US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021
US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021
复制标题
DOI：
10.1001/jama.2021.7517
复制
发表时间：
2021-04-30
影响因子：
120.7
通讯作者：
Broder, Karen R.
中科院分区：
文献类型：
--
作者：
See, Isaac;Su, John R.;Broder, Karen R.
在欧洲，在使用黑猩猩腺病毒载体接种ChAdOx1 nCoV-19疫苗（牛津大学/阿斯利康公司）后，出现了伴血小板减少的脑静脉窦血栓形成（CVST），这是一种罕见且严重的疾病。一种类似于自身免疫性肝素诱导的血小板减少症（HIT）的机制已被提出。在美国，Ad26.COV2。S COVID-19疫苗（Janssen/Johnson & Johnson）使用人类腺病毒载体，于2021年2月27日获得紧急使用授权（EUA）。到2021年4月12日，大约700万Ad26.COV2。美国已经接种了5剂疫苗，在接种者中发现6例CVST伴血小板减少，导致2021年4月13日全国暂时停止接种该产品。目的总结Ad26.COV2术后CVST伴血小板减少的报告。S疫苗收据。设计、环境和参与者：12例美国CVST和血小板减少患者在使用Ad26.COV2后的病例系列。2021年3月2日至4月21日，EUA下的S疫苗向疫苗不良事件报告系统（VAERS）报告（随访报告至2021年4月21日）。收到Ad26.COV2。年代的疫苗。临床过程、影像学、实验室检查以及从VAERS报告、病历回顾和与临床医生讨论中获得的CVST诊断后的结果。结果患者年龄从18岁到60岁以下；全部为白人女性，来自11个州。7例患者至少有1个CVST危险因素，包括肥胖（n = 6）、甲状腺功能减退（n = 1）和口服避孕药（n = 1）；没有人有肝素暴露史。时间来自Ad26.COV2。接种S疫苗至出现症状的时间为6至15天。11例患者最初表现为头痛；1例患者最初表现为背部疼痛，后来出现头痛。12例CVST患者中，7例合并脑出血；8例有非cvst血栓形成。确诊CVST后，6例患者最初接受肝素治疗。血小板最低点为9 × 10(3)/ μ L ~ 127 × 10(3)/ μ L。11例患者经酶联免疫吸附试验（ELISA）筛选肝素-血小板因子4 HIT抗体均为阳性。所有患者均住院治疗（10例在重症监护病房[ICU]）。截至2021年4月21日，结果为死亡（n = 3）、继续ICU治疗（n = 3）、继续非ICU住院（n = 2）和出院回家（n = 4）。结论及相关性：在Ad26.COV2治疗后，美国首批12例CVST伴血小板减少。S疫苗接种代表严重事件。该病例系列可作为Ad26.COV2提供临床指导。美国恢复了Ad26.COV2的疫苗接种，并调查了Ad26.COV2和Ad26.COV2之间的潜在关系。S疫苗和CVST伴血小板减少症。
IMPORTANCE Cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare and serious condition, has been described in Europe following receipt of the ChAdOx1 nCoV-19 vaccine (Oxford/AstraZeneca), which uses a chimpanzee adenoviral vector. A mechanism similar to autoimmune heparin-induced thrombocytopenia (HIT) has been proposed. In the US, the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson), which uses a human adenoviral vector, received Emergency Use Authorization (EUA) on February 27, 2021. By April 12, 2021, approximately 7 million Ad26.COV2.S vaccine doses had been given in the US, and 6 cases of CVST with thrombocytopenia had been identified among the recipients, resulting in a temporary national pause in vaccination with this product on April 13, 2021.OBJECTIVE To describe reports of CVST with thrombocytopenia following Ad26.COV2.S vaccine receipt.DESIGN, SETTING, AND PARTICIPANTS Case series of 12 US patients with CVST and thrombocytopenia following use of Ad26.COV2.S vaccine under EUA reported to the Vaccine Adverse Event Reporting System (VAERS) from March 2 to April 21, 2021 (with follow-up reported through April 21, 2021).EXPOSURES Receipt of Ad26.COV2.S vaccine.MAIN OUTCOMES AND MEASURES Clinical course, imaging, laboratory tests, and outcomes after CVST diagnosis obtained from VAERS reports, medical record review, and discussion with clinicians.RESULTS Patients' ages ranged from 18 to younger than 60 years; all were White women, reported from 11 states. Seven patients had at least 1 CVST risk factor, including obesity (n = 6), hypothyroidism (n = 1), and oral contraceptive use (n = 1); none had documented prior heparin exposure. Time from Ad26.COV2.S vaccination to symptom onset ranged from 6 to 15 days. Eleven patients initially presented with headache; 1 patient initially presented with back pain and later developed headache. Of the 12 patients with CVST, 7 also had intracerebral hemorrhage; 8 had non-CVST thromboses. After diagnosis of CVST, 6 patients initially received heparin treatment. Platelet nadir ranged from 9 x10(3)/mu L to 127 x10(3)/mu L. All 11 patients tested for the heparin-platelet factor 4 HIT antibody by enzyme-linked immunosorbent assay (ELISA) screening had positive results. All patients were hospitalized (10 in an intensive care unit [ICU]). As of April 21, 2021, outcomes were death (n = 3), continued ICU care (n = 3), continued non-ICU hospitalization (n = 2), and discharged home (n = 4).CONCLUSIONS AND RELEVANCE The initial 12 US cases of CVST with thrombocytopenia after Ad26.COV2.S vaccination represent serious events. This case series may inform clinical guidance as Ad26.COV2.S vaccination resumes in the US as well as investigations into the potential relationship between Ad26.COV2.S vaccine and CVST with thrombocytopenia.