Abstract
Microvascular thrombosis is considered an important pathogenetic factor in renal failure associated with OJ. Plasma levels of PA-I, measured by an amidolytic assay in 29 patients with OJ, were significantly increased as compared with 20 control patients (X ± SEM: 26.5 ± 3.5 vs 6.0 ± 1 units/ml; p < 0.001). Fibrin autography of plasma supplemented with tissue plasminogen activator (t-PA,50 IU/ml) revealed that in jaundiced samples most of the added activator migrated with an apparent Mr of 100 Kd, corresponding to t-PA-PA-I complex, whereas in control samples virtually all t-PA migrated as free enzyme. Rabbits made icteric by bile duct ligation showed an early and progressive increase in plasma PA-I activity (3- and 6-fold higher than the preoperative levels on the 3rd and 10th day respectively) indicating that OJ itself may cause a rise in circulating PA-I. Venous stasis (10 min) in jaundiced patients (n=4) was neither associated with an increase in blood fibrinolytic activity nor with a decrease in PA-I activity. t-PA antigen determination showed that activator release was impaired in 3 out of 4 patients. In controls (n=4), venous occlusion induced a rise in both fibrinolytic activity and t-PA antigen and a reduction in PA-I activity. Finally, bile duct recanalization in patients subjected to surgery (n=7) was accompanied by a decrease in plasma PA-I activity which paralleled the decrease in seric bilirubin levels. It is concluded that OJ, independently of the primary disease, may induce a marked increase in circulating PA-I and perhaps an impairment of t-PA release. Defective fibrinolysis may well contribute to microvascular thrombosis and renal failure associated with OJ.