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

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.

Keywords

adenovirus - platelet - hemorrhage - thrombocytopenia - thrombosis

Note

Please find the completed PRISMA 2020 statement available in the Supplementary Material (available in the online version).

Data Availability Statement

The raw data supporting the results of this study will be made available upon reasonable request.

Authors' Contribution

G.M.P. and S.B. conceptualized the study and coordinated the group. C.A. and B.P. performed study selection and, together with E.P. and B.C., performed data extraction. C.A. prepared the figure. E.P., C.P., and R.P. analyzed the data and prepared the tables. B.C. and E.P. wrote the first draft of the manuscript. G.M.P., M.S., and S.B. critically reviewed the content and edited the manuscript. All authors read and approved the final manuscript.

^* These authors contributed equally as co-first authors.

Publication History

Received: 19 August 2023

Accepted: 26 October 2023

Article published online:
18 December 2023

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