Elevated PAI-1 and F1.2 levels in children with Escherichia coli O157:H7 related hemolytic urémie syndrome

Approximately 10% of children infected with Escherichia coli O157:H7 develop the hemolytic urémie syndrome (HUS), a microangiopathic hemolytic anemia. To study the prothrombotic changes that occur in this disease, we obtained citrated blood samples from 18 children (mean 4 years old, range 1 to 8 years) with E. coli O157:H7 infection. Overall, 6 of the 18 children (33%) developed clinical HUS (hemolytic anemia, thrombocytopenia and renal impairment). Compared to children that did not develop HUS, children with HUS had evidence of coagulation activation (F1.2 1.3±0.4 vs6.0±3.8 nmol/L, P = 0.0005), suppression of fibrinolysis (PAI-1 activity 3±3 vs 21±12 U/mL, P = 0.0001) and increased thrombus formation (D-dimer 0.9±0.4vs 18.3±17.6ng/mL,P = 0.003). Overall, the level of D-dimer was positively correlated with both Fl .2 (r2 = 0.53) and PAI-1 activity (r² = 0.73). The strongest correlation though was between D-dimer and the product of F1.2 × PAI-1 activity (r2 = 0.96). While elevated D- dimer levels indicate fibrinolysis is occurring, high PAI-1 activity correlated with high D-dimers suggests that reduced fibrinolytic activation favors more rapid thrombus accretion, which in turn leads to a greater volume of clot to lyse and thus elevated D-dimers. We conclude that children with E. coli O157:H7 associated HUS have both an activated coagulation system and a suppressed fibrinolytic system which in turn leads to increased microthrombi and elevated D-dimers.