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Background: Throughout the COVID-19 pandemic, the mortality of critically ill patients remained high. Our group developed a treatment regimen targeting sepsis and ARDS which we labeled "triple therapy" consisting of (1) corticosteroids, (2) therapeutic plasma exchange (TPE), and (3) timely intubation with lung protective ventilation. Our propensity analysis assesses the impact of triple therapy on survival in COVID-19 patients with sepsis and ARDS., Methods: Retrospective propensity analysis comparing triple therapy to no triple therapy in adult critically ill COVID-19 patients admitted to the Intensive Care Unit at Lexington Medical Center from 1 March 2020 through 31 October 2021., Results: Eight hundred and fifty-one patients were admitted with COVID-19 and 53 clinical and laboratory variables were analyzed. Multivariable analysis revealed that triple therapy was associated with increased survival (OR: 1.91; P = .008). Two propensity score-adjusted models demonstrated an increased likelihood of survival in patients receiving triple therapy. Patients with thrombocytopenia were among those most likely to experience increased survival if they received early triple therapy. Decreased survival was observed with endotracheal intubation ≥7 days from hospital admission (P < .001) and there was a trend toward decreased survival if TPE was initiated ≥6 days from hospital admission (P = .091)., Conclusion: Our analysis shows that early triple therapy, defined as high-dose methylprednisolone, TPE, and timely invasive mechanical ventilation within the first 96 hours of admission, may improve survival in critically ill septic patients with ARDS secondary to COVID-19 infection. Further studies are needed to define specific phenotypes and characteristics that will identify those patients most likely to benefit., (© 2024 The Authors. Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has also expanded. Among these are clinical conditions such as postcardiopulmonary bypass, sepsis, ECMO cardiopulmonary resuscitation, and even severe coronavirus disease 2019 (COVID-19). Not surprisingly, the number of ECMO cases has increased according to the Extracorporeal Life Support Organization Registry and prolonged ECMO support has become more prevalent. It is not uncommon for patients with COVID-19 to be on ECMO support for more than 1 year until recovery or lung transplant. With that being said, complications of bleeding, thrombosis, clot formation in the circuit, and intravascular hemolysis still remain and continue to be major challenges. Here, several clinical ECMO experts, including the "Father of ECMO"-Dr. Robert Bartlett, describe the history and advances of ECMO., Competing Interests: D.J.A. received research funding from Bayer plc and Leo Pharma. J.T. received honorarium from Entegrion and member of DSMB for Evaheart. T.R. has the patent of activators of factor XII. M.C. received grants from Genentech, Agios Pharmaceutical, and Novartis, and honoraria from Genentech, Agios Pharmaceuticals, Takeda, BPL, CSL Behring, Genzyme Corp, Emerging Therapies Solutions, and Novo Nordisk; all outside this article., (Thieme. All rights reserved.)

Neonatal and pediatric extracorporeal membrane oxygenation (ECMO) has evolved over the past 50 years. Advances in technology, expertise, and application have increased the number of centers providing ECMO with expanded indications for use. However, increasing the use of ECMO in recent years to more medically complex critically ill children has not changed overall survival despite increased experience and improvements in technology. This review focuses on ECMO history, circuits, indications and contraindications, management, complications, and outcome data. The authors highlight important areas of progress, including unintubated and awake patients on ECMO, application during the COVID-19 pandemic, and future directions., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers., Design: A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity., Setting: ICU at an academic medical center and an academic laboratory., Patients: Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis., Interventions: None., Measurements and Main Results: Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3-16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis., Conclusions: We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition., Competing Interests: Drs. Brubaker and Martinez-Vargas are supported by grant no. T32 HL139425 from the National Institutes of Health (NIH) and National Heart, Lung, and Blood Institute. Drs. Nguyen and Cruz are supported in part by NIH National Institute of General Medical Sciences (NIGMS) R01 GM112806. Dr. Cruz is also supported in part by NIH-National Institute of Neurological Disorders and Stroke R01 NS094280 and by the Merit Review Award I01 BX002551 from the U.S. Department of Veterans Affairs Biomedical Laboratory Research and Development Service. Dr. Cruz also reported being the founder of A2 Therapeutics and owning patent no. 7879793. The research does not involve any products or commercial interest related to A2 therapeutics or the patent held by Dr. Cruz. Dr. Lam is supported by NIH-NIGMS K08 GM123261. Dr. Brubaker’s institution received funding from the National Heart, Lung, and Blood Institute and A2 Therapeutics. Drs. Nguyen, Lam, and Cruz received support for article research from the NIH. Dr. Nguyen’s institution received funding from the NIH. Dr. Lam received funding from NIH-NIGMS (K08 GM123261); he disclosed that he is listed as an inventor on U.S. Patents 10617751 (Edible Vaccines) and 10695401 (Recombinant Vimentin for Inflammation). Dr. Cruz’s institution received funding from the National Institute of Neurological Disorders and Stroke (R01 NS094280) and the Merit Review Award I01 BX002551 from the U.S. Department of Veteran’s Affairs Biomedical Laboratory Research and Development Service; he disclosed that he is the founder of A2 Therapeutics and owns patent no. 7879793. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)