SummaryDiarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin producing Eschericia coli. We hypothesized that verotoxin binding to glomerular endothelial cells causes localised endothelial cell activation and thus activation of coagulation and reduction of fibrinolytic potential. We also proposed that treatment with fresh frozen plasma or dialysis would not affect these changes. Markers of activation of coagulation and fibrinolysis were measured in 30 children with acute D+ HUS serially, in healthy children and in children on dialysis.In acute D+ HUS, levels of thrombin-antithrombin III complex and prothrombin fragment 1+2 were significantly increased (p <0.001). The source of thrombin generation was unclear. Factor Xlla levels were increased in patients and controls with renal failure. Factor VIIa levels were not significantly raised in children with acute D+ HUS. D-dimers were increased, but fibrinolytic potential as measured by fibrin plate was reduced. Levels of plasminogen activator inhibitor antigen and activity and tissue plasminogen activator antigen were increased.Neither peritoneal dialysis nor administration of blood products, the most common treatments, altered parameters of coagulation or fibrinolysis.

Diarrhoea-associated haemolytic uraemic syndrome (D+ HUS) is usually caused by verotoxin-producing Escherichia coli. Histology shows endothelial swelling with localised thrombus. Activation of coagulation and fibrinolysis also occurs. These facts, combined with the knowledge that recovery usually follows within weeks, led us to hypothesise that verotoxin causes localised endothelial cell activation but not injury. Markers of endothelial cell activation and injury were measured serially in 30 children with acute D+ HUS, healthy children, and children receiving chronic dialysis. Interpretation of markers was complicated by the renal dysfunction characteristic of D+ HUS. Nevertheless there was no evidence for endothelial cell injury, as soluble tissue factor levels were not increased and soluble thrombomodulin levels were lower than dialysed controls (P<0.001). In the acute phase, soluble vascular cell adhesion molecule levels were raised above normal (P<0.001), but were lower than dialysed controls (P<0.001), and soluble E-selectin levels were not significantly increased compared with normal controls (P=0.2). Hence, there was no evidence for endothelial cell damage or endothelial cell activation by the time children reached hospital; but this study did not exclude the possibility that endothelial cell activation occurred prior to hospital admission.

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SummaryA deficiency of von Willebrand factor (vWF)-cleaving protease, either due to a congenital deficiency or to the presence of a protease inhibitor of vWF-cleaving protease has been associated with thrombotic thrombocytopenic purpura (TTP). We have studied vWF-cleaving protease in diarrhoea-associated haemolytic uraemic syndrome (D+ HUS), which shares clinical features with TTP. 29 children with acute D+ HUS and 13 control children were studied.vWF-cleaving protease activity was normal (range 50-150%) in 39 of 42 plasma samples. Levels of protease activity between 25 and 50% were noted in plasma from two D+ HUS patients. One D+HUS patient, who had clinical features of TTP, had a vWF-cleaving protease inhibitor producing a severe deficiency of vWF-cleaving protease.Thus a deficiency of vWF-cleaving protease appears to be atypical in D+HUS. The detection of a vWF-cleaving protease inhibitor in one patient suggests it may be associated with infection such as E. coli 0157.

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