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Browsing by Author "Kwaan, Hau C."
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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 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 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 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 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.Item Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices(MDPI, 2022-02-07) Volod, Oksana; Bunch, Connor M.; Zackariya, Nuha; Moore, Ernest E.; Moore, Hunter B.; Kwaan, Hau C.; Neal, Matthew D.; Al-Fadhl, Mahmoud D.; Patel, Shivani S.; Wiarda, Grant; Al-Fadhl, Hamid D.; McCoy, Max L.; Thomas, Anthony V.; Thomas, Scott G.; Gillespie, Laura; Khan, Rashid Z.; Zamlut, Mahmud; Kamphues, Peter; Fries, Dietmar; Walsh, Mark M.; Medicine, School of MedicineViscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.Item Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review(MDPI, 2021-01-17) Walsh, Mark; Moore, Ernest E.; Moore, Hunter B.; Thomas, Scott; Kwaan, Hau C.; Speybroeck, Jacob; Marsee, Mathew; Bunch, Connor M.; Stillson, John; Thomas, Anthony V.; Grisoli, Annie; Aversa, John; Fulkerson, Daniel; Vande Lune, Stefani; Sjeklocha, Lucas; Tran, Quincy K.; Medicine, School of MedicineThis narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.