMARIN-RESPONSIVE CHRONIC RELAPSING PURPURA FULMINANS IN A NEWBORN INFANT , 1983, The Lancet.

[15]  R. Marlar,et al.  Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme , 1982 .

[16]  C. Esmon,et al.  Generation of fibrinolytic activity by infusion of activated protein C into dogs. , 1981, The Journal of clinical investigation.

[17]  J. Griffin,et al.  Deficiency of protein C in congenital thrombotic disease. , 1981, The Journal of clinical investigation.

[18]  C. Esmon,et al.  Identification of an endothelial cell cofactor for thrombin-catalyzed activation of protein C. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Emekli Nb,et al.  The protective effect of autoprothrombin II - anticoagulant on experimental DIC in animals. , 1980 .

[20]  F. Walker.  Regulation of activated protein C by a new protein. A possible function for bovine protein S. , 1980, The Journal of biological chemistry.

[21]  E. Davie,et al.  Preparation and properties of bovine factor VIII (antihemophilic factor). , 1980, Biochemistry.

[22]  N. Emekli,et al.  The protective effect of autoprothrombin II - anticoagulant on experimental DIC in animals. , 1980, Haematologica.

[23]  W. Kisiel.  ISOLATION, CHARACTERIZATION, AND MECHANISM OF ACTIVATION BY a-THROMBIN , 1979 .