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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 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.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 Tension pneumomediastinum and diffuse subcutaneous emphysema with severe acute respiratory syndrome coronavirus 2 infection requiring operative management for impending airway collapse: A case report(Wiley, 2021-08) Lin, Kevin P.; Stefaniak, Christopher; Bunch, Connor M.; March, Robert; Zamlut, Mahmud; Raza, Syed; Osorio, Walter; Korzan, Josh; Show, Jeffery; Mjaess, Nicolas; Patel, Shivani; Zackariya, Sufyan; Sualeh, Ali; Wiarda, Grant; Al‐Fadhl, Hamid; Thomas, Anthony V.; Khan, Rashid Z.; Gillespie, Laura; Walsh, Mark M.; Medicine, School of MedicineTension pneumomediastinum is a rare complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that has increased in incidence with the novel coronavirus disease 2019 pandemic. Although traditionally managed with conservative measures, we present the indications and methods for the first operative management of tension pneumomediastinum with concomitant SARS-CoV-2 infection.Item Thromboelastography-Guided Anticoagulant Therapy for the Double Hazard of Thrombohemorrhagic Events in COVID-19: A Report of 3 Cases(International Scientific Information, 2021) Bunch, Connor M.; Thomas, Anthony V.; Stillson, John E.; Gillespie, Laura; Lin, Kevin P.; Speybroeck, Jacob; Kwaan, Hau C.; Fulkerson, Daniel H.; Zamlut, Mahmud; Khan, Rashid; Walsh, Mark M.; Medicine, School of MedicineBACKGROUND: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often manifests a coagulopathy in severely ill patients, which may cause hemorrhage and/or thrombosis of varying severity. This report comprises the cases of 3 patients with COVID-19-associated coagulopathy who were evaluated with thromboelastography (TEG) and activated partial thromboplastin time (aPTT) to enable personalized anticoagulant therapy. CASE REPORT: Three patients presented with COVID-19 pneumonia, confirmed by reverse transcription-polymerase chain reaction, who developed thrombohemorrhagic coagulopathy. Case 1: A 72-year-old woman on long-term warfarin therapy for a history of venous thromboembolism developed a right upper lobe pulmonary embolus, despite an international normalized ratio of 6.4 and aPTT of 120.7 s. TEG enabled successful anticoagulation with heparin, and her pulmonary infarct was no longer present 2 weeks later. Case 2: A 55-year-old woman developed a rectus sheath hematoma while on heparin, and TEG demonstrated increased fibrinolysis despite COVID-19 patients more commonly undergoing fibrinolytic shutdown. Case 3: A 43-year-old woman had significant thrombus burden while severely hypocoagulable according to laboratory testing. As the venous thrombi enlarged in a disseminated intravascular coagulopathic-like state, the heparin dose was escalated to achieve a target aPTT of 70 to 80 s, resulting in a flat line TEG tracing. CONCLUSIONS: These 3 cases of COVID-19 pneumonia with complex and varied clinical histories demonstrated the clinical value of TEG combined with the measurement of aPTT to facilitate personalized anticoagulation, resulting in good clinical outcomes.