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Ferrata Storti Foundation
Haematologica 2021 Volume 106(12):3034-3045
Interactions of adenoviruses with platelets and coagulation and the vaccine-induced immune thrombotic thrombocytopenia syndrome
Paolo Gresele,1 Stefania Momi,1 Rossella Marcucci,2 Francesco Ramundo,3 Valerio De Stefano3 and Armando Tripodi4
1Department of Medicine and Surgery, Section of Internal and Cardiovascular Medicine,
2
University of Perugia, Perugia; Department of Experimental and Clinical Medicine,
University of Florence; Atherothrombosis Center, AOU Careggi, Florence; 3Section of Hematology, Department of Radiological and Hematological Sciences, Catholic University, Fondazione Policlinico A. Gemelli IRCCS, Rome and 4Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
ABSTRACT
The COVID-19 pandemic has had a heavy impact on global health and economy and vaccination remains the primary way of con- trolling the infection. During the ongoing vaccination campaign some unexpected thrombotic events have emerged in subjects who had recently received the AstraZeneca (Vaxzevria) vaccine or the Johnson&Johnson (Janssen) vaccine, two adenovirus vector-based vac- cines. Epidemiological studies confirm that the observed/expected ratio of these unusual thromboses is abnormally increased, especially in women in fertile age. The characteristics of this complication, with venous thromboses at unusual sites, most frequently in the cerebral vein sinuses but also in splanchnic vessels, often with multiple associated thromboses, thrombocytopenia, and sometimes disseminated intravas- cular coagulation, are unique and the time course and tumultuous evolu- tion are suggestive of an acute immunological reaction. Indeed, platelet- activating anti-PF4 antibodies have been detected in a large proportion of the affected patients. Several data suggest that adenoviruses may interact with platelets, the endothelium and the blood coagulation system. Here we review interactions between adenoviral vectors and the hemostatic system that are of possible relevance in vaccine-associated thrombotic thrombocytopenia syndrome. We systematically analyze the clinical data on the reported thrombotic complications of adenovirus-based ther- apeutics and discuss all the current hypotheses on the mechanisms trig- gering this novel syndrome. Although, considering current evidence, the benefit of vaccination clearly outweighs the potential risks, it is of para- mount importance to fully unravel the mechanisms leading to vaccine- associated thrombotic thrombocytopenia syndrome and to identify prognostic factors through further research.
Introduction
The coronavirus disease 19 (COVID-19) pandemic has prompted an unprecedent- ed effort to develop highly effective vaccines to prevent further spreading of the infection, the associated mortality and the enormous strain on healthcare systems. Indeed, in a previously unimaginable short time, many vaccines have been devel- oped. Several of them underwent controlled randomized phase III clinical trials and, as of 22 June, 2021, 13 have been licensed globally for clinical use. By July 18, 2021 they had been administered to more than 1.9 billion subjects worldwide (923 mil- lion of whom are fully vaccinated; 3.66 billion doses have been administered glob- ally; 26.3% of the world’s population has received at least one dose of a COVID-19 vaccine). This represents the most massive vaccination campaign ever undertaken
Correspondence:
PAOLO GRESELE
paolo.gresele@unipg.it
Received: May 24, 2021 Accepted: August 4, 2021. Pre-published: August 19, 2021.
https://doi.org/10.3324/haematol.2021.279289 ©2021 Ferrata Storti Foundation
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