PROLONGED ACTIVATION OF PROTHROMBIN ON THE VASCULAR WALL AFTER ARTERIAL INJURY

This study was designed to characterize the relative roles of bound Xa /Va and thrombin activity in vascular wall procoagulant activity? afte r balloon-induced injury and the extent to which intravenous aspirin a nd heparin attenuate procoagulant activity associated with the vascula r wall. Abdominal aortic injury was induced in rabbits by overinflatio n and multiple passages of a 4F embolectomy catheter. Rabbits were kil led 15 minutes or 4, 8, 24, 48, 72, 96, or 120 hours after injury. Aor tic segments were incubated ex vivo to define bound procoagulant activ ity, Thrombin activity bound to the aorta was detected by 4 hours afte r injury and was most marked over the first 24 hours, as estimated by increases in concentration of fibrinopeptide A during incubation of se gments with recalcified barium-adsorbed plasma or activity against the thrombin-synthetic substrate S-2238. Based on comparison with purifie d human thrombin incubated under the same conditions, a maximum of 0.0 4 to 0.1 nmol/L per square centimeter of thrombin activity was associa ted with the vascular wall during the first 24 hours and remained dete ctable for 72 hours. In contrast, bound Xa/Va complex activity to inju red segments was detected within lj minutes and induced activation of prothrombin added to recalcified barium-adsorbed plasma incubated with injured segments for 96 hours. Aspirin (15 mg/kg) administered 30 min utes before injury attenuated In-111-platelet deposition at 4 hours by 67%, with an associated decrease in bound Xa/Va and thrombin activity at 15 minutes and 4 hours, However, intravenous heparin did not atten uate bound Xa/Va activity at 15 minutes or thrombin activity at 15 min utes and 4 hours. Platelet-dependent bound Xa/Va activity occurs rapid ly alter arterial injury and may promote thrombin elaboration for up t o 96 hours,Bound thrombin activity and de novo thrombin elaboration on the vascular wall may play an important role in the progression of th rombosis and vascular wall remodeling.