Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2021 Nov 1;78(11):1314-1323.
doi: 10.1001/jamaneurol.2021.3619.

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

Mayte Sánchez van Kammen  1 , Diana Aguiar de Sousa  2 , Sven Poli  3   4 , Charlotte Cordonnier  5 , Mirjam R Heldner  6 , Anita van de Munckhof  1 , Katarzyna Krzywicka  1 , Thijs van Haaps  7 , Alfonso Ciccone  8 , Saskia Middeldorp  9 , Marcel M Levi  10 , Johanna A Kremer Hovinga  11 , Suzanne Silvis  12 , Sini Hiltunen  13 , Maryam Mansour  14 , Antonio Arauz  15 , Miguel A Barboza  16 , Thalia S Field  17 , Georgios Tsivgoulis  18 , Simon Nagel  19 , Erik Lindgren  20   21 , Turgut Tatlisumak  20   21 , Katarina Jood  20   21 , Jukka Putaala  13 , Jose M Ferro  2 , Marcel Arnold  6 , Jonathan M Coutinho  1 ; Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group; Aarti R Sharma  22 , Ahmed Elkady  23 , Alberto Negro  24 , Albrecht Günther  25 , Alexander Gutschalk  19 , Silvia Schönenberger  19 , Alina Buture  26 , Sean Murphy  26   27   28 , Ana Paiva Nunes  29 , Andreas Tiede  30 , Anemon Puthuppallil Philip  31 , Annerose Mengel  32 , Antonio Medina  33 , Åslög Hellström Vogel  34 , Audrey Tawa  35 , Avinash Aujayeb  36 , Barbara Casolla  36   37 , Brian Buck  38 , Carla Zanferrari  39 , Carlos Garcia-Esperon  40 , Caroline Vayne  41 , Catherine Legault  42 , Christian Pfrepper  43 , Clement Tracol  44 , Cristina Soriano  45 , Daniel Guisado-Alonso  46 , David Bougon  47 , Domenico S Zimatore  48 , Dominik Michalski  49 , Dylan Blacquiere  50 , Elias Johansson  51 , Elisa Cuadrado-Godia  52 , Emmanuel De Maistre  53 , Emmanuel Carrera  54 , Fabrice Vuillier  55 , Fabrice Bonneville  56 , Fabrizio Giammello  57 , Felix J Bode  58 , Julian Zimmerman  58 , Florindo d'Onofrio  59 , Francesco Grillo  60 , Francois Cotton  61 , François Caparros  5 , Laurent Puy  5 , Frank Maier  62 , Giosue Gulli  63 , Giovanni Frisullo  64 , Gregory Polkinghorne  65 , Guillaume Franchineau  66 , Hakan Cangür  67 , Hans Katzberg  68 , Igor Sibon  69 , Irem Baharoglu  70 , Jaskiran Brar  71 , Jean-François Payen  72 , Jim Burrow  73 , João Fernandes  74 , Judith Schouten  75 , Katharina Althaus  76 , Katia Garambois  77 , Laurent Derex  78 , Lisa Humbertjean  79 , Lucia Lebrato Hernandez  80 , Lukas Kellermair  81 , Mar Morin Martin  82 , Marco Petruzzellis  83 , Maria Cotelli  84 , Marie-Cécile Dubois  85 , Marta Carvalho  86 , Matthias Wittstock  87 , Miguel Miranda  88 , Mona Skjelland  89 , Monica Bandettini di Poggio  90 , Moritz J Scholz  91 , Nicolas Raposo  92 , Robert Kahnis  92 , Nyika Kruyt  93 , Olivier Huet  94 , Pankaj Sharma  95 , Paolo Candelaresi  96 , Peggy Reiner  97 , Ricardo Vieira  98 , Roberto Acampora  99 , Rolf Kern  100 , Ronen Leker  101 , Shelagh Coutts  102 , Simerpreet Bal  102 , Shyam S Sharma  103 , Sophie Susen  104 , Thomas Cox  105 , Thomas Geeraerts  106 , Thomas Gattringer  107 , Thorsten Bartsch  108 , Timothy J Kleinig  109 , Vanessa Dizonno  17 , Yildiz Arslan  110
Affiliations
Multicenter Study

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

Mayte Sánchez van Kammen et al. JAMA Neurol. .

Abstract

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson).

Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS.

Design, setting, and participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination.

Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria.

Main outcomes and measures: Clinical characteristics and mortality rate.

Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later.

Conclusions and relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Aguiar de Sousa has received travel support from Boehringer Ingelheim and personal fees for advisory board participation from AstraZeneca. Dr Poli has received personal fees from AstraZeneca, Werfen, Portola, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, and Bayer; grants from the German Federal Ministry of Education and Research (REVISION randomized trial), German Federal Joint Committee Innovation Fund (APICES project), Daiichi Sankyo (SPOCT-DOAC 1 study), Bristol Myers Squibb/Pfizer (ATTICUS randomized trial), and European Union (PROOF randomized trial); and nonfinancial support from Werfen and Boehringer Ingelheim (REVISION randomized trial). Dr Cordonnier has received speaker honoraria from Boehringer Ingelheim, personal fees for advisory board participation from AstraZeneca and Biogen, and personal fees for steering committee participation from Biogen and Bristol Myers Squibb. Dr Heldner has received grants from the Swiss Heart Foundation and Bangerter Foundation; travel support from Bayer; personal fees for data safety monitoring board or advisory board participation from Amgen; and is a member of the European Stroke Organisation Board of Directors and European Stroke Organisation Education Committee. Dr Krzywicka has received travel support from Amgen. Dr Middeldorp has received grants from Bayer, Pfizer, Boehringer Ingelheim, and Daiichi Sankyo paid to her institution and personal fees from Bayer, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, AbbVie, Portola/Alexion, and Daiichi Sankyo paid to her institution. Dr Kremer Hovinga has received grants from Baxalta as well as personal fees paid to her institution from Shire, Ablynx, Roche, Sobi, and the Swiss Federal Office of Public Health. Dr Barboza has received payment or honoraria from Abbott, Pfizer, Roche, and Bayer. Dr Field has received grants and nonfinancial support from Bayer Canada as well as personal fees from Servier. Dr Nagel has received personal fees from Brainomix, Boehringer Ingelheim, and Pfizer. Dr Lindgren has received grants from the Swedish Neurological Society Academic, Elsa and Gustav Lindh’s Foundation, Per Olof Ahl’s Foundation, and Ulla Amlöv Foundation. Dr Tatlisumak has received personal fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Portola Pharmaceuticals. Dr Putaala has received personal fees from Boehringer Ingelheim, Bayer, Herantis Pharma, and Abbott and owns stock in Vital Signum. Dr Ferro has received personal fees from Boehringer Ingelheim, Bayer, and Daiichi Sankyo as well as grants from Bayer. Dr Arnold has received personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Medtronic, Novartis, Sanofi, Pfizer, and Amgen and grants from the Swiss National Science Foundation and Swiss Heart Foundation. Dr Coutinho has received grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for data safety monitoring board participation by Bayer. Dr Günther has received personal fees from Bayer Vital, Bristol Myers Squibb, and Daiichi Sankyo. Dr Blacquiere has received personal fees from Servier Canada. Dr Johansson has received grants from WCMM Umeå, Region Västerbotten, Svenska Läkaresällskapet, Strokeriskförbundet, and Hjärt-lungfonden. Dr d’Onofrio has received personal fees from Lilly, Teva, and Novartis. Dr Kern has received personal fees from Bristol Myers Squibb/Pfizer and Sanofi Genzyme. Dr Leker has received personal fees from Boehringer Ingelheim, Abbott, and Janssen. Dr Bartsch has received personal fees from Roche and Biogen and grants from Novartis. Dr Kleinig has received personal fees from Boehringer Ingelheim. No other disclosures were reported.

Figures

Figure.
Figure.. Flowchart of Patient Selection
CVST indicates cerebral venous sinus thrombosis; ICVTC, International Cerebral Venous Thrombosis Consortium; TTS, thrombosis with thrombocytopenia syndrome.
See this image and copyright information in PMC

References

    1. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092-2101. doi:10.1056/NEJMoa2104840 - DOI - PMC - PubMed
    1. Schultz NH, Sørvoll IH, Michelsen AE, et al. . Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(22):2124-2130. doi:10.1056/NEJMoa2104882 - DOI - PMC - PubMed
    1. See I, Su JR, Lale A, et al. . US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021;325(24):2448-2456. doi:10.1001/jama.2021.7517 - DOI - PMC - PubMed
    1. European Medicines Agency . Use of Vaxzevira to prevent COVID-19—article 5(3) procedure: assessment report. Accessed July 13, 2021. https://www.ema.europa.eu/en/documents/referral/use-vaxzevria-prevent-co...
    1. MacNeil JR, Su JR, Broder KR, et al. . Updated recommendations from the Advisory Committee on Immunization Practices for use of the Janssen (Johnson & Johnson) COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome among vaccine recipients—United States, April 2021. MMWR Morb Mortal Wkly Rep. 2021;70(17):651-656. doi:10.15585/mmwr.mm7017e4 - DOI - PMC - PubMed

Publication types

MeSH terms