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Item Evaluation of Tranexamic Acid and Calcium Chloride in Major Traumas in a Prehospital Setting: A Narrative Review(Wolters Kluwer, 2023) Bell, Kameron T.; Salmon, Chase M.; Purdy, Benjamin A.; Canfield, Scott G.; Anatomy, Cell Biology and Physiology, School of MedicineExcessive blood loss in the prehospital setting poses a significant challenge and is one of the leading causes of death in the United States. In response, emergency medical services (EMS) have increasingly adopted the use of tranexamic acid (TXA) and calcium chloride (CaCl2) as therapeutic interventions for hemorrhagic traumas. Tranexamic acid functions by inhibiting plasmin formation and restoring hemostatic balance, while calcium plays a pivotal role in the coagulation cascade, facilitating the conversion of factor X to factor Xa and prothrombin to thrombin. Despite the growing utilization of TXA and CaCl2 in both prehospital and hospital environments, a lack of literature exists regarding the comparative effectiveness of these agents in reducing hemorrhage and improving patient outcomes. Notably, Morgan County Indiana EMS recently integrated the administration of TXA with CaCl2 into their treatment protocols, offering a valuable opportunity to gather insight and formulate updated guidelines based on patient-centered outcomes. This narrative review aims to comprehensively evaluate the existing evidence concerning the administration of TXA and CaCl2 in the prehospital management of hemorrhages, while also incorporating and analyzing data derived from the co-administration of these medications within the practices of Morgan County EMS. This represents the inaugural description of the concurrent use of both TXA and CaCl2 to manage hemorrhages in the scientific literature.Item Hemostasis biomarkers and incident cognitive impairment: the REGARDS study(Wiley, 2018-07) Gillett, S.R.; McClure, L.A.; Callas, P.W.; Thacker, E.L.; Unverzagt, F.W.; Wadley, V.G.; Letter, A.J.; Cushman, M.; Psychiatry, IU School of MedicineEssentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk. SUMMARY: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 μg mL-1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant.Item SHock-INduced Endotheliopathy (SHINE): A mechanistic justification for viscoelastography-guided resuscitation of traumatic and non-traumatic shock(Frontiers Media, 2023-02-27) Bunch, Connor M.; Chang, Eric; Moore, Ernest E.; Moore, Hunter B.; Kwaan, Hau C.; Miller, Joseph B.; Al-Fadhl, Mahmoud D.; Thomas, Anthony V.; Zackariya, Nuha; Patel, Shivani S.; Zackariya, Sufyan; Haidar, Saadeddine; Patel, Bhavesh; McCurdy, Michael T.; Thomas, Scott G.; Zimmer, Donald; Fulkerson, Daniel; Kim, Paul Y.; Walsh, Matthew R.; Hake, Daniel; Kedar, Archana; Aboukhaled, Michael; Walsh, Mark M.; Graduate Medical Education, School of MedicineIrrespective of the reason for hypoperfusion, hypocoagulable and/or hyperfibrinolytic hemostatic aberrancies afflict up to one-quarter of critically ill patients in shock. Intensivists and traumatologists have embraced the concept of SHock-INduced Endotheliopathy (SHINE) as a foundational derangement in progressive shock wherein sympatho-adrenal activation may cause systemic endothelial injury. The pro-thrombotic endothelium lends to micro-thrombosis, enacting a cycle of worsening perfusion and increasing catecholamines, endothelial injury, de-endothelialization, and multiple organ failure. The hypocoagulable/hyperfibrinolytic hemostatic phenotype is thought to be driven by endothelial release of anti-thrombogenic mediators to the bloodstream and perivascular sympathetic nerve release of tissue plasminogen activator directly into the microvasculature. In the shock state, this hemostatic phenotype may be a counterbalancing, yet maladaptive, attempt to restore blood flow against a systemically pro-thrombotic endothelium and increased blood viscosity. We therefore review endothelial physiology with emphasis on glycocalyx function, unique biomarkers, and coagulofibrinolytic mediators, setting the stage for understanding the pathophysiology and hemostatic phenotypes of SHINE in various etiologies of shock. We propose that the hyperfibrinolytic phenotype is exemplified in progressive shock whether related to trauma-induced coagulopathy, sepsis-induced coagulopathy, or post-cardiac arrest syndrome-associated coagulopathy. Regardless of the initial insult, SHINE appears to be a catecholamine-driven entity which early in the disease course may manifest as hyper- or hypocoagulopathic and hyper- or hypofibrinolytic hemostatic imbalance. Moreover, these hemostatic derangements may rapidly evolve along the thrombohemorrhagic spectrum depending on the etiology, timing, and methods of resuscitation. Given the intricate hemochemical makeup and changes during these shock states, macroscopic whole blood tests of coagulative kinetics and clot strength serve as clinically useful and simple means for hemostasis phenotyping. We suggest that viscoelastic hemostatic assays such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are currently the most applicable clinical tools for assaying global hemostatic function—including fibrinolysis—to enable dynamic resuscitation with blood products and hemostatic adjuncts for those patients with thrombotic and/or hemorrhagic complications in shock states.Item Systems biology of platelet-vessel wall interactions(Springer, 2014) Chen, Yolande; Corey, Seth Joel; Kim, Oleg V.; Alber, Mark S.; Department of Medicine, IU School of MedicinePlatelets are small, anucleated cells that participate in primary hemostasis by forming a hemostatic plug at the site of a blood vessel's breach, preventing blood loss. However, hemostatic events can lead to excessive thrombosis, resulting in life-threatening strokes, emboli, or infarction. Development of multi-scale models coupling processes at several scales and running predictive model simulations on powerful computer clusters can help interdisciplinary groups of researchers to suggest and test new patient-specific treatment strategies.Item Use of Thromboelastography in the Evaluation and Management of Patients With Traumatic Brain Injury: A Systematic Review and Meta-Analysis(Wolters Kluwer, 2021-09-14) Cannon, Jeremy W.; Dias, João D.; Kumar, Monisha A.; Walsh, Mark; Thomas, Scott G.; Cotton, Bryan A.; Schuster, James M.; Evans, Susan L.; Schreiber, Martin A.; Adam, Elisabeth H.; Zacharowsk, Kai; Hartmann, Jan; Schöchl, Herbert; Kaplan, Lewis J.; Medicine, School of MedicineTraumatic 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.Item VIBe Scale: Validation of the Intraoperative Bleeding Severity Scale by Spine Surgeons(International Society for the Advancement of Spine Surgery (ISASS), 2022) Sciubba, Daniel M.; Khanna, Nitin; Pennington, Zach; Singh, Rahul K.; Orthopaedic Surgery, School of MedicineBackground: The Validated Intraoperative Bleeding Scale (VIBe Scale) was initially validated with surgeons who operate on cardiothoracic, abdominal, and pelvic cavities and fulfilled criteria for a clinician-reported scale. However, there is a need for a tool to aid in intraoperative blood management during spine surgeries. The purpose of the present study was to establish the reliability and consistency of the VIBe Scale as a tool for spine surgeons to assess intraoperative bleeding. Methods: Orthopedic (n = 16) and neurological (n = 9) spine surgeons scored videos depicting surgical bleeding and assessed the VIBe Scale's relevance and clarity. Inter- and intraobserver agreement (Kendall's W) were calculated for all surgeons and pooled with responses from the original study to establish agreement across specialties. Results: All of the spine surgeons indicated that the scale was clinically relevant for evaluating hemostasis and could be implemented in a clinical study. Twenty-two spine surgeons (88%) reported that the scale represents the range of bleeding site sizes and severities expected in their practice. Twenty-four spine surgeons (96%) indicated that the scale would be useful in communicating bleeding severity with other members of the surgical team. Interobserver agreement was acceptable (0.79) for orthopedic specialists, appreciable (0.88) for neurological specialists, and appreciable (0.88) for the combined specialists. Intraobserver agreement was excellent for orthopedic (0.91) and neurological (0.91) spine surgeons and excellent (0.96) for the combined specialists. Conclusions: The results highlight the reliability of the VIBe Scale and potential utility for quantifying intraoperative blood loss in spine surgery. Clinical relevance: The VIBe Scale may be useful for evaluating the efficacy of untested intraoperative hemostatic agents and for comparing the relative efficacy of 2 or more analogous agents. It may also prove useful for intraoperative staff by quantifying ongoing intraoperative blood loss and correlating losses with the potential transfusion and intraoperative hemostatic agent requirements.