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. 2022 Jan:12:100270.
doi: 10.1016/j.lanepe.2021.100270. Epub 2021 Dec 6.

Laboratory confirmed vaccine-induced immune thrombotic thrombocytopenia: Retrospective analysis of reported cases after vaccination with ChAdOx-1 nCoV-19 in Germany

Thomas Thiele  1 , Karin Weisser  2 , Linda Schönborn  1 , Markus B Funk  2 , Gabriele Weber  2 , Andreas Greinacher  1 , Brigitte Keller-Stanislawski  2
Affiliations

Laboratory confirmed vaccine-induced immune thrombotic thrombocytopenia: Retrospective analysis of reported cases after vaccination with ChAdOx-1 nCoV-19 in Germany

Thomas Thiele et al. Lancet Reg Health Eur. 2022 Jan.

Abstract

Background: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe adverse event of SARS-CoV-2 vaccination. We describe the characteristics of patients reported in Germany based on the Brighton Collaboration (BC) case definition criteria for Thrombosis and Thrombocytopenia Syndrome (TTS) and focus on patients with complete anti-platelet factor 4 (PF4)-antibody laboratory work up.

Methods: The adverse drug reaction database of the Paul-Ehrlich Institute was queried for TTS cases following ChAdOx1 nCoV-19 vaccination from February 1, until May 21, 2021. Cases with reports from the Greifswald laboratory were analysed in detail.

Findings: PF4 antibody tests were available for 69 suspected TTS cases reported to the Paul-Ehrlich Institute, of whom 52 patients fulfilled the BC case definition; 37 (71%) women, 15 (29%) men, median age 46·0 years (interquartile range 31·0-60·3 years). Cerebral venous sinus thrombosis was confirmed in 37 (71%), (additional) multiple thromboses in 19 (37%) patients. Twelve patients died. Non-survivors showed lower platelet counts compared to survivors (median nadir 15,000/µL vs 49,000/µL; p<0·0001). Combined anti-PF4/heparin IgG ELISA and PF4-dependent platelet activation testing yielded sensitivity of 96% (95% confidence interval 87-100%) and specificity of 77% (50-93%) for TTS. Four patients with thrombocytopenia but without thrombosis presented with severe headache or cerebral bleeding, explaining the lower specificity.

Interpretation: VITT has high mortality and can present with isolated thrombocytopenia, severe headache, and bleeding. Demonstration of platelet activating anti-PF4 IgG has high sensitivity for TTS and captures a wider spectrum of clinically relevant VITT than the current BC case definition.

Funding: Deutsche Forschungsgemeinschaft: 374031971-TRR240; Domagk-Programm Universitätsmedizin Greifswald.

Keywords: Sars-CoV-2; TTS; VITT; Vaccine; thrombocytopenia; thrombosis.

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Conflict of interest statement

Dr. Thiele reports grants from Deutsche Forschungsgemeinschaft, during the conduct of the study; personal fees, non-financial support and other from Bristol Myers Squibb, personal fees, non-financial support and other from Pfizer, personal fees from Bayer, personal fees, non-financial support and other from Chugai Pharma, non-financial support and other from Novo Nordisk, personal fees from Novartis, non-financial support and other from Daichii Sankyo, outside the submitted work; Dr. Greinacher reports grants from Deutsche Forschungsgemeinschaft, grants from Deutsche Forschungsgemeinschaft, during the conduct of the study; personal fees from Aspen, grants from Ergomed, grants from Boehringer Ingelheim, personal fees from Bayer Vital, grants from Rovi, grants from Sagent, personal fees from Chromatec, personal fees from Instrumentation Laboratory, grants and personal fees from Macopharma, grants from Portola, grants from Biokit, personal fees from Sanofi-Aventis, grants from Fa. Blau Farmaceutics, grants from Prosensa/Biomarin, grants and other from DRK-BSD NSTOB, grants from DRK-BSD Baden-Würtemberg/Hessen, personal fees from Roche, personal fees from GTH e.V., outside the submitted work; In addition, Dr. Greinacher has a patent modified SARS CoV 2 vaccine pending. Dr. Weisser, Dr. Funk, Dr. Weber, Dr. Schönborn and Dr. Keller-Stanislawski have nothing to disclose. All conflict of interest statements are uploaded as separate files.

Figures

Figure 1
Figure 1
Notified cases of thrombosis, thrombocytopenia, and TTS in Germany (01.02. - 21.05.2021) after ChAdOx-1 nCoV-19 vaccination.
See this image and copyright information in PMC

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