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.