Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story

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.

COVID-19 vaccines: Current evidence and considerations

“…It has been proposed that all vaccinated cases remain at the vaccination site for 30 min to detect any serious side effects. It has been reported that the AstraZeneca and Johnson & Johnson/Janssen vaccines may have a possible link to a very rare side effect of unusual blood clots combined with low levels of platelet levels [ 7 , 20 ].…”

Platelet factor 4 polyanion immune complexes: heparin induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia

“…PF4 may play a role in innate immune responses through binding to polyanionic lipids of bacterial cellular walls (Gram-positive and Gram-negative) [55,56]. Recently, PF4 also has been associated with vector-based SARS-CoV-2 vaccine-induced thrombosis with thrombocytopenia syndrome (VITT/TTS), thus, emphasizing the clinical significance of PF4 in PF4/polyanion complex formation, and the occurrence of VITT/TTS [57][58][59][60][61][62]. Administration of ChAdOx1 nCov-19 vaccines results in rare incidents of spontaneous VITT in some patients [63].…”

The effect of COVID-19 pandemic on the attendance and clinical outcomes of patients with ophthalmic disease: A mini-review

“…Finally, remote monitoring of patients with the use of telemedicine seems to offer many advantages and implementation of such practices in ophthalmology along with the continuation of vaccination programs worldwide and the ongoing research for effective medical treatments, will help minimize the above mentioned effects of the pandemic in the management and outcomes of patients with ophthalmic disease [ [40] , [41] , [42] ].…”