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

doi:10.1001/jamaneurol.2021.3619

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 Kammen¹, Diana Aguiar de Sousa², Sven Poli^{3

4}, Charlotte Cordonnier⁵, Mirjam R Heldner⁶, Anita van de Munckhof¹, Katarzyna Krzywicka¹, Thijs van Haaps⁷, Alfonso Ciccone⁸, Saskia Middeldorp⁹, Marcel M Levi¹⁰, Johanna A Kremer Hovinga¹¹, Suzanne Silvis¹², Sini Hiltunen¹³, Maryam Mansour¹⁴, Antonio Arauz¹⁵, Miguel A Barboza¹⁶, Thalia S Field¹⁷, Georgios Tsivgoulis¹⁸, Simon Nagel¹⁹, Erik Lindgren^{20

21}, Turgut Tatlisumak^{20

21}, Katarina Jood^{20

21}, Jukka Putaala¹³, Jose M Ferro², Marcel Arnold⁶, Jonathan M Coutinho¹; Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group; Aarti R Sharma²², Ahmed Elkady²³, Alberto Negro²⁴, Albrecht Günther²⁵, Alexander Gutschalk¹⁹, Silvia Schönenberger¹⁹, Alina Buture²⁶, Sean Murphy^{26

27

28}, Ana Paiva Nunes²⁹, Andreas Tiede³⁰, Anemon Puthuppallil Philip³¹, Annerose Mengel³², Antonio Medina³³, Åslög Hellström Vogel³⁴, Audrey Tawa³⁵, Avinash Aujayeb³⁶, Barbara Casolla^{36

37}, Brian Buck³⁸, Carla Zanferrari³⁹, Carlos Garcia-Esperon⁴⁰, Caroline Vayne⁴¹, Catherine Legault⁴², Christian Pfrepper⁴³, Clement Tracol⁴⁴, Cristina Soriano⁴⁵, Daniel Guisado-Alonso⁴⁶, David Bougon⁴⁷, Domenico S Zimatore⁴⁸, Dominik Michalski⁴⁹, Dylan Blacquiere⁵⁰, Elias Johansson⁵¹, Elisa Cuadrado-Godia⁵², Emmanuel De Maistre⁵³, Emmanuel Carrera⁵⁴, Fabrice Vuillier⁵⁵, Fabrice Bonneville⁵⁶, Fabrizio Giammello⁵⁷, Felix J Bode⁵⁸, Julian Zimmerman⁵⁸, Florindo d'Onofrio⁵⁹, Francesco Grillo⁶⁰, Francois Cotton⁶¹, François Caparros⁵, Laurent Puy⁵, Frank Maier⁶², Giosue Gulli⁶³, Giovanni Frisullo⁶⁴, Gregory Polkinghorne⁶⁵, Guillaume Franchineau⁶⁶, Hakan Cangür⁶⁷, Hans Katzberg⁶⁸, Igor Sibon⁶⁹, Irem Baharoglu⁷⁰, Jaskiran Brar⁷¹, Jean-François Payen⁷², Jim Burrow⁷³, João Fernandes⁷⁴, Judith Schouten⁷⁵, Katharina Althaus⁷⁶, Katia Garambois⁷⁷, Laurent Derex⁷⁸, Lisa Humbertjean⁷⁹, Lucia Lebrato Hernandez⁸⁰, Lukas Kellermair⁸¹, Mar Morin Martin⁸², Marco Petruzzellis⁸³, Maria Cotelli⁸⁴, Marie-Cécile Dubois⁸⁵, Marta Carvalho⁸⁶, Matthias Wittstock⁸⁷, Miguel Miranda⁸⁸, Mona Skjelland⁸⁹, Monica Bandettini di Poggio⁹⁰, Moritz J Scholz⁹¹, Nicolas Raposo⁹², Robert Kahnis⁹², Nyika Kruyt⁹³, Olivier Huet⁹⁴, Pankaj Sharma⁹⁵, Paolo Candelaresi⁹⁶, Peggy Reiner⁹⁷, Ricardo Vieira⁹⁸, Roberto Acampora⁹⁹, Rolf Kern¹⁰⁰, Ronen Leker¹⁰¹, Shelagh Coutts¹⁰², Simerpreet Bal¹⁰², Shyam S Sharma¹⁰³, Sophie Susen¹⁰⁴, Thomas Cox¹⁰⁵, Thomas Geeraerts¹⁰⁶, Thomas Gattringer¹⁰⁷, Thorsten Bartsch¹⁰⁸, Timothy J Kleinig¹⁰⁹, Vanessa Dizonno¹⁷, Yildiz Arslan¹¹⁰

Affiliations

¹ Department of Neurology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte, University of Lisbon, Lisbon, Portugal.
³ Department of Neurology and Stroke, Eberhard-Karls University, Tuebingen, Germany.
⁴ Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tuebingen, Germany.
⁵ Department of Neurosciences and Cognition, Lille University Hospital, Lille, France.
⁶ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁸ Department of Neurology, Carlo Poma Hospital, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy.
⁹ Department of Internal Medicine, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁰ National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom.
¹¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Neurology, Albert Schweitzer Hospital, Dordrecht, the Netherlands.
¹³ Department of Neurology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹⁴ Sina Hospital, Hamadan University of Medical Science, Hamadan, Iran.
¹⁵ National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico.
¹⁶ Neurosciences Department, Hospital Dr R.A. Calderón Guardia, San José, Costa Rica.
¹⁷ Division of Neurology, University of British Columbia, Vancouver Stroke Program, Vancouver, British Columbia, Canada.
¹⁸ Second Department of Neurology in National, Kapodistrian University of Athens School of Medicine, Athens, Greece.
¹⁹ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
²⁰ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
²¹ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
²² Imperial College London School of Medicine, Imperial College London, London, United Kingdom.
²³ Department of Neurology, Saudi German Hospital, Jeddah, Saudi Arabia.
²⁴ Department of Neuroradiology, Ospedale del Mare, Naples, Italy.
²⁵ Department of Neurology, Jena University Hospital, Jena, Germany.
²⁶ Acute Stroke Service, Mater Misericordiae University Hospital, Dublin, Ireland.
²⁷ UCD School of Medicine, University College Dublin, Dublin, Ireland.
²⁸ School of Medicine, University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
²⁹ Department of Neurology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
³⁰ Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
³¹ Department of Neurology, Hamilton General Hospital, Hamilton, Ontario, Canada.
³² Department of Neurology and Stroke, University Hospital Tuebingen, Tuebingen, Germany.
³³ Department of Neurology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
³⁴ Department of Internal Medicine, Skåne University Hospital, Lund, Sweden.
³⁵ Department of Anesthesia and Intensive Care, University Hospital of Rennes, Rennes, France.
³⁶ Respiratory Department, Northumbria Healthcare NHS Foundation Trust, Cramlington, United Kingdom.
³⁷ Stroke Unit, Hôpital Pasteur 2, URRIS - UR2CA, Unité de Recherche Clinique Cote d'Azur, Cote d'Azur University, Nice, France.
³⁸ Division of Neurology, University of Alberta Hospital, Edmonton, Alberta, Canada.
³⁹ Department of Neurology, Azienda Ospedaliera di Melegnano e della Martesana, Melegnano, Italy.
⁴⁰ Department of Neurology, John Hunter Hospital, Newcastle, Australia.
⁴¹ Department of Hematology and Hemostasis, Tours University Hospital, Tours, France.
⁴² Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal, Quebec, Canada.
⁴³ Division of Hemostaseology, Leipzig University Hospital, Leipzig, Germany.
⁴⁴ Department of Neurology, CHU Rennes, Rennes, France.
⁴⁵ Department of Neurology, Hospital General de Castellón, Castelló, Spain.
⁴⁶ Department of Neurology, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.
⁴⁷ Department of Critical Care, Annecy Genevois Hospital, Annecy, France.
⁴⁸ Department of Neuroradiology, Policlinico di Bari, Bari, Italy.
⁴⁹ Department of Neurology, Leipzig University Hospital, Leipzig, Germany.
⁵⁰ Division of Neurology, The Ottawa Hospital, Ottawa, Ontario, Canada.
⁵¹ Department Clinical Science, Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden.
⁵² Department of Neurology, University Hospital del Mar, Barcelona, Spain.
⁵³ Department of Biological Haematology, CHU Dijon, Dijon, France.
⁵⁴ Department of Neurology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
⁵⁵ Stroke Unit, University Hospital of Besancon, Besancon, France.
⁵⁶ Department of Neuroradiology, Toulouse University Hospital, Toulouse, France.
⁵⁷ Translational Molecular Medicine and Surgery, XXXV Cycle, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
⁵⁸ Department of Neurology, Universitätsklinikum Bonn, Bonn, Germany.
⁵⁹ Department of Neurology, San Giuseppe Moscati Hospital, Avellino, Italy.
⁶⁰ Stroke Unit, Department of Clinical and Experimental Medicine, University Hospital G. Martino, Messina, Italy.
⁶¹ Department of Radiology, Lyon University Hospital, Lyon, France.
⁶² Department of Neurology, Caritas Hospital Saarbrücken, Saarbrücken, Germany.
⁶³ Department of Medicine, Ashford and St Peters Hospital NHS Foundation Trust, Surrey, United Kingdom.
⁶⁴ Department of Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁶⁵ Princess Alexandra Hospital, Brisbane, Australia.
⁶⁶ Department of Intensive Care, Centre Hospitalier Intercommunal de Poissy Saint Germain en Laye, Poissy, France.
⁶⁷ Department of Neurology, Hospital of the City of Wolfsburg, Wolfsburg, Germany.
⁶⁸ Department of Neuromuscular Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
⁶⁹ Department of Neurology, Bordeaux University Hospital, Bordeaux, France.
⁷⁰ Department of Neurology, Haga Hospital, The Hague, the Netherlands.
⁷¹ Department of Neurology, Surrey Memorial Hospital, Surrey, British Columbia, Canada.
⁷² Department of Anesthesia and Critical Care, CHU Grenoble, Grenoble, France.
⁷³ Department of Neurology, Royal Darwin Hospital, Tiwi, Australia.
⁷⁴ Department of Neurology, Norra Älvsborgs Länssjukhus, Trollhattan, Sweden.
⁷⁵ Department of Neurology, Rijnstate Hospital Arnhem, Arnhem, the Netherlands.
⁷⁶ Department of Neurology, Ulm University Hospital, Ulm, Germany.
⁷⁷ Stroke Unit, University Hospital of Grenoble, Grenoble, France.
⁷⁸ Department of Neurology, Hospices Civils de Lyon, Lyon, France.
⁷⁹ Stroke Unit, University Hospital of Nancy, Nancy, France.
⁸⁰ Department of Neurology, Virgen del Rocio University Hospital, Seville, Spain.
⁸¹ Department of Neurology, Johannes Kepler University Linz, Linz, Austria.
⁸² Department of Neurology, Hospital Complex of Toledo, Toledo, Spain.
⁸³ Department of Neurology, AOU Consorziale Policlinico di Bari, Bari, Italy.
⁸⁴ Department of Neurology, ASL Vallecamonica-Sebino, Breno, Italy.
⁸⁵ Department of Anesthesia and Intensive Care, University Hospital of Poitiers, Poitiers, France.
⁸⁶ Department of Neurology, Centro Hospitalar Universitário de São João, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
⁸⁷ Department of Neurology, University Hospital Rostock, Rostock, Germany.
⁸⁸ Department of Neurology, Hospital de Cascais Dr José de Almeida, Cascais, Portugal.
⁸⁹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁹⁰ Department of Neuroscience, Policlinic San Martino Hospital, Genoa, Italy.
⁹¹ Department of Neurology, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.
⁹² Department of Neurology, Toulouse University Hospital, Toulouse, France.
⁹³ Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
⁹⁴ UFR de Bio-médecine, Hospital de la Cavale Blanche, CHRU de Brest, Brest, France.
⁹⁵ Institute of Cardiovascular Research, Royal Holloway University of London, London, United Kingdom.
⁹⁶ Department of Neurology and Stroke, Cardarelli Hospital, Naples, Italy.
⁹⁷ Department of Neurology, Lariboisière Hospital, Paris, France.
⁹⁸ Department of Hematology, Universidade Federal do Cariri, Juazeiro do Norte, Brazil.
⁹⁹ Department of Neurology, Ospedale del Mare, Naples, Italy.
¹⁰⁰ Department of Neurology, Kempten Hospital, Kempten, Germany.
¹⁰¹ Department of Neurology, Hadassah University Medical Center, Jerusalem, Israel.
¹⁰² Department of Clinical Neurosciences, Radiology, and Community Health Sciences, Foothills Medical Centre, Calgary, Alberta, Canada.
¹⁰³ Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom.
¹⁰⁴ Department of Hematology and Transfusion, Lille University Hospital, Lille, France.
¹⁰⁵ Department of Neurology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
¹⁰⁶ Department of Anesthesiology and Critical Care, Toulouse University Hospital, Toulouse, France.
¹⁰⁷ Department of Neurology, Medical University of Graz, Graz, Austria.
¹⁰⁸ Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
¹⁰⁹ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
¹¹⁰ Neurology Clinic, Medicana İzmir International Hospital, Izmir, Turkey.

PMID: 34581763
PMCID: PMC8479648
DOI: 10.1001/jamaneurol.2021.3619

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. 2021.

. 2021 Nov 1;78(11):1314-1323.

doi: 10.1001/jamaneurol.2021.3619.

Authors

Affiliations

¹ Department of Neurology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
² Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte, University of Lisbon, Lisbon, Portugal.
³ Department of Neurology and Stroke, Eberhard-Karls University, Tuebingen, Germany.
⁴ Hertie Institute for Clinical Brain Research, Eberhard-Karls University, Tuebingen, Germany.
⁵ Department of Neurosciences and Cognition, Lille University Hospital, Lille, France.
⁶ Department of Neurology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
⁷ Department of Internal Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
⁸ Department of Neurology, Carlo Poma Hospital, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy.
⁹ Department of Internal Medicine, Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁰ National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, United Kingdom.
¹¹ Department of Hematology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
¹² Department of Neurology, Albert Schweitzer Hospital, Dordrecht, the Netherlands.
¹³ Department of Neurology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
¹⁴ Sina Hospital, Hamadan University of Medical Science, Hamadan, Iran.
¹⁵ National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City, Mexico.
¹⁶ Neurosciences Department, Hospital Dr R.A. Calderón Guardia, San José, Costa Rica.
¹⁷ Division of Neurology, University of British Columbia, Vancouver Stroke Program, Vancouver, British Columbia, Canada.
¹⁸ Second Department of Neurology in National, Kapodistrian University of Athens School of Medicine, Athens, Greece.
¹⁹ Department of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
²⁰ Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden.
²¹ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
²² Imperial College London School of Medicine, Imperial College London, London, United Kingdom.
²³ Department of Neurology, Saudi German Hospital, Jeddah, Saudi Arabia.
²⁴ Department of Neuroradiology, Ospedale del Mare, Naples, Italy.
²⁵ Department of Neurology, Jena University Hospital, Jena, Germany.
²⁶ Acute Stroke Service, Mater Misericordiae University Hospital, Dublin, Ireland.
²⁷ UCD School of Medicine, University College Dublin, Dublin, Ireland.
²⁸ School of Medicine, University of Medicine and Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland.
²⁹ Department of Neurology, Centro Hospitalar de Lisboa Central, Lisbon, Portugal.
³⁰ Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
³¹ Department of Neurology, Hamilton General Hospital, Hamilton, Ontario, Canada.
³² Department of Neurology and Stroke, University Hospital Tuebingen, Tuebingen, Germany.
³³ Department of Neurology, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
³⁴ Department of Internal Medicine, Skåne University Hospital, Lund, Sweden.
³⁵ Department of Anesthesia and Intensive Care, University Hospital of Rennes, Rennes, France.
³⁶ Respiratory Department, Northumbria Healthcare NHS Foundation Trust, Cramlington, United Kingdom.
³⁷ Stroke Unit, Hôpital Pasteur 2, URRIS - UR2CA, Unité de Recherche Clinique Cote d'Azur, Cote d'Azur University, Nice, France.
³⁸ Division of Neurology, University of Alberta Hospital, Edmonton, Alberta, Canada.
³⁹ Department of Neurology, Azienda Ospedaliera di Melegnano e della Martesana, Melegnano, Italy.
⁴⁰ Department of Neurology, John Hunter Hospital, Newcastle, Australia.
⁴¹ Department of Hematology and Hemostasis, Tours University Hospital, Tours, France.
⁴² Department of Neurology and Neurosurgery, McGill University Health Centre, Montreal, Quebec, Canada.
⁴³ Division of Hemostaseology, Leipzig University Hospital, Leipzig, Germany.
⁴⁴ Department of Neurology, CHU Rennes, Rennes, France.
⁴⁵ Department of Neurology, Hospital General de Castellón, Castelló, Spain.
⁴⁶ Department of Neurology, Hospital de La Santa Creu I Sant Pau, Barcelona, Spain.
⁴⁷ Department of Critical Care, Annecy Genevois Hospital, Annecy, France.
⁴⁸ Department of Neuroradiology, Policlinico di Bari, Bari, Italy.
⁴⁹ Department of Neurology, Leipzig University Hospital, Leipzig, Germany.
⁵⁰ Division of Neurology, The Ottawa Hospital, Ottawa, Ontario, Canada.
⁵¹ Department Clinical Science, Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden.
⁵² Department of Neurology, University Hospital del Mar, Barcelona, Spain.
⁵³ Department of Biological Haematology, CHU Dijon, Dijon, France.
⁵⁴ Department of Neurology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
⁵⁵ Stroke Unit, University Hospital of Besancon, Besancon, France.
⁵⁶ Department of Neuroradiology, Toulouse University Hospital, Toulouse, France.
⁵⁷ Translational Molecular Medicine and Surgery, XXXV Cycle, Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Messina, Italy.
⁵⁸ Department of Neurology, Universitätsklinikum Bonn, Bonn, Germany.
⁵⁹ Department of Neurology, San Giuseppe Moscati Hospital, Avellino, Italy.
⁶⁰ Stroke Unit, Department of Clinical and Experimental Medicine, University Hospital G. Martino, Messina, Italy.
⁶¹ Department of Radiology, Lyon University Hospital, Lyon, France.
⁶² Department of Neurology, Caritas Hospital Saarbrücken, Saarbrücken, Germany.
⁶³ Department of Medicine, Ashford and St Peters Hospital NHS Foundation Trust, Surrey, United Kingdom.
⁶⁴ Department of Neurology, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
⁶⁵ Princess Alexandra Hospital, Brisbane, Australia.
⁶⁶ Department of Intensive Care, Centre Hospitalier Intercommunal de Poissy Saint Germain en Laye, Poissy, France.
⁶⁷ Department of Neurology, Hospital of the City of Wolfsburg, Wolfsburg, Germany.
⁶⁸ Department of Neuromuscular Medicine, Toronto General Hospital, Toronto, Ontario, Canada.
⁶⁹ Department of Neurology, Bordeaux University Hospital, Bordeaux, France.
⁷⁰ Department of Neurology, Haga Hospital, The Hague, the Netherlands.
⁷¹ Department of Neurology, Surrey Memorial Hospital, Surrey, British Columbia, Canada.
⁷² Department of Anesthesia and Critical Care, CHU Grenoble, Grenoble, France.
⁷³ Department of Neurology, Royal Darwin Hospital, Tiwi, Australia.
⁷⁴ Department of Neurology, Norra Älvsborgs Länssjukhus, Trollhattan, Sweden.
⁷⁵ Department of Neurology, Rijnstate Hospital Arnhem, Arnhem, the Netherlands.
⁷⁶ Department of Neurology, Ulm University Hospital, Ulm, Germany.
⁷⁷ Stroke Unit, University Hospital of Grenoble, Grenoble, France.
⁷⁸ Department of Neurology, Hospices Civils de Lyon, Lyon, France.
⁷⁹ Stroke Unit, University Hospital of Nancy, Nancy, France.
⁸⁰ Department of Neurology, Virgen del Rocio University Hospital, Seville, Spain.
⁸¹ Department of Neurology, Johannes Kepler University Linz, Linz, Austria.
⁸² Department of Neurology, Hospital Complex of Toledo, Toledo, Spain.
⁸³ Department of Neurology, AOU Consorziale Policlinico di Bari, Bari, Italy.
⁸⁴ Department of Neurology, ASL Vallecamonica-Sebino, Breno, Italy.
⁸⁵ Department of Anesthesia and Intensive Care, University Hospital of Poitiers, Poitiers, France.
⁸⁶ Department of Neurology, Centro Hospitalar Universitário de São João, Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
⁸⁷ Department of Neurology, University Hospital Rostock, Rostock, Germany.
⁸⁸ Department of Neurology, Hospital de Cascais Dr José de Almeida, Cascais, Portugal.
⁸⁹ Department of Neurology, Oslo University Hospital, Oslo, Norway.
⁹⁰ Department of Neuroscience, Policlinic San Martino Hospital, Genoa, Italy.
⁹¹ Department of Neurology, Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany.
⁹² Department of Neurology, Toulouse University Hospital, Toulouse, France.
⁹³ Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands.
⁹⁴ UFR de Bio-médecine, Hospital de la Cavale Blanche, CHRU de Brest, Brest, France.
⁹⁵ Institute of Cardiovascular Research, Royal Holloway University of London, London, United Kingdom.
⁹⁶ Department of Neurology and Stroke, Cardarelli Hospital, Naples, Italy.
⁹⁷ Department of Neurology, Lariboisière Hospital, Paris, France.
⁹⁸ Department of Hematology, Universidade Federal do Cariri, Juazeiro do Norte, Brazil.
⁹⁹ Department of Neurology, Ospedale del Mare, Naples, Italy.
¹⁰⁰ Department of Neurology, Kempten Hospital, Kempten, Germany.
¹⁰¹ Department of Neurology, Hadassah University Medical Center, Jerusalem, Israel.
¹⁰² Department of Clinical Neurosciences, Radiology, and Community Health Sciences, Foothills Medical Centre, Calgary, Alberta, Canada.
¹⁰³ Edinburgh Medical School, University of Edinburgh, Edinburgh, United Kingdom.
¹⁰⁴ Department of Hematology and Transfusion, Lille University Hospital, Lille, France.
¹⁰⁵ Department of Neurology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
¹⁰⁶ Department of Anesthesiology and Critical Care, Toulouse University Hospital, Toulouse, France.
¹⁰⁷ Department of Neurology, Medical University of Graz, Graz, Austria.
¹⁰⁸ Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany.
¹⁰⁹ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia.
¹¹⁰ Neurology Clinic, Medicana İzmir International Hospital, Izmir, Turkey.

PMID: 34581763
PMCID: PMC8479648
DOI: 10.1001/jamaneurol.2021.3619

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

See this image and copyright information in PMC

Cited by

Evolution and advances in endovascular mechanical thrombectomy of cerebral venous sinus thrombosis.
Kan Y, Song B, Jiang M, Zhang Y, Li C, Wu C, Zhou W, Li A, Zhao W, Zhang B, Wu Y, Li M, Ji X. Kan Y, et al. Int J Med Sci. 2024 Sep 23;21(13):2450-2463. doi: 10.7150/ijms.99362. eCollection 2024. Int J Med Sci. 2024. PMID: 39439462 Free PMC article. Review.
Neurovascular Adverse Effects of Sars-Cov-2 Vaccination.
Panos LD, Bargiotas P, Hadjigeorgiou G, Panos GD. Panos LD, et al. Drug Des Devel Ther. 2024 May 30;18:1891-1905. doi: 10.2147/DDDT.S464394. eCollection 2024. Drug Des Devel Ther. 2024. PMID: 38836116 Free PMC article. Review.
Characteristics and outcomes of cerebral venous thrombosis associated with COVID-19.
Scutelnic A, van de Munckhof A, Miraclin AT, Aaron S, Hameed S, Wasay M, Grosu O, Krzywicka K, Sánchez van Kammen M, Lindgren E, Moreira T, Acampora R, Negro A, Karapanayiotides T, Yaghi S, Revert A, Cuadrado Godia E, Garcia-Madrona S, La Spina P, Grillo F, Giammello F, Nguyen TN, Abdalkader M, Buture A, Sofia Cotelli M, Raposo N, Tsivgoulis G, Candelaresi P, Ciacciarelli A, Mbroh J, Batenkova T, Scoppettuolo P, Zedde M, Pascarella R, Antonenko K, Kristoffersen ES, Kremer Hovinga JA, Jood K, Aguiar de Sousa D, Poli S, Tatlisumak T, Putaala J, Coutinho JM, Ferro JM, Arnold M, Heldner MR. Scutelnic A, et al. Eur Stroke J. 2024 Sep;9(3):676-686. doi: 10.1177/23969873241241885. Epub 2024 Apr 4. Eur Stroke J. 2024. PMID: 38572798 Free PMC article.
ABO blood group associated with cerebral venous thrombosis after Oxford-AstraZeneca COVID-19 vaccination: a case-control study.
Ken-Dror G, Sharma P; international Bio-Repository to Establish the Aetiology of Sinovenous Thrombosis (BEAST) collaborators and Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group. Ken-Dror G, et al. J R Soc Med. 2024 Feb;117(2):69-76. doi: 10.1177/01410768231214341. Epub 2023 Dec 12. J R Soc Med. 2024. PMID: 38086410 Free PMC article.
[Potential Impact of Public Communication on Emergency Presentations due to Headache during the Covid-19 Pandemic].
Wittayer M, Sandikci V, Ebert A, Koehler C, Szabo K, Hoyer C. Wittayer M, et al. Gesundheitswesen. 2024 Mar;86(3):232-236. doi: 10.1055/a-2146-6286. Epub 2023 Dec 8. Gesundheitswesen. 2024. PMID: 38065548 Free PMC article. German.

See all "Cited by" articles

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

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

[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

[2] 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

[3] 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

[4] 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

[5] 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

[6] 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

[7] 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...

[8] 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...

[9] 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

[10] 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

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous

Abstract

Conflict of interest statement

Figures

Similar articles

Cited by

References

Publication types

MeSH terms

Substances

Related information

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous