Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase

Anita van de Munckhof¹, Erik Lindgren^{2

3}, Timothy J Kleinig⁴, Thalia S Field⁵, Charlotte Cordonnier⁶, Katarzyna Krzywicka¹, Sven Poli^{7

8}, Mayte Sánchez van Kammen¹, Afshin Borhani-Haghighi⁹, Robin Lemmens¹⁰, Adrian Scutelnic¹¹, Alfonso Ciccone¹², Thomas Gattringer¹³, Matthias Wittstock¹⁴, Vanessa Dizonno⁵, Annemie Devroye¹⁰, Ahmed Elkady¹⁵, Albrecht Günther¹⁶, Alvaro Cervera¹⁷, Annerose Mengel⁷, Beng Lim Alvin Chew¹⁸, Brian Buck¹⁹, Carla Zanferrari²⁰, Carlos Garcia-Esperon¹⁸, Christian Jacobi²¹, Cristina Soriano²², Dominik Michalski²³, Zohreh Zamani²⁴, Dylan Blacquiere²⁵, Elias Johansson²⁶, Elisa Cuadrado-Godia²⁷, Fabrice Vuillier²⁸, Felix J Bode²⁹, François Caparros⁶, Frank Maier³⁰, Georgios Tsivgoulis³¹, Hans D Katzberg³², Jiangang Duan³³, Jim Burrow³⁴, Johann Pelz²³, Joshua Mbroh^{7

8}, Joyce Oen³⁵, Judith Schouten³⁶, Julian Zimmermann²⁹, Karl Ng³⁷, Katia Garambois³⁸, Marco Petruzzellis³⁹, Mariana Carvalho Dias⁴⁰, Masoud Ghiasian⁴¹, Michele Romoli⁴², Miguel Miranda⁴³, Miriam Wronski³⁷, Mona Skjelland⁴⁴, Mostafa Almasi-Dooghaee⁴⁵, Pauline Cuisenier³⁸, Seán Murphy⁴⁶, Serge Timsit⁴⁷, Shelagh B Coutts⁴⁸, Silvia Schönenberger⁴⁹, Simon Nagel⁴⁹, Sini Hiltunen⁵⁰, Sophie Chatterton³⁷, Thomas Cox⁵¹, Thorsten Bartsch⁵², Vahid Shaygannejad^{53

54}, Zahra Mirzaasgari⁴⁵, Saskia Middeldorp⁵⁵, Marcel M Levi^{56

57}, Johanna A Kremer Hovinga⁵⁸, Katarina Jood^{2

3}, Turgut Tatlisumak^{2

3

50}, Jukka Putaala³⁹, Mirjam R Heldner¹¹, Marcel Arnold¹¹, Diana Aguiar de Sousa^{59

60}, José M Ferro⁶⁰, Jonathan M Coutinho¹; Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group

Affiliations

¹ Department of Neurology (A.v.d.M., K.K., M.S.v.K., J.M.C.), Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
² Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (E.L., K.J., T.T.).
³ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (E.L., K.J., T.T.).
⁴ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia (T.J.K.).
⁵ Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, Canada (T.S.F., V.D.).
⁶ University Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, France (C.C., F.C.).
⁷ Department of Neurology and Stroke, University Hospital Tuebingen (S.P., A.M., J.M.), Eberhard-Karls University, Germany.
⁸ Hertie Institute for Clinical Brain Research (S.P., J.M.), Eberhard-Karls University, Germany.
⁹ Clinical Neurology Research Center, Shiraz University of Medical Sciences, Iran (A.B.-H.).
¹⁰ Department of Neurology, University Hospitals Leuven, Belgium (R.L., A.D.).
¹¹ Department of Neurology (A.S., M.R.H., M.A.), Inselspital, Bern University Hospital, University of Bern, Switzerland.
¹² Department of Neurology, Carlo Poma Hospital, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy (A. Ciccone).
¹³ Department of Neurology, Medical University of Graz, Austria (T.G.).
¹⁴ Department of Neurology, University Hospital Rostock, Germany (M. Wittstock).
¹⁵ Department of Neurology, Saudi German Hospital, Jeddah, Saudi Arabia (A.E.).
¹⁶ Department of Neurology, Jena University Hospital, Germany (A.G.).
¹⁷ Royal Darwin Hospital, Darwin, Northern Territory, Australia (A. Cervera).
¹⁸ Department of Neurology, John Hunter Hospital, Newcastle, Australia (B.L.A.C., C.G.-E.).
¹⁹ Division of Neurology, University of Alberta Hospital, Edmonton, Canada (B.B.).
²⁰ Department of Neurology, Azienda Ospedaliera di Melegnano e della Martesana, Italy (C.Z.).
²¹ Department of Neurology, Krankenhaus Nordwest, Frankfurt am Main, Germany (C.J.).
²² Department of Neurology, Hospital General de Castellón, Castelló, Spain (C.S.).
²³ Department of Neurology, Leipzig University Hospital, Germany (D.M., J. Pelz).
²⁴ Department of Neurology, Firoozabadi Hospital (Z.Z.), Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran.
²⁵ Division of Neurology, The Ottawa Hospital, Canada (D.B.).
²⁶ Department Clinical Science, Wallenberg Center for Molecular Medicine (WCMM), Umeå University, Sweden (E.J.).
²⁷ Department of Neurology, University Hospital del Mar, Barcelona, Spain (E.C.-G.).
²⁸ Stroke Unit, University Hospital of Besancon, France (F.V.).
²⁹ Department of Neurology, Universitätsklinikum Bonn, Germany (F.J.B., J.Z.).
³⁰ Department of Neurology, Caritas Hospital Saarbrücken, Germany (F.M.).
³¹ Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, Greece (G.T.).
³² Department of Neuromuscular Medicine, Toronto General Hospital, Canada (H.D.K.).
³³ Department of Neurology and Emergency, Xuanwu Hospital, Capital Medical University, Beijing, China (J.D.).
³⁴ Department of Neurology, Royal Darwin Hospital, Tiwi, Australia (J.B.).
³⁵ Department of Neurology, Antonius Ziekenhuis, Sneek, the Netherlands (J.O.).
³⁶ Department of Neurology, Rijnstate Hospital Arnhem, the Netherlands (J.S.).
³⁷ Department of Neurology, Royal North Shore Hospital, Sydney, Australia (K.N., M. Wronski, S.C.).
³⁸ Department of Neurology, CHU Grenoble Alpes, France (K.G., P.C.).
³⁹ Department of Neurology, AOU Consorziale Policlinico di Bari, Italy (M.P.).
⁴⁰ Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte, University of Lisbon, Portugal (M.C.D.).
⁴¹ Department of Neurology, Sina Hospital, Hamadan University of Medical Science, Iran (M.G.).
⁴² Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy (M.R.).
⁴³ Department of Neurology, Hospital de Cascais Dr. José de Almeida, Cascais, Portugal (M.M.).
⁴⁴ Department of Neurology, Oslo University Hospital, Norway (M.S.).
⁴⁵ Department of Neurology (M.A.-D., Z.M.), Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran.
⁴⁶ Acute Stroke Service, Mater Misericordiae University Hospital, UCD School of Medicine and RCSI Medical School, Dublin, Ireland (S. Murphy).
⁴⁷ Department of Neurology, Stroke Unit, Hôpital de la Cavale Blanche, CHRU de Brest (University Hospital), Université de Bretagne Occidentale, Inserm 1078, Brest, France (S.T.).
⁴⁸ Department of Clinical Neurosciences, Radiology, and Community Health Sciences, Foothills Medical Centre, Calgary, Canada (S.B.C.).
⁴⁹ Department of Neurology, Heidelberg University Hospital, Germany (S.S., S.N.).
⁵⁰ Department of Neurology, Helsinki University Hospital, University of Helsinki, Finland (S.H., T.T., J. Putaala).
⁵¹ Department of Neurology, University Hospital Southampton NHS Foundation Trust, United Kingdom (T.C.).
⁵² Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany (T.B.).
⁵³ Isfahan University of Medical Sciences (IUMS), Isfahan Neurosciences Research Center (INRC), Iran (V.S.).
⁵⁴ Department of Internal (INRC), Iran (V.S.).
⁵⁵ Department of Internal Medicine and Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (S. Middeldorp).
⁵⁶ Department of Vascular Medicine (M.M.L.), Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
⁵⁷ National Institute for Health Research, University College London Hospitals (UCLH), Biomedical Research Centre, London, United Kingdom (M.M.L.).
⁵⁸ Department of Hematology (J.A.K.H.), Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵⁹ Stroke Centre, Lisbon Central University Hospital Centre, Portugal (D.A.d.S.).
⁶⁰ Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., J.M.F.).

PMID: 36082668
PMCID: PMC9508952
DOI: 10.1161/STROKEAHA.122.039575

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase

Anita van de Munckhof et al. Stroke. 2022 Oct.

. 2022 Oct;53(10):3206-3210.

doi: 10.1161/STROKEAHA.122.039575. Epub 2022 Sep 9.

Authors

Affiliations

¹ Department of Neurology (A.v.d.M., K.K., M.S.v.K., J.M.C.), Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
² Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden (E.L., K.J., T.T.).
³ Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Sweden (E.L., K.J., T.T.).
⁴ Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia (T.J.K.).
⁵ Division of Neurology, Vancouver Stroke Program, University of British Columbia, Vancouver, Canada (T.S.F., V.D.).
⁶ University Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, France (C.C., F.C.).
⁷ Department of Neurology and Stroke, University Hospital Tuebingen (S.P., A.M., J.M.), Eberhard-Karls University, Germany.
⁸ Hertie Institute for Clinical Brain Research (S.P., J.M.), Eberhard-Karls University, Germany.
⁹ Clinical Neurology Research Center, Shiraz University of Medical Sciences, Iran (A.B.-H.).
¹⁰ Department of Neurology, University Hospitals Leuven, Belgium (R.L., A.D.).
¹¹ Department of Neurology (A.S., M.R.H., M.A.), Inselspital, Bern University Hospital, University of Bern, Switzerland.
¹² Department of Neurology, Carlo Poma Hospital, Azienda Socio Sanitaria Territoriale di Mantova, Mantua, Italy (A. Ciccone).
¹³ Department of Neurology, Medical University of Graz, Austria (T.G.).
¹⁴ Department of Neurology, University Hospital Rostock, Germany (M. Wittstock).
¹⁵ Department of Neurology, Saudi German Hospital, Jeddah, Saudi Arabia (A.E.).
¹⁶ Department of Neurology, Jena University Hospital, Germany (A.G.).
¹⁷ Royal Darwin Hospital, Darwin, Northern Territory, Australia (A. Cervera).
¹⁸ Department of Neurology, John Hunter Hospital, Newcastle, Australia (B.L.A.C., C.G.-E.).
¹⁹ Division of Neurology, University of Alberta Hospital, Edmonton, Canada (B.B.).
²⁰ Department of Neurology, Azienda Ospedaliera di Melegnano e della Martesana, Italy (C.Z.).
²¹ Department of Neurology, Krankenhaus Nordwest, Frankfurt am Main, Germany (C.J.).
²² Department of Neurology, Hospital General de Castellón, Castelló, Spain (C.S.).
²³ Department of Neurology, Leipzig University Hospital, Germany (D.M., J. Pelz).
²⁴ Department of Neurology, Firoozabadi Hospital (Z.Z.), Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran.
²⁵ Division of Neurology, The Ottawa Hospital, Canada (D.B.).
²⁶ Department Clinical Science, Wallenberg Center for Molecular Medicine (WCMM), Umeå University, Sweden (E.J.).
²⁷ Department of Neurology, University Hospital del Mar, Barcelona, Spain (E.C.-G.).
²⁸ Stroke Unit, University Hospital of Besancon, France (F.V.).
²⁹ Department of Neurology, Universitätsklinikum Bonn, Germany (F.J.B., J.Z.).
³⁰ Department of Neurology, Caritas Hospital Saarbrücken, Germany (F.M.).
³¹ Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, Greece (G.T.).
³² Department of Neuromuscular Medicine, Toronto General Hospital, Canada (H.D.K.).
³³ Department of Neurology and Emergency, Xuanwu Hospital, Capital Medical University, Beijing, China (J.D.).
³⁴ Department of Neurology, Royal Darwin Hospital, Tiwi, Australia (J.B.).
³⁵ Department of Neurology, Antonius Ziekenhuis, Sneek, the Netherlands (J.O.).
³⁶ Department of Neurology, Rijnstate Hospital Arnhem, the Netherlands (J.S.).
³⁷ Department of Neurology, Royal North Shore Hospital, Sydney, Australia (K.N., M. Wronski, S.C.).
³⁸ Department of Neurology, CHU Grenoble Alpes, France (K.G., P.C.).
³⁹ Department of Neurology, AOU Consorziale Policlinico di Bari, Italy (M.P.).
⁴⁰ Department of Neurosciences and Mental Health, Hospital de Santa Maria, Centro Hospitalar Universitario Lisboa Norte, University of Lisbon, Portugal (M.C.D.).
⁴¹ Department of Neurology, Sina Hospital, Hamadan University of Medical Science, Iran (M.G.).
⁴² Neurology and Stroke Unit, Department of Neuroscience, Bufalini Hospital, Cesena, Italy (M.R.).
⁴³ Department of Neurology, Hospital de Cascais Dr. José de Almeida, Cascais, Portugal (M.M.).
⁴⁴ Department of Neurology, Oslo University Hospital, Norway (M.S.).
⁴⁵ Department of Neurology (M.A.-D., Z.M.), Firoozgar Hospital, School of Medicine, Iran University of Medical Sciences, Tehran.
⁴⁶ Acute Stroke Service, Mater Misericordiae University Hospital, UCD School of Medicine and RCSI Medical School, Dublin, Ireland (S. Murphy).
⁴⁷ Department of Neurology, Stroke Unit, Hôpital de la Cavale Blanche, CHRU de Brest (University Hospital), Université de Bretagne Occidentale, Inserm 1078, Brest, France (S.T.).
⁴⁸ Department of Clinical Neurosciences, Radiology, and Community Health Sciences, Foothills Medical Centre, Calgary, Canada (S.B.C.).
⁴⁹ Department of Neurology, Heidelberg University Hospital, Germany (S.S., S.N.).
⁵⁰ Department of Neurology, Helsinki University Hospital, University of Helsinki, Finland (S.H., T.T., J. Putaala).
⁵¹ Department of Neurology, University Hospital Southampton NHS Foundation Trust, United Kingdom (T.C.).
⁵² Department of Neurology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany (T.B.).
⁵³ Isfahan University of Medical Sciences (IUMS), Isfahan Neurosciences Research Center (INRC), Iran (V.S.).
⁵⁴ Department of Internal (INRC), Iran (V.S.).
⁵⁵ Department of Internal Medicine and Radboud Institute of Health Sciences, Radboud University Medical Center, Nijmegen, the Netherlands (S. Middeldorp).
⁵⁶ Department of Vascular Medicine (M.M.L.), Amsterdam University Medical Centers, University of Amsterdam, the Netherlands.
⁵⁷ National Institute for Health Research, University College London Hospitals (UCLH), Biomedical Research Centre, London, United Kingdom (M.M.L.).
⁵⁸ Department of Hematology (J.A.K.H.), Inselspital, Bern University Hospital, University of Bern, Switzerland.
⁵⁹ Stroke Centre, Lisbon Central University Hospital Centre, Portugal (D.A.d.S.).
⁶⁰ Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal (D.A.d.S., J.M.F.).

PMID: 36082668
PMCID: PMC9508952
DOI: 10.1161/STROKEAHA.122.039575

Abstract

Background: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization.

Methods: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization).

Results: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed).

Conclusions: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

Keywords: hospitalization; intracranial thrombosis; mortality; thrombocytopenia; vaccination; venous thrombosis.

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References

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Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase

Affiliations

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase

Authors

Affiliations

Abstract

Figures

References

Publication types

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous