Association of fibrinolysis phenotype with patient outcomes following traumatic brain injury.

BACKGROUND: Impaired coagulation is associated with elevated risk of mortality in trauma patients. Prior studies have demonstrated increased mortality in patients with hyperfibrinolysis (HF) and fibrinolysis shutdown (SD). In addition, prior studies have demonstrated no effect of tranexamic acid (TXA) on fibrinolysis phenotypes. We examined the association of admission fibrinolysis phenotype with traumatic brain injury (TBI) patient outcomes. METHODS: Data were extracted from a placebo-controlled multicenter clinical trial. Patients ≥15 years with TBI (Glasgow Coma Scale score, 3-12) and systolic blood pressure ≥90 mm Hg were randomized in the out-of-hospital setting to receive placebo bolus/placebo infusion (Placebo), 1 gram (g) TXA bolus/1 g TXA infusion (bolus maintenance [BM]); or 2 g TXA bolus/placebo infusion (bolus only [BO]). Fibrinolysis phenotypes on admission were determined by clot lysis at 30 minutes (LY30): SD, ≤0.8%; physiologic, 0.9% to 2.9%; HF, ≥3%. Logistic regression was used to control for age, sex, penetrating injury, Injury Severity Score, maximum head AIS, and TXA treatment group. RESULTS: Seven hundred forty-seven patients met inclusion criteria. Fibrinolysis shutdown was the most common phenotype in all treatment groups and was associated with increased age, Injury Severity Score, and presence of intracranial hemorrhage (ICH). Inpatient mortality was 15.2% for SD and HF, and 10.6% for physiologic ( p = 0.49). No differences in mortality, disability rating scale at 6 months, acute kidney injury, acute respiratory distress syndrome, or multi-organ failure were noted between fibrinolysis phenotypes. CONCLUSION: SD is the most common phenotype expressed in moderate to severe TBI. In TBI, there is no association between fibrinolysis phenotype and mortality or other major complications. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

TXA does not affect levels of TBI-related biomarkers in blunt TBI with ICH: A secondary analysis of the prehospital TXA for TBI trial.

BACKGROUND: Brain specific biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) have been identified as tools for diagnosis in traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown to decrease mortality in patients with intracranial hemorrhage (ICH). The effect of TXA on these biomarkers is unknown. We investigated whether TXA affects levels of GFAP, UCH-L1, and MAP-2, and whether biomarker levels are associated with mortality in patients receiving TXA. METHODS: Patients enrolled in the prehospital TXA for TBI trial had GFAP, UCHL-1 and MAP-2 levels drawn at 0 hour and 24 hours postinjury (n = 422). Patients with ICH from blunt trauma with a GCS <13 and SBP >90 were randomized to placebo, 2 g TXA bolus, or 1 g bolus +1 g/8 hours TXA infusion. Associations of TXA and 24-hour biomarker change were assessed with multivariate linear regression. Association of biomarkers with 28-day mortality was assessed with multivariate logistic regression. All models were controlled for age, GCS, ISS, and AIS head. RESULTS: Administration of TXA was not associated with a change in biomarkers over 24 hours postinjury. Changes in biomarker levels were associated with AIS head and age. On admission, higher GFAP (odds ratio [OR], 1.75; confidence interval [CI], 1.31-2.38; p < 0.001) was associated with increased 28-day mortality. At 24 hours postinjury, higher levels of GFAP (OR, 2.09; CI, 1.37-3.30; p < 0.001 and UCHL-1 (OR, 2.98; CI, 1.77-5.25; p < 0.001) were associated with mortality. A change in UCH levels from 0 hour to 24 hours postinjury was also associated with increased mortality (OR, 1.68; CI, 1.15-2.49; p < 0.01). CONCLUSION: Administration of TXA does not impact change in GFAP, UCHL-1, or MAP-2 during the first 24 hours after blunt TBI with ICH. Higher levels of GFAP and UCH early after injury may help identify patients at high risk for 28-day mortality. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Prehospital Time Following Traumatic Injury Is Independently Associated With the Need for In-Hospital Blood and Early Mortality for Specific Injury Types.

OBJECTIVE: Treating traumatic hemorrhage is time sensitive. Prehospital care and transport modes (eg, helicopter and ground) may influence in-hospital events. We hypothesized that prehospital time (on-scene time [OST] and total prehospital time [TPT]) and transport mode are associated with same-day transfusion and mortality. Furthermore, we sought to identify regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. METHODS: We obtained prehospital, in-hospital, and trauma registry data from an 8-center cohort of adult nonburn trauma patients from 2017 to 2022 directly transported from the scene to the hospital and having an Injury Severity Score (ISS) > 9 for the Task Order 1 project of the Linking Investigators in Trauma and Emergency Services research network. We excluded patients missing prehospital times, patients < 18 years of age, patients from interfacility transfers, and recipients of prehospital blood. Our same-day outcomes were in-hospital transfusions within 4 hours and 24-hour mortality. Each outcome was adjusted using multivariable logistic regression for covariates of prehospital phases (OST and TPT), mode of transport (helicopter and ground), age, sex, ISS, Glasgow Coma Scale motor subscale score < 6, and field hypotension (systolic blood pressure < 90 mm Hg). We evaluated the association of prehospital time on outcomes for scene missions by transport mode across severe injury patterns defined by Abbreviated Injury Scale > 2 body regions. RESULTS: Of 78,198 subjects, 34,504 were eligible for the study with a mean age of 47.6 ± 20.3 years, ISS of 18 ± 11, OST of 15.9 ± 9.5 minutes, and TPT of 48.7 ± 20.3 minutes. Adjusted for injury severity and demographic factors, transport type significantly modified the relationship between prehospital time and outcomes. The association of OST and TPT with the odds of 4-hour transfusion was absent for the ground emergency medical services (GEMS) cohort and present for the helicopter emergency medical services (HEMS) ambulance cohort, whereas these times were associated with decreased 24-hour mortality for both transport types. When stratifying by injury to most anatomic regions, OST and TPT were associated with a decreased need for 4-hour transfusions in the GEMS cohort. However, OST was associated with increased early transfusion only among patients with severe injuries of the thorax, and this association persisted after adjusting additionally for injury type (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.00-1.05; P = .02). The presence of polytrauma supported an association between prehospital time and decreased 24-hour mortality for the GEMS cohort (OST: OR = 0.97; 95% CI, 0.95-0.99; P < .01; TPT: OR = 0.99; 95% CI, 0.98-0.99; P = .02), whereas no injuries showed significant association of helicopter prehospital time on mortality after adjustment. CONCLUSION: We determined that transport type affects the relationship between prehospital time and hospital outcomes (4-hour transfusion: positive relationship for HEMS and negative for GEMS, 24-hour mortality: negative for both transport types). Furthermore, we identified regions of anatomic injury that modify the relationship between prehospital time and outcomes in strata corresponding to transport types. Of these regions, most notable were severe isolated injuries to the thorax that supported a positive relationship between HEMS OST and 4-hour transfusions and polytrauma that showed a negative relationship between GEMS OST or TPT and 24-hour mortality after adjustment.

Committee on Surgical Combat Casualty Care position statement: Neurosurgical capability for the optimal management of traumatic brain injury during deployed operations.

BACKGROUND: Experiences over the last three decades of war have demonstrated a high incidence of traumatic brain injury (TBI) resulting in a persistent need for a neurosurgical capability within the deployed theater of operations. Despite this, no doctrinal requirement for a deployed neurosurgical capability exists. Through an iterative process, the Joint Trauma System Committee on Surgical Combat Casualty Care (CoSCCC) developed a position statement to inform medical and nonmedical military leaders about the risks of the lack of a specialized neurosurgical capability. METHODS: The need for deployed neurosurgical capability position statement was identified during the spring 2021 CoSCCC meeting. A triservice working group of experienced forward-deployed caregivers developed a preliminary statement. An extensive iterative review process was then conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. To provide additional context and a civilian perspective, statement commentaries were solicited from civilian clinical experts including a recently retired military trauma surgeon boarded in neurocritical care, a trauma surgeon instrumental in developing the Brain Injury Guidelines, a practicing neurosurgeon with world-renowned expertise in TBI, and the chair of the Committee on Trauma. RESULTS: After multiple revisions, the position statement was finalized, and approved by the CoSCCC membership in February 2023. Challenges identified include (1) military neurosurgeon attrition, (2) the lack of a doctrinal neurosurgical capabilities requirement during deployed combat operations, and (3) the need for neurosurgical telemedicine capability and in-theater computed tomography scans to triage TBI casualties requiring neurosurgical care. CONCLUSION: Challenges identified regarding neurosurgical capabilities within the deployed trauma system include military neurosurgeon attrition and the lack of a doctrinal requirement for neurosurgical capability during deployed combat operations. To mitigate risk to the force in a future peer-peer conflict, several evidence-based recommendations are made. The solicited civilian commentaries strengthen these recommendations by putting them into the context of civilian TBI management. This neurosurgical capabilities position statement is intended to be a forcing function and a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level V.

Whole Blood Resuscitation and Association with Survival in Injured Patients with an Elevated Probability of Mortality.

BACKGROUND: Low-titer group O whole blood (LTOWB) resuscitation is becoming common in both military and civilian settings and may represent the ideal resuscitation intervention. We sought to characterize the safety and efficacy of LTOWB resuscitation relative to blood component resuscitation. STUDY DESIGN: A prospective, multicenter, observational cohort study was performed using 7 trauma centers. Injured patients at risk of massive transfusion who required both blood transfusion and hemorrhage control procedures were enrolled. The primary outcome was 4-hour mortality. Secondary outcomes included 24-hour and 28-day mortality, achievement of hemostasis, death from exsanguination, and the incidence of unexpected survivors. RESULTS: A total of 1,051 patients in hemorrhagic shock met all enrollment criteria. The cohort was severely injured with >70% of patients requiring massive transfusion. After propensity adjustment, no significant 4-hour mortality difference across LTOWB and component patients was found (relative risk [RR] 0.90, 95% CI 0.59 to 1.39, p = 0.64). Similarly, no adjusted mortality differences were demonstrated at 24 hours or 28 days for the enrolled cohort. When patients with an elevated prehospital probability of mortality were analyzed, LTOWB resuscitation was independently associated with a 48% lower risk of 4-hour mortality (relative risk [RR] 0.52, 95% CI 0.32 to 0.87, p = 0.01) and a 30% lower risk of 28-day mortality (RR 0.70, 95% CI 0.51 to 0.96, p = 0.03). CONCLUSIONS: Early LTOWB resuscitation is safe but not independently associated with survival for the overall enrolled population. When patients were selected with an elevated probability of mortality based on prehospital injury characteristics, LTOWB was independently associated with a lower risk of mortality starting at 4 hours after arrival through 28 days after injury.

Role of single-dose intravenous iron therapy for the treatment of anaemia after orthopaedic trauma: protocol for a pilot randomised controlled trial.

INTRODUCTION: Orthopaedic trauma and fracture care commonly cause perioperative anaemia and associated functional iron deficiency due to a systemic inflammatory state. Modern, strict transfusion thresholds leave many patients anaemic; managing this perioperative anaemia is an opportunity to impact outcomes in orthopaedic trauma surgery. The primary outcome of this pilot study is feasibility for a large randomised controlled trial (RCT) to evaluate intravenous iron therapy (IVIT) to improve patient well-being following orthopaedic injury. Measurements will include rate of participant enrolment, screening failure, follow-up, missing data, adverse events and protocol deviation. METHODS AND ANALYSIS: This single-centre, pilot, double-blind RCT investigates the use of IVIT for acute blood loss anaemia in traumatically injured orthopaedic patients. Patients are randomised to receive either a single dose infusion of low-molecular weight iron dextran (1000 mg) or placebo (normal saline) postoperatively during their hospital stay for trauma management. Eligible subjects include adult patients admitted for lower extremity or pelvis operative fracture care with a haemoglobin of 7-11 g/dL within 7 days postoperatively during inpatient care. Exclusion criteria include history of intolerance to intravenous iron supplementation, active haemorrhage requiring ongoing blood product resuscitation, multiple planned procedures, pre-existing haematologic disorders or chronic inflammatory states, iron overload on screening or vulnerable populations. We follow patients for 3 months to measure the effect of iron supplementation on clinical outcomes (resolution of anaemia and functional iron deficiency), patient-reported outcomes (fatigue, physical function, depression and quality of life) and translational measures of immune cell function. ETHICS AND DISSEMINATION: This study has ethics approval (Oregon Health & Science University Institutional Review Board, STUDY00022441). We will disseminate the findings through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT05292001; ClinicalTrials.gov.

The effect of the Belmont rapid infuser on cold stored whole blood coagulability.

INTRODUCTION: With the large-scale use of whole blood in massive transfusion using rapid infusers/fluid warmers such as the Belmont, questions remain as to whether coagulation potency, platelet number and function are preserved.  We aimed to study functional coagulation capacity and cell counts in whole blood before and after infusion through the Belmont rapid infuser utilizing TEG analysis and complete blood counts. METHODS: We evaluated 10 whole blood units before and after infusion through a Belmont Fluid Management System at a set rate of 200 mL/min and a temperature of 37.4 °C.  Cell counts and thromboelastography function of the specimens were measured. Parameters were compared utilizing paired Student's t-tests and paired Wilcoxon Rank Sign tests. RESULTS: Platelet count, R time, and Maximum amplitude showed significant decreases (defined as p<0.05) after being infused through the Belmont. Hemoglobin, hematocrit, MCV, and alpha angle were not statistically different before and after infusion. CONCLUSION: Infusion of cold stored whole blood in a Belmont infuser, appeared to decrease platelet counts and function as well as activate clotting factors as demonstrated by a shorter R time while not affecting red cell counts or fibrin cross-linking as measured by TEG parameters and cell counts. This suggests that while it is possible to transfuse whole blood through a rapid infuser, platelet quantity and function may be negatively impacted.

The effects of timing of prehospital tranexamic acid on outcomes after traumatic brain injury: Subanalysis of a randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic that has shown some promise in improving outcomes in traumatic brain injury (TBI), but only when given early after injury. We examined the association between timing of prehospital TXA administration and outcomes in patients with moderate to severe TBI. METHODS: Patients enrolled in the multi-institutional, double-blind randomized prehospital TXA for TBI trial with blunt or penetrating injury and suspected TBI (Glasgow Coma Scale score ≤ 12, SBP ≥90) who received either a 2-g TXA bolus or a 1-g bolus plus 1 g 8 hour infusion within 2 hours of injury were analyzed. Outcomes were compared between early administration (<45 minutes from injury) and late administration ≥45 minutes from injury) using a χ 2 , Fischer's exact test, t test, or Mann-Whitney U test as indicated. Logistic regression examined time to drug as an independent variable. A p value less than 0.05 was considered significant. RESULTS: Six hundred forty-nine patients met inclusion criteria (354 early and 259 late). Twenty-eight-day and 6-month mortalities, 6-month Glasgow Outcome Scale-Extended, and disability rating scale scores were not different between early and late administration. Late administration was associated with higher rates of deep venous thrombosis (0.8 vs. 3.4%, p = 0.02), cerebral vasospasm (0% vs. 2%, p = 0.01), as well as prolonged EMS transport and need for a prehospital airway ( p < 0.01). CONCLUSION: In patients with moderate or severe TBI who received TXA within 2 hours of injury, no mortality benefit was observed in those who received treatment within 45 minutes of injury, although lower rates of select complications were seen. These results support protocols that recommend TXA administration within 45 minutes of injury for patients with suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Detection of neutralizing antibodies against multiple SARS-CoV-2 strains in dried blood spots using cell-free PCR.

An easily implementable serological assay to accurately detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies is urgently needed to better track herd immunity, vaccine efficacy and vaccination rates. Herein, we report the Split-Oligonucleotide Neighboring Inhibition Assay (SONIA) which uses real-time qPCR to measure the ability of neutralizing antibodies to block binding between DNA-barcoded viral spike protein subunit 1 and the human angiotensin-converting enzyme 2 receptor protein. The SONIA neutralizing antibody assay using finger-prick dried blood spots displays 91-97% sensitivity and 100% specificity in comparison to the live-virus neutralization assays using matched serum specimens for multiple SARS-CoV-2 variants-of-concern. The multiplex version of this neutralizing antibody assay, using easily collectable finger-prick dried blood spots, can be a valuable tool to help reveal the impact of age, pre-existing health conditions, waning immunity, different vaccination schemes and the emergence of new variants-of-concern.

Committee on Surgical Combat Casualty Care position statement on the use of single surgeon teams and invited commentaries.

BACKGROUND: Over the last 20 years of war, there has been an operational need for far forward surgical teams near the point of injury. Over time, the medical footprint of these teams has decreased and the utilization of mobile single surgeon teams (SSTs) by the Services has increased. The increased use of SSTs is because of a tactical mobility requirement and not because of proven noninferiority of clinical outcomes. Through an iterative process, the Committee on Surgical Combat Casualty Care (CoSCCC) reviewed the utilization of SSTs and developed an expert-opinion consensus statement addressing the risks of SST utilization and proposed mitigation strategies. METHODS: A small triservice working group of surgeons with deployment experience, to include SST deployments, developed a statement regarding the risks and benefits of SST utilization. The draft statement was reviewed by a working group at the CoSCCC meeting November 2021 and further refined. This was followed by an extensive iterative review process, which was conducted to ensure that the intended messaging was clear to senior medical leaders and operational commanders. The final draft was voted on by the entire CoSCCC membership. To inform the civilian trauma community, commentaries were solicited from civilian trauma leaders to help put this practice into context and to further the discussion in both military and civilian trauma communities. RESULTS: After multiple revisions, the SST statement was finalized in January 2022 and distributed to the CoSCCC membership for a vote. Of 42 voting members, there were three nonconcur votes. The SST statement underwent further revisions to address CoSCCC voting membership comments. Statement commentaries from the President of the American Association for the Surgery for Trauma, the chair of the Committee on Trauma, the Medical Director of the Military Health System Strategic Partnership with the American College of Surgeons and a recently retired military surgeon we included to put this military relevant statement into a civilian context and further delineate the risks and benefits of including the trauma care paradigm in the Department of Defense (DoD) deployed trauma system. CONCLUSION: The use of SSTs has a role in the operational environment; however, operational commanders must understand the tradeoff between tactical mobility and clinical capabilities. As SST tactical mobility increases, the ability of teams to care for multiple casualty incidents or provide sustained clinical operations decreases. The SST position statement is a communication tool to inform operational commanders and military medical leaders on the use of these teams on current and future battlefields.

Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial.

BACKGROUND: A 2-g bolus of tranexamic acid (TXA) has been shown to reduce 28-day mortality in a randomized controlled trial. This study investigates whether out-of-hospital TXA use is associated with adverse events or unfavorable outcomes in suspected traumatic brain injury (TBI) when intracranial hemorrhage (ICH) is absent on initial computed tomography. METHODS: This study used data from a 2015 to 2017, multicenter, randomized trial studying the effect of the following TXA doses on moderate to severe TBI: 2-g bolus, 1-g bolus plus 1-g infusion over 8 hours, and a placebo bolus with placebo infusion. Of the 966 participants enrolled, 395 with an initial computed tomography negative for ICH were included in this analysis. Fifteen adverse events (28-day incidence) were studied: myocardial infarction, deep vein thrombosis, seizure, pulmonary embolism, acute respiratory distress syndrome, cardiac failure, liver failure, renal failure, cerebrovascular accident, cardiac arrest, cerebral vasospasm, "any thromboembolism," hypernatremia, acute kidney injury, and infection. Other unfavorable outcomes analyzed include mortality at 28 days and 6 months, Glasgow Outcome Scale-Extended score of ≤4 at discharge and 6 months, intensive care unit-free days, ventilator-free days, hospital-free days, and combined unfavorable outcomes. In both study drug groups, the incidence of dichotomous outcomes and quantity of ordinal outcomes were compared with placebo. RESULTS: No statistically significant increase in adverse events or unfavorable outcomes was found between either TXA dosing regimen and placebo. Demographics and injury scores were not statistically different other than two methods of injury, which were overrepresented in the 1-g TXA bolus plus 1-g TXA infusion. CONCLUSION: Administration of either a 2-g TXA bolus or a 1-g TXA bolus plus 1-g TXA 8-hour infusion in suspected TBIs without ICH is not associated with increased adverse events or unfavorable outcomes. Because the out-of-hospital 2-g bolus is associated with a mortality benefit, it should be administered in suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Viscoelastic Testing in Traumatic Brain Injury: Key Research Insights.

The role of viscoelastic testing in the evaluation and management of traumatic brain injury (TBI) remains a subject of ongoing exploration. This review highlights four key publications that provide significant insights into this subject. Holcomb et al. provided early evidence of the relationship between thromboelastography (TEG) and conventional coagulation tests (CCTs). Later, Samuels et al. used TEG to identify a unique coagulopathy phenotype in TBI characterized by a notable absence of fibrinolytic abnormalities. Dixon et al. built upon these findings by exploring the application of TEG in the context of antifibrinolytic administration, noting a similar lack of effect on LY30. Finally, Guillotte et al. demonstrated the utility of TEG-PM in assessing platelet dysfunction in TBI. While these studies provide key early support for the utility of viscoelastic testing in the TBI, further exploration is needed to define evidence-based guidelines for clinical application.

Protect Our Kids: a novel program bringing hemorrhage control to schools.

BACKGROUND: Following the shooting at Sandy Hook Elementary School, the Hartford Consensus produced the Stop the Bleed program to train bystanders in hemorrhage control. In our region, the police bureau delivers critical incident training to public schools, offering instruction in responding to violent or dangerous situations. Until now, widespread training in hemorrhage control has been lacking. Our group developed, implemented and evaluated a novel program integrating hemorrhage control into critical incident training for school staff in order to blunt the impact of mass casualty events on children. METHODS: The staff of 25 elementary and middle schools attended a 90-minute course incorporating Stop the Bleed into the critical incident training curriculum, delivered on-site by police officers, nurses and doctors over a three-day period. The joint program was named Protect Our Kids. At the conclusion of the course, hemorrhage control kits and educational materials were provided and a four-question survey to assess the quality of training using a ten-point Likert scale was completed by participants and trainers. RESULTS: One thousand eighteen educators underwent training. A majority were teachers (78.2%), followed by para-educators (5.8%), counselors (4.4%) and principals (2%). Widely covered by local and state media, the Protect Our Kids program was rated as excellent and effective by a majority of trainees and all trainers rated the program as excellent. CONCLUSIONS: Through collaboration between trauma centers, police and school systems, a large-scale training program for hemorrhage control and critical incident response can be effectively delivered to schools.

Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Traumatic brain injury is associated with coagulopathy that increases mortality risk. Viscoelastic hemostatic assays such as thromboelastography (Haemonetics SA, Signy, Switzerland) provide rapid coagulopathy assessment and may be particularly useful for goal-directed treatment of traumatic brain injury patients. We conducted a systematic review to assess thromboelastography in the evaluation and management of coagulopathy in traumatic brain injury patients. DATA SOURCES: MEDLINE, PubMed Central, Embase, and CENTRAL. STUDY SELECTION: Clinical studies of adult patients with traumatic brain injury (isolated or polytrauma) who were assessed by either standard thromboelastography or thromboelastography with platelet mapping plus either conventional coagulation assays or platelet function assays from January 1999 to June 2021. DATA EXTRACTION: Demographics, injury mechanism and severity, diagnostic, laboratory data, therapies, and outcome data were extracted for analysis and comparison. DATA SYNTHESIS: Database search revealed 1,169 sources; eight additional articles were identified by the authors. After review, 31 publications were used for qualitative analysis, and of these, 16 were used for quantitative analysis. Qualitative and quantitative analysis found unique patterns of thromboelastography and thromboelastography with platelet mapping parameters in traumatic brain injury patients. Patterns were distinct compared with healthy controls, nontraumatic brain injury trauma patients, and traumatic brain injury subpopulations including those with severe traumatic brain injury or penetrating traumatic brain injury. Abnormal thromboelastography K-time and adenosine diphosphate % inhibition on thromboelastography with platelet mapping are associated with decreased survival after traumatic brain injury. Subgroup meta-analysis of severe traumatic brain injury patients from two randomized controlled trials demonstrated improved survival when using a viscoelastic hemostatic assay-guided resuscitation strategy (odds ratio, 0.39; 95% CI, 0.17-0.91; p = 0.030). CONCLUSIONS: Thromboelastography and thromboelastography with platelet mapping characterize coagulopathy patterns in traumatic brain injury patients. Abnormal thromboelastography profiles are associated with poor outcomes. Conversely, treatment protocols designed to normalize abnormal parameters may be associated with improved traumatic brain injury patient outcomes. Current quality of evidence in this population is low; so future efforts should evaluate viscoelastic hemostatic assay-guided hemostatic resuscitation in larger numbers of traumatic brain injury patients with specific focus on those with traumatic brain injury-associated coagulopathy.

Civilian walking blood bank emergency preparedness plan.

BACKGROUND: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. METHODS AND MATERIALS: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. RESULTS AND CONCLUSIONS: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Temporal profile of the pro- and anti-inflammatory responses to severe hemorrhage in patients with venous thromboembolism: Findings from the PROPPR trial.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE. STUDY DESIGN: Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance. RESULTS: Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1ß, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 ß (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation. CONCLUSION: Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events. LEVEL OF EVIDENCE: Prognostic, level III.

Fibrinolytic Activation in Patients with Progressive Intracranial Hemorrhage after Traumatic Brain Injury.

Progression of intracranial hemorrhage (PICH) is a significant cause of secondary brain injury in patients with traumatic brain injury (TBI). Previous studies have implicated a variety of mediators that contribute to PICH. We hypothesized that patients with PICH would display either a hypocoagulable state, hyperfibrinolysis, or both. We conducted a prospective study of adult trauma patients with isolated TBI. Blood was obtained for routine coagulation assays, platelet count, fibrinogen, thrombelastography, markers of thrombin generation, and markers of fibrinolysis at admission and 6, 12, 24, and 48 h. Univariate analyses were performed to compare baseline characteristics between groups. Linear regression models were created, adjusting for baseline differences, to determine the relationship between individual assays and PICH. One hundred forty-one patients met entry criteria, of whom 71 had hemorrhage progression. Patients with PICH had a higher Injury Severity Score and Abbreviated Injury Scale score (head), a lower Glasgow Coma Scale score, and lower plasma sodium on admission. Patients with PICH had higher D-dimers on admission. After adjusting for baseline differences, elevated D-dimers remained significantly associated with PICH compared to patients without PICH at admission. Hypocoagulation was not significantly associated with PICH in these patients. The association between PICH and elevated D-dimers early after injury suggests that fibrinolytic activation may contribute to PICH in patients with TBI.