Accessibility navigation

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

Mitchell, J. L., Little, G., Bye, A. P. ORCID:, 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:, Whyte, C. S., Mutch, N. J. and Jones, C. I. ORCID: (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

Text (Open Access) - Published Version
· Available under License Creative Commons Attribution.
· Please see our End User Agreement before downloading.

[img] Text - Accepted Version
· Restricted to Repository staff only


It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1016/j.rpth.2023.100200


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
Divisions:Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:112382


Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation