Thrombosis with Thrombocytopenia Syndrome after SARS-CoV-2 vaccination
Projectomschrijving
Trombose in combinatie met een laag aantal bloedplaatjes treedt in zeldzame gevallen op na vaccinatie met de COVID-19 vaccins van AstraZeneca en Janssen. De meeste van deze patiënten ontwikkelden een trombose in het hoofd (sinustrombose). De ziekte wordt “vaccine-induced immune thrombotic thrombocytopenia” (VITT) genoemd.
Er zijn veel onbeantwoorde vragen over VITT, waaronder:
1. Hoe vaak komt VITT voor?
2. Wat zijn de klinische verschijnselen en prognose van VITT?
3. Is de prognose verbeterd na invoering van internationale behandelrichtlijnen?
4. Hoe vaak komen PF4 antistoffen (de vermoedelijke oorzaak van VITT) voor bij gezonden mensen die gevaccineerd worden?
5. Welke rol spelen het stollings- en afweersysteem bij VITT?
Het doel van dit onderzoek is om antwoord op deze vragen te geven. Hiermee verschaffen we aan artsen en beleidsmakers wetenschappelijk bewijs dat gebruikt kan worden voor de optimalisatie van vaccinatie strategieën en de behandeling van patiënten met VITT.
Producten
Titel:
Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination.
Auteur: Krzywicka K, van de Munckhof A, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi MM, Cordonnier C, Arnold M, Zwinderman AH, Ferro JM, Coutinho JM, Aguiar de Sousa D.
Magazine: Neurology
Auteur: Krzywicka K, van de Munckhof A, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi MM, Cordonnier C, Arnold M, Zwinderman AH, Ferro JM, Coutinho JM, Aguiar de Sousa D.
Magazine: Neurology
Titel: Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination
Auteur: Scutelnic A, Krzywicka K, Mbroh J, van de Munckhof A, van Kammen MS, de Sousa DA, Lindgren E, Jood K, Günther A .... Kremer Hovinga JA, Kruip MJHA, Tatlisumak T, Ferro JM, Coutinho JM, Arnold M, Poli S, Heldner MR.
Magazine: Annals of Neurology
Auteur: Scutelnic A, Krzywicka K, Mbroh J, van de Munckhof A, van Kammen MS, de Sousa DA, Lindgren E, Jood K, Günther A .... Kremer Hovinga JA, Kruip MJHA, Tatlisumak T, Ferro JM, Coutinho JM, Arnold M, Poli S, Heldner MR.
Magazine: Annals of Neurology
Titel: Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia
Auteur: Krzywicka K, Aguiar de Sousa D, Cordonnier C, Bode FJ, Field TS, Michalski D, Pelz J, Skjelland M, Wiedmann M, Zimmermann J, Wittstock M, Zanotti B, ..., van de Munckhof A, Sánchez van Kammen M, Lindgren E, Jood K, Scutelnic A, Heldner MR, Poli S, Kruip MJHA, Arauz A, Conforto AB, Aaron S, Middeldorp S, Tatlisumak T, Arnold M, Coutinho JM, Ferro JM
Magazine: European Journal of Neurology
Auteur: Krzywicka K, Aguiar de Sousa D, Cordonnier C, Bode FJ, Field TS, Michalski D, Pelz J, Skjelland M, Wiedmann M, Zimmermann J, Wittstock M, Zanotti B, ..., van de Munckhof A, Sánchez van Kammen M, Lindgren E, Jood K, Scutelnic A, Heldner MR, Poli S, Kruip MJHA, Arauz A, Conforto AB, Aaron S, Middeldorp S, Tatlisumak T, Arnold M, Coutinho JM, Ferro JM
Magazine: European Journal of Neurology
Titel: Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination
Auteur: Krzywicka K, van de Munckhof A, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi MM, Cordonnier C, Arnold M, Zwinderman AH, Ferro JM, Coutinho JM, Aguiar de Sousa D
Magazine: Neurology
Auteur: Krzywicka K, van de Munckhof A, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi MM, Cordonnier C, Arnold M, Zwinderman AH, Ferro JM, Coutinho JM, Aguiar de Sousa D
Magazine: Neurology
Titel:
6
Cite Share
Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.
Auteur: 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; Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group
Magazine: JAMA Neurology
Auteur: 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; Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group
Magazine: JAMA Neurology
Titel: Cerebral venous thrombosis due to vaccine-induced immune thrombotic thrombocytopenia after a second ChAdOx1 nCoV-19 dose
Auteur: Krzywicka K, van de Munckhof A, Zimmermann J, Bode FJ, Frisullo G, Karapanayiotides T, Pötzsch B, Sánchez van Kammen M, Heldner MR, Arnold M, Kremer Hovinga JA, Ferro JM, Aguiar de Sousa D, Coutinho JM
Magazine: Blood
Auteur: Krzywicka K, van de Munckhof A, Zimmermann J, Bode FJ, Frisullo G, Karapanayiotides T, Pötzsch B, Sánchez van Kammen M, Heldner MR, Arnold M, Kremer Hovinga JA, Ferro JM, Aguiar de Sousa D, Coutinho JM
Magazine: Blood
Titel: Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia.
Auteur: 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 for the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group
Magazine: JAMA Neurology
Auteur: 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 for the Cerebral Venous Sinus Thrombosis With Thrombocytopenia Syndrome Study Group
Magazine: JAMA Neurology
Titel: Management of cerebral venous thrombosis due to adenoviral COVID-19 vaccination.
Auteur: Scutelnic A, Krzywicka K, Mbroh J, van de Munckhof A, Sánchez van Kammen M, Aguiar de Sousa D, Lindgren E, Jood K, Günther A, Hiltunen S, Putaala J, Tiede A, Maier F, Kern R, Bartsch T, Althaus K, Ciccone A, Wiedmann M, Skjelland M, Medina A, Cuadrado-Godia E, Cox T, Aujayeb A, Raposo N, Garambois K, Payen JF, Vuillier F, Franchineau G, Timsit S, Bougon D, Dubois MC, Tawa A, Tracol C, De Maistre E, Bonneville F, Vayne C, Mengel A, Michalski D, Pelz J, Wittstock M, Bode F, Zimmermann J, Schoute
Magazine: Annals of Neurology
Auteur: Scutelnic A, Krzywicka K, Mbroh J, van de Munckhof A, Sánchez van Kammen M, Aguiar de Sousa D, Lindgren E, Jood K, Günther A, Hiltunen S, Putaala J, Tiede A, Maier F, Kern R, Bartsch T, Althaus K, Ciccone A, Wiedmann M, Skjelland M, Medina A, Cuadrado-Godia E, Cox T, Aujayeb A, Raposo N, Garambois K, Payen JF, Vuillier F, Franchineau G, Timsit S, Bougon D, Dubois MC, Tawa A, Tracol C, De Maistre E, Bonneville F, Vayne C, Mengel A, Michalski D, Pelz J, Wittstock M, Bode F, Zimmermann J, Schoute
Magazine: Annals of Neurology
Titel: Declining mortality of cerebral venous sinus thrombosis with thrombocytopenia after SARS-CoV-2 vaccination
Auteur: van de Munckhof A, Krzywicka K, Aguiar de Sousa D, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi M, Arnold M, Ferro JM, Coutinho JM
Magazine: European Journal of Neurology
Auteur: van de Munckhof A, Krzywicka K, Aguiar de Sousa D, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi M, Arnold M, Ferro JM, Coutinho JM
Magazine: European Journal of Neurology
Titel: Declining mortality of cerebral venous sinus thrombosis with thrombocytopenia after SARS-CoV-2 vaccination.
Auteur: van de Munckhof A, Krzywicka K, Aguiar de Sousa D, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi M, Arnold M, Ferro JM, Coutinho JM.
Magazine: European Journal of Neurology
Auteur: van de Munckhof A, Krzywicka K, Aguiar de Sousa D, Sánchez van Kammen M, Heldner MR, Jood K, Lindgren E, Tatlisumak T, Putaala J, Kremer Hovinga JA, Middeldorp S, Levi M, Arnold M, Ferro JM, Coutinho JM.
Magazine: European Journal of Neurology
Titel: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia in middle-income countries
Auteur: van de Munckhof A, Borhani-Haghighi A, Aaron S, Krzywicka K, van Kammen MS, Cordonnier C, Kleinig TJ, Field TS, Poli S, Lemmens R, Scutelnic A, Lindgren E, Duan J, Arslan Y, van Gorp EC, Kremer Hovinga JA, Günther A, Jood K, Tatlisumak T, Putaala J, Heldner MR, Arnold M, de Sousa DA, Wasay M, Arauz A, Conforto AB, Ferro JM, Coutinho JM for the Cerebral Venous Sinus Thrombosis with Thrombocytopenia Syndrome Study Group
Magazine: International Journal of Stroke
Auteur: van de Munckhof A, Borhani-Haghighi A, Aaron S, Krzywicka K, van Kammen MS, Cordonnier C, Kleinig TJ, Field TS, Poli S, Lemmens R, Scutelnic A, Lindgren E, Duan J, Arslan Y, van Gorp EC, Kremer Hovinga JA, Günther A, Jood K, Tatlisumak T, Putaala J, Heldner MR, Arnold M, de Sousa DA, Wasay M, Arauz A, Conforto AB, Ferro JM, Coutinho JM for the Cerebral Venous Sinus Thrombosis with Thrombocytopenia Syndrome Study Group
Magazine: International Journal of Stroke
Titel: Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase
Auteur: van de Munckhof A, Lindgren E, Kleinig TJ, Field TS, Cordonnier C, Krzywicka K, Poli S, Sánchez van Kammen M, Borhani-Haghighi A, Lemmens R, Scutelnic A, ...., Jood K, Tatlisumak T, Putaala J, Heldner MR, Arnold M, Aguiar de Sousa D, Ferro JM, Coutinho JM
Magazine: Stroke
Auteur: van de Munckhof A, Lindgren E, Kleinig TJ, Field TS, Cordonnier C, Krzywicka K, Poli S, Sánchez van Kammen M, Borhani-Haghighi A, Lemmens R, Scutelnic A, ...., Jood K, Tatlisumak T, Putaala J, Heldner MR, Arnold M, Aguiar de Sousa D, Ferro JM, Coutinho JM
Magazine: Stroke
Titel: Sex differences in cerebral venous sinus thrombosis after adenoviral vaccination against COVID-19
Auteur: Scutelnic A, van de Munckhof A, Krzywicka K, van Kammen MS, Lindgren E, Cordonnier C, Kleinig TJ, Field TS, Poli S, Lemmens R, Middeldorp S, Aaron S, Borhani-Haghighi A, Arauz A, Kremer Hovinga JA, Günther A, Putaala J, Wasay M, Conforto AB, de Sousa DA, Jood K, Tatlisumak T, Ferro JM, Coutinho JM, Arnold M, Heldner MR for the Cerebral Venous Sinus Thrombosis with Thrombocytopenia Syndrome Study Group
Magazine: European Stroke Journal
Auteur: Scutelnic A, van de Munckhof A, Krzywicka K, van Kammen MS, Lindgren E, Cordonnier C, Kleinig TJ, Field TS, Poli S, Lemmens R, Middeldorp S, Aaron S, Borhani-Haghighi A, Arauz A, Kremer Hovinga JA, Günther A, Putaala J, Wasay M, Conforto AB, de Sousa DA, Jood K, Tatlisumak T, Ferro JM, Coutinho JM, Arnold M, Heldner MR for the Cerebral Venous Sinus Thrombosis with Thrombocytopenia Syndrome Study Group
Magazine: European Stroke Journal
Titel: Transient Autoreactive PF4 and Antiphospholipid Antibodies in COVID-19 Vaccine Recipients
Auteur: Raadsen MP, Visser C, Lavell AHA, van de Munckhof AAGA, Coutinho JM, de Maat MPM, GeurtsvanKessel CH, Amsterdam Umc Covid-S/Hcw Study Group, Bomers MK, Haagmans BL, van Gorp ECM, Porcelijn L, Kruip MJHA
Magazine: Vaccines
Auteur: Raadsen MP, Visser C, Lavell AHA, van de Munckhof AAGA, Coutinho JM, de Maat MPM, GeurtsvanKessel CH, Amsterdam Umc Covid-S/Hcw Study Group, Bomers MK, Haagmans BL, van Gorp ECM, Porcelijn L, Kruip MJHA
Magazine: Vaccines
Titel: Post-SARS-CoV-2-vaccination cerebral venous sinus thrombosis: an analysis of cases notified to the European Medicines Agency.
Auteur: Krzywicka K, Heldner MR, Sánchez van Kammen M, van Haaps T, Hiltunen S, Silvis SM, Levi M, Kremer Hovinga JA, Jood K, Lindgren E, Tatlisumak T, Putaala J, Aguiar de Sousa D, Middeldorp S, Arnold M, Coutinho JM, Ferro JM.
Magazine: European Journal of Neurology
Auteur: Krzywicka K, Heldner MR, Sánchez van Kammen M, van Haaps T, Hiltunen S, Silvis SM, Levi M, Kremer Hovinga JA, Jood K, Lindgren E, Tatlisumak T, Putaala J, Aguiar de Sousa D, Middeldorp S, Arnold M, Coutinho JM, Ferro JM.
Magazine: European Journal of Neurology
Verslagen
Samenvatting van de aanvraag
In March 2021, the first reports appeared of patients who developed thrombosis with thrombocytopenia shortly after receiving an adenovirus-based COVID-19 vaccine. For unknown reasons the majority of these patients developed thrombosis at unusual sites, most notably cerebral venous sinus thrombosis (CVST) and splanchnic vein thrombosis (SVT). Investigators discovered circulating platelet-activating platelet factor 4 (PF4) antibodies in the majority of cases and named the condition “vaccine-induced immune thrombotic thrombocytopenia” (VITT).
Since this is a new disease, many questions need to be answered. In this project the following research questions will be addressed. By collecting data of VITT-cases from the EudraVigilance database of the European Medicines Agency we will calculate the absolute risk of VITT, stratified by vaccine type, age, and sex (RQ1). Using the infrastructure of the International CVST Consortium, which is co-led by one of the applicants, we are collecting the largest worldwide registry-based database on VITT cases, which we use to study the clinical manifestations and outcome of CVST-VITT and how these differ from CVST unrelated to COVID-19 vaccination (RQ2), as well as the effect of the introduction of the newly established guideline-based therapy on the outcome of VITT patients (RQ3). Using samples and data of vaccination cohort studies in combination with in vitro work we will investigate if vaccination induces production of auto-antibodies against PF4 and if so, which components of the vaccine are responsible (RQ4), as well as if (COVID-19) vaccination results in complement activation and/or a procoagulant state (RQ5).
The answers to these research questions will shed a light on the epidemiology and pathophysiology of VITT and will provide solid evidence to policy makers and physicians, which can be used for optimization of vaccination strategies, and on treatment of VITT.