Consideration Needed for early Anticoagulation Following Intravenous tPA in Patients with COVID-19

Abstract

We read the article by Carneiro et al with great interest.1Carneiro T Dashkoff J Leung L et al.Intravenous tPA for acute ischemic stroke in patients with COVID-19.J Stroke Cerebrovasc Dis. 2020; 29105201https://doi.org/10.1016/j.jstrokecerebrovasdis.2020.105201Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar We have similar experiences at two downtown Los Angeles certified stroke centers with the use of intravenous tPA. However, there are concerning observations lately among COVID-19 patients who developed large vessel re-occlusions shortly after their original stroke symptoms were aborted by intravenous tPA. Intravenous tPA, Alteplase, is a plasminogen activator (serine protease) which specifically cleaves the arginine-valine bond of plasminogen resulting in the formation of plasmin. Plasmin is the enzyme responsible for clot dissolution. Fibrin-bound alteplase has an increased affinity for plasminogen. This high affinity of alteplase for plasminogen in the presence of fibrin allows efficient activation on the fibrin clot. The initial plasma half-life of alteplase is less than 5 min. Following a 90 min infusion, the elimination half-life is 26.5 to 46 min.2https://www.micromedexsolutions.comGoogle Scholar Several studies have demonstrated a strong relationship between COVID-19 and a hypercoagulable state as evidenced by the high rates of pulmonary embolism, venous thromboembolism, and in some cases arterial thrombosis, with incidence rates ranging from 15% to 79% depending on the study and patient population focus (ICU vs non-ICU).3Kichloo A Dettloff K Aljadah M et al.COVID-19 and hypercoagulability: a review.Clin Appl Thromb Hemost. 2020; 261076029620962853https://doi.org/10.1177/1076029620962853Crossref Scopus (44) Google Scholar Although the pathogenesis of the COVID-19-induced hypercoagulable state is incompletely understood, direct invasion of endothelial cells by SARS-CoV-2 and subsequent release of inflammatory cytokines (such as IL-6) coupled with the various coagulation abnormalities commonly seen (elevated PT, aPTT, platelet count, vWF, Factor VIII, D-Dimer, Fibrinogen) further support the mechanism of action.4Singhania N Bansal S Nimmatoori DP Ejaz AA McCullough PA Singhania G. Current overview on hypercoagulability in COVID-19.Am J Cardiovasc Drugs. 2020; 20: 393-403https://doi.org/10.1007/s40256-020-00431-zCrossref PubMed Scopus (95) Google Scholar,5Panigada M Bottino N Tagliabue P et al.Hypercoagulability of COVID-19 patients in intensive care unit: a report of thromboelastography findings and other parameters of hemostasis.J Thromb Haemost. 2020; 18: 1738-1742https://doi.org/10.1111/jth.14850Crossref PubMed Scopus (801) Google Scholar Arterial thrombosis seen in COVID-19 infection is of particular interest here, with emerging evidence demonstrating a relationship between higher incidence rates of ischemic stroke, particularly in the young.6Oxley TJ Mocco J Majidi S et al.Large-vessel stroke as a presenting feature of COVID-19 in the young.N Engl J Med. 2020; 382: e60https://doi.org/10.1056/NEJMc2009787Crossref PubMed Scopus (1355) Google Scholar Indeed, in our own clinical experience the rates of COVID-19-induced CVA in patients as young as their 30s and 40s have risen to levels not seen prior to the pandemic. Recently, 4 neurologically intact patients with COVID-19 suffered acute strokes as inpatient. Their NIHSS at time of tPA consideration ranged from 8 to 17. Intravenous tPA were administered in timely fashion and all experienced improvement afterwards with NIHSS reduced to a range of 1 to 12. There were 2 left middle cerebral artery (MCA), 1 right MCA and 1 basilar artery strokes. Their improvements lasted 90 min to 3 h. All developed re-occlusion of the original affected arteries. Only 2 patients were candidate for thrombectomy. Their eventually discharge NIHSS ranged from 12 to 25. No anticoagulation and no antiplatelet agents for the first 24 h remains the current recommendation for post tPA management . In face of an active hypercoagulable state that will outlast the half-life of thrombolytics, we hope to see studies/consideration for early anticoagulation in COVID-19 patients post intravenous tPA administration. Intravenous tPA for Acute Ischemic Stroke in Patients with COVID-19Journal of Stroke and Cerebrovascular DiseasesVol. 29Issue 11PreviewBackground/Purpose: Coronavirus disease 2019 (COVID-19) is associated with increased risk of acute ischemic stroke (AIS), however, there is a paucity of data regarding outcomes after administration of intravenous tissue plasminogen activator (IV tPA) for stroke in patients with COVID-19. Methods: We present a multicenter case series from 9 centers in the United States of patients with acute neurological deficits consistent with AIS and COVID-19 who were treated with IV tPA. Results: We identified 13 patients (mean age 62 (±9.8) years, 9 (69.2%) male). Full-Text PDF Response to the Letter to the Editor: Consideration Needed for Early Anticoagulation Following Intravenous tPA in Patients with COVID-19Journal of Stroke and Cerebrovascular DiseasesVol. 30Issue 7PreviewWe thank Dr. Angelo Jimenez and his colleagues for their letter to the editor regarding our report of a multicenter series of patients with coronavirus disease 2019 (COVID-19) who received intravenous (IV) tissue plasminogen activator (tPA) for suspected acute ischemic stroke. Their letter emphasizes the important contribution of a hypercoagulable state in patients with COVID-19. Full-Text PDF