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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.
摘要：
对疫苗诱导的血栓性血小板减少症（VITT）的罕见但严重且可能致命的并发症的认识引起了人们对COVID-19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疫苗的接受者中的VITT之后，Ad26后对类似病例的审查。COV2·S疫苗接种引起了一个问题，即该实体是否可能构成所有腺病毒载体疫苗的潜在类效应。大多数病例是女性，通常年龄小于60岁，在接种血小板减少症和血栓表现后不久（范围：5-30天）出现，偶尔在多个网站。在最初的不确定之后，指导诊断的具体建议(临床怀疑，初步实验室筛查，PF4-聚阴离子-抗体ELISA）和VITT（非肝素抗凝剂，皮质类固醇,静脉注射免疫球蛋白)已经发行。这种罕见综合征背后的机制目前是活跃研究的主题，包括以下内容：1）PF4-聚阴离子自身抗体的产生；2）腺病毒载体进入巨细胞中，随后在血小板表面表达刺突蛋白；3）腺病毒载体指导血小板和内皮细胞的结合和激活；4）PF4-聚阴离子自身抗体激活内皮细胞和炎性细胞；除了分析潜在的潜在机制外，这篇综述旨在概述VITT的临床和流行病学特征，提出当前关于VITT诊断和治疗工作的循证建议，并讨论描述该实体后出现的新困境和观点。
