TY - JOUR
T1 - Age-Stratified Risk of Cerebral Venous Sinus Thrombosis After SARS-CoV-2 Vaccination
AU - Krzywicka, Katarzyna
AU - van de Munckhof, Anita
AU - Sánchez van Kammen, Mayte
AU - Heldner, Mirjam R.
AU - Jood, Katarina
AU - Lindgren, Erik
AU - Tatlisumak, Turgut
AU - Putaala, Jukka
AU - Kremer Hovinga, Johanna A.
AU - Middeldorp, Saskia
AU - Levi, Marcel M.
AU - Cordonnier, Charlotte
AU - Arnold, Marcel
AU - Zwinderman, Aeilko H.
AU - Ferro, José M.
AU - Coutinho, Jonathan M.
AU - Aguiar de Sousa, Diana
N1 - Funding Information: K. Krzywicka, A. van de Munckhof, and M. Sanchez van Kammen report no disclosures relevant to the manuscript. M.R. Heldner reports grants from the Swiss Heart Foundation and Bangerter Foundation, travel support from Bayer, and Data Safety Monitoring Board (DSMB) or Advisory Board participation for Amgen, as well as being a member of the ESO Board of Directors and of the ESO Education Committee. K. Jood reports no disclosures relevant to the manuscript. E. Lindgren reports academic grants from the Swedish Neurological Society, Elsa and Gustav Lindh's Foundation, P-O Ahl's Foundation, and Rune and Ulla Amlöv's Foundation. T. Tatlisumak reports academic grants from Sahlgrenska University Hospital, University of Gothenburg, Sigrid Juselius Foundation, Wennerström Foundation, and European Union; advisory board membership/steering committee membership Bayer, Bristol Myers Squibb, Boehringer Ingelheim, and Portola Pharma; and lecture honorarium from University of Krems, Austria; all outside the submitted work. J. Putaala reports grants paid to his institution from the Academy of Finland, Hospital District of Helsinki and Uusimaa, and Finnish Foundation for Cardiovascular Research; consulting fees from Boehringer-Ingelheim, Bayer, and Herantis Pharma; payment for honoraria, lectures, presentations, speaker bureaus, manuscript writing, or educational events from Boehringer Ingelheim, Bayer, and Abbot; and stock ownership in Vital Signum. J.A. Kremer Hovinga reports no disclosures relevant to the manuscript. S. Middeldorp reports grants from Bayer, Pfizer, Boehringer Ingelheim, and Daiichi Sankyo paid to her institution, as well as personal fees from Bayer, BMS/Pfizer, Boehringer Ingelheim, Abbvie, Portola/Alexion, and Daiichi Sankyo paid to her institution, outside the submitted work. M.M. Levi reports no disclosures relevant to the manuscript. C. Cordonnier reports speaker honoraria from Boehringer Ingelheim, Advisory Board participation for AstraZeneca and Biogen, and Steering Committee participation for Biogen and Bristol Myers Squibb. M. Arnold reports honoraria for lectures from Bayer, AstraZeneca, Covidien, and Medtronic, as well as honoraria for scientific advisory board participation from Amgen, Bayer, BMS, Daiichi Sankyo, Medtronic, and Novartis. A.H. Zwinderman reports no disclosures relevant to the manuscript. J.M. Ferro reports fees and DSMB or Advisory Board participation for Boehringer Ingelheim and consulting fees from Bayer. J.M. Coutinho reports grants paid to his institution from Boehringer Ingelheim and Bayer and payments paid to his institution for DSMB participation by Bayer. D. Aguiar de Sousa reports travel support from Boehringer Ingelheim, DSMB participation for the Study of Rivaroxaban for CeREbral Venous Thrombosis (SECRET) study, advisory board participation for AstraZeneca, and being a member of the ESO Executive Committee. Go to Neurology.org/N for full disclosures. Publisher Copyright: © American Academy of Neurology.
PY - 2022/2/15
Y1 - 2022/2/15
N2 - BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. METHODS: We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. RESULTS: The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group ≥70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to ≥60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001). DISCUSSION: The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.
AB - BACKGROUND AND OBJECTIVES: Cerebral venous sinus thrombosis (CVST) as a part of the thrombosis and thrombocytopenia syndrome is a rare adverse drug reaction of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) vaccination. Estimated background rate of CVST with thrombocytopenia is 0.1 per million per month. We assessed the age-stratified risk of CVST with and without thrombocytopenia after SARS-CoV-2 vaccination. METHODS: We estimated the absolute risk of CVST with and without thrombocytopenia within 28 days of a first dose of 4 SARS-CoV-2 vaccinations using data from the European Medicines Agency's EudraVigilance database (until June 13, 2021). As a denominator, we used data on vaccine delivery from 31 European countries. For 22.8 million adults from 25 countries, we estimated the absolute risk of CVST after the first dose of ChAdOx1 nCov-19 per age category. RESULTS: The absolute risk of CVST within 28 days of first-dose vaccination was 7.5 (95% confidence interval [CI] 6.9-8.3), 0.7 (95% CI 0.2-2.4), 0.6 (95% CI 0.5-0.7), and 0.6 (95% CI 0.3-1.1) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. The absolute risk of CVST with thrombocytopenia within 28 days of first dose vaccination was 4.4 (95% CI 3.9-4.9), 0.7 (95% CI 0.2-2.4), 0.0 (95% CI 0.0-0.1), and 0.0 (95% CI 0.0-0.2) per million of first doses of ChAdOx1 nCov-19, Ad26.COV2.S, BNT162b2, and mRNA-1273, respectively. In recipients of ChAdOx1 nCov-19, the absolute risk of CVST, both with and without thrombocytopenia, was the highest in the 18- to 24-year-old group (7.3 per million, 95% CI 2.8-18.8 and 3.7 per million, 95% CI 1.0-13.3, respectively). The risk of CVST with thrombocytopenia in ChAdOx1 nCov-19 recipients was the lowest in the age group ≥70 years (0.2, 95% CI 0.0-1.3). Age <60 years compared to ≥60 years was a predictor for CVST with thrombocytopenia (incidence rate ratio 5.79, 95% CI 2.98-11.24, p < 0.001). DISCUSSION: The risk of CVST with thrombocytopenia within 28 days of first-dose vaccination with ChAdOx1 nCov-19 was higher in younger age groups. The risk of CVST with thrombocytopenia was slightly increased in patients receiving Ad26.COV2.S compared with the estimated background risk. The risk of CVST with thrombocytopenia was not increased in recipients of SARS-CoV-2 mRNA vaccines.
UR - http://www.scopus.com/inward/record.url?scp=85124633559&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000013148
DO - https://doi.org/10.1212/WNL.0000000000013148
M3 - Article
C2 - 34921101
SN - 0028-3878
VL - 98
SP - e759-e768
JO - Neurology
JF - Neurology
IS - 7
ER -