ALBERT

Description: Abstract 3360 Background- Apheresed platelet concentrates accumulate biologic response modulators (BRMs) with prolonged storage. BRMs have been localized to the supernatant fraction of stored blood products and BRM levels correlate with length of storage. BRMs, and hence transfusion, have been demonstrated to function as a recipient immune “second hits”, in the construct of the two hit model of multiple organ dysfunction and failure. Furthermore, contemporary practices for apheresed platelet processing and storage restricts transfusibility to five days or less from time of collection. Platelet processing by lyophilization offers the potential for long term platelet storage and transfusibility. Lyophilized platelets (LP) are preserved in a metabolically inactive state until rehydrated in sterile water immediately prior to infusion and therefore, intuitively, of limited BRM activity. We hypothesized that LP transfusion will not constitute an immunologic “second hit”. Methods- Rhesus Macaques were anesthetized and subjected to grade III hemorrhagic shock to induce a systemic inflammatory profile consistent with an immunological “first hit”. To determine the “second hit” capability of LP, 2 × 1010 reconstituted LP (a weight based equivalent dose of an average size human receiving 1 six pack of platelets) were infused at 15 minutes (T=15) following the initiation of shock. In parallel experiments, normal saline (NS) or 2 × 1010 fresh (day 1 – 3) apheresed human platelets (FAP) were infused at T=15 15 minutes following initiation of shock to serve as controls. Subsequently, volume resuscitation with additional normal saline, per ATLS guidelines, was performed and all animals survived for 480 minutes (T=480) post-shock initiation. Physiologic parameters were continually monitored, serum collected immediately preceding shock (T=0), T=240 and T=480 for TNF α, IL-1β, IL-6, and IL-8 analysis. Supernatants from the LP and FAP administered during the study were assayed for pro-inflammatory cytokines. All cytokine detection was performed on a Luminex IS 100. Analysis: paired sample t-test and one-way ANOVA; results reported as mean (SEM). Results- Grade III hemorrhagic shock, determined by a reduction in MAP (43% (4.5), p

Description: Introduction: In the CRASH II trial, administration of tranexamic acid (TXA) 〉3 hours after injury was associated with increased mortality. Recent evidence indicates that fibrinolysis inhibition upon presentation to the emergency department (ED) is associated with increased mortality from organ failure. However, it remains unclear if fibrinolysis status changes in response to resuscitation. We hypothesize that the incidence of fibrinolysis resistance (shutdown) increases after resuscitation and is associated with increased post injury complications, prolonged respiratory failure, and prolonged ICU stay. Methods: Blood samples were collected prospectively on injured patients with documented prehospital shock (SBP 〈 90mm HG ) identified by the emergency medical service as part of an ongoing study to measure the impact of resusciation on coagulation in trauma. Patients had thrombelastography (TEG) samples drawn at admission and sequentially over 24 hours. Susceptibility to fibrinolysis was quantified using a tissue plasminogen activator (tPA) modified TEG. Fibrinolysis shutdown was defined as the lysis at 30 minutes (LY30) 〈 5thpercentile of healthy volunteers (n=160). Kaplan-Meier plot was generated to identify the timing and cumulative incidence of fibrinolysis shutdown in the first 24 hours after injury. Outcomes were contrasted between patients with and without shutdown at different time intervals from injury using a Mann Whitney U test to assess for 30 day post-injury complications, mechanical ventilator free days, and intensive care unit free days. A nested population of twelve patients that had elevated fibrinolysis activity on presentation to the emergency department and did not receive TXA were analyzed for endogenous tPA and plasminogen activator inhibitor-1(PAI-1) activity during their first 24 hours post injury, which also including pre hospital samples before resuscitation. Results: Ninety patients (median ISS of 27 and prehospital SBP of 72 mmHG) were included in the analysis, with a mortality rate of 13%. Overall, 76 % of patients developed fibrinolysis shutdown. Fifty percent of the population developed fibrinolysis shutdown within 2 hours of injury, and 75% of patients reached shutdown by 4 hours post injury (figure 1). Patients who remained in shutdown at 12 hours postinjury had significantly fewer ventilator free days (median 23 vs 26 p=0.005) and fewer ICU free days (median 20 vs 26 p= 0.004) with longer hospitalization (median 16 days vs 5 p=0.001). Patients in shutdown at 12 hours also had an increased incidence of in hospital complications (40% vs 15% p=0.048). Patients that were in fibrinolysis shutdown at 12 hours had increased plasma (p=0.010) platelet (p=0.007) and TXA (p=0.033) transfusions in the first 6 hours of resuscitation compared to those patients not in shutdown. In the nested cohort of patients with elevated LY30 upon presentation to the hospital, the median tPA activity peaked in prehospital samples (median 0.87 IU/ml) and decreased 10 fold by 4 hours postinjury (0.08 p