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Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story.
Metabol Open. 2021 Sep; 11:100101.MO

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.

Authors+Show Affiliations

First Department of Propaedeutic Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Laiko General Hospital, 17 St Thomas Street, 11527, Athens, Greece.First Department of Internal Medicine, Evangelismos General Hospital, 45-47 Ipsilantou Str, 10676, Athens, Greece.Second Department of Critical Care, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini St, Haidari, 12462, Athens, Greece.Department of Biological Chemistry, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34179744

Citation

Tsilingiris, Dimitrios, et al. "Vaccine Induced Thrombotic Thrombocytopenia: the Shady Chapter of a Success Story." Metabolism Open, vol. 11, 2021, p. 100101.
Tsilingiris D, Vallianou NG, Karampela I, et al. Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story. Metabol Open. 2021;11:100101.
Tsilingiris, D., Vallianou, N. G., Karampela, I., & Dalamaga, M. (2021). Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story. Metabolism Open, 11, 100101. https://doi.org/10.1016/j.metop.2021.100101
Tsilingiris D, et al. Vaccine Induced Thrombotic Thrombocytopenia: the Shady Chapter of a Success Story. Metabol Open. 2021;11:100101. PubMed PMID: 34179744.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vaccine induced thrombotic thrombocytopenia: The shady chapter of a success story. AU - Tsilingiris,Dimitrios, AU - Vallianou,Natalia G, AU - Karampela,Irene, AU - Dalamaga,Maria, Y1 - 2021/06/18/ PY - 2021/06/03/received PY - 2021/06/14/accepted PY - 2021/6/28/entrez PY - 2021/6/29/pubmed PY - 2021/6/29/medline KW - Adenoviral vector KW - Adenovirus KW - CAR, Coxsackie-adenovirus receptor KW - CDC, Centers for Disease Control and Prevention KW - COVID-19 KW - COVID-19, Coronavirus disease 2019 KW - CVST, cerebellar sinus thrombosis KW - FDA, Food and Drug Administration KW - HIT, Heparin-induced thrombocytopenia KW - ICU, Intensive Care Unit KW - IVIG, Intravenous immunoglobulin KW - LMWH, low molecular weight heparin KW - PF4, Platelet factor 4 KW - PLT, Platelet KW - PRAC, Pharmacovigilance Risk Assessment Committee KW - PT, prothrombin time KW - SARS-CoV-2 KW - SARS-Cov-2, severe acute respiratory syndrome coronavirus 2 KW - SVT, splanchnic vein thrombosis KW - TTS, thrombosis-thrombocytopenia-syndrome KW - VCAM-1, vascular cell adhesion molecule 1 KW - VIPIT, vaccine-induced prothrombotic immune thrombocytopenia KW - VITT, vaccine induced thrombotic thrombocytopenia KW - Vaccine KW - Vaccine induced thrombotic thrombocytopenia KW - aPTT, activated partial thromboplastin time KW - ΕΜΑ, European Medicines Agency SP - 100101 EP - 100101 JF - Metabolism open JO - Metabol Open VL - 11 N2 - 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. SN - 2589-9368 UR - https://www.unboundmedicine.com/medline/citation/34179744/Vaccine_induced_thrombotic_thrombocytopenia:_The_shady_chapter_of_a_success_story_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2589-9368(21)00025-6 DB - PRIME DP - Unbound Medicine ER -
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