Tsilingiris Dimitrios, Vallianou Natalia G, Karampela Irene, Dalamaga Maria
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.
Metabol Open. 2021 Sep;11:100101. doi: 10.1016/j.metop.2021.100101. Epub 2021 Jun 18.
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.
疫苗诱导的血栓性血小板减少症（VITT）这一罕见但严重且可能致命的并发症被认识后，引发了对新冠疫苗安全性的担忧，并导致许多国家重新考虑疫苗接种策略。在描述腺病毒载体ChAdOx1疫苗接种者中出现VITT之后，对Ad26.COV2.S疫苗接种后类似病例的回顾引发了一个问题，即这种情况是否可能是所有腺病毒载体疫苗的潜在类效应。大多数病例为女性，通常年龄小于60岁，在接种疫苗后不久（范围：5 - 30天）出现血小板减少和血栓形成表现，偶尔累及多个部位。在最初的不确定性之后，已发布了指导VITT诊断（临床怀疑、初始实验室筛查、PF4 - 多聚阴离子 - 抗体ELISA）和管理（非肝素抗凝剂、皮质类固醇、静脉注射免疫球蛋白）的具体建议。这种罕见综合征背后的机制目前是积极研究的主题，包括以下几点：1）PF4 - 多聚阴离子自身抗体的产生；2）腺病毒载体进入巨核细胞并随后在血小板表面表达刺突蛋白；3）腺病毒载体直接与血小板和内皮细胞结合并激活；4）PF4 - 多聚阴离子自身抗体激活内皮细胞和炎症细胞；5）存在炎症共信号；6）接种疫苗后循环可溶性刺突蛋白变体的大量存在。除了分析潜在的潜在机制外，本综述旨在概述VITT的临床和流行病学特征，介绍目前关于VITT诊断和治疗检查的循证建议，并讨论在描述这一实体后出现的新困境和观点。
