Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis

Ah Young Kim; Wongi Woo; Dong Keon Yon; Seung Won Lee; Jae Won Yang; Ji Hong Kim; Seoyeon Park; Ai Koyanagi; Min Seo Kim; Sungsoo Lee; Jae Il Shin; Lee Smith

doi:10.1016/j.ijid.2022.03.034

Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis

Ah Young Kim, Wongi Woo, Dong Keon Yon, Seung Won Lee, Jae Won Yang, Ji Hong Kim, Seoyeon Park, Ai Koyanagi, Min Seo Kim, Sungsoo Lee, Jae Il Shin, Lee Smith

Department of Pediatrics

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I²=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I²=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I²=0%) and the overall mortality was 32% (95% CI 24-41, I²=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I²=0%). Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.

Original language	English
Pages (from-to)	130-139
Number of pages	10
Journal	International Journal of Infectious Diseases
Volume	119
DOIs	https://doi.org/10.1016/j.ijid.2022.03.034
Publication status	Published - 2022 Jun

Bibliographical note

Funding Information:
The authors disclose no financial or non-financial conflicts of interest, including funding, provision of study materials, medical writing, and article processing charges. Not applicable. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ah Young Kim and Wongi Woo are spouses. Both equally contributed to the conceptualization, data curation, analysis, and writing of the manuscript. Ah Young Kim: Conceptualization, Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Wongi Woo: Conceptualization, Methodology, Data Curation, Formal analysis, Investigation, Software, Writing - Original Draft, Writing – Review & Editing. Dong Keon Yon: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Seung Won Lee: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Jae Won Yang: Resources, Writing – Review & Editing. Ji Hong Kim: Resources, Writing – Review & Editing. Seoyeon Park: Software, Visualization, Writing – Review & Editing. Ai Koyanagi: Writing – Review & Editing. Min Seo Kim: Writing – Review & Editing. Sungsoo Lee: Writing – Review & Editing. Jae Il Shin: Conceptualization, Methodology, Validation, Supervision, Project administration Writing – Review & Editing. Smith Lee: Writing – Review & Editing. The data underlying this article will be shared by the corresponding author on reasonable request.

Publisher Copyright:
© 2022

All Science Journal Classification (ASJC) codes

Microbiology (medical)
Infectious Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ijid.2022.03.034

Cite this

Kim, A. Y., Woo, W., Yon, D. K., Lee, S. W., Yang, J. W., Kim, J. H., Park, S., Koyanagi, A., Kim, M. S., Lee, S., Shin, J. I., & Smith, L. (2022). Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis. International Journal of Infectious Diseases, 119, 130-139. https://doi.org/10.1016/j.ijid.2022.03.034

@article{855b06c80e1f43f8843c1f7720b160b0,

title = "Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis",

abstract = "Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.",

author = "Kim, {Ah Young} and Wongi Woo and Yon, {Dong Keon} and Lee, {Seung Won} and Yang, {Jae Won} and Kim, {Ji Hong} and Seoyeon Park and Ai Koyanagi and Kim, {Min Seo} and Sungsoo Lee and Shin, {Jae Il} and Lee Smith",

note = "Funding Information: The authors disclose no financial or non-financial conflicts of interest, including funding, provision of study materials, medical writing, and article processing charges. Not applicable. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ah Young Kim and Wongi Woo are spouses. Both equally contributed to the conceptualization, data curation, analysis, and writing of the manuscript. Ah Young Kim: Conceptualization, Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Wongi Woo: Conceptualization, Methodology, Data Curation, Formal analysis, Investigation, Software, Writing - Original Draft, Writing – Review & Editing. Dong Keon Yon: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Seung Won Lee: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Jae Won Yang: Resources, Writing – Review & Editing. Ji Hong Kim: Resources, Writing – Review & Editing. Seoyeon Park: Software, Visualization, Writing – Review & Editing. Ai Koyanagi: Writing – Review & Editing. Min Seo Kim: Writing – Review & Editing. Sungsoo Lee: Writing – Review & Editing. Jae Il Shin: Conceptualization, Methodology, Validation, Supervision, Project administration Writing – Review & Editing. Smith Lee: Writing – Review & Editing. The data underlying this article will be shared by the corresponding author on reasonable request. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = jun,

doi = "10.1016/j.ijid.2022.03.034",

language = "English",

volume = "119",

pages = "130--139",

journal = "International Journal of Infectious Diseases",

issn = "1201-9712",

publisher = "Elsevier",

}

Kim, AY, Woo, W, Yon, DK, Lee, SW, Yang, JW, Kim, JH, Park, S, Koyanagi, A, Kim, MS, Lee, S, Shin, JI & Smith, L 2022, 'Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis', International Journal of Infectious Diseases, vol. 119, pp. 130-139. https://doi.org/10.1016/j.ijid.2022.03.034

TY - JOUR

T1 - Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia

T2 - A Systematic Review and Meta-Analysis

AU - Kim, Ah Young

AU - Woo, Wongi

AU - Yon, Dong Keon

AU - Lee, Seung Won

AU - Yang, Jae Won

AU - Kim, Ji Hong

AU - Park, Seoyeon

AU - Koyanagi, Ai

AU - Kim, Min Seo

AU - Lee, Sungsoo

AU - Shin, Jae Il

AU - Smith, Lee

N1 - Funding Information: The authors disclose no financial or non-financial conflicts of interest, including funding, provision of study materials, medical writing, and article processing charges. Not applicable. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Ah Young Kim and Wongi Woo are spouses. Both equally contributed to the conceptualization, data curation, analysis, and writing of the manuscript. Ah Young Kim: Conceptualization, Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Wongi Woo: Conceptualization, Methodology, Data Curation, Formal analysis, Investigation, Software, Writing - Original Draft, Writing – Review & Editing. Dong Keon Yon: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Seung Won Lee: Methodology, Data Curation, Formal analysis, Resources, Investigation, Writing - Original Draft, Writing – Review & Editing. Jae Won Yang: Resources, Writing – Review & Editing. Ji Hong Kim: Resources, Writing – Review & Editing. Seoyeon Park: Software, Visualization, Writing – Review & Editing. Ai Koyanagi: Writing – Review & Editing. Min Seo Kim: Writing – Review & Editing. Sungsoo Lee: Writing – Review & Editing. Jae Il Shin: Conceptualization, Methodology, Validation, Supervision, Project administration Writing – Review & Editing. Smith Lee: Writing – Review & Editing. The data underlying this article will be shared by the corresponding author on reasonable request. Publisher Copyright: © 2022

PY - 2022/6

Y1 - 2022/6

N2 - Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.

AB - Objectives: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. Methods: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. Results: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). Conclusions: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.

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Thrombosis patterns and clinical outcome of COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A Systematic Review and Meta-Analysis

Abstract

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