Aleem Abdul, Nadeem Ahmed J.
Community Health Network
Lehigh Valley Health Network
Coronavirus disease 2019 (COVID-19), the illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause significant morbidity and mortality worldwide, with many nations enduring multiple outbreaks of this viral illness. Besides the importance of infection control measures to prevent or decrease the transmission of SARS-CoV-2, the most crucial step to contain this global pandemic is to vaccinate individuals to prevent SARS-CoV-2 infection in communities across the world. Many vaccines have been developed at an unprecedented speed using distinctive technologies to prevent COVID-19. Vaccination triggers the immune system resulting in the production of neutralizing antibodies against SARS-CoV-2. Four vaccines, namely the BNT162b2, mRNA-1273, Ad26.COV2.S, and ChAdOx1 nCoV-19 have been approved to prevent COVID-19 in many nations worldwide, including the United States. The BNT162b2, mRNA-1273 have been approved by the U.S. FDA and the Ad26.COV2.S has received Emergency Use Authorization. One exception is the ChAdOx1 nCoV-19 vaccine, which has not yet received a EUA or approval from the U.S. Food and Drug Administration (FDA) for use in the U.S. The BNT162b2 and mRNA-1273 vaccines are both mRNA-based, while the Ad26.COV2. S and ChAdOx1 nCoV-19 vaccines incorporate replication-incompetent adenoviral vectors in them. In late February 2021, a new clinical syndrome characterized by thrombosis at atypical sites combined with thrombocytopenia was observed in multiple patients days after vaccination with the ChAdOx1 nCoV-19 vaccine. In April 2021, similar clinical sequelae were reported in patients after vaccination with the Ad26.COV2. S vaccine. Preceding the approval of these vaccines, the clinical constellation of this new syndrome was not observed in clinical trials of the ChAdOx1 nCoV-19 vaccine, and a single case was observed in the Ad26.COV2. S vaccine trial recipient.Furthermore, the incidence of major adverse effects has remained exceptionally low following the vaccination of more than 400 million people worldwide. This novel clinical syndrome demonstrated striking similarities to heparin-induced thrombocytopenia; however, in the absence of prior heparin exposure was named vaccine-induced immune thrombotic thrombocytopenia (VITT). It is also known as vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) in some European nations and Canada. Conversely, in millions of doses of BNT162b2 or mRNA-1273 vaccines administered so far, this clinical syndrome has not been reported. Due to the concern of VITT associated with the Ad26.COV2. S vaccine, the FDA modified the EUA and recommends limiting the use of this vaccine only to individuals > 18 years of age who are otherwise ineligible to receive any other FDA-approved vaccines due to anaphylaxis to mRNA vaccines or its components or are unable/unwilling to receive any other vaccine. Per the American Society of Hematology, vaccine-induced immune thrombotic thrombocytopenia (VITT) is defined as a clinical syndrome characterized by all of the below described abnormal laboratory and radiologic abnormalities occurring in individuals 4 to 42 days after vaccination with Ad26.COV2. S or ChAdOx1 nCoV-19 vaccines. Development of thrombosis at uncommon sites includes cerebral venous sinus thrombosis (CSVT)/splanchnic venous thrombosis. Mild to severe thrombocytopenia. However, a normal platelet count does not exclude the possibility of this syndrome in its early stages. Positive antibodies against platelet factor 4(PF4) identified by enzyme-linked immunosorbent assay (ELISA) assay. Significantly elevated D-dimer ( > 4 times ULN). This review article aims to describe the etiology, epidemiology, pathophysiology, clinical features, diagnosis, and management of COVID-19 vaccine-induced thrombotic immune thrombocytopenia based on the latest available published literature.
2019冠状病毒病(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的疾病,在全球范围内继续导致大量发病和死亡,许多国家都经历了这种病毒性疾病的多次暴发。除了感染控制措施对于预防或减少SARS-CoV-2传播的重要性外,遏制这一全球大流行的最关键步骤是为个人接种疫苗,以防止SARS-CoV-2在世界各地的社区中感染。许多疫苗以前所未有的速度利用独特技术开发出来,用于预防COVID-19。接种疫苗会触发免疫系统,从而产生针对SARS-CoV-2的中和抗体。四种疫苗,即BNT162b2、mRNA-1273、Ad26.COV2.S和ChAdOx1 nCoV-19,已在包括美国在内的世界许多国家被批准用于预防COVID-19。BNT162b2、mRNA-1273已获得美国食品药品监督管理局(FDA)批准,Ad26.COV2.S已获得紧急使用授权。一个例外是ChAdOx1 nCoV-19疫苗,它尚未获得美国食品药品监督管理局(FDA)的紧急使用授权或批准在美国使用。BNT162b2和mRNA-1273疫苗都是基于信使核糖核酸(mRNA)的,而Ad26.COV2.S和ChAdOx1 nCoV-19疫苗则包含无复制能力的腺病毒载体。2021年2月下旬,在多名接种ChAdOx1 nCoV-19疫苗数天后的患者中,观察到一种以非典型部位血栓形成并伴有血小板减少为特征的新临床综合征。2021年4月,接种Ad26.COV2.S疫苗后的患者也报告了类似的临床后遗症。在这些疫苗获批之前,在ChAdOx1 nCoV-19疫苗的临床试验中未观察到这种新综合征的临床症状组合,在Ad26.COV2.S疫苗试验接受者中仅观察到1例。此外,在全球超过4亿人接种疫苗后,主要不良反应的发生率一直异常低。这种新型临床综合征与肝素诱导的血小板减少症有惊人的相似之处;然而,在没有先前肝素暴露的情况下,它被命名为疫苗诱导的免疫性血栓性血小板减少症(VITT)。在一些欧洲国家和加拿大,它也被称为疫苗诱导的促血栓形成免疫性血小板减少症(VIPIT)。相反,在迄今为止接种的数百万剂BNT162b2或mRNA-1273疫苗中,尚未报告这种临床综合征。由于对与Ad26.COV2.S疫苗相关的VITT的担忧,FDA修改了紧急使用授权,并建议仅将这种疫苗用于18岁以上的个体,这些个体因对mRNA疫苗或其成分过敏而无法接种任何其他FDA批准的疫苗,或者无法/不愿意接种任何其他疫苗。根据美国血液学会的定义免疫性血栓性血小板减少症(VITT)是一种临床综合征,其特征为在接种Ad26.COV2.S或ChAdOx1 nCoV-19疫苗后4至42天内出现以下所有异常实验室和影像学异常。在不常见部位发生血栓形成,包括脑静脉窦血栓形成(CSVT)/内脏静脉血栓形成。轻度至重度血小板减少。然而,血小板计数正常并不能排除该综合征在早期阶段的可能性。通过酶联免疫吸附测定(ELISA)检测到针对血小板因子4(PF4)的阳性抗体。D-二聚体显著升高(>4倍正常上限)。这篇综述文章旨在根据最新发表的文献描述COVID-19疫苗诱导的血栓性免疫性血小板减少症的病因、流行病学、病理生理学、临床特征、诊断和管理。