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

Mayte Sánchez van Kammen; Diana Aguiar de Sousa; Sven Poli; Charlotte Cordonnier; Mirjam R. Heldner; Anita van de Munckhof; Katarzyna Krzywicka; Thijs van Haaps; Alfonso Ciccone; Saskia Middeldorp; Marcel M. Levi; Johanna A. Kremer Hovinga; Suzanne Silvis; Sini Hiltunen; Maryam Mansour; Antonio Arauz; Miguel A. Barboza; Thalia S. Field; Georgios Tsivgoulis; Simon Nagel; Erik Lindgren; Turgut Tatlisumak; Katarina Jood; Jukka Putaala; Jose M. Ferro; Marcel Arnold; Jonathan M. Coutinho; Aarti R. Sharma; Ahmed Elkady; Alberto Negro; Albrecht Günther; Alexander Gutschalk; Silvia Schönenberger; Alina Buture; Sean Murphy; Ana Paiva Nunes; Andreas Tiede; Anemon Puthuppallil Philip; Annerose Mengel; Antonio Medina; Åslög Hellström Vogel; Audrey Tawa; Avinash Aujayeb; Barbara Casolla; Brian Buck; Carla Zanferrari; Carlos Garcia-Esperon; Caroline Vayne; Catherine Legault; Christian Pfrepper; Clement Tracol; Cristina Soriano; Daniel Guisado-Alonso; David Bougon; Domenico S. Zimatore; Dominik Michalski; Dylan Blacquiere; Elias Johansson; Elisa Cuadrado-Godia; Emmanuel de Maistre; Emmanuel Carrera; Fabrice Vuillier; Fabrice Bonneville; Fabrizio Giammello; Felix J. Bode; Julian Zimmerman; Florindo D'Onofrio; Francesco Grillo; Francois Cotton; François Caparros; Laurent Puy; Frank Maier; Giosue Gulli; Giovanni Frisullo; Gregory Polkinghorne; Guillaume Franchineau; Hakan Cangür; Hans Katzberg; Igor Sibon; Irem Baharoglu; Jaskiran Brar; Jean-François Payen; Jim Burrow; João Fernandes; Judith Schouten; Katharina Althaus; Katia Garambois; Laurent Derex; Lisa Humbertjean; Lucia Lebrato Hernandez; Lukas Kellermair; Mar Morin Martin; Marco Petruzzellis; Maria Cotelli; Marie-C. cile Dubois; Marta Carvalho; Matthias Wittstock; Miguel Miranda; Mona Skjelland; Monica Bandettini di Poggio; Moritz J. Scholz; Nicolas Raposo; Robert Kahnis; Nyika Kruyt; Olivier Huet; Pankaj Sharma; Paolo Candelaresi; Peggy Reiner; Ricardo Vieira; Roberto Acampora; Rolf Kern; Ronen Leker; Shelagh Coutts; Simerpreet Bal; Shyam S. Sharma; Sophie Susen; Thomas Cox; Thomas Geeraerts; Thomas Gattringer; Thorsten Bartsch; Timothy J. Kleinig; Vanessa Dizonno; Yildiz Arslan

doi:https://doi.org/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, Diana Aguiar de Sousa, Sven Poli, Charlotte Cordonnier, Mirjam R. Heldner, Anita van de Munckhof, Katarzyna Krzywicka, Thijs van Haaps, Alfonso Ciccone, Saskia Middeldorp, Marcel M. Levi, Johanna A. Kremer Hovinga, Suzanne Silvis, Sini Hiltunen, Maryam Mansour, Antonio Arauz, Miguel A. Barboza, Thalia S. Field, Georgios Tsivgoulis, Simon NagelErik Lindgren, Turgut Tatlisumak, Katarina Jood, Jukka Putaala, Jose M. Ferro, Marcel Arnold, Jonathan M. Coutinho, Aarti R. Sharma, Ahmed Elkady, Alberto Negro, Albrecht Günther, Alexander Gutschalk, Silvia Schönenberger, Alina Buture, Sean Murphy, Ana Paiva Nunes, Andreas Tiede, Anemon Puthuppallil Philip, Annerose Mengel, Antonio Medina, Åslög Hellström Vogel, Audrey Tawa, Avinash Aujayeb, Barbara Casolla, Brian Buck, Carla Zanferrari, Carlos Garcia-Esperon, Caroline Vayne, Catherine Legault, Christian Pfrepper, Clement Tracol, Cristina Soriano, Daniel Guisado-Alonso, David Bougon, Domenico S. Zimatore, Dominik Michalski, Dylan Blacquiere, Elias Johansson, Elisa Cuadrado-Godia, Emmanuel de Maistre, Emmanuel Carrera, Fabrice Vuillier, Fabrice Bonneville, Fabrizio Giammello, Felix J. Bode, Julian Zimmerman, Florindo D'Onofrio, Francesco Grillo, Francois Cotton, François Caparros, Laurent Puy, Frank Maier, Giosue Gulli, Giovanni Frisullo, Gregory Polkinghorne, Guillaume Franchineau, Hakan Cangür, Hans Katzberg, Igor Sibon, Irem Baharoglu, Jaskiran Brar, Jean-François Payen, Jim Burrow, João Fernandes, Judith Schouten, Katharina Althaus, Katia Garambois, Laurent Derex, Lisa Humbertjean, Lucia Lebrato Hernandez, Lukas Kellermair, Mar Morin Martin, Marco Petruzzellis, Maria Cotelli, Marie-C. cile Dubois, Marta Carvalho, Matthias Wittstock, Miguel Miranda, Mona Skjelland, Monica Bandettini di Poggio, Moritz J. Scholz, Nicolas Raposo, Robert Kahnis, Nyika Kruyt, Olivier Huet, Pankaj Sharma, Paolo Candelaresi, Peggy Reiner, Ricardo Vieira, Roberto Acampora, Rolf Kern, Ronen Leker, Shelagh Coutts, Simerpreet Bal, Shyam S. Sharma, Sophie Susen, Thomas Cox, Thomas Geeraerts, Thomas Gattringer, Thorsten Bartsch, Timothy J. Kleinig, Vanessa Dizonno, Yildiz Arslan

Research output: Contribution to journal › Article › Academic › peer-review

80 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1314-1323
Number of pages	10
Journal	JAMA Neurology
Volume	78
Issue number	11
Early online date	2021
DOIs	https://doi.org/doi:10.1001/jamaneurol.2021.3619 https://doi.org/10.1001/jamaneurol.2021.3619 https://doi.org/10.1001/jamaneurol.2021.3619
Publication status	Published - Nov 2021

Keywords

Ad26COVS1
Adult
Aged
BNT162 Vaccine
COVID-19 Vaccines/adverse effects
ChAdOx1 nCoV-19
Cohort Studies
Drug-Related Side Effects and Adverse Reactions/mortality
Female
Hospital Mortality
Humans
Male
Middle Aged
Outcome Assessment, Health Care
Registries
Sex Factors
Sinus Thrombosis, Intracranial/blood
Syndrome
Thrombocytopenia/blood
Venous Thromboembolism/blood
Young Adult

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Sánchez van Kammen, M., Aguiar de Sousa, D., Poli, S., Cordonnier, C., Heldner, M. R., van de Munckhof, A., Krzywicka, K., van Haaps, T., Ciccone, A., Middeldorp, S., Levi, M. M., Kremer Hovinga, J. A., Silvis, S., Hiltunen, S., Mansour, M., Arauz, A., Barboza, M. A., Field, T. S., Tsivgoulis, G., ... Arslan, Y. (2021). Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. JAMA Neurology, 78(11), 1314-1323. https://doi.org/doi:10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619

@article{aace2019de8a4da6ab5a4f163d97096d,

title = "Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia",

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.",

keywords = "Ad26COVS1, Adult, Aged, BNT162 Vaccine, COVID-19 Vaccines/adverse effects, ChAdOx1 nCoV-19, Cohort Studies, Drug-Related Side Effects and Adverse Reactions/mortality, Female, Hospital Mortality, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Registries, Sex Factors, Sinus Thrombosis, Intracranial/blood, Syndrome, Thrombocytopenia/blood, Venous Thromboembolism/blood, Young Adult",

author = "{S{\'a}nchez van Kammen}, Mayte and {Aguiar de Sousa}, Diana and Sven Poli and Charlotte Cordonnier and Heldner, {Mirjam R.} and {van de Munckhof}, Anita and Katarzyna Krzywicka and {van Haaps}, Thijs and Alfonso Ciccone and Saskia Middeldorp and Levi, {Marcel M.} and {Kremer Hovinga}, {Johanna A.} and Suzanne Silvis and Sini Hiltunen and Maryam Mansour and Antonio Arauz and Barboza, {Miguel A.} and Field, {Thalia S.} and Georgios Tsivgoulis and Simon Nagel and Erik Lindgren and Turgut Tatlisumak and Katarina Jood and Jukka Putaala and Ferro, {Jose M.} and Marcel Arnold and Coutinho, {Jonathan M.} and Sharma, {Aarti R.} and Ahmed Elkady and Alberto Negro and Albrecht G{\"u}nther and Alexander Gutschalk and Silvia Sch{\"o}nenberger and Alina Buture and Sean Murphy and {Paiva Nunes}, Ana and Andreas Tiede and {Puthuppallil Philip}, Anemon and Annerose Mengel and Antonio Medina and {Hellstr{\"o}m Vogel}, {\AA}sl{\"o}g and Audrey Tawa and Avinash Aujayeb and Barbara Casolla and Brian Buck and Carla Zanferrari and Carlos Garcia-Esperon and Caroline Vayne and Catherine Legault and Christian Pfrepper and Clement Tracol and Cristina Soriano and Daniel Guisado-Alonso and David Bougon and Zimatore, {Domenico S.} and Dominik Michalski and Dylan Blacquiere and Elias Johansson and Elisa Cuadrado-Godia and {de Maistre}, Emmanuel and Emmanuel Carrera and Fabrice Vuillier and Fabrice Bonneville and Fabrizio Giammello and Bode, {Felix J.} and Julian Zimmerman and Florindo D'Onofrio and Francesco Grillo and Francois Cotton and Fran{\c c}ois Caparros and Laurent Puy and Frank Maier and Giosue Gulli and Giovanni Frisullo and Gregory Polkinghorne and Guillaume Franchineau and Hakan Cang{\"u}r and Hans Katzberg and Igor Sibon and Irem Baharoglu and Jaskiran Brar and Jean-Fran{\c c}ois Payen and Jim Burrow and Jo{\~a}o Fernandes and Judith Schouten and Katharina Althaus and Katia Garambois and Laurent Derex and Lisa Humbertjean and {Lebrato Hernandez}, Lucia and Lukas Kellermair and {Morin Martin}, Mar and Marco Petruzzellis and Maria Cotelli and Dubois, {Marie-C. cile} and Marta Carvalho and Matthias Wittstock and Miguel Miranda and Mona Skjelland and {Bandettini di Poggio}, Monica and Scholz, {Moritz J.} and Nicolas Raposo and Robert Kahnis and Nyika Kruyt and Olivier Huet and Pankaj Sharma and Paolo Candelaresi and Peggy Reiner and Ricardo Vieira and Roberto Acampora and Rolf Kern and Ronen Leker and Shelagh Coutts and Simerpreet Bal and Sharma, {Shyam S.} and Sophie Susen and Thomas Cox and Thomas Geeraerts and Thomas Gattringer and Thorsten Bartsch and Kleinig, {Timothy J.} and Vanessa Dizonno and Yildiz Arslan",

note = "Funding Information: 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{\textquoteright}s Foundation, Per Olof Ahl{\textquoteright}s Foundation, and Ulla Aml{\"o}v 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 G{\"u}nther 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 Ume{\aa}, Region V{\"a}sterbotten, Svenska L{\"a}kares{\"a}llskapet, Strokeriskf{\"o}rbundet, and Hj{\"a}rt-lungfonden. Dr d{\textquoteright}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. Funding Information: 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 Publisher Copyright: {\textcopyright} 2021 American Medical Association. All rights reserved.",

year = "2021",

month = nov,

doi = "https://doi.org/doi:10.1001/jamaneurol.2021.3619",

language = "English",

volume = "78",

pages = "1314--1323",

journal = "JAMA Neurology",

issn = "2168-6149",

publisher = "American Medical Association",

number = "11",

}

Sánchez van Kammen, M, Aguiar de Sousa, D, Poli, S, Cordonnier, C, Heldner, MR, van de Munckhof, A , Krzywicka, K , van Haaps, T, Ciccone, A, Middeldorp, S , Levi, MM, Kremer Hovinga, JA, Silvis, S, Hiltunen, S, Mansour, M, Arauz, A, Barboza, MA, Field, TS, Tsivgoulis, G, Nagel, S, Lindgren, E, Tatlisumak, T, Jood, K, Putaala, J, Ferro, JM, Arnold, M, Coutinho, JM, Sharma, AR, Elkady, A, Negro, A, Günther, A, Gutschalk, A, Schönenberger, S, Buture, A, Murphy, S, Paiva Nunes, A, Tiede, A, Puthuppallil Philip, A, Mengel, A, Medina, A, Hellström Vogel, Å, Tawa, A, Aujayeb, A, Casolla, B, Buck, B, Zanferrari, C, Garcia-Esperon, C, Vayne, C, Legault, C, Pfrepper, C, Tracol, C, Soriano, C, Guisado-Alonso, D, Bougon, D, Zimatore, DS, Michalski, D, Blacquiere, D, Johansson, E, Cuadrado-Godia, E, de Maistre, E, Carrera, E, Vuillier, F, Bonneville, F, Giammello, F, Bode, FJ, Zimmerman, J, D'Onofrio, F, Grillo, F, Cotton, F, Caparros, F, Puy, L, Maier, F, Gulli, G, Frisullo, G, Polkinghorne, G, Franchineau, G, Cangür, H, Katzberg, H, Sibon, I, Baharoglu, I, Brar, J, Payen, J-F, Burrow, J, Fernandes, J, Schouten, J, Althaus, K, Garambois, K, Derex, L, Humbertjean, L, Lebrato Hernandez, L, Kellermair, L, Morin Martin, M, Petruzzellis, M, Cotelli, M, Dubois, M-CC, Carvalho, M, Wittstock, M, Miranda, M, Skjelland, M, Bandettini di Poggio, M, Scholz, MJ, Raposo, N, Kahnis, R, Kruyt, N, Huet, O, Sharma, P, Candelaresi, P, Reiner, P, Vieira, R, Acampora, R, Kern, R, Leker, R, Coutts, S, Bal, S, Sharma, SS, Susen, S, Cox, T, Geeraerts, T, Gattringer, T, Bartsch, T, Kleinig, TJ, Dizonno, V & Arslan, Y 2021, 'Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia', JAMA Neurology, vol. 78, no. 11, pp. 1314-1323. https://doi.org/doi:10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619

TY - JOUR

T1 - Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia

AU - Sánchez van Kammen, Mayte

AU - Aguiar de Sousa, Diana

AU - Poli, Sven

AU - Cordonnier, Charlotte

AU - Heldner, Mirjam R.

AU - van de Munckhof, Anita

AU - Krzywicka, Katarzyna

AU - van Haaps, Thijs

AU - Ciccone, Alfonso

AU - Middeldorp, Saskia

AU - Levi, Marcel M.

AU - Kremer Hovinga, Johanna A.

AU - Silvis, Suzanne

AU - Hiltunen, Sini

AU - Mansour, Maryam

AU - Arauz, Antonio

AU - Barboza, Miguel A.

AU - Field, Thalia S.

AU - Tsivgoulis, Georgios

AU - Nagel, Simon

AU - Lindgren, Erik

AU - Tatlisumak, Turgut

AU - Jood, Katarina

AU - Putaala, Jukka

AU - Ferro, Jose M.

AU - Arnold, Marcel

AU - Coutinho, Jonathan M.

AU - Sharma, Aarti R.

AU - Elkady, Ahmed

AU - Negro, Alberto

AU - Günther, Albrecht

AU - Gutschalk, Alexander

AU - Schönenberger, Silvia

AU - Buture, Alina

AU - Murphy, Sean

AU - Paiva Nunes, Ana

AU - Tiede, Andreas

AU - Puthuppallil Philip, Anemon

AU - Mengel, Annerose

AU - Medina, Antonio

AU - Hellström Vogel, Åslög

AU - Tawa, Audrey

AU - Aujayeb, Avinash

AU - Casolla, Barbara

AU - Buck, Brian

AU - Zanferrari, Carla

AU - Garcia-Esperon, Carlos

AU - Vayne, Caroline

AU - Legault, Catherine

AU - Pfrepper, Christian

AU - Tracol, Clement

AU - Soriano, Cristina

AU - Guisado-Alonso, Daniel

AU - Bougon, David

AU - Zimatore, Domenico S.

AU - Michalski, Dominik

AU - Blacquiere, Dylan

AU - Johansson, Elias

AU - Cuadrado-Godia, Elisa

AU - de Maistre, Emmanuel

AU - Carrera, Emmanuel

AU - Vuillier, Fabrice

AU - Bonneville, Fabrice

AU - Giammello, Fabrizio

AU - Bode, Felix J.

AU - Zimmerman, Julian

AU - D'Onofrio, Florindo

AU - Grillo, Francesco

AU - Cotton, Francois

AU - Caparros, François

AU - Puy, Laurent

AU - Maier, Frank

AU - Gulli, Giosue

AU - Frisullo, Giovanni

AU - Polkinghorne, Gregory

AU - Franchineau, Guillaume

AU - Cangür, Hakan

AU - Katzberg, Hans

AU - Sibon, Igor

AU - Baharoglu, Irem

AU - Brar, Jaskiran

AU - Payen, Jean-François

AU - Burrow, Jim

AU - Fernandes, João

AU - Schouten, Judith

AU - Althaus, Katharina

AU - Garambois, Katia

AU - Derex, Laurent

AU - Humbertjean, Lisa

AU - Lebrato Hernandez, Lucia

AU - Kellermair, Lukas

AU - Morin Martin, Mar

AU - Petruzzellis, Marco

AU - Cotelli, Maria

AU - Dubois, Marie-C. cile

AU - Carvalho, Marta

AU - Wittstock, Matthias

AU - Miranda, Miguel

AU - Skjelland, Mona

AU - Bandettini di Poggio, Monica

AU - Scholz, Moritz J.

AU - Raposo, Nicolas

AU - Kahnis, Robert

AU - Kruyt, Nyika

AU - Huet, Olivier

AU - Sharma, Pankaj

AU - Candelaresi, Paolo

AU - Reiner, Peggy

AU - Vieira, Ricardo

AU - Acampora, Roberto

AU - Kern, Rolf

AU - Leker, Ronen

AU - Coutts, Shelagh

AU - Bal, Simerpreet

AU - Sharma, Shyam S.

AU - Susen, Sophie

AU - Cox, Thomas

AU - Geeraerts, Thomas

AU - Gattringer, Thomas

AU - Bartsch, Thorsten

AU - Kleinig, Timothy J.

AU - Dizonno, Vanessa

AU - Arslan, Yildiz

N1 - Funding Information: 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. Funding Information: 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 Publisher Copyright: © 2021 American Medical Association. All rights reserved.

PY - 2021/11

Y1 - 2021/11

N2 - 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.

AB - 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.

KW - Ad26COVS1

KW - Adult

KW - Aged

KW - BNT162 Vaccine

KW - COVID-19 Vaccines/adverse effects

KW - ChAdOx1 nCoV-19

KW - Cohort Studies

KW - Drug-Related Side Effects and Adverse Reactions/mortality

KW - Female

KW - Hospital Mortality

KW - Humans

KW - Male

KW - Middle Aged

KW - Outcome Assessment, Health Care

KW - Registries

KW - Sex Factors

KW - Sinus Thrombosis, Intracranial/blood

KW - Syndrome

KW - Thrombocytopenia/blood

KW - Venous Thromboembolism/blood

KW - Young Adult

UR - http://www.scopus.com/inward/record.url?scp=85116170456&partnerID=8YFLogxK

U2 - https://doi.org/doi:10.1001/jamaneurol.2021.3619

DO - https://doi.org/doi:10.1001/jamaneurol.2021.3619

M3 - Article

C2 - 34581763

SN - 2168-6149

VL - 78

SP - 1314

EP - 1323

JO - JAMA Neurology

JF - JAMA Neurology

IS - 11

ER -

Sánchez van Kammen M, Aguiar de Sousa D, Poli S, Cordonnier C, Heldner MR, van de Munckhof A et al. Characteristics and Outcomes of Patients with Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia. JAMA Neurology. 2021 Nov;78(11):1314-1323. Epub 2021. doi: https://doi.org/doi:10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619, https://doi.org/10.1001/jamaneurol.2021.3619

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

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