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 Thromboelastography (TEG) is used to diagnose perturbations in clot formation and lysis that are characteristic of acute traumatic coagulopathy (ATC). With novel functional fibrinogen (FF) TEG, fibrin- and platelet-based contributions to clot formation can be elucidated to tailor resuscitation and thromboprophylaxis. We sought to describe the longitudinal contributions of fibrinogen and platelets to clot strength after injury, hypothesizing that low levels of functional fibrinogen and a low contribution of fibrinogen to clot strength on admission would be associated with coagulopathy, increased transfusion requirements, and worse outcomes. METHODS 603 longitudinal plasma samples were prospectively collected from 251 critically-injured patients at a single Level 1 Trauma Center from 0–120h. TEG maximal amplitude (MA), FF MA, FF levels (FLEV), von Clauss fibrinogen, and standard coagulation measures were performed in parallel. Percentage contributions of FF (%MAFF) and platelets (%MAplatelets) were calculated as each MA divided by overall kaolin TEG MA. RESULTS Coagulopathic patients (INR>=1.3) had significantly lower admission %MAFF than non-coagulopathic patients (24.7% vs. 31.2%, p<0.05). Patients requiring plasma transfusion had a significantly lower admission %MAFF (26.6% vs. 30.6%, p<0.05). Higher admission %MAFF was predictive of reduced mortality (HR 0.815, p<0.001). %MAplatelets was higher than %MAFF at all time points, decreased over time, and stabilized at 72 hours (69.4% at 0h, 56.2% at 72h). In contrast, %MAFF increased over time and stabilized at 72 hours (30.6% at 0h, 43.8% at 72). CONCLUSION FF TEG affords differentiation of fibrin- versus platelet-based clot dynamics. Coagulopathy and plasma transfusion were associated with a lower %MAFF. Despite this importance of fibrinogen, platelets had a greater contribution to clot strength at all time points after injury. This suggests that attention to these relative contributions should guide resuscitation and thromboprophylaxis, and that antiplatelet therapy may be of under-recognized importance to thromboprophylaxis after trauma. LEVEL OF EVIDENCE Level IV; prognostic

Background Recent studies identify a survival benefit from the administration of antifibrinolytic agents in severely injured trauma patients. However, identification of hyperfibrinolysis requires thromboelastometry, which is not widely available. We hypothesized that analysis of patients with thromboelastometry-diagnosed hyperfibrinolysis would identify clinical criteria for empiric antifibrinolytic treatment in the absence of thromboelastometry. Methods From 11/2010 – 3/2012, serial blood samples were collected from 115 critically-injured patients on arrival to the emergency department of an urban level I trauma center. Rotational thromboelastometry (ROTEM®) was performed to assess viscoelastic properties of clot formation in the presence and absence of aprotinin to identify treatable hyperfibrinolysis. In 20 patients identified with treatable hyperfibrinolysis, clinical predictors were investigated using receiver-operator characteristic analysis. Results Of 115 patients evaluated, 20% had hyperfibrinolysis, defined as an admission maximal clot lysis ≥10% reversible by aprotinin treatment. Patients with hyperfibrinolysis had significantly lower temperature, pH, and platelet counts, and higher INR, PTT, and D-dimer. Hyperfibrinolysis was associated with multiorgan failure (63.2% vs. 24.6%, p=0.004) and mortality (52.2% vs. 12.9%, p<0.001). We then evaluated all non-ROTEM clinical and laboratory parameters predictive of hyperfibrinolysis using receiver-operator characteristic analysis to evaluate potential empiric treatment guidelines. The presence of hypothermia (temperature ≤36.0), acidosis (pH ≤7.2), relative coagulopathy (INR ≥1.3 or PTT ≥30), or relative thrombocytopenia (platelet count ≤200) identified hyperfibrinolysis with 100% sensitivity and 55.4% specificity (area under the curve 0.777). Conclusions Consideration of empiric antifibrinolytic therapy is warranted for critically-injured trauma patients who present with acidosis, hypothermia, coagulopathy, or relative thrombocytopenia. These clinical predictors identified hyperfibrinolysis with 100% sensitivity while simultaneously eliminating 46.6% of inappropriate therapy compared to the empiric treatment of all injured patients. These criteria will facilitate empiric treatment of hyperfibrinolysis for clinicians without access to thromboelastography. Level of evidence Prognostic study, Level I