title: Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern.
abstract: BACKGROUND
  Following trauma and systemic inflammatory response syndrome (SIRS), the typical response is an elevation of the total complete blood count (CBC) and a reduction of the lymphocyte count. This leukocytosis typically returns to normal within 48 hours. The persistence of a leukocytosis following trauma is associated with adverse outcomes. Although lymphocyte anergy and dysfunction following trauma is associated with increased risk for infection and sepsis, there is a paucity of data regarding the impact of a persistence of a low lymphocyte count in trauma patients.
  
  
  METHODS
  This is a retrospective review of prospectively collected data from trauma patients collected over the 5 years of September 2003 to September 2008. Patients were included if the injury severity score (ISS) was >or=15, and they survived at least 3 days. Demographic data, mechanism and injury severity score, mortality, and length of stay were collected from the medical record. Laboratory values for the first 4 hospital days were collected. Leukocyte, neutrophil and lymphocyte counts were extracted from the daily complete blood count (CBC). Patients were then grouped based on response (elevation/depression) of each component of the CBC, and their return, or failure thereof, to normal. Proportional hazards regression with time-varying covariates as well as Kaplan-Meier curves were used to predict risk of death, time to death and time to healthy discharge based on fluctuations of the individual components of the CBC.
  
  
  RESULTS
  There were 2448 patients admitted over the 5 years included in the analysis. When adjusting for age, gender and ISS the relative risk of death was elevated with a persistent leukocytosis (2.501 (95% CI=1.477-4.235)) or failure to normalize lymphopenia (1.639 (95% CI=10.17-2.643)) within the first 4 days following admission. Similar results were seen when Kaplan-Meier curves were created. Persistent lymphopenia was associated with shortest time to death. Paradoxically in survivors persistent lymphopenia was associated with the shortest time to discharge.
  
  
  CONCLUSIONS
  Persistently abnormal CBC responses are associated with a higher mortality following trauma. This is the first report noting that a failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality.
authors.affiliation: Division of Surgical Research, Department of Surgery, Warren Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA. Dheffernan@brown.edu
authors.forename: Daithi S
authors.initials: DS
authors.lastname: Heffernan
authors.forename: Sean F
authors.initials: SF
authors.lastname: Monaghan
authors.forename: Rajan K
authors.initials: RK
authors.lastname: Thakkar
authors.forename: Jason T
authors.initials: JT
authors.lastname: Machan
authors.forename: William G
authors.initials: WG
authors.lastname: Cioffi
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D007964:Leukocytosis / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008231:Lymphopenia / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012042:Registries; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014193:Trauma Centers / Q000639:trends; D017211:Treatment Failure