Cellular origin and procoagulant properties of microparticles in meningococcal sepsis

Patients with meningococcal sepsis generally suffer from disseminated intra vascular coagulation (DIC), The aim of this study was to address whether th ese patients have elevated numbers of circulating microparticles that contr ibute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurv ivors, and 5 healthy volunteers were analyzed for the presence of micropart icles by flow cytometry, Ongoing coagulation activation in vivo was quantif ied by enzyme-linked immunosorbent assay of plasma prothrombin fragment F12, and procoagulant properties of microparticles in vitro were estimated by thrombin-generation assay. On admission, ail patients had increased number s of micro particles originating from platelets or granulocytes when compar ed with controls (P = .004 and P = .008, respectively). Patients had elevat ed levels of F1+2 (P = .004), and their microparticles supported thrombin g eneration more strongly in vitro (P = .003) than those of controls. Plasma from the patient with the most fulminant disease course and severe DIC cont ained microparticles that expressed both CD14 and tissue factor, and these microparticles demonstrated extreme thrombin generation in vitro, We conclu de that patients with meningococcal sepsis have elevated numbers of circula ting microparticles that are procoagulant. These findings may suggest a nov el therapeutic approach to combat clinical conditions with excessive coagul ation activation. (C) 2000 by The American Society of Hematology.