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1.
J Thromb Haemost ; 18(7): 1752-1755, 2020 07.
Article in English | MEDLINE | ID: covidwho-1317980

ABSTRACT

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.


Subject(s)
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
4.
Am J Emerg Med ; 41: 261.e1-261.e3, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-688657

ABSTRACT

OBJECTIVE: No guidelines exist for the management of massive pulmonary embolism (PE) in COVID-19. We present a COVID-19 patient with refractory acute respiratory syndrome (ARDS), and life-threatening PE who underwent successful thrombolysis. CASE PRESENTATION: A previously healthy 47 year old male was admitted to our hospital due to severe COVID-19 pneumonia [confirmed by Real-Time-Polymerase-Chain-Reaction (RT-PCR)]. He had rapidly evolving ARDS [partial arterial pressure of oxygen to fractional inspired concentration of oxygen ratio: 175], and sepsis. Laboratory results showed lymphocytopenia, and increased D-dimer levels (7.7 µg/ml; normal: 0-0.5 µg/ml). The patient was treated in the intensive care unit. On day-1, ARDS-net/prone positioning ventilation, and empiric anti-COVID treatment integrating prophylactic anticoagulation was administered. On hospital day-2, the patient developed shock with worsening oxygenation. Point-of-care-ultrasound depicted a large thrombus migrating from the right atrium to the pulmonary circulation. Intravenous alteplase (100 mg over 2 h) was administered as rescue therapy. The patient made an uneventful recovery, and was discharged to home isolation (day-20) on oral rivaroxaban. CONCLUSION: Thrombolysis may have a critical therapeutic role for massive PE in COVID-19; however the risk of potential bleeding should not be underestimated. Point-of-care ultrasound has a pivotal role in the management of refractory ARDS in COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/therapeutic use , Pulmonary Embolism/drug therapy , Pulmonary Embolism/etiology , Thrombolytic Therapy , Tissue Plasminogen Activator/therapeutic use , Critical Care , Fibrinolytic Agents/adverse effects , Hemorrhage/chemically induced , Hemorrhage/prevention & control , Humans , Male , Middle Aged , Point-of-Care Testing , Pulmonary Embolism/diagnostic imaging , SARS-CoV-2 , Tissue Plasminogen Activator/adverse effects , Ultrasonography
5.
J Thromb Haemost ; 18(7): 1548-1555, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-116254

ABSTRACT

The global pandemic of coronavirus disease 2019 (COVID-19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D-dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Repositioning , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome
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