IMPAIRED FIBRINOLYSIS IN THE HEMOLYTIC-UREMIC SYNDROME OF CHILDHOOD

Thrombotic obstruction of glomerular capillaries causes acute renal fa ilure in patients with hemolytic-uremic syndrome (HUS). Recanalization of occluded vessels normally occurs by activation of the endogenous f ibrinolytic system, mediated by plasminogen activators, which are stor ed and synthesized in the endothelial cells. However, endothelial inju ry is considered the primary event in the pathogenesis of HUS, and thi s may result in impaired fibrinolysis. In five chil dren with HUS we p erformed a prospective study of plasminogen activator activity and two plasminogen activator antigens: tissue-type plasminogen activator and urokinase-type plasminogen activator before and after intravenous des mopressin. Plasminogen activator inhibitor type-1 antigen was also stu died. In the acute stage of HUS plasminogen activating activity was lo w, in spite of elevated levels of total plasminogen activator antigens . This decrease of plasminogen activating activity was due to high lev els of the plasminogen activator inhibitor. Improvement of fibrinolysi s paralleled recovery from HUS. We conclude that decreased fibrinolysi s is an important pathophysiologic feature of HUS.