title: D-dimer correlates with proinflammatory cytokine levels and outcomes in critically ill patients.
abstract: OBJECTIVE
  To determine the relationship between d-dimer (DD) and both proinflammatory and anti-inflammatory cytokine levels, and to confirm the association between DD status and outcomes in critically ill patients.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  Medical ICU (MICU) of a tertiary care, academic medical center.
  
  
  METHODS
  Individuals admitted to the MICU.
  
  
  METHODS
  Within 24 h of MICU admission, patients had DD status determined and interleukin (IL) levels (IL-6, IL-8, and IL-10) and tumor necrosis factor (TNF)-alpha measured. The strength of the DD level was also noted. Subjects were then monitored prospectively to determine mortality rate and the incidence of organ failure.
  
  
  RESULTS
  The study cohort included 79 patients (mean age, 65.2 years; 54.5% male patients). DD was present in 53.2% of subjects. The DD reaction was weak (1+) in 15 patients and strong (2+) in 27 patients. The TNF-alpha, IL-6, and IL-8 levels all increased in parallel with the increasing strength of the DD level. IL-10 levels did not differ based on DD status. Similarly, the severity of illness as measured by the APACHE (acute physiology and chronic health evaluation) II score was highest among those with higher DD levels: 24.7 +/- 6.2 for those with 2+ DD vs 17.2 +/- 3.1 and 11.5 +/- 2.7 for those with 1+ DD and no circulating DD, respectively (p < 0.001). For patients lacking DD, the mortality rate was 8.1%, compared to 13.3% and 55.6% for those with 1+ and 2+ DD levels, respectively (p < 0.001). No patient without DD had multisystem organ failure (MSOF) develop, while the incidence of MSOF also increased with increasing DD levels. As a screening test for mortality, the DD performed as well as the APACHE II system.
  
  
  CONCLUSIONS
  The coagulation system is active in critically ill patients, and DD levels correlate with activation of the proinflammatory cytokine cascade. The absence of a relationship between DD and anti-inflammatory cytokines (IL-10) suggests that the presence of DD may reflect the imbalance between proinflammatory and anti-inflammatory cytokines. DD identifies patients at increased risk for both MSOF and death.
authors.affiliation: Pulmonary and Critical Care Medicine Service, Walter Reed Army Medical Center, Washington, DC, USA. AFSHORR@DNAMAIL.COM
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Shorr
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Alkins
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Fitzpatrick
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ling
mesh_terms: D018806:APACHE; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D003422:Critical Care; D016207:Cytokines / Q000097:blood*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D017052:Hospital Mortality; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000276:immunology / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000401:mortality; D016896:Treatment Outcome
chemical_list: D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; C036309:fibrin fragment D