Reperfusion treatment for high-risk pulmonary embolism associated with COVID-19.

Abstract

Free AccessReperfusion treatment for high-risk pulmonary embolism associated with COVID-19Comment on Galastri et al., pp. 333–337Stefano Barco, Mario Münger, Tim Sebastian, and Nils KucherStefano Barco Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland Center for Thrombosis and Hemostasis, Johannes Gutenberg University Mainz, Mainz, Germany Search for more papers by this author, Mario Münger Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland Search for more papers by this author, Tim Sebastian Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland Search for more papers by this author, and Nils Kucherhttps://orcid.org/0000-0002-7352-8709 Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland Search for more papers by this authorPublished Online:June 24, 2020https://doi.org/10.1024/0301-1526/a000884PDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInReddit SectionsMoreCoronavirus disease (COVID-19) has emerged as a pandemic and a public health crisis of global proportions. As of 13 May 2020, a total of 4,343,371 COVID-19 cases have been diagnosed worldwide and almost 300,000 deaths have been recorded. Endothelial cell infection, bilateral pneumonia, pronounced inflammatory immune response, pulmonary-induced coagulopathy, and cardiovascular complications represent key features of the disease [1, 2].Initial reports from China indicated that myocarditis and ischemic arterial events frequently occur [3]. However, subsequent studies from Europe and Northern America showed that not only venous thromboembolism represents the predominant vascular complications in COVID-19 patients [4, 5], but also that its incidence might be higher than previously observed in other groups of patients admitted to hospital for acute conditions [6, 7]. Venous thromboembolism can already be present at the time of initial COVID-19 clinical presentation [4].It has been postulated that local lung (immuno-)thrombosis, involving the segmental or subsegmental branches of the pulmonary arteries, is typically associated with severe COVID-19 pneumonia [7, 8]. In contrast, autopsy data and sparse reports demonstrated that deep vein thrombosis can be often detected and that COVID-19-related hypercoagulability may also manifest as “massive” PE leading to haemodynamic instability and shock [9, 10]. While initial data are available on the incidence of venous thrombotic and thromboembolic complications in COVID-19 patients, reports focusing on treatment, especially of the most severe cases, are still lacking and disease-specific issues may be present.The case reported by Galastri and colleagues published in this issue of Vasa informs us of a 57-year-old patient presenting with severe COVID-19 [11]. During hospitalization, the patient developed deep vein thrombosis and acute bilateral pulmonary embolism causing haemodynamic decompensation and requiring initial inotropic support. The patient was considered to be at a higher risk of bleeding and the treating physicians deemed the use of standard-dose systemic thrombolysis unsafe. Local catheter-directed thrombolysis with 10 mg alteplase was initially administered, followed by embolectomy with two different devices and the administration of 18 mg alteplase. Due to the development of supraventricular tachycardia, the treatment was prematurely suspended and an inferior cava filter placed. The patient received additional 50 mg alteplase, delivered in one hour, with progressive improvement of the haemodynamic status and no further complications.This is one of the first reports of the management of hemodynamically unstable, high-risk acute pulmonary embolism associated with COVID-19. The first take-home message is that COVID-19 may manifest as a venous thrombotic or thromboembolic complication with “classic” embolic features. Therefore, patients with suggestive signs or symptoms, including a rapid worsening of the respiratory function, unresponsive hypotension, or a dramatic and rapid rise of D-Dimer levels, should undergo imaging for right ventricular dysfunction and venous thromboembolism at low threshold not to delay the diagnosis and treatment of acute pulmonary embolism. Missed pulmonary embolism may have represented a leading cause of death in COVID-19 patients globally [9]: future epidemiological studies will unveil current trends in pulmonary embolism testing and mortality [12].The use of different reperfusion treatments, as described in this report, is quite unconventional and it remains unclear which therapeutic approach ultimately improved the patient’s haemodynamic status. Current evidence-based guidelines recommend the use of systemic thrombolytic therapy for high-risk (haemodynamically unstable) pulmonary embolism patients [13]. However, if systemic thrombolysis is contraindicated due to an increased risk of bleeding, as it seemed to be the case here, percutaneous catheter-directed treatment should be considered [13]. It is unknown, if COVID-19 patients are characterized by a higher risk of bleeding and should be treated differently from the current standard of care. Indeed, thrombocytopenia and hemoptysis may be present and should be carefully evaluated. There is no validated risk assessment model available that could be used to guide the decision on the dose and way of administration of thrombolytic treatment. Therefore, the “standard” contraindications to systemic thrombolysis, including but not limited to prior stroke or cerebral neoplasms, recent trauma, or active bleeding, should primarily be assessed to decide on thrombolytic treatment [13].Beyond the treatment of high-risk acute pulmonary embolism, for which current evidence falls short also in the non-COVID-19 setting, there are other dilemmas that urgently need answers from interventional trials, management studies, and multicenter registries. The first one is whether standard-dose thromboprophylaxis suffices to prevent thromboembolic events in hospitalized COVID-19 patients. A number of trials (identifiers: NCT04344756, NCT04345848, NCT04359212, NCT04362085 and NCT04359277) are being conducted to compare the efficacy and safety of different heparin dosages in COVID-19 patients during hospitalization. The second question is what the actual venous thromboembolism incidence among hospitalized patients is, to which extent it depends on the use of imaging/laboratory tests, and whether it represents an independent risk factor for death [14]. The third one is whether early thromboprophylaxis with standard low-molecular-weight heparin for symptomatic quarantined outpatients with COVID-19 may reduce hospitalizations and all-cause death by improving coagulopathy and limiting the early risk of thromboembolic events. Today, there is no evidence supporting the routine use of anticoagulant prophylaxis in outpatients with a mild or moderate acute respiratory illness, including COVID-19 [15]. The randomized controlled OVID trial (NCT04400799) is being planned to answer this question.COVID-19 is a multifaceted disease encompassing characteristics typical of a broad group of inflammatory, infectious, haematological, and thromboembolic conditions. 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Phone: +41 44 255 33 44, E-mail nils.kucher@usz.chFiguresReferencesRelatedDetails Volume 49Issue 4June 2020ISSN: 0301-1526eISSN: 1664-2872 Published onlineJune 24, 2020 InformationVasa (2020), 49, pp. 257-258 https://doi.org/10.1024/0301-1526/a000884.© 2020Hogrefe AGConflicts of interests:Stefano Barco reports personal fees from Biocompatibles Group UK and Bayer HealthCare, non-financial support from Bayer HealthCare and Daiichi Sankyo, outside the submitted work.PDF download Funding: The work of Stefano Barco is supported by the German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503).