The fibrinolytic system in the hemolytic uremic syndrome: in vivo and in vitro studies.
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-alpha 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-alpha- and VT-1-treated endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
van de Kar
N C
NC
Gaubius Laboratory, IVVO-TNO, Leiden, The Netherlands.
van Hinsbergh
V W
VW
Brommer
E J
EJ
Monnens
L A
LA
D001427:Bacterial Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D002675:Child, Preschool; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000209:etiology; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D022622:Shiga Toxin 1; D010959:Tissue Plasminogen Activator / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014841:von Willebrand Factor / Q000378:metabolism
D001427:Bacterial Toxins; D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D022622:Shiga Toxin 1; D014409:Tumor Necrosis Factor-alpha; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin