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Am J Respir Crit Care Med ; 2022 Sep 29.
Article in English | MEDLINE | ID: covidwho-2228217
Pediatr Pulmonol ; 57(2): 529-537, 2022 02.
Article in English | MEDLINE | ID: covidwho-1490884


BACKGROUND AND OBJECTIVES: Plastic bronchitis (PB) is a condition characterized by the formation of thick airway casts leading to acute and often life-threatening airway obstruction. PB occurs mainly in pediatric patients with congenital heart disease (CHO) who have undergone staged surgical palliation (Glenn, Fontan), but can also occur after chemical inhalation, H1N1, severe COVID-19, sickle cell disease, severe asthma, and other diseases. Mortality risk from PB can be up to 40%-60%, and no treatment guideline exist. The objectives herein are to develop a standardized evaluation, classification, and treatment guideline for PB patients presenting with tracheobronchial casts, based on our experience with PB at the Children's Hospital of Colorado in Denver. METHODS: We describe 11 patients with CHO-associated PB (post-Fontan [n = 9], pre-Fontan [n = 2]) who presented with their initial episodes. We utilized histopathological analysis of tracheobronchial casts to guide treatment in these patients, utilizing our hospital-wide guideline document and classification system. RESULTS: We found that 100% of post-Fontan PB patients had fibrinous airway casts, while pre-Fontan PB casts were fibrinous only in one of two patients (50%). Utilizing histopathology as a guide to therapy, PB patients with fibrin airway casts were treated with airway-delivered fibrinolytics and anticoagulants, as well as aggressive airway clearance and other supportive care measures. These therapies resulted in successful cast resolution and improved survival in post-Fontan PB patients. CONCLUSION: We have shown an improved outcome in PB patients whose treatment plan was based on Denver's PB classification schema and standardized treatment guideline based on tracheobronchial cast histopathology.

Airway Obstruction , Bronchitis , COVID-19 , Fontan Procedure , Influenza A Virus, H1N1 Subtype , Airway Obstruction/etiology , Airway Obstruction/therapy , Bronchitis/diagnosis , Bronchitis/therapy , Child , Fibrin , Humans , SARS-CoV-2
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317980


A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.

Betacoronavirus/pathogenicity , Blood Coagulation Disorders/drug therapy , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , Aged , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/diagnosis , Blood Coagulation Disorders/virology , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Fatal Outcome , Female , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Recovery of Function , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
Res Pract Thromb Haemost ; 4(4): 524-531, 2020 May.
Article in English | MEDLINE | ID: covidwho-601382


The coronavirus disease 2019 (COVID-19) pandemic has caused respiratory failure and associated mortality in numbers that have overwhelmed global health systems. Thrombotic coagulopathy is present in nearly three quarters of patients with COVID-19 admitted to the intensive care unit, and both the clinical picture and pathologic findings are consistent with microvascular occlusive phenomena being a major contributor to their unique form of respiratory failure. Numerous studies are ongoing focusing on anticytokine therapies, antibiotics, and antiviral agents, but none to date have focused on treating the underlying thrombotic coagulopathy in an effort to improve respiratory failure in COVID-19. There are animal data and a previous human trial demonstrating a survival advantage with fibrinolytic therapy to treat acute respiratory distress syndrome. Here, we review the extant and emerging literature on the relationship between thrombotic coagulopathy and pulmonary failure in the context of COVID-19 and present the scientific rationale for consideration of targeting the coagulation and fibrinolytic systems to improve pulmonary function in these patients.