Print Email Facebook Twitter The fibrinolytic system in the hemolytic uremic syndrome: In vivo and in vitro studies Title The fibrinolytic system in the hemolytic uremic syndrome: In vivo and in vitro studies Author van de Kar, N.C.A.J. van Hinsbergh, V.W.M. Brommer, E.J.P. Monnens, L.A.H. Gaubius Laboratory TNO Preventie en Gezondheid Instituut voor verouderings- en vaatziekten onderzoek TNO Publication year 1994 Abstract Fibrinolytic parameters and von Willebrand factor (vWF) antigen were measured in the plasma of 10 patients with hemolytic uremic syndrome (HUS). Samples were taken at presentation and again 2 wk later, before and after infusion of 1-desamino-8-arginine vasopressin. Compared with the plasma values of healthy control children, levels of tissue-plasminogen activator (t-PA) antigen, plasminogen activator inhibitor type I (PAI-1) activity, and vWF as well as fibrin(ogen) degradation products were significantly elevated in the plasma of HUS patients on admission. No response of the fibrinolytic parameters and vWF were seen when 1-desamino-8-arginine vasopressin infusion was given on admission. After 2 wk, t-PA antigen and vWF had partially returned to basal values, and t-PA antigen increased rapidly again after 1- desamino-8-arginine vasopressin infusion. To investigate whether verocytotoxin contributes to the alteration of the fibrinolytic system found in HUS patients, purified verocytotoxin-1 (VT-1) was added to the media of cultured human endothelial cells. Addition of VT-1 alone did not change the production of t-PA, plasminogen activator inhibitor type I, and vWF antigen in these cells. However, when the endothelial cells were preincubated with tumor necrosis factor-α to increase the number of VT-1 receptors, VT-1 induced a marked decrease of the synthesis of t-PA, plasminogen activator inhibitor type I, and vWF. This was caused by a decrease in overall protein synthesis in the tumor necrosis factor-α- and VT-1-treated endothelial cells. We conclude from this study that the systemic fibrinolytic parameters measured in the plasma of HUS patients are probably 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 affected. Chemicals/CAS: argipressin[1 deamino], 113-81-5; plasminogen activator inhibitor 1, 140208-23-7; tissue plasminogen activator, 105913-11-9; verotoxin, 108066-86-0; von Willebrand factor, 109319-16-6; Bacterial Toxins; Desmopressin, 16679-58-6; Fibrin Fibrinogen Degradation Products; Plasminogen Activator Inhibitor 1; Shiga-Like Toxin I; Tissue Plasminogen Activator, EC 184.108.40.206; Tumor Necrosis Factor; von Willebrand Factor Subject HealthArgipressin[1 deamino]Plasminogen activator inhibitor 1Tumor necrosis factor alphaVerotoxinBlood levelChildClinical articleEndothelium cellHemolytic uremic syndromePathogenesisPriority journalProtein synthesisBacterial ToxinsCells, CulturedChild, PreschoolDesmopressinEndothelium, VascularFemaleFibrin Fibrinogen Degradation ProductsFibrinolysisHemolytic-Uremic SyndromeHumanIn VitroInfantMalePlasminogen Activator Inhibitor 1Shiga-Like Toxin ISupport, Non-U.S. Gov'tTissue Plasminogen ActivatorTumor Necrosis Factorvon Willebrand Factor To reference this document use: http://resolver.tudelft.nl/uuid:b38b327a-e887-4b6b-84e6-846c7e5a60e9 TNO identifier 232425 ISSN 0031-3998 Source Pediatric Research, 36 (2), 257-264 Document type article Files To receive the publication files, please send an e-mail request to TNO Library.