Review

. 2021 Aug 15:427:117532.

doi: 10.1016/j.jns.2021.117532. Epub 2021 Jun 5.

Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions

Kiran T Thakur¹, Arina Tamborska², Greta K Wood³, Emily McNeill⁴, David Roh⁴, Imo J Akpan⁵, Eliza C Miller⁴, Alyssa Bautista⁴, Jan Claassen⁴, Carla Y Kim⁴, Alla Guekht⁶, Carlos A Pardo⁷, Olajide Williams⁴, David García-Azorín⁸, Kameshwar Prasad⁹, Erich Schmutzhard¹⁰, Benedict D Michael¹¹, Sherry H-Y Chou¹², Andrea S Winkler¹³, Tom Solomon¹⁴, Mitchell S Elkind⁴

Affiliations

¹ Department of Neurology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA. Electronic address: ktt2115@cumc.columbia.edu.
² National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Institute of Infection, Veterinary and Ecological Science, University of Liverpool, Liverpool, UK.
³ Institute of Infection, Veterinary and Ecological Science, University of Liverpool, Liverpool, UK.
⁴ Department of Neurology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA.
⁵ Department of Hematology/Oncology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA.
⁶ Moscow Research and Clinical Center for Neuropsychiatry & Russian National Research Medical University, Moscow, Russia.
⁷ Divisions of Neuroimmunology and Neuroinfectious Disorders & Advanced Clinical Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Headache Unit, Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
⁹ Rajendra Institute of Medical Sciences, Ranchi 834009, Jharkhand, India.
¹⁰ Department of Neurology, Division of Neurocritical Care, Medical University Innsbruck, Innsbruck, Austria.
¹¹ Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital/Harvard University, Boston, MA, USA.
¹² Department of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹³ Center for Global Health, Department of Neurology, Technical University of Munich, Munich, Germany; Centre for Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway.
¹⁴ National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.

PMID: 34134058
PMCID: PMC8178065
DOI: 10.1016/j.jns.2021.117532

Review

Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions

Kiran T Thakur et al. J Neurol Sci. 2021.

. 2021 Aug 15:427:117532.

doi: 10.1016/j.jns.2021.117532. Epub 2021 Jun 5.

Authors

Affiliations

¹ Department of Neurology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA. Electronic address: ktt2115@cumc.columbia.edu.
² National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK; Institute of Infection, Veterinary and Ecological Science, University of Liverpool, Liverpool, UK.
³ Institute of Infection, Veterinary and Ecological Science, University of Liverpool, Liverpool, UK.
⁴ Department of Neurology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA.
⁵ Department of Hematology/Oncology, Columbia University Irving Medical Center/New York Presbyterian Hospital, New York, NY, USA.
⁶ Moscow Research and Clinical Center for Neuropsychiatry & Russian National Research Medical University, Moscow, Russia.
⁷ Divisions of Neuroimmunology and Neuroinfectious Disorders & Advanced Clinical Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Headache Unit, Department of Neurology, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
⁹ Rajendra Institute of Medical Sciences, Ranchi 834009, Jharkhand, India.
¹⁰ Department of Neurology, Division of Neurocritical Care, Medical University Innsbruck, Innsbruck, Austria.
¹¹ Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital/Harvard University, Boston, MA, USA.
¹² Department of Critical Care Medicine, Neurology, and Neurosurgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
¹³ Center for Global Health, Department of Neurology, Technical University of Munich, Munich, Germany; Centre for Global Health, Institute of Health and Society, University of Oslo, Oslo, Norway.
¹⁴ National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections, University of Liverpool, Liverpool, UK.

PMID: 34134058
PMCID: PMC8178065
DOI: 10.1016/j.jns.2021.117532

Abstract

Background: Vaccine induced immune mediated thrombocytopenia or VITT, is a recent and rare phenomenon of thrombosis with thrombocytopenia, frequently including cerebral venous thromboses (CVT), that has been described following vaccination with adenovirus vaccines ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2·S Johnson and Johnson (Janssen/J&J). The evaluation and management of suspected cases of CVT post COVID-19 vaccination are critical skills for a broad range of healthcare providers.

Methods: A collaborative comprehensive review of literature was conducted among a global group of expert neurologists and hematologists.

Findings: Strategies for rapid evaluation and treatment of the CVT in the context of possible VITT exist, including inflammatory marker measurements, PF4 assays, and non-heparin anticoagulation.

Keywords: COVID-19; Cerebral venous thrombosis; Vaccination.

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Conflict of interest statement

KTT is a member of the World Health Organization (WHO) working group on clinical guidance of VITT in the context of COVID-19 vaccinations, reports funding from the National Institute of Health (NIH) and Center for Disease Control and Prevention (CDC) on neurological conditions in the context of COVID-19 and COVID-19 vaccinations. AT receives funding from the National Institute for Health Research (NIHR) Academic Clinical Fellowship. DR reports funding from the National Blood Foundation, NIH, National Institute of Allergies and Infectious Disease (NIAID), Department of Defense (DOD), and Apellis Pharmaceuticals. ECM reports funding from the NIH, National Institute of Neurological Disorders and Stroke (NINDS), National Institute on Aging (NIA), and the Louis V. Gerstner, Jr. Foundation (Gerstner Scholars Program). JC reports funding from the NINDS and the McDonnell Foundation. AG reports funding from the Russian Scientific Foundation. CAP reports funding from the NIH and Bart McLean Fund for Neuroimmunology Research. DGA reports funding from the Spanish Society of Neurology, Fundación Estudios de Ciencias de la Salud de Castilla y León, Colegio de Médicos de Valladolid, the International Headache Society and the WHO. BDM reports funding from the United Kingdom Research Institute / Medical Research Council (UKRI/MRC) and Wellcome. SHYC reports funding from the NIH, NINDS, National Center for Advancing Translational Sciences (NCATS), and the University of Pittsburgh School of Medicine Dean's Faculty Advancement Award. ASW reports funding from the German Federal Ministry of Education and Research and the European Union (EU). TS was Chair/Co-Chair of the United Kingdom Research and Innovation / National Institute for Health Research COVID-19 Rapid Response and Rolling Funding Initiatives (which funded the development of COVID-19 vaccines), is an Advisor to the UK COVID-19 Therapeutics Advisory Panel and a member of the UK Medicines and Healthcare Products Regulatory Agency COVID-19 Vaccines Benefit Risk Expert Working Group. TS is supported by the National Institute for Health Research (NIHR) Health Protection Research Unit in Emerging and Zoonotic Infections, NIHR Programme Grant for Applied Research, NIHR Global Health Research Group on Brain Infections, the UK Medical Research Council's Global Effort on COVID-19 Programme, and the European Union‘s Horizon 2020 research and innovation program ZikaPLAN (Preparedness Latin America Network). MSE reports royalties for a chapter on COVID-19 and neurological disease in UpToDate. All other authors declare no competing interests.

Figures

**Fig. 2**
Evaluation and management algorithm for cerebral venous thromboses in the context of possible vaccine induced thrombocytopenia.

**Fig. 1**
Neuroimaging in a cerebral venous thrombosis (CVT) case. A Axial T2/fluid attenuated inversion recovery sequence (FLAIR) magnetic resonance imaging (MRI) showing left anterior parietal hyperintensity. B Susceptibility weighted imaging (SWI) axial view MRI showing area of low susceptibility signal at left anterior parietal lobe. C Sagittal T1 post‑gadolinium MRI showing early subacute sinus thrombosis involving the superior sagittal sinus and left transverse sinus.

See this image and copyright information in PMC

References

1. Wise J. Covid-19: European countries suspend use of Oxford-AstraZeneca vaccine after reports of blood clots. BMJ. 2021;372:n699. - PubMed
1. European Medicines Agency COVID-19 Vaccine Janssen: EMA Finds Possible Link to Very Rare Cases of Unusual Blood Clots with Low Blood Platelets. 2021. https://www.ema.europa.eu/en/news/covid-19-vaccine-janssen-ema-finds-pos... Available from:
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Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions

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Clinical review of cerebral venous thrombosis in the context of COVID-19 vaccinations: Evaluation, management, and scientific questions

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Conflict of interest statement

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