Faculty of Medicine, Department of Immunology and Inflammation, Imperial College London, Room 5S5b, The Hammersmith Hospital, Hammersmith Campus, Du Cane Road, London W12 0NN, UK.
Sue Rees Consultancy Ltd, Verulam Point, Station Way, St. Albans AL1 5HE, UK.
Vaccine. 2022 Sep 9;40(38):5585-5593. doi: 10.1016/j.vaccine.2022.08.007. Epub 2022 Aug 19.
Post-marketing surveillance for COVID-19 vaccines during the pandemic identified an extremely rare thrombosis with thrombocytopenia syndrome (TTS) reported post-vaccination, requiring further characterisation to improve diagnosis and management.
We searched the AstraZeneca Global Safety Database (through April 26, 2021) for cases with co-reported thrombocytopenia and thrombosis (using standardised MedDRA queries/high-level terms) following AZD1222 (ChAdOx1 nCoV-19). Cases were adjudicated by experts as 'typical','possible', 'no' or 'unknown' according to available TTS criteria. Additional confirmatory datasets (May 20-June 20, October 1-December 28) were evaluated.
We identified 573 reports, including 273 (47.6 %) 'typical' and 171 (29.8 %) 'possible' TTS cases. Of these 444 cases, 275 (61.9 %) were female, median age was 50.0 years (IQR: 38.0-60.0). Cerebral venous sinus thrombosis was reported in 196 (44.1 %) cases, splanchnic venous thrombosis in 65 (14.6 %) and thromboses at multiple sites in 119 (26.8 %). Median time to onset was 12.0 days (IQR: 9.0-15.0). Comparison with a pre-pandemic reference population indicated higher rates of autoimmune disorders (13.8 %, 4.4 %), previous heparin therapy (7.4 %, 1.2 %), history of thrombosis (5.5 %, 1.4 %), and immune thrombocytopenia (6.1 %, 0.2 %). Fatality rate was 22.2 % (127/573) overall and 23.6 % (105/444) in 'typical'/'possible' TTS, which decreased from 39.0 % (60/154) in February/March to 15.5 % (45/290) in April. Overall patterns were similar in confirmatory datasets.
The reporting rate of 'typical'/'possible' TTS post first-dose vaccination in this dataset is 7.5 per million vaccinated persons; few cases were reported after subsequent doses, including booster doses. Peak reporting coincided with media-driven attention. Medical history differences versus a reference population indicate potentially unidentified risk factors. The decreasing fatality rate correlates with increasing awareness and publication of diagnostic/treatment guidelines. Adjudication was hindered by unreported parameters, and an algorithm was developed to classify potential TTS cases; comprehensive reporting could help further improve definition and management of this extremely rare syndrome.
大流行期间，COVID-19 疫苗的上市后监测发现了一种极其罕见的疫苗接种后血栓性血小板减少综合征（TTS），需要进一步进行特征描述以改善诊断和管理。
我们通过阿斯利康全球安全数据库（截至 2021 年 4 月 26 日），使用标准化 MedDRA 查询/高级术语，对 AZD1222（ChAdOx1 nCoV-19）接种后伴血小板减少和血栓形成的病例进行了搜索。根据可用的 TTS 标准，专家对病例进行了“典型”、“可能”、“否”或“未知”的判定。评估了另外两个确认数据集（2021 年 5 月 20 日至 6 月 20 日和 2021 年 10 月 1 日至 12 月 28 日）。
我们共发现了 573 例报告，其中 273 例（47.6%）为“典型”TTS 病例，171 例（29.8%）为“可能”TTS 病例。在这 444 例病例中，275 例（61.9%）为女性，中位年龄为 50.0 岁（IQR：38.0-60.0）。196 例（44.1%）报告了脑静脉窦血栓形成，65 例（14.6%）报告了内脏静脉血栓形成，119 例（26.8%）报告了多处血栓形成。中位发病时间为 12.0 天（IQR：9.0-15.0）。与大流行前参考人群相比，该人群自身免疫性疾病（13.8%，4.4%）、肝素治疗史（7.4%，1.2%）、血栓形成史（5.5%，1.4%）和免疫性血小板减少症（6.1%，0.2%）的发病率更高。总体死亡率为 22.2%（573 例中有 127 例），“典型”/“可能”TTS 的死亡率为 23.6%（444 例中有 105 例），从 2 月/3 月的 39.0%（60/154）降至 4 月的 15.5%（45/290）。确认数据集的总体模式相似。
本数据集第一剂疫苗接种后“典型”/“可能”TTS 的报告率为每百万接种者 7.5 例；随后几剂疫苗接种后报告的病例较少，包括加强针。报告高峰与媒体驱动的关注度相吻合。与参考人群相比，病史差异表明可能存在未被识别的风险因素。死亡率的下降与诊断/治疗指南的不断普及和发布有关。由于缺乏报告参数，鉴定受到了阻碍，因此开发了一种算法来对潜在的 TTS 病例进行分类；全面的报告有助于进一步改善这种极其罕见综合征的定义和管理。
