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. 2012 Jan 20;16(1):R12.
doi: 10.1186/cc11157.

Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern

Daithi S Heffernan  1 , Sean F Monaghan, Rajan K Thakkar, Jason T Machan, William G Cioffi, Alfred Ayala
Affiliations

Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern

Daithi S Heffernan et al. Crit Care. .

Abstract

Introduction: 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.

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Figures

Figure 1
Figure 1
Kaplan-Meier survival graph with respect to the leukocyte groupings. Patients who developed a leukocytosis which never returned to normal had the lowest probability of survival (65% survival rate at 21 days). Group 1 = (green dashed line) Ever Leukocytosis = 1; Back to Normal = 1; 80% 21 day survival, Group 2 = (red dashed line) Ever Leukocytosis = 1; Back to Normal = 0; 65% 21 day survival, Group 3 = (blue dashed line) Ever Leukocytosis = 0; Back to Normal = 0; 77% 21 day survival.
Figure 2
Figure 2
Kaplan-Meier survival curve with respect to the pattern of the neutrophil fluctuations. There was no difference in survival comparing the 3 patterns, namely elevated-returned to normal, elevated-stayed elevated and never elevated. Group 1 = (green dashed line) Ever Neutrophilia = 1; Back to Normal = 1; 81.2% 21 day survival, Group 2 = (red dashed line) Ever Leukocytosis = 1; Back to Normal = 0; 81.8% 21 day survival, Group 3 = (blue dashed line) Ever Leukocytosis = 0; Back to Normal = 0; 74.7% 21 day survival.
Figure 3
Figure 3
Kaplan-Meier survival graph with respect to the Lymphocyte groupings. Patients who displayed lymphocyte loss with no subsequent recover of Lymphocyte number had the lowest survival of 71%. Group 1 = (green dashed line) Ever Lymphopenic = 1; Back to Normal = 1; 83% 21 day survival, Group 2 = (red dashed line) Ever Lymphopenic = 1; Back to Normal = 0; 71.3% 21 day survival, Group 3 = (blue dashed line) Ever Lymphopenic = 0; Back to Normal = 0; 83.75% 21 day survival.
Figure 4
Figure 4
Time to Death Curves. Patients who were never Lymphopenic displayed the shortest average time to death. Patients with lymphopenia which returned to normal in the first 4 days displayed the longest average time to death. Group 1 = (green dashed line) Ever Lymphopenic = 1; Back to Normal = 1; Group 2 = (red dashed line) Ever Lymphopenic = 1; Back to Normal = 0; Group 3 = (blue dashed line) Ever Lymphopenic = 0; Back to Normal = 0;
Figure 5
Figure 5
Time to discharge. Of the survivors, patients in whom lymphocytes did not fall low had the shortest quickest time to discharge. There was no difference between the other 2 groups. Group 1 = (green dashed line) Ever Lymphopenic = 1; Back to Normal = 1; Group 2 = (red dashed line) Ever Lymphopenic = 1; Back to Normal = 0; Group 3 = (blue dashed line) Ever Lymphopenic = 0; Back to Normal = 0;
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Comment in

  • CD4+ T-lymphocyte alterations in trauma patients.
    Gouel-Chéron A, Venet F, Allaouchiche B, Monneret G. Gouel-Chéron A, et al. Crit Care. 2012 Jun 26;16(3):432. doi: 10.1186/cc11376. Crit Care. 2012. PMID: 22734607 Free PMC article. No abstract available.

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