"Abstract
The recognition of the rare but serious and potentially lethal complication of vaccine induced thrombotic thrombocytopenia (VITT) raised concerns regarding the safety of COVID-19 vaccines and led to the reconsideration of vaccination strategies in many countries. Following the description of VITT among recipients of adenoviral vector ChAdOx1 vaccine, a review of similar cases after Ad26.COV2·S vaccination gave rise to the question whether this entity may constitute a potential class effect of all adenoviral vector vaccines. Most cases are females, typically younger than 60 years who present shortly (range: 5–30 days) following vaccination with thrombocytopenia and thrombotic manifestations, occasionally in multiple sites. Following initial incertitude, concrete recommendations to guide the diagnosis (clinical suspicion, initial laboratory screening, PF4-polyanion-antibody ELISA) and management of VITT (non-heparin anticoagulants, corticosteroids, intravenous immunoglobulin) have been issued. The mechanisms behind this rare syndrome are currently a subject of active research and include the following: 1) production of PF4-polyanion autoantibodies; 2) adenoviral vector entry in megacaryocytes and subsequent expression of spike protein on platelet surface; 3) direct platelet and endothelial cell binding and activation by the adenoviral vector; 4) activation of endothelial and inflammatory cells by the PF4-polyanion autoantibodies; 5) the presence of an inflammatory co-signal; and 6) the abundance of circulating soluble spike protein variants following vaccination. Apart from the analysis of potential underlying mechanisms, this review aims to synopsize the clinical and epidemiologic features of VITT, to present the current evidence-based recommendations on diagnostic and therapeutic work-up of VITT and to discuss new dilemmas and perspectives that emerged after the description of this entity.
2. An account of early VITT-related events
In March 2021, EMA's Pharmacovigilance Risk Assessment Committee (PRAC) began an assessment οn signals of increased incidence of thrombotic events, including splanchnic vein and cerebellar sinus thrombosis (SVT and CVST, respectively) accompanied by thrombocytopenia, especially among females aged less than 60 years, within the 2 weeks following the 1st dose of adenoviral vector ChAdOx1 vaccine Vaxzevria® (Oxford/AstraZeneca)...
On April 7, 2021, the committee concluded that a causal link between this rare side-effect and the vaccination could not be ruled out...
In a similar course of events, on April 13, 2021 the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) in the USA recommended a pause of the administration of another adenovirus vector vaccine, Ad26.COV2·S (Johnson & Johnson/Janssen)...
5. Impact of VITT on COVID-19 vaccination strategies
... Recent reports have indicated that the incidence of VITT/TTS may be in reality considerably higher than previously presumed, and this may possibly further rise as awareness and understanding of the syndrome becomes more widespread among physicians. The estimated incidence of VITT varies between reports from 1 for every roughly 25,000 individuals vaccinated with ChAdOx1 to 1 for every more than 500,000 Ad26.COV2·S vaccinations."
© 2021 The Authors. Published by Elsevier Inc.
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