Thrombosis with thrombocytopenia after AZD1222 (ChAdOx1 nCov-19) vaccination: Case characteristics and associations. Issue 38 (9th September 2022)

• Record Type: Journal Article
• Authors: Laffan, Michael A; Rees, Sue; Yadavalli, Madhavi; Ferstenberg, Lisa Beth; Kumar Shankar, Nirmal; Medin, Jennie; Foskett, Nadia; Arnold, Matthew; Gomes da Silva, Hugo; Bhuyan, Prakash; Nord, Magnus
• Is Part Of: Vaccine. Volume 40:Issue 38(2022)
• Page Start: 5585
• Page End: 5593
• Publication Date: 2022-09-09
• Subjects: AZD1222 -- ChAdOx1 nCoV-19 -- COVID-19 -- Thrombosis -- Thrombocytopenia -- TTS; CVST cerebral venous sinus thrombosis -- DVT deep vein thrombosis -- EU European Union -- EEA European Economic Area -- IQR interquartile range -- MI myocardial infarction -- PE pulmonary embolism -- PF-4 platelet factor 4 -- TTS thrombosis with thrombocytopenia syndrome; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2022.08.007
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Surveillance captured extremely rare reports of TTS following COVID-19 vaccination. The AstraZeneca Database contains the most complete set of TTS reports post-AZD1222. This global database was used to assess TTS rates, characteristics and outcomes. Fatality rate decreased over time with higher awareness and new clinical guidance. Comprehensive reporting could inform further improvements to TTS case management. Abstract: Background: 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. Methods: 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. Findings: 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. Conclusions: 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.