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Impact of COVID-19 on thrombus composition and response to thrombolysis: Insights from a monocentric cohort population of COVID-19 patients with acute ischemic stroke.


ABSTRACT:

Background

Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however.

Objectives

We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare their response to thrombolysis to that of AIS thrombi from non-COVID-19 patients.

Patients/methods

For this monocentric cohort study, 14 thrombi from COVID-19 AIS patients and 16 thrombi from non-COVID-19 patients, all recovered by endovascular therapy, were analyzed by immunohistology or subjected to ex vivo thrombolysis by tissue-type plasminogen (tPA)/plasminogen.

Results

COVID-19 AIS thrombi were rich in neutrophils and contained NETs, but not spike protein. Thrombolysis assays revealed a mean resistance profile to tPA/plasminogen of COVID-19 AIS thrombi similar to that of non-COVID-19 AIS thrombi. The addition of DNase 1 successfully improved thrombolysis by potentiating fibrinolysis irrespective of COVID-19 status. Levels of neutrophil, NETs, and platelet markers in lysis supernatants were comparable between AIS thrombi from non-COVID-19 and COVID-19 patients.

Conclusions

These results show that COVID-19 does not impact NETs content or worsen fibrinolysis resistance of AIS thrombi, a therapeutic hurdle that could be overcome by DNase 1 even in the context of SARS-CoV-2 infection.

SUBMITTER: Desilles JP 

PROVIDER: S-EPMC9906142 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Impact of COVID-19 on thrombus composition and response to thrombolysis: Insights from a monocentric cohort population of COVID-19 patients with acute ischemic stroke.

Desilles Jean-Philippe JP   Solo Nomenjanahary Mialitiana M   Consoli Arturo A   Ollivier Véronique V   Faille Dorothée D   Bourrienne Marie-Charlotte MC   Hamdani Mylène M   Dupont Sébastien S   Di Meglio Lucas L   Escalard Simon S   Maier Benjamin B   Blanc Raphael R   Piotin Michel M   Lapergue Bertrand B   Ajzenberg Nadine N   Vasse Marc M   Mazighi Mikael M   Ho-Tin-Noé Benoît B   Désilles Jean-Philippe JP   Mazighi Mikael M   Piotin Michel M   Blanc Raphael R   Redjem Hocine H   Smajda Stanislas S   Seners Pierre P   Escalard Simon S   Delvoye Francois F   Maier Benjamin B   Hebert Solene S   Ben Maacha Malek M   Hamdani Mylene M   Sabben Candice C   Obadia Michael M   Deschildre Catherine C   Lapergue Bertrand B   Consoli Arturo A   Rodesch Georges G   Maria Federico F   Coskun Okuzan O   Lopez Delphine D   Bourcier Romain R   Detraz Lili L   Desal Hubert H   Roy Monica M   Clavier Delphine D   Marnat Gaultier G   Gariel Florent F   Lucas Ludovic L   Sibon Igor I   Eugene Francois F   Vannier Stéphane S   Ferre Jean-Christophe JC   LeBras Anthony A   Raoult Hélène H   Paya Christophe C   Gauvrit Jean-Yves JY   Richard Sébastien S   Gory Benjamin B   Barbier Charlotte C   Vivien Denis D   Touze Emmanuel E   Gauberti Maxime M   Blaizot Gaetane G   Ifergan Héloïse H   Herbreteau Denis D   Bibi Richard R   Janot Kevin K   Charron Vladimir V   Boulouis Grégoire G  

Journal of thrombosis and haemostasis : JTH 20220130 4


<h4>Background</h4>Resistance to fibrinolysis, levels of procoagulant/antifibrinolytic neutrophil extracellular traps (NETs), and the severity of acute ischemic stroke (AIS) are increased by COVID-19. Whether NETs are components of AIS thrombi from COVID-19 patients and whether COVID-19 impacts the susceptibility of these thrombi to thrombolytic treatments remain unknown, however.<h4>Objectives</h4>We aimed to characterize AIS thrombi from COVID-19 patients by immunohistology and to compare thei  ...[more]

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