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

Abstract

IntroductionFollowing 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.MethodsThis 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 >/=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.ResultsThere 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.ConclusionsPersistently 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.

Frailty syndrome and pre-operative risk evaluation: A systematic review

“…These findings support the notion that frailty is not strictly related to biological age and that the number of comorbidities does not fully correlate with their severity (Afilalo et al, 2012;Farhat et al, 2012;Fernández-Garrido et al, 2014a;Fried et al, 2004;Partridge et al, 2012;Robinson et al, 2013) As the frailty burden increases, the occurrence of one or more complications are more likely. Robinson et al (2013) reported that infection was the most common complication in both surgical groups, and perhaps related to this, a decrease in immune function has also been described in frail individuals (Furlan et al, 2013;Heffernan et al, 2012;Leng et al, 2009;Reddan et al, 2003). Length of hospital stay increased as the frailty burden accumulated, and thus these patients also accrued higher economic and health-professional costs during this postsurgical period (Cohen et al, 2012;Lasithiotakis et al, 2013;Lee et al, 2010;Makary et al, 2010;Robinson et al, 2013).…”

Innate immune responses to trauma

“…On the other hand, lymphocytes and crypt intestinal epithelial cells can be driven to apoptosis after severe trauma 38 . Furthermore, an inability to normalize posttraumatic lymphopenia in a timely fashion is associated with a poor outcome, irrespective of the dynamics of the leukocytosis 39 . Excessive immune, coagulatory and ROS responses can lead to substantial endotheliopathy and dysfunction of cellular barriers 40 that facilitate the transit and generation of more PAMPs and DAMPs, which amplifies a vicious cycle of tissue injury and damaging immunological processes 6,11,14 .…”

A Novel Role for Programmed Cell Death Receptor Ligand-1 in Sepsis-Induced Intestinal Dysfunction

“…Therefore, more information about the pathophysiology of this syndrome is needed if we are to better understand it and identify/develop novel clinical therapies. In this respect, studies have demonstrated that septic patients exhibited an impaired immunity associated with sustained loss of important immune cells (2,3). Several aberrations in leukocyte function have also been documented in septic patients, which are associated with poor outcome (4)(5)(6).…”