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Semin Thromb Hemost
DOI: 10.1055/a-2552-9525
Review Article

Red Blood Cells in Thrombosis: Active Participants in Clot Formation and Stability: A Systematic Review

Authors

  • Amin A. Alamin 

    1   Department of Pathology, College of Medicine, Taif University, Taif, Saudi Arabia

  • Amar I.O. Yahia

    2   Department of Pathology, College of Medicine, University of Bisha, Bisha, Saudi Arabia

  • Hatim M. Hussien

    3   Department of Clinical Pathology, Laboratory and Blood Bank Director, Hayat National Hospital, Abha, Saudi Arabia
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Abstract

Thrombosis, the formation of blood clots within blood vessels, has traditionally been attributed to platelets and clotting factors. Red blood cells (RBCs) play a significant role in thrombosis by impacting clot formation, stability, and fibrinolysis through mechanisms such as platelet margination, thrombin generation, and microvesicle release. However, their prothrombotic functions remain insufficiently studied. In this systematic review, which follows PRISMA guidelines, the aim is to explore how RBCs contribute to thrombus formation, stabilization, and resolution. This review analyzed peer-reviewed English-language studies and reviews on RBC involvement in thrombosis, focusing on clot formation, stability, and fibrinolysis. Studies in humans and relevant animal models were included, while case reports, non-English studies, and articles lacking methodological details were excluded. The research commenced in September 2024, utilizing PubMed, Scopus, SpringerLink, and Web of Science databases, with searches conducted up to that date. The risk of bias was assessed using the Newcastle–Ottawa Scale, and data were synthesized qualitatively. A total of 37 studies were included. RBCs contribute to thrombosis by influencing blood viscosity, interacting with platelets, and integrating into clots. Procoagulant activity induced by phosphatidylserine exposure and RBC-derived microvesicle products that promote thrombin generation and clot stability were also identified as key mechanisms. In conclusion, RBCs play an active role in thrombosis formation, contributing to clot formation and stability. Targeting RBC-mediated processes, such as aggregation, deformability, and microvesicle release, may offer novel strategies for thrombosis management. Further research and meta-analyses are needed to refine these therapeutic approaches.

Keywords

red blood cells - thrombosis - clot formation - fibrinolysis - microvesicles

Ethical Approval and Registration

No ethical approval was needed as this was a systematic review of published literature. To ensure transparency and the use of best practices methodology in systematic reviews, the review protocol was registered in PROSPERO (CRD42024595699).


Supplementary Material



Publication History

Received: 15 November 2024

Accepted: 06 March 2025

Article published online:
28 March 2025

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