THROMBOSIS AND HEMOSTASIS Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli–induced hemolytic uremic syndrome

Hemolytic uremic syndrome (HUS) is commonly associated with Shiga toxin (Stx)– producing Escherichia coli O157:H7 infection. This study examined patient samples for complement activation on leukocyteplatelet complexes and microparticles, as well as donor samples for Stx and lipopolysaccharide (O157LPS)–induced complement activation on plateletleukocyte complexes and microparticles. Results, analyzed by flow cytometry, showed that whole blood from a child with HUS had surface-bound C3 on 30% of platelet-monocyte complexes compared with 14% after recovery and 12% in pediatric controls. Plasma samples from 12 HUS patients were analyzed for the presence of microparticles derived from platelets, monocytes, and neutrophils. Acute-phase samples exhibited high levels of platelet microparticles and, to a lesser extent, monocyte microparticles, both bearing C3 and C9. Levels decreased significantly at recovery. Stx or O157LPS incubated with donor whole blood increased the population of plateletmonocyte and platelet-neutrophil complexes with surface-bound C3 and C9, an effect enhanced by costimulation with Stx and O157LPS. Both Stx and O157LPS induced the release of C3and C9bearing microparticles from platelets and monocytes. Released microparticles were phagocytosed by neutrophils. The presence of complement on plateletleukocyte complexes and microparticles derived from these cells suggests a role in the inflammatory and thrombogenic events that occur during HUS. (Blood. 2011;117(20):5503-5513)