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

Clin Appl Thromb Hemost. 2021 Jan-Dec:27:10760296211048815. doi: 10.1177/10760296211048815.


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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / adverse effects*
  • Humans
  • SARS-CoV-2 / isolation & purification
  • Thrombocytopenia / etiology*
  • Thrombosis / etiology*


  • COVID-19 Vaccines