Plasma Transfusion Products and Contamination with Cellular and Associated Pro-Inflammatory Debris.

BACKGROUND: Stored plasma products are widely regarded as being functionally acellular, obviating the need for leukoreduction. We tested the hypothesis that donor plasma is contaminated by leukocytes and platelets, which, after frozen storage, would release cellular debris in quantities sufficient to elicit significant pro-inflammatory responses. STUDY DESIGN: Samples of never-frozen liquid plasma from 2 regional Level I trauma centers were analyzed for leukocyte and platelet contamination. To determine if the cellular contamination and associated debris found in liquid plasma were at levels sufficient to evoke an innate immune response, known quantities of leukocytes were subjected to a freeze-thaw cycle, added to whole blood, and the magnitude of the inflammatory response was determined by induction of interleukin-6. RESULTS: Units of never-frozen plasma from 2 regional Level I trauma centers located in Alabama and Louisiana contained significant amounts of leukocyte contamination (Louisiana, n = 22; 17.3 ± 4.5 million vs Alabama, n = 22; 11.3 ± 2.2 million) and platelet contamination (Louisiana, n = 21; 0.86 ± 0.20 billion vs Alabama, n = 22; 1.0 ± 0.3 billion). Cellular debris from as few as 1 million leukocytes induced significant increases in interleukin-6 levels (R2 = 0.74; p < 0.0001). CONCLUSIONS: Stored plasma units from trauma center blood banks were highly contaminated with leukocytes and platelets, at levels more than 15-fold higher than sufficient to elicit ex vivo inflammatory responses. In light of paradigm shifts toward the use of more empiric plasma for treatment of hypovolemia, this study suggests that new manufacturing and quality-control processes are needed to eliminate previously unrecognized cellular contamination present in stored plasma products.

Traumatic brain injury is not associated with coagulopathy out of proportion to injury in other body regions.

BACKGROUND: Coagulopathy following trauma is associated with poor outcomes. Traumatic brain injury has been associated with coagulopathy out of proportion to other body regions. We hypothesized that injury severity and shock determine coagulopathy independent of body region injured. METHODS: We performed a prospective, multicenter observational study at three Level 1 trauma centers. Conventional coagulation tests (CCTs) and rapid thrombelastography (r-TEG) were used. Admission vital signs, base deficit (BD), CCTs, and r-TEG data were collected. The Abbreviated Injury Scale (AIS) score and Injury Severity Score (ISS) were obtained. Severe injury was defined as AIS score greater than or equal to 3 for each body region. Patients were grouped according to their dominant AIS region of injury. Dominant region of injury was defined as the single region with the highest AIS score. Patients with two or more regions with the same greatest AIS score and patients without a region with an AIS score greater than or equal to 3 were excluded. Coagulation parameters were compared between the dominant AIS region. Significant hypoperfusion was defined as BD greater than or equal to 6. RESULTS: Of the 795 patients enrolled, 462 met criteria for grouping by dominant AIS region. Patients were predominantly white (59%), were male (75%), experienced blunt trauma (71%), and had a median ISS of 25 (interquartile range, 14-29). Patients with BD greater than or equal to 6 (n = 110) were hypocoagulable by CCT and r-TEG compared with patients with BD less than 6 (n = 223). Patients grouped by dominant AIS region showed no significant differences for any r-TEG or CCT parameter. Patients with BD greater than or equal to 6 demonstrated no difference in any r-TEG or CCT parameter between dominant AIS regions. CONCLUSION: Coagulopathy results from a combination of tissue injury and shock independent of the dominant region of injury. With the use of AIS as a measure of injury severity, traumatic brain injury was not independently associated with more profound coagulopathy. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Clinical and mechanistic drivers of acute traumatic coagulopathy.

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 1,198 patients with laboratory results, of whom 41.6% were coagulopathic. Using international normalized ratio of 1.3 or greater, 41.6% of patients (448) were coagulopathic, while 20.5% (214) were coagulopathic using partial thromboplastin time of 35 or greater. Coagulopathy was primarily associated with a combination of an Injury Severity Score (ISS) of greater than 15 and a base deficit (BD) of less than -6 (p < 0.05). Regression modeling for international normalized ratio-based coagulopathy shows that prehospital crystalloid (odds ratio [OR], 1.05), ISS (OR, 1.03), Glasgow Coma Scale (GCS) score (OR, 0.93), heart rate (OR, 1.08), systolic blood pressure (OR, 0.96), BD (OR, 0.92), and temperature (OR, 0.84) were significant predictors of coagulopathy (all p < 0.03). 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 < 0.05). Reductions in factors I, II, V, VIII and an increase in aPC drive ATC (all p < 0.04). Similar results were found for partial thromboplastin time-defined coagulopathy. CONCLUSION: ATC is associated with the 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.