title: Platelet-monocyte aggregate formation and mortality risk in older patients with severe sepsis and septic shock.
abstract: BACKGROUND
  Aging-related changes in platelet and monocyte interactions may contribute to adverse outcomes in sepsis but remain relatively unexamined. We hypothesized that differential platelet-monocyte aggregate (PMA) formation in older septic patients alters inflammatory responses and mortality.
  
  
  METHODS
  We prospectively studied 113 septic adults admitted to the intensive care unit with severe sepsis or septic shock. Patients were dichotomized a priori into one of two groups: older (age ≥ 65 years, n = 28) and younger (age < 65 years, n = 85). PMA levels were measured in whole blood via flow cytometry within 24 hours of admission. Plasma levels of IL-6 and IL-8, proinflammatory cytokines produced by monocytes upon PMA formation, were determined by commercial assays. Patients were followed for the primary outcome of 28-day, all-cause mortality.
  
  
  RESULTS
  Elevated PMA levels were associated with an increased risk of mortality in older septic patients (hazard ratio for mortality 5.64, 95% confidence interval 0.64-49.61). This association remained after adjusting for potential confounding variables in multivariate regression. Receiver operating curve analyses demonstrated that PMA levels greater than or equal to 8.43% best predicted 28-day mortality in older septic patients (area under the receiver operating curve 0.82). Plasma IL-6 and IL-8 levels were also significantly higher in older nonsurvivors. In younger patients, neither PMA levels nor plasma monokines were significantly associated with mortality.
  
  
  CONCLUSIONS
  Increased PMA formation, and associated proinflammatory monokine synthesis, predicts mortality in older septic patients. Although larger studies are needed, our findings suggest that heightened PMA formation in older septic patients may contribute to injurious inflammatory responses and an increased risk of mortality.
authors.affiliation: Division of General Internal Medicine, Program in Molecular Medicine.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Rondina
authors.affiliation: Program in Molecular Medicine.
authors.forename: McKenzie
authors.initials: M
authors.lastname: Carlisle
authors.affiliation: Program in Molecular Medicine, Department of Psychology, and.
authors.forename: Tamra
authors.initials: T
authors.lastname: Fraughton
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City. Division of Pulmonary and Critical Care Medicine,Intermountain Medical Center, Murray, Utah.
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Brown
authors.affiliation: Division of Pulmonary and Critical Care Medicine,Intermountain Medical Center, Murray, Utah.
authors.forename: Russell R
authors.initials: RR
authors.lastname: Miller
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Estelle S
authors.initials: ES
authors.lastname: Harris
authors.affiliation: Program in Molecular Medicine, Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City.
authors.forename: Guy A
authors.initials: GA
authors.lastname: Zimmerman
authors.affiliation: Division of Geriatric Medicine and Salt Lake City VA GRECC, University of Utah.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Supiano
authors.affiliation: Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Utah, Salt Lake City. Division of Pulmonary and Critical Care Medicine,Intermountain Medical Center, Murray, Utah.
authors.forename: Colin K
authors.initials: CK
authors.lastname: Grissom
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000502:physiology*; D002449:Cell Aggregation / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D009000:Monocytes / Q000502:physiology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood / Q000401:mortality*; D012772:Shock, Septic / Q000097:blood / Q000401:mortality*
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8
keywords: Inflammation; Mortality.; Platelet; Platelet–monocyte aggregates; Sepsis