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Case Reports
. 2021 Jun 22;325(24):2448-2456.
doi: 10.1001/jama.2021.7517.

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021

Isaac See  1 , John R Su  1 , Allison Lale  1 , Emily Jane Woo  2 , Alice Y Guh  1 , Tom T Shimabukuro  1 , Michael B Streiff  3 , Agam K Rao  1 , Allison P Wheeler  4 , Suzanne F Beavers  1 , Anna P Durbin  3 , Kathryn Edwards  4 , Elaine Miller  1 , Theresa A Harrington  1 , Adamma Mba-Jonas  2 , Narayan Nair  2 , Duong T Nguyen  1 , Kawsar R Talaat  3 , Victor C Urrutia  3 , Shannon C Walker  4 , C Buddy Creech  4 , Thomas A Clark  1 , Frank DeStefano  1 , Karen R Broder  1
Affiliations
Case Reports

US Case Reports of Cerebral Venous Sinus Thrombosis With Thrombocytopenia After Ad26.COV2.S Vaccination, March 2 to April 21, 2021

Isaac See et al. JAMA. .

Abstract

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 ×103/µL to 127 ×103/µL. 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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Streiff reported receiving grants from Janssen for the Cassini clinical trial of rivaroxaban for prevention of cancer-associated thrombosis; personal fees from Janssen for serving on the advisory board for the Cassini trial; from Bayer, Bristol Myers Squibb, and Dispersol for providing consultative advice; from Bayer for CME lectures; and from Pfizer for CME lectures and serving on the advisory board. Dr Strieff also reported receiving grants from NHLBI for a study on missed doses in VTE prophylaxis, from AHRQ for work on individualized feedback on VTE prophylaxis practices, and from PCORI for research on patient education to improve acceptance of VTE prophylaxis. Dr Durbin reported receiving grants from Pfizer as an investigator for the Pfizer COVID-19 vaccine trial and grants from NIH for serving as the site principal investigator for the AstraZeneca COVID-19 vaccine trial; receiving personal fees from Merck for consultative advice on dengue vaccine development; and serving on the scientific advisory board for Valneva. Dr Edwards reported receiving grants from NIH and providing consultative advice to BioNet and IBM; she also reported serving on data and safety monitoring boards of Pfizer, Moderna, Merck, Sanofi, Roche, X-4 Pharma, and Seqirus. Dr Talaat reported receiving grants from Pfizer for serving as the site principal investigator for the phase 3 adult COVID-19 vaccine study and the phase 1-3 pediatric (under 12) COVID-19 vaccine study, both at Johns Hopkins University; she also reported receiving grants from the NIH-Coronavirus Prevention Network for serving as a co-investigator on the phase 3 AstraZeneca COVID-19 vaccine trial in adults. Dr Urratia reported receiving grants from Genentech Inc for serving as the site principal investigator on the TIMELESS trial and his work on the investigator-sponsored OPTIMIST main trial. Dr Creech reported receiving grants from Merck as well as personal fees from Altimmune, Horizon, Karius, Premier, and Astellas for providing consultative advice. No other disclosures were reported.

Comment in

References

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