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Item Brodifacoum contamination of synthetic cannabinoid causing unexplained coagulopathy in multiple trauma: A case report(Elsevier, 2024-04-01) Thomas, Anthony V.; Johnson, Mackenzie L.; Tincher, Anna M.; Zackariya, Saniya; Khan, Hassaan; Rizvi, Uzma; Thomas, Scott G.; Noveroske, Timothy W.; Fulkerson, Daniel H.; Moore, Ernest E.; Walsh, Mark M.; Medicine, School of MedicineAn 18-year-old female presented to the emergency department after a motor vehicle collision. Initial imaging revealed a liver laceration. Subsequent labs showed significantly elevated prothrombin time, international normalized ratio, and activated partial thromboplastin time. Thromboelastography demonstrated a flatline tracing. The patient denied use of anticoagulation but admitted to synthetic cannabinoid use. It was believed the patient had taken synthetic cannabinoid contaminated by brodifacoum. She was therefore given prothrombin complex concentrate and vitamin K with blood products. The patient underwent sequential embolization, laparotomy, thoracotomy, and repair of the vena cava with a shunt. Thirty minutes postoperatively, her coagulation tests and thromboelastography were much improved. Two and a half hours postoperatively, it was determined she had sustained non-survivable injuries. The patient experienced brain death due to prolonged hypotension as a result of hemorrhagic shock with bleeding exacerbated by brodifacoum. To our knowledge, this is the first case reported of a trauma-induced coagulopathy exacerbated by brodifacoum-contaminated synthetic cannabinoid. Her coagulopathy was clearly not due to trauma alone and contributed greatly to the difficulty in controlling hemorrhage. The synthetic cannabinoid-associated coagulopathy rendered her otherwise potentially survivable injuries fatal. Given the frequency of multiple trauma and the recent increase in the prevalence of synthetic cannabinoid, it can be expected that the incidence of trauma complicated by synthetic cannabinoid-associated coagulopathy will increase in the near future. For patients that present with prolonged prothrombin time and/or activated partial thromboplastin time, it is important to inquire about recent synthetic cannabinoid use.Item A Case Series of Thromboelastography-Guided Anticoagulation in COVID-19 Patients with Inherited and Acquired Hypercoagulable States(Hindawi, 2021-08-03) Thomas, Anthony V.; Lin, Kevin P.; Stillson, John E.; Bunch, Connor M.; Speybroeck, Jacob; Wiarda, Grant; Al-Fadhl, Hamid; Gillespie, Laura; Zamlut, Mahmud; Fulkerson, Daniel H.; Khan, Rashid Z.; Kwaan, Hau C.; Walsh, Mark M.; Emergency Medicine, School of MedicineOne of the complications of the novel coronavirus disease 2019 (COVID-19) is hypercoagulability. For this reason, patients presenting with COVID-19 are often put on therapeutic or intermediate anticoagulation upon hospitalization. A common issue of this anticoagulation is the progression to hypocoagulability resulting in hemorrhage. Therefore, monitoring the hemostatic integrity of critically ill COVID-19 patients is of utmost importance. In this case series, we present the cases of three coagulopathic COVID-19 patients whose anticoagulation was guided by thromboelastography (TEG). In each case, TEG permitted the clinical team to simultaneously prevent thrombotic and hemorrhagic events, a difficult task for COVID-19 patients admitted to the intensive care unit. The first two cases illustrate the utility of TEG to guide anticoagulant dosing for COVID-19 patients when the activated partial thromboplastin time (aPTT) is inaccurate. The first case was a severely ill COVID-19 patient with end-stage renal disease and a falsely elevated aPTT secondary to hypertriglyceridemia. The second case was a severely ill COVID-19 patient with chronic pulmonary disease who demonstrated a falsely elevated aPTT due to polycythemia and hemoconcentration. In both cases, TEG was sensitive to the hypercoagulability caused by the metabolic derangements which enabled the goal-directed titration of anticoagulants. The last case depicts a severely ill COVID-19 patient with an inherited factor V Leiden mutation who required abnormally high dosing to achieve therapeutic anticoagulation, guided by TEG. Hypercoagulopathic COVID-19 patients are difficult to anticoagulate without development of hypocoagulopathy. Treatment of these patients demands goal-directed therapy by diligent laboratory monitoring. This can be accomplished by the use of TEG coupled with aPTT to guide anticoagulation. This case series illustrates the necessity for active hemostatic monitoring of critically ill COVID-19 patients.Item Corrigendum: Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies(Frontiers Media, 2024-02-06) Marsh, Phillip L.; Moore, Ernest E.; Moore, Hunter B.; Bunch, Connor M.; Aboukhaled, Michael; Condon, Shaun M., II; Al-Fadhl, Mahmoud D.; Thomas, Samuel J.; Larson, John R.; Bower, Charles W.; Miller, Craig B.; Pearson, Michelle L.; Twilling, Christopher L.; Reser, David W.; Kim, George S.; Troyer, Brittany M.; Yeager, Doyle; Thomas, Scott G.; Srikureja, Daniel P.; Patel, Shivani S.; Añón, Sofía L.; Thomas, Anthony V.; Miller, Joseph B.; Van Ryn, David E.; Pamulapati, Saagar V.; Zimmerman, Devin; Wells, Byars; Martin, Peter L.; Seder, Christopher W.; Aversa, John G.; Greene, Ryan B.; March, Robert J.; Kwaan, Hau C.; Fulkerson, Daniel H.; Vande Lune, Stefani A.; Mollnes, Tom E.; Nielsen, Erik W.; Storm, Benjamin S.; Walsh, Mark M.; Medicine, School of Medicine[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].Item COVID-associated non-vasculitic thrombotic retiform purpura of the face and extremities: A case report(Wiley, 2022-12-27) Bunch, Connor M.; Zackariya, Nuha; Thomas, Anthony V.; Langford, Jack H.; Aboukhaled, Michael; Thomas, Samuel J.; Ansari, Aida; Patel, Shivani S.; Buckner, Hallie; Miller, Joseph B.; Annis, Christy L.; Quate-Operacz, Margaret A.; Schmitz, Leslie A.; Pulvirenti, Joseph J.; Konopinski, Jonathan C.; Kelley, Kathleen M.; Hassna, Samer; Nelligan, Luke G.; Walsh, Mark M.; Medicine, School of MedicineSARS-CoV-2 infection can manifest many rashes. However, thrombotic retiform purpura rarely occurs during COVID-19 illness. Aggressive anti-COVID-19 therapy with a high-dose steroid regimen led to rapid recovery. This immunothrombotic phenomenon likely represents a poor type 1 interferon response and complement activation on the endothelial surface in response to acute infection.Item Hemorrhagic Resuscitation Guided by Viscoelastography in Far-Forward Combat and Austere Civilian Environments: Goal-Directed Whole-Blood and Blood-Component Therapy Far from the Trauma Center(MDPI, 2022-01-12) Lantry, James H.; Mason, Phillip; Logsdon, Matthew G.; Bunch, Connor M.; Peck, Ethan E.; Moore, Ernest E.; Moore, Hunter B.; Neal, Matthew D.; Thomas, Scott G.; Khan, Rashid Z.; Gillespie, Laura; Florance, Charles; Korzan, Josh; Preuss, Fletcher R.; Mason, Dan; Saleh, Tarek; Marsee, Mathew K.; Vande Lune, Stefani; Ayoub, Qamarnisa; Fries, Dietmar; Walsh, Mark M.; Emergency Medicine, School of MedicineModern approaches to resuscitation seek to bring patient interventions as close as possible to the initial trauma. In recent decades, fresh or cold-stored whole blood has gained widespread support in multiple settings as the best first agent in resuscitation after massive blood loss. However, whole blood is not a panacea, and while current guidelines promote continued resuscitation with fixed ratios of blood products, the debate about the optimal resuscitation strategy-especially in austere or challenging environments-is by no means settled. In this narrative review, we give a brief history of military resuscitation and how whole blood became the mainstay of initial resuscitation. We then outline the principles of viscoelastic hemostatic assays as well as their adoption for providing goal-directed blood-component therapy in trauma centers. After summarizing the nascent research on the strengths and limitations of viscoelastic platforms in challenging environmental conditions, we conclude with our vision of how these platforms can be deployed in far-forward combat and austere civilian environments to maximize survival.Item Immuno-Thrombotic Complications of COVID-19: Implications for Timing of Surgery and Anticoagulation(Frontiers Media, 2022-05-04) Bunch, Connor M.; Moore, Ernest E.; Moore, Hunter B.; Neal, Matthew D.; Thomas, Anthony V.; Zackariya, Nuha; Zhao, Jonathan; Zackariya, Sufyan; Brenner, Toby J.; Berquist, Margaret; Buckner, Hallie; Wiarda, Grant; Fulkerson, Daniel; Huff, Wei; Kwaan, Hau C.; Lankowicz, Genevieve; Laubscher, Gert J.; Lourens, Petrus J.; Pretorius, Etheresia; Kotze, Maritha J.; Moolla, Muhammad S.; Sithole, Sithembiso; Maponga, Tongai G.; Kell, Douglas B.; Fox, Mark D.; Gillespie, Laura; Khan, Rashid Z.; Mamczak, Christiaan N.; March, Robert; Macias, Rachel; Bull, Brian S.; Walsh, Mark M.; Surgery, School of MedicineEarly in the coronavirus disease 2019 (COVID-19) pandemic, global governing bodies prioritized transmissibility-based precautions and hospital capacity as the foundation for delay of elective procedures. As elective surgical volumes increased, convalescent COVID-19 patients faced increased postoperative morbidity and mortality and clinicians had limited evidence for stratifying individual risk in this population. Clear evidence now demonstrates that those recovering from COVID-19 have increased postoperative morbidity and mortality. These data-in conjunction with the recent American Society of Anesthesiologists guidelines-offer the evidence necessary to expand the early pandemic guidelines and guide the surgeon's preoperative risk assessment. Here, we argue elective surgeries should still be delayed on a personalized basis to maximize postoperative outcomes. We outline a framework for stratifying the individual COVID-19 patient's fitness for surgery based on the symptoms and severity of acute or convalescent COVID-19 illness, coagulopathy assessment, and acuity of the surgical procedure. Although the most common manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is COVID-19 pneumonitis, every system in the body is potentially afflicted by an endotheliitis. This endothelial derangement most often manifests as a hypercoagulable state on admission with associated occult and symptomatic venous and arterial thromboembolisms. The delicate balance between hyper and hypocoagulable states is defined by the local immune-thrombotic crosstalk that results commonly in a hemostatic derangement known as fibrinolytic shutdown. In tandem, the hemostatic derangements that occur during acute COVID-19 infection affect not only the timing of surgical procedures, but also the incidence of postoperative hemostatic complications related to COVID-19-associated coagulopathy (CAC). Traditional methods of thromboprophylaxis and treatment of thromboses after surgery require a tailored approach guided by an understanding of the pathophysiologic underpinnings of the COVID-19 patient. Likewise, a prolonged period of risk for developing hemostatic complications following hospitalization due to COVID-19 has resulted in guidelines from differing societies that recommend varying periods of delay following SARS-CoV-2 infection. In conclusion, we propose the perioperative, personalized assessment of COVID-19 patients' CAC using viscoelastic hemostatic assays and fluorescent microclot analysis.Item Markers of Futile Resuscitation in Traumatic Hemorrhage: A Review of the Evidence and a Proposal for Futility Time-Outs during Massive Transfusion(MDPI, 2024-08-09) Walsh, Mark M.; Fox, Mark D.; Moore, Ernest E.; Johnson, Jeffrey L.; Bunch, Connor M.; Miller, Joseph B.; Lopez-Plaza, Ileana; Brancamp, Rachel L.; Waxman, Dan A.; Thomas, Scott G.; Fulkerson, Daniel H.; Thomas, Emmanuel J.; Khan, Hassaan A.; Zackariya, Sufyan K.; Al-Fadhl, Mahmoud D.; Zackariya, Saniya K.; Thomas, Samuel J.; Aboukhaled, Michael W.; Futile Indicators for Stopping Transfusion in Trauma (FISTT) Collaborative Group; Medicine, School of MedicineThe reduction in the blood supply following the 2019 coronavirus pandemic has been exacerbated by the increased use of balanced resuscitation with blood components including whole blood in urban trauma centers. This reduction of the blood supply has diminished the ability of blood banks to maintain a constant supply to meet the demands associated with periodic surges of urban trauma resuscitation. This scarcity has highlighted the need for increased vigilance through blood product stewardship, particularly among severely bleeding trauma patients (SBTPs). This stewardship can be enhanced by the identification of reliable clinical and laboratory parameters which accurately indicate when massive transfusion is futile. Consequently, there has been a recent attempt to develop scoring systems in the prehospital and emergency department settings which include clinical, laboratory, and physiologic parameters and blood products per hour transfused as predictors of futile resuscitation. Defining futility in SBTPs, however, remains unclear, and there is only nascent literature which defines those criteria which reliably predict futility in SBTPs. The purpose of this review is to provide a focused examination of the literature in order to define reliable parameters of futility in SBTPs. The knowledge of these reliable parameters of futility may help define a foundation for drawing conclusions which will provide a clear roadmap for traumatologists when confronted with SBTPs who are candidates for the declaration of futility. Therefore, we systematically reviewed the literature regarding the definition of futile resuscitation for patients with trauma-induced hemorrhagic shock, and we propose a concise roadmap for clinicians to help them use well-defined clinical, laboratory, and viscoelastic parameters which can define futility.Item Preventing Thrombohemorrhagic Complications of Heparinized COVID-19 Patients Using Adjunctive Thromboelastography: A Retrospective Study(MDPI, 2021-07-14) Bunch, Connor M.; Thomas, Anthony V.; Stillson, John E.; Gillespie, Laura; Khan, Rashid Z.; Zackariya, Nuha; Shariff, Faadil; Al-Fadhl, Mahmoud; Mjaess, Nicolas; Miller, Peter D.; McCurdy, Michael T.; Fulkerson, Daniel H.; Miller, Joseph B.; Kwaan, Hau C.; Moore, Ernest E.; Moore, Hunter B.; Neal, Matthew D.; Martin, Peter L.; Kricheff, Mark L.; Walsh, Mark M.; Medicine, School of MedicineBACKGROUND: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. METHODS: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. RESULTS: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). CONCLUSIONS: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography.Item Resonant Acoustic Rheometry to Measure Coagulation Kinetics in Hemophilia A and Healthy Plasma: A Novel Viscoelastic Method(Thieme, 2023) Li, Weiping; Hobson, Eric C.; Bunch, Connor M.; Miller, Joseph B.; Nehme, Jimmy; Kwaan, Hau C.; Walsh, Mark M.; McCurdy, Michael T.; Aversa, John G.; Thomas, Anthony V.; Zackariya, Nuha; Thomas, Samuel J.; Smith, Stephanie A.; Cook, Bernard C.; Boyd, Bryan; Stegemann, Jan P.; Deng, Cheri X.; Surgery, School of MedicineCompared with conventional coagulation tests and factor-specific assays, viscoelastic hemostatic assays (VHAs) can provide a more thorough evaluation of clot formation and lysis but have several limitations including clot deformation. In this proof-of-concept study, we test a noncontact technique, termed resonant acoustic rheometry (RAR), for measuring the kinetics of human plasma coagulation. Specifically, RAR utilizes a dual-mode ultrasound technique to induce and detect surface oscillation of blood samples without direct physical contact and measures the resonant frequency of the surface oscillation over time, which is reflective of the viscoelasticity of the sample. Analysis of RAR results of normal plasma allowed defining a set of parameters for quantifying coagulation. RAR detected a flat-line tracing of resonant frequency in hemophilia A plasma that was corrected with the addition of tissue factor. Our RAR results captured the kinetics of plasma coagulation and the newly defined RAR parameters correlated with increasing tissue factor concentration in both healthy and hemophilia A plasma. These findings demonstrate the feasibility of RAR as a novel approach for VHA, providing the foundation for future studies to compare RAR parameters to conventional coagulation tests, factor-specific assays, and VHA parameters.Item Serial “death diamond” TEGs are a bedside indicator of futile resuscitation during massive transfusion(Wolters Kluwer, 2023) Moore, Ernest E.; Moore, Hunter B.; Thomas, Scott G.; Farrell, Michael S.; Sixta, Sherry; Coleman, Julia R.; Miller, Joseph B.; Bunch, Connor M.; Waxman, Dan; Walsh, Mark M.; Emergency Medicine, School of MedicineSerial DDs could serve as rapid check points to gauge the likelihood of success of continued resuscitation. Loudon et al.’s work combined with the use of serial DDs may serve as building blocks toward a trial using VETs to predict continued futile resuscitation.