Low dose infusion of adenosine diphosphate prolongs bleeding time in rats and rabbits

The effect of intravenous infusion of adenosine diphosphate (ADP) on haemostatic and thrombotic mechanisms was studied in rats and rabbits. Infusion of ADP (0.2-1 microMol/kg/min) in rabbits prolonged the skin capillary bleeding time threefold after between 1/2 and 2 hours of infusion. Prolongation of the bleeding time was parallelled by reduced in vitro sensitivity of platelets to ADP in citrated platelet-rich plasma. No major changes in respiratory frequency and heart rate were observed. On the other hand, infusion of adenosine (1 microMol/kg/min) did not affect the bleeding times. Intravenous ADP (0.1 microMol/kg/min) significantly prolonged the bleeding time in anaesthetized rats. Platelet and red cell counts before and during the ADP infusion indicated slight, reversible platelet aggregation. After 75 min the ratio between red cells and platelets resumed a steady pre-experimental level. Platinum wires placed in the abdominal aorta of rats to monitor thrombus formation during ADP infusion indicated an antithrombotic effect of prolonged, low dose infusion of ADP. Since infusion of adenosine did not affect the haemostatic mechanisms, these observations may indicate that ADP infusion desensitized the platelet responsiveness to aggregating stimuli in vivo, and/or that prostacyclin production by endothelium was stimulated by infusion of ADP.