THE FIBRINOLYTIC SYSTEM IN THE HEMOLYTIC-UREMIC SYNDROME - IN-VIVO AND IN-VITRO STUDIES

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were m easured in the plasma of 10 patients with hemolytic uremic syndrome (H US). Samples were taken at presentation and again 2 wk later, before a nd after infusion of l-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasmi nogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation product s were significantly elevated in the plasma of HUS patients on admissi on. No response of the fibrinolytic parameters and vWF were seen when l-desamino-8-arginine vasopressin infusion was given on admission. Aft er 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after l-desamino-8-arginine v asopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, pu rified verocytotoxin-l (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the producti on of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated wi th tumor necrosis factor-or to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen a ctivator inhibitor type I, and vWF. This was caused by a decrease in o verall protein synthesis in the tumor necrosis factor-alpha-VT-1-treat ed endothelial cells. We conclude from this study that the systemic fi brinolytic parameters measured in the plasma of HUS patients are proba bly not a direct effect of VT-1 on the endothelium but are sequelae of the disease in which the intestine and the kidney are predominantly a ffected.