Background The increased morbidity and mortality associated with coagulopathy and thrombocytopenia after trauma are well-described. However, few studies have assessed platelet function after injury. Methods Blood samples were prospectively collected from 101 critically-injured trauma patients on arrival to the emergency department and serially after admission to a Level I urban trauma ICU from November 2010 to October 2011, and functionally assayed for responsiveness to adenosine diphosphate, thrombin receptor-activating peptide (TRAP), arachidonic acid (AA), and collagen using multiple electrode impedance aggregometry. Results Of 101 enrolled patients, 46 (45.5%) had below-normal platelet response to at least one agonist (‘platelet hypofunction’) on admission, and 92 patients (91.1%) had platelet hypofunction at some time during their ICU stay. Admission platelet hypofunction was associated with low Glasgow coma score (GCS) and a nearly 10-fold higher early mortality. Logistic regression identified admission GCS (odds ratio 0.819, p=0.008) and base deficit (odds ratio 0.872, p=0.033) as independent predictors of platelet hypofunction. Admission AA and collagen responsiveness were significantly lower in patients who died (p<0.01), while admission platelet counts were similar (p=0.278); Cox regression confirmed TRAP, AA, and collagen responsiveness as independent predictors of in-hospital mortality (p<0.05). Receiver operator characteristic analysis identified admission AA and collagen responsiveness as negative predictors of both 24-hour (AA AUC: 0.874, collagen AUC: 0.904) and in-hospital mortality (AA AUC: 0.769, collagen AUC: 0.717). Conclusions In this prognostic study, we identify clinically significant platelet dysfunction after trauma in the presence of an otherwise reassuring platelet count and standard clotting studies, with profound implications for mortality. Multiple electrode impedance aggregometry reliably identifies this dysfunction in injured patients, and admission arachidonic acid and collagen responsiveness are sensitive and specific independent predictors of both early and late mortality. Level of evidence Level I

Background Recent studies have identified an acute traumatic coagulopathy that is present on admission to the hospital and is independent of iatrogenic causes. We have previously reported that this coagulopathy is due to the association of severe injury and shock and is characterized by a decrease in plasma protein C levels. Whether this early coagulopathy and later propensity to infection, MOF and mortality are associated with the activation of protein C pathway has not been demonstrated and constitutes the aim of this study. Methods and Findings This was a prospective cohort study of 203 major trauma patients. Serial blood samples were drawn on arrival in the ED, and at 6, 12, and 24 hours after admission to the hospital. PT, PTT, Va, VIIIa, PC aPC t-PA and D-Dimer levels were assayed. Comprehensive injury, resuscitation and outcome data were prospectively collected. A total of 203 patients were enrolled. Patients with tissue hypoperfusion and severe traumatic injury showed a strong activation of the protein C which was associated with a coagulopathy characterized by inactivation of the coagulation factors V and VIII and a derepression of the fibrinolysis with high plasma levels of plasminogen activator and high D-dimers. Elevated plasma levels of activated protein C were significantly associated with increased mortality, organ injury, increased blood transfusion requirements, and reduced ICU ventilator-free days. Finally early depletion of protein C after trauma is associated with a propensity to post-traumatic ventilator-associated pneumonia. Conclusions Acute traumatic coagulopathy occurs in the presence of tissue hypoperfusion and severe traumatic injury and is mediated by activation of the protein C pathway. Higher plasma levels of aPC upon admission are predictive of poor clinical outcomes following major trauma. After activation, patients who fail to recover physiologic plasma values of protein C have an increased propensity to later nosocomial lung infection.

Background Acute Traumatic Coagulopathy (ATC) occurs after severe injury and shock and is associated with increased bleeding, morbidity and mortality. The effects of ATC and hemostatic resuscitation on outcome are not well-explored. The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study provided a unique opportunity to characterize coagulation and the effects of resuscitation on ATC after severe trauma. Methods Blood samples were collected upon arrival on a subset of PROMMTT patients. Plasma clotting factor levels were prospectively assayed for coagulation factors. These data were analyzed with comprehensive PROMMTT clinical data. Results There were 1198 patients with laboratory results of whom 41.6% were coagulopathic. Using International Normalized Ratio (INR)≥1.3, 41.6% (448) of patients were coagulopathic while 20.5% (214) were coagulopathic using partial thromboplastin time (PTT)≥35. Coagulopathy was primarily associated with a combination of an ISS>15 and a BD<−6 (P<.05). Regression modeling for INR-based coagulopathy shows that pre-hospital crystalloid (odds ratio (OR)=1.05), Injury Severity Score (ISS, OR=1.03), Glasgow Coma Scale (OR=0.93), heart rate (OR=1.08), systolic blood pressure (OR=0.96), base deficit (BD, OR=0.92) and temperature (OR=0.84) were significant predictors of coagulopathy (all P<.03). A subset of 165 patients had blood samples collected and coagulation factor analysis performed. Elevated ISS and BD were associated with elevation of aPC and depletion of factors (all P<.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p<.04). Similar results were found for PTT-defined coagulopathy. Conclusions ATC is associated with depletion of factors I, II, V, VII, VIII, IX and X and is driven by the activation of the protein C system. These data provide additional mechanistic understanding of the drivers of coagulation abnormalities after injury. Further understanding of the drivers of ATC and the effects of resuscitation can guide factor guided resuscitation and correction of coagulopathy after injury.

After severe blunt trauma, a history of smoking is related to lung microbiota composition, both at the time of ICU admission and at 48 hours. ARDS development is also correlated with respiratory microbial community structure at 48 hours and with taxa that are relatively enriched in smokers at ICU admission. The data derived from this pilot study suggest that smoking-related changes in the lung microbiota could be related to ARDS development after severe trauma.