deamino-arginine-vasopressin and Coronary-Thrombosis

The interaction between von Willebrand factor (VWF) and platelet glycoprotein Ibalpha (GPIbalpha) is a critical step that allows platelet adhesion, activation and subsequent thrombus formation to the injured vessel wall under high-shear conditions. In this study, we sought to investigate 1) whether GPG-290, a recombinant human GPIbalpha chimeric protein, would prevent thrombosis in a canine model of coronary thrombosis by blocking VWF-GPIbalpha interaction; and 2) whether desmopressin (DDAVP), a VWF release stimulant, could reduce the prolonged bleeding time caused by a 10x efficacious dose of GPG-290. The antithrombotic efficacy of GPG-290 was evaluated by the in-vivo ability to prevent cyclic flow reductions (CFRs) and ex-vivo inhibition of platelet adhesion/aggregation reflected by prolongation of Platelet Function Analyzer (PFA-100) collagen/ADP closure time. The anti-hemostatic effect was assessed by template bleeding time. GPG-290 at doses of 25, 50 and 100 microg/kg abolished CFRs in 67%, 100% and 100% of the treated dogs without bleeding time prolongation, respectively; GPG-290 dose-dependently prolonged the ex-vivo collagen/ADP-closure time, while it had no effects on plasma VWF antigen level (VWF:Ag) and VWF-collagen binding activity (VWF:CB); the prolonged template bleeding time caused by 500 microg/kg of GPG-290 was prevented by intravenous infusion of DDAVP (0.3 microg/kg). In conclusion, GPG-290 appears to be an effective agent for treating arterial thrombosis without bleeding time prolongation.

Topics: Animals; Bleeding Time; Coronary Thrombosis; Deamino Arginine Vasopressin; Dogs; Dose-Response Relationship, Drug; Humans; Membrane Glycoproteins; Membrane Proteins; Platelet Activation; Platelet Function Tests; Platelet Glycoprotein GPIb-IX Complex; Recombinant Fusion Proteins; von Willebrand Factor

Topics: Adult; Case-Control Studies; Coronary Thrombosis; Deamino Arginine Vasopressin; Endothelium, Vascular; Fibrinolysis; Forearm; Hemostatics; Humans; Hypertension; Infusions, Intra-Arterial; Male; Methacholine Chloride; Middle Aged; Parasympathomimetics; Plasminogen Activator Inhibitor 1; Tissue Plasminogen Activator

Topics: Aminocaproates; Antithrombin III Deficiency; Coronary Artery Bypass; Coronary Thrombosis; Deamino Arginine Vasopressin; Heparin; Humans; Male; Middle Aged

Topics: Adult; Coronary Thrombosis; Deamino Arginine Vasopressin; Fatal Outcome; Hemophilia A; Humans; Male

Topics: Adult; Coronary Thrombosis; Deamino Arginine Vasopressin; Fatal Outcome; Hemophilia A; Hip Prosthesis; Humans; Male; Premedication

Topics: Coronary Disease; Coronary Thrombosis; Deamino Arginine Vasopressin; Humans; Myocardial Infarction