Recombinant tissue plasminogen activator (rTPA) management for first onset acute ischemic stroke with covid -19 and non-covid -19 patients.

OBJECTIVES: Cerebrovascular stroke (CVS) is one of the well-known complications of coronavirus-2019 (Covid-19), but less is known about the outcome and safety of thrombolytic therapy in these patients. In this study we compare the efficacy and safety of Tissue plasminogen activator (rTPA) in acute ischemic stroke (AIS) patients with or without Covid-19 infection. MATERIALS AND METHODS: A comparative prospective study in which all patients who presented with AIS and eligible for rTPA were recruited from the emergency department and classified into 2 groups (AIS with Covid-19 infection and AIS without Covid-19 as controls). Demographic data, symptoms of Covid-19, clinical examination, neuroimaging, and laboratory investigations were obtained in each patient. National Institute of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS) were assessed before, immediately after rTPA, and 3 months later. RESULTS: There were 22 patients in the COVID-19 group and 25 control patients. Those with COVID-19 were more likely to have a history of smoking and Diabetes Mellitus than controls. On admission, motor symptoms were more severe in patients with COVID-19. COVID-19 patients were more likely to have symptomatic intra-cerebral hemorrhage and radiological hemorrhagic transformation than controls. Onset to door time (ODT) and onset to successful reperfusion time were significantly longer in Covid-19 patients than controls. Clinical improvement and frequency of re-occlusion and recurrent ischemic stroke at 3 months follow-up did not differ between groups, although there was higher number of deaths (27.3%) in the Covid-19 group than controls (16%). CONCLUSIONS: Using rTPA is safe and effective in patients with AIS with or without COVID-19 infection despite the high frequency of hemorrhagic transformation and high number of deaths.

Concealment of Allergic Reactions to Alteplase by Face Masks in Non-Communicating Acute Stroke Patients: A Warning Call to Improve Our Physical Examination Practices during the COVID-19 Pandemic.

Neurological emergencies, such as acute stroke, are especially challenging during the current Coronavirus disease-2019 (COVID-19) pandemic. Symptoms as aphasia or dysarthria are severely impacting cooperation and communication with patients. During physical examination, both the patient and the medical team are fitted routinely with surgical masks to minimize potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, such a practice can lead to concealment of particularly relevant physical signs. We report a case series of four acute stroke patients who were transferred for endovascular mechanical thrombectomy to our institute after intravenous thrombolysis was initiated at primary stroke centers. Upon arrival, after removing their masks, we observed oral angioedema, as a reaction to thrombolytic agent alteplase. Symptoms remained obscured by face masks through patient care at the referring stroke unit and during transportation, nevertheless they resolved after treatment. Most probably, there are a number of similar cases encountered at emergency departments and acute stroke units. To improve patient safety, a compromise between ensuring protection against the novel coronavirus and facilitating detection of potentially life-threatening physical signs must be found.

Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations.

PURPOSE: Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed. SUMMARY: Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase. CONCLUSION: Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.

Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): A case series.

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.

Thrombolysis in severe COVID-19 pneumonia with massive pulmonary embolism.

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.

Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19.

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.