Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability

Mitchell, J. L., Little, G., Bye, A. P. ORCID: https://orcid.org/0000-0002-2061-2253, Gaspar, R. S., Unsworth, A. J., Kriek, N., Sage, T., Stainer, A., Sangowawa, I., Morrow, G. B., Bastos, R. N., Shapiro, S., Desborough, M. J. R., Curry, N., Gibbins, J. M. ORCID: https://orcid.org/0000-0002-0372-5352, Whyte, C. S., Mutch, N. J. and Jones, C. I. ORCID: https://orcid.org/0000-0001-7537-1509 (2023) Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability. Research and Practice in Thrombosis and Haemostasis, 7 (5). 100200. ISSN 2475-0379 doi: 10.1016/j.rpth.2023.100200

Abstract/Summary

Background: Factor XIII (FXIII) is an important proenzyme enzyme in the haemostatic system. The active plasma-derived enzyme FXIIIa cross-links fibrin fibres within thrombi to increase their mechanical strength and fibrinolytic inhibitors, specifically 2antiplasmin (2AP) to fibrin to increase fibrinolytic resistance. We have previously shown that cellular factor XIII (FXIII-A), which is abundant in the platelet cytoplasm, is externalised onto the activated membrane and cross-links extracellular substrates. The contribution of FXIII-A to platelet activation and platelet function has not been extensively studied. Objectives: This study aims to identify the role of platelet factor XIII in platelet function. Patients/methods: We have utilised normal healthy platelets with a cell permeable FXIII inhibitor and platelets from FXIII-deficient patients as a FXIII free platelet model in a range of platelet function and clotting tests. Results: Our data demonstrate that platelet FXIII-A enhances fibrinogen binding to the platelet surface upon agonist stimulation and improves the binding of platelets to fibrinogen under flow in a whole blood thrombus formation assay. In the absence of FXIII-A, platelets show reduced sensitivity to agonist stimulation, including decreased P-selectin exposure and fibrinogen binding. We show that FXIII-A is involved in platelet spreading where a lack of FXIII-A reduces the ability of platelets to fully spread on fibrinogen and collagen. Conclusions: Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent. Overall, this study shows that platelet FXIII-A functions during thrombus formation by aiding platelet activation and thrombus retraction in addition to its antifibrinolytic roles.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/112382
Identification Number/DOI	10.1016/j.rpth.2023.100200
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	Elsevier
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