Dabbiru Venkata A S, Müller Luisa, Schönborn Linda, Greinacher Andreas
Institut für Transfusionsmedizin, Universitätsmedizin Greifswald, 17489 Greifswald, Germany.
J Clin Med. 2023 Sep 22;12(19):6126. doi: 10.3390/jcm12196126.
An effective worldwide vaccination campaign started and is still being carried out in the face of the coronavirus disease 2019 (COVID-19) pandemic. While vaccines are great tools to confront the pandemic, predominantly adenoviral vector-based vaccines can cause a rare severe adverse effect, termed vaccine-induced immune thrombocytopenia and thrombosis (VITT), in about 1 in 100,000 vaccinated individuals. VITT is diagnosed 5-30 days post-vaccination and clinically characterized by thrombocytopenia, strongly elevated D-dimer levels, platelet-activating anti-platelet factor 4 (PF4) antibodies and thrombosis, especially at atypical sites such as the cerebral venous sinus and/or splanchnic veins. There are striking similarities between heparin-induced thrombocytopenia (HIT) and VITT. Both are caused by anti-PF4 antibodies, causing platelet and leukocyte activation which results in massive thrombo-inflammation. However, it is still to be determined why PF4 becomes immunogenic in VITT and which constituent of the vaccine triggers the immune response. As VITT-like syndromes are increasingly reported in patients shortly after viral infections, direct virus-PF4 interactions might be most relevant. Here we summarize the current information and hypotheses on the pathogenesis of VITT and address in vivo models, especially murine models for further studies on VITT.
面对2019冠状病毒病（COVID-19）大流行，一场有效的全球疫苗接种运动已经启动，并且仍在进行中。虽然疫苗是应对大流行的有力工具，但主要基于腺病毒载体的疫苗可能会在每10万名接种者中导致约1人出现一种罕见的严重不良反应，称为疫苗诱导的免疫性血小板减少症和血栓形成（VITT）。VITT在接种疫苗后5至30天被诊断出来，其临床特征为血小板减少、D-二聚体水平大幅升高、血小板活化抗血小板因子4（PF4）抗体以及血栓形成，尤其是在非典型部位，如脑静脉窦和/或内脏静脉。肝素诱导的血小板减少症（HIT）和VITT之间存在显著相似之处。两者均由抗PF4抗体引起，导致血小板和白细胞活化，进而引发大规模血栓炎症。然而，PF4在VITT中为何具有免疫原性以及疫苗的哪种成分触发免疫反应仍有待确定。由于在病毒感染后不久的患者中越来越多地报告了类似VITT的综合征，病毒与PF4的直接相互作用可能最为关键。在此，我们总结了目前关于VITT发病机制的信息和假说，并介绍了体内模型，特别是用于VITT进一步研究的小鼠模型。
