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. 2021 Jan-Dec:27:10760296211048815.
doi: 10.1177/10760296211048815.

COVID-19 Vaccine-Associated Thrombosis With Thrombocytopenia Syndrome (TTS): A Systematic Review and Post Hoc Analysis

Muhammad Usman Hafeez  1 , Maha Ikram  2 , Zunaira Shafiq  3 , Azza Sarfraz  4 , Zouina Sarfraz  3 , Vikash Jaiswal  5 , Muzna Sarfraz  6 , Ivan Chérrez-Ojeda  7   8
Affiliations

COVID-19 Vaccine-Associated Thrombosis With Thrombocytopenia Syndrome (TTS): A Systematic Review and Post Hoc Analysis

Muhammad Usman Hafeez et al. Clin Appl Thromb Hemost. 2021 Jan-Dec.

Abstract

Background: A new clinical syndrome has been recognized following the COVID-19 vaccine, termed thrombosis with thrombocytopenia syndrome (TTS). The following systematic review focuses on extrapolating thrombotic risk factors, clinical manifestations, and outcomes of patients diagnosed with TTS following the COVID-19 vaccine.

Methods: We utilized the World Health Organization's criteria for a confirmed and probable case of TTS following COVID-19 vaccination and conducted a systematic review and posthoc analysis using the PRISMA 2020 statement. Data analysis was conducted using SPSS V25 for factors associated with mortality, including age, gender, anti-PF4/heparin antibodies, platelet nadir, D-dimer peak, time to event diagnosis, arterial or venous thrombi.

Results: Of the 175 studies identified, a total of 25 studies with 69 patients were included in this systematic review and post hoc analysis. Platelet nadir (P < .001), arterial or venous thrombi (χ2 = 41.911, P = .05), and chronic medical conditions (χ2 = 25.507, P = .041) were statistically associated with death. The ROC curve analysis yielded D-dimer (AUC = .646) and platelet nadir (AUC = .604) as excellent models for death prediction.

Conclusion: Adenoviral COVID-19 vaccines have been shown to trigger TTS, however, reports of patients having received mRNA COVID-19 vaccines are also present. Healthcare providers are recommended to maintain a high degree of suspicion among individuals who have received the COVID-19 vaccine within the last 4 weeks.

Keywords: COVID-19; TTS; VITT; anti-platelet factor-4; heparin-induced thrombocytopenia; thrombosis with thrombocytopenia syndrome; vaccine; vaccine-induced immune thrombotic thrombocytopenia.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
PRISMA flowchart.
Figure 2.
Figure 2.
The country of origin for 58 patients. UK = United Kingdom, US = United States.
Figure 3.
Figure 3.
ROC Curve for Vaccine Dosage (in blue), Gender (in green), and Age (in yellow) associated with Death (in purple) as the reference line.
See this image and copyright information in PMC

References

    1. Greinacher A, Thiele T, Warkentin TE, et al. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021;384(22):2092-2101. - PMC - PubMed
    1. Muir K-L, Kallam A, Koepsell SA, et al. Thrombotic thrombocytopenia after Ad26. COV2. S vaccination. N Engl J Med. 2021;384:1964-1965. - PMC - PubMed
    1. Shay DK. Safety monitoring of the Janssen (Johnson & Johnson) COVID-19 vaccine—United States. MMWR Morb Mortal Wkly Rep. 2021;70. - PMC - PubMed
    1. Dong Y, Dai T, Wei Y, et al. A systematic review of SARS-CoV-2 vaccine candidates. Signal Transduct Target Ther. 2020;5:1-14. - PMC - PubMed
    1. Vayne C, Rollin J, Gruel Y, et al. PF4 Immunoassays in vaccine-induced thrombotic thrombocytopenia. N Engl J Med. - PMC - PubMed

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