Cooper Neurological Institute, Cooper University Hospital, Camden, NJ (J.E.S.).
Boston Medical Center, Boston University School of Medicine, MA (P.K., M.A., T.N.N.).
Stroke. 2021 Aug;52(9):3045-3053. doi: 10.1161/STROKEAHA.121.035613. Epub 2021 Jul 26.
In the spring of 2021, reports of rare and unusual venous thrombosis in association with the ChAdOx1 and Ad26.COV2.S adenovirus-based coronavirus vaccines led to a brief suspension of their use by several countries. Thromboses in the cerebral and splanchnic veins among patients vaccinated in the preceding 4 weeks were described in 17 patients out of 7.98 million recipients of the Ad26.COV2.S vaccine (with 3 fatalities related to cerebral vein thrombosis) and 169 cases of cerebral vein thrombosis among 35 million ChAdOx1 recipients. Events were associated with thrombocytopenia and anti-PF4 (antibodies directed against platelet factor 4), leading to the designation vaccine-induced immune thrombotic thrombocytopenia. Unlike the related heparin-induced thrombotic thrombocytopenia, with an estimated incidence of <1:1000 patients treated with heparin, and a mortality rate of 25%, vaccine-induced immune thrombotic thrombocytopenia has been reported in 1:150 000 ChAdOx1 recipients and 1:470 000 Ad26.COV.2 recipients, with a reported mortality rate of 20% to 30%. Early recognition of this complication should prompt testing for anti-PF4 antibodies and acute treatment targeting the autoimmune and prothrombotic processes. Intravenous immunoglobulin (1 g/kg for 2 days), consideration of plasma exchange, and nonheparin anticoagulation (argatroban, fondaparinux) are recommended. In cases of cerebral vein thrombosis, one should monitor for and treat the known complications of venous congestion as they would in patients without vaccine-induced immune thrombotic thrombocytopenia. Now that the Ad26.COV2.S has been reapproved for use in several countries, it remains a critical component of our pharmacological armamentarium in stopping the spread of the human coronavirus and should be strongly recommended to patients. At this time, the patient and community-level benefits of these two adenoviral vaccines vastly outweigh the rare but serious risks of vaccination. Due to the relatively low risk of severe coronavirus disease 2019 (COVID-19) in young women (<50 years), it is reasonable to recommend an alternative vaccine if one is available. Ongoing postmarketing observational studies are important for tracking new vaccine-induced immune thrombotic thrombocytopenia cases and other rare side effects of these emergent interventions.
2021 年春季,有报道称罕见且异常的静脉血栓与 ChAdOx1 和 Ad26.COV2.S 腺病毒为基础的冠状病毒疫苗有关,随后几个国家暂停了这两种疫苗的使用。在接种 Ad26.COV2.S 疫苗的 790 万名受种者中,有 17 例(3 例与脑静脉血栓相关)和 3500 万名 ChAdOx1 受种者中 169 例(有 3 例与脑静脉血栓相关)在接种疫苗前 4 周内发生了脑和内脏静脉血栓。这些事件与血小板减少和抗 PF4(针对血小板因子 4 的抗体)有关,导致疫苗诱导的免疫性血栓性血小板减少症的诊断。与肝素诱导的血栓性血小板减少症不同,肝素治疗患者估计发病率为<1/1000,死亡率为 25%,而疫苗诱导的免疫性血栓性血小板减少症在 1/150000 ChAdOx1 受种者和 1/470000 Ad26.COV.2 受种者中报告,死亡率为 20%至 30%。早期识别这种并发症应促使检测抗 PF4 抗体,并针对自身免疫和促血栓形成过程进行急性治疗。建议静脉内免疫球蛋白(2 天内 1g/kg)、考虑血浆置换和非肝素抗凝(阿加曲班、磺达肝素钠)。在发生脑静脉血栓的情况下,人们应该监测并治疗已知的静脉充血并发症,就像在没有疫苗诱导的免疫性血栓性血小板减少症的患者中一样。现在,Ad26.COV2.S 已在多个国家重新获准使用,它仍然是我们阻止人类冠状病毒传播的药理学武器库中的一个重要组成部分,应该强烈推荐给患者。此时,这两种腺病毒疫苗在患者和社区层面的益处远远超过了罕见但严重的疫苗接种风险。由于年轻女性(<50 岁)患严重 2019 年冠状病毒病(COVID-19)的风险相对较低,如果有替代疫苗,建议使用替代疫苗。正在进行的上市后观察性研究对于跟踪这些新出现的干预措施引起的疫苗诱导性免疫性血栓性血小板减少症病例和其他罕见副作用非常重要。