Thrombosis with thrombocytopenia after AZD1222 (ChAdOx1 nCov-19) vaccination: Case characteristics and associations.

Autor: Laffan MA; 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. Electronic address: m.laffan@imperial.ac.uk., Rees S; Sue Rees Consultancy Ltd, Verulam Point, Station Way, St. Albans AL1 5HE, UK. Electronic address: sue.rees22@btinternet.com., Yadavalli M; Patient Safety, Chief Medical Office, R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA. Electronic address: madhavi.yadavalli@astrazeneca.com., Ferstenberg LB; Patient Safety, Chief Medical Office, R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA. Electronic address: lisabeth.ferstenberg@astrazeneca.com., Kumar Shankar N; Patient Safety, Chief Medical Office, R&D, AstraZeneca, India Pvt. Ltd, Rachenahalli, Outer Ring Road, Bangalore 560045, India. Electronic address: nirmalkumar.shankar@astrazeneca.com., Medin J; BioPharmaceuticals Medical, AstraZeneca, Pepparedsleden 1, Mölndal SE431 83, Gothenburg, Sweden. Electronic address: jennie.medin@astrazeneca.com., Foskett N; BioPharmaceuticals Medical, AstraZeneca, Academy House 136 Hills Road, Cambridge CB2 8PA, UK. Electronic address: nadia.foskett@astrazeneca.com., Arnold M; BioPharmaceuticals Medical, AstraZeneca, Granta Park, Cambridge CB21 6GP, UK. Electronic address: matthew.arnold2@astrazeneca.com., Gomes da Silva H; Vaccines & Immune Therapies, BioPharmaceuticals Medical, AstraZeneca, Rua Humberto Madeira 7 / 7A, 2730-097 Lisboa, Portugal. Electronic address: hugo.gomesdasilva@astrazeneca.com., Bhuyan P; Clinical Development, Vaccines & Immune Therapies, BioPharmaceuticals R&D, AstraZeneca, 1 Medimmune Way, Gaithersburg, MD 20878, USA. Electronic address: prakash.bhuyan@astrazeneca.com., Nord M; Patient Safety, Chief Medical Office, R&D, AstraZeneca, Pepparedsleden 1, Mölndal SE431 83, Gothenburg, Sweden. Electronic address: magnus.nord@astrazeneca.com.
Jazyk: angličtina
Zdroj: Vaccine [Vaccine] 2022 Sep 09; Vol. 40 (38), pp. 5585-5593. Date of Electronic Publication: 2022 Aug 19.
DOI: 10.1016/j.vaccine.2022.08.007
Abstrakt: 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.
Competing Interests: Declaration of Competing Interest MAL declares consultancy work for AstraZeneca in relation to AZD1222, including for the present analyses. SR is a previous employee of AstraZeneca (2006–2010) and declares consultancy work for AstraZeneca in relation to the present analyses. MY, LBF, NKS, JM, NF, MA, HGdS, PB and MN are employees of AstraZeneca and may hold stock and/or stock options. MN participates on a Data Safety Monitoring Board or Advisory Board at the Karolinska Institute.
(Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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