Thrombosis and Bleeding in Patients with Vaccine-Induced Immune Thrombotic Thrombocytopenia: A Systematic Review of Published Cases

Thromb Haemost. 2024 May;124(5):423-431. doi: 10.1055/s-0043-1777134. Epub 2023 Dec 18.

Abstract

Introduction: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a highly prothrombotic reaction to COVID-19 (coronavirus disease 2019) adenoviral vector vaccines. Its distinct bleeding and thrombotic patterns compared with other platelet consumptive disorders remain unclear.

Methods: We performed a systematic review of the literature (PubMed and Embase) up to July 31, 2022, including case reports and case series providing nonaggregate data of VITT patients. Accurate VITT diagnosis required fulfillment of the following criteria: (1) endorsement by the authors, (2) consistent vaccine type and timing, (3) presence of thrombocytopenia and thrombosis, (4) detection of anti-platelet factor 4 antibodies. Data are presented as frequencies with 95% confidence intervals (CIs) calculated with the exact binomial method.

Results: We retrieved 143 eligible studies, describing 366 patients. Of 647 thrombotic events, 53% (95% CI: 49-56) were venous thromboses at unusual sites and 30% (95% CI: 27-34) were cerebral venous sinus thromboses (CVSTs). The ratio of venous-to-arterial events was 4.1. Thromboses in most sites were associated with at least another thrombotic event, with the exception of CVST and CNS arterial thrombosis (isolated in 49 and 39% of cases, respectively). Bleeding occurred in 36% (95% CI: 31-41) of patients; 68% (95% CI: 59-75) of bleeding events were intracranial hemorrhages (ICHs). Overall mortality was 24% (95% CI: 19-29), and 77% (95% CI: 58-90) in patients with isolated CVST complicated by ICH.

Conclusion: VITT displays a venous-to-arterial thrombosis ratio comparable to heparin-induced thrombocytopenia. However, VITT is characterized by a higher prevalence of CVST and ICH, which contribute to the increased bleeding frequency and mortality.

Publication types

  • Systematic Review

MeSH terms

  • Anticoagulants / adverse effects
  • COVID-19 Vaccines* / adverse effects
  • COVID-19* / complications
  • Case Reports as Topic
  • Hemorrhage*
  • Humans
  • Platelet Factor 4 / immunology
  • Risk Factors
  • SARS-CoV-2 / immunology
  • Sinus Thrombosis, Intracranial / etiology
  • Thrombosis / etiology
  • Venous Thrombosis

Substances

  • Anticoagulants
  • COVID-19 Vaccines
  • Platelet Factor 4