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

Janice Wang, Negin Hajizadeh, Ernest E Moore, Robert C McIntyre, Peter K Moore, Livia A Veress, Michael B Yaffe, Hunter B Moore, Christopher D Barrett, Janice Wang, Negin Hajizadeh, Ernest E Moore, Robert C McIntyre, Peter K Moore, Livia A Veress, Michael B Yaffe, Hunter B Moore, Christopher D Barrett

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.

Keywords: COVID-19; acute respiratory distress syndrome (ARDS); case report; fibrinolysis; tissue plasminogen activator (tPA).

© 2020 International Society on Thrombosis and Haemostasis.

References

    1. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–847.
    1. Han H., Yang L., Liu R., et al. Prominent changes in blood coagulation of patients with SARS‐CoV‐2 infection. Clin Chem Lab Med. 2020;58:1116–1120.
    1. Wang D., Hu B., Hu C., et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus‐infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061.
    1. Yang X., Yu Y., Xu J., et al. Clinical course and outcomes of critically ill patients with SARS‐CoV‐2 pneumonia in Wuhan, China: a single‐centered, retrospective, observational study. Lancet Respir Med. 2020;8:475–481.
    1. Li T., Lu H., Zhang W. Clinical observation and management of COVID‐19 patients. Emerg Microbes Infect. 2020;9:687–690.
    1. Xu J.F., Wang L., Zhao L., et al. Risk assessment of venous thromboembolism and bleeding in COVID‐19 patients. Respir Res. 2020;120:937–948.
    1. Luo W, Yu H, Gou J, et al. Clinical pathology of critical patient with novel coronavirus pneumonia (COVID‐19). Preprints (not peer reviewed). Posted 9 March 2020. 10.1101/2020.03.07.20032573
    1. Hardaway R.M., Williams C.H., Marvasti M., et al. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med. 1990;18:1413–1418.
    1. Stringer K.A., Hybertson B.M., Cho O.J., Cohen Z., Repine J.E. Tissue plasminogen activator (tPA) inhibits interleukin‐1 induced acute lung leak. Free Radic Biol Med. 1998;25:184–188.
    1. Liu C., Ma Y., Su Z., et al. Meta‐analysis of preclinical studies of fibrinolytic therapy for acute lung injury. Front Immunol. 2018;9:1898.
    1. Konstantinides S., Geibel A., Heusel G., Heinrich F., Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347:1143–1150.
    1. Investigators G. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. N Engl J Med. 1993;329(10):673–682.

Source: PubMed

3
Subskrybuj