title: Cellular origin and procoagulant properties of microparticles in meningococcal sepsis.
abstract: Patients with meningococcal sepsis generally suffer from disseminated intravascular coagulation (DIC). The aim of this study was to address whether these patients have elevated numbers of circulating microparticles that contribute to the development of DIC. Plasma samples from 5 survivors, 2 nonsurvivors, and 5 healthy volunteers were analyzed for the presence of microparticles by flow cytometry. Ongoing coagulation activation in vivo was quantified by enzyme-linked immunosorbent assay of plasma prothrombin fragment F(1 + 2), and procoagulant properties of microparticles in vitro were estimated by thrombin-generation assay. On admission, all patients had increased numbers of microparticles originating from platelets or granulocytes when compared with controls (P =.004 and P =.008, respectively). Patients had elevated levels of F(1 + 2) (P =.004), and their microparticles supported thrombin generation more strongly in vitro (P =.003) than those of controls. Plasma from the patient with the most fulminant disease course and severe DIC contained microparticles that expressed both CD14 and tissue factor, and these microparticles demonstrated extreme thrombin generation in vitro. We conclude that patients with meningococcal sepsis have elevated numbers of circulating microparticles that are procoagulant. These findings may suggest a novel therapeutic approach to combat clinical conditions with excessive coagulation activation.
authors.affiliation: Department of Clinical Chemistry, Leiden University Medical Center, Leiden, The Netherlands. rnieuwland@ckcl.azl.nl
authors.forename: R
authors.initials: R
authors.lastname: Nieuwland
authors.forename: R J
authors.initials: RJ
authors.lastname: Berckmans
authors.forename: S
authors.initials: S
authors.lastname: McGregor
authors.forename: A N
authors.initials: AN
authors.lastname: Böing
authors.forename: F P
authors.initials: FP
authors.lastname: Romijn
authors.forename: R G
authors.initials: RG
authors.lastname: Westendorp
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: A
authors.initials: A
authors.lastname: Sturk
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D001779:Blood Coagulation Factors / Q000032:analysis*; D001792:Blood Platelets / Q000648:ultrastructure*; D002648:Child; D002675:Child, Preschool; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology* / Q000401:mortality; D005260:Female; D006098:Granulocytes / Q000648:ultrastructure*; D006801:Humans; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008297:Male; D008589:Meningococcal Infections / Q000097:blood* / Q000150:complications / Q000401:mortality; D010316:Particle Size; D018805:Sepsis / Q000097:blood* / Q000150:complications / Q000401:mortality; D017741:Survivors; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*; D013925:Thromboplastin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D001779:Blood Coagulation Factors; D018950:Lipopolysaccharide Receptors; C045071:leukocyte procoagulant activity; C049426:platelet procoagulant factor; D013925:Thromboplastin; D013917:Thrombin