von Willebrand factor-cleaving protease in childhood diarrhoea-associated haemolytic uraemic syndrome. Hunt BJ, Lammle B, Nevard CH, Haycock GB, Furlan M. Thrombosis and Haemostasis 2001;85(6):975-978.

A 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). The authors studied vWF-cleaving protease in diarrhea-associated hemolytic uremic syndrome (D+ HUS), which shares clinical features with TTP, in 29 children with acute D+ HUS and 13 control children. The D+HUS children ranged in age between 6 months and 16 years (mean 4 years). All children made a full recovery except one patient who died of gastrointestinal obstruction caused by sepsis. The control patients ranged in age from 6 months to 18 years (median 14 years) and were significantly older than the D+HUS children. These control patients were on chronic dialysis. 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 with a positive stool culture for E. coli O157H:7, who had clinical features of TTP, had a vWF-cleaving protease inhibitor producing a severe deficiency of vWF-cleaving protease. At age 5 years, this child and family members had normal levels of vWF-cleaving protease. There were no episodes of TTP recurrence and renal function was within normal limits three years after recovery. 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 O157.