Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability
© 2023 The Authors..
Background: Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied.
Objectives: This study aims to identify the role of platelet FXIII-A in platelet function.
Methods: We used 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 and aggregation 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. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent.
Conclusion: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:7 |
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| Enthalten in: |
Research and practice in thrombosis and haemostasis - 7(2023), 5 vom: 01. Juli, Seite 100200 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mitchell, Joanne L [VerfasserIn] |
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| Links: |
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| Themen: |
Clot retraction |
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| Anmerkungen: |
Date Revised 14.02.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.rpth.2023.100200 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM360997090 |
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| 100 | 1 | |a Mitchell, Joanne L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 14.02.2024 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 The Authors. | ||
| 520 | |a Background: Factor XIII (FXIII) is an important proenzyme in the hemostatic system. The plasma-derived enzyme activated FXIII cross-links fibrin fibers within thrombi to increase their mechanical strength and cross-links fibrin to fibrinolytic inhibitors, specifically α2-antiplasmin, to increase resistance to fibrinolysis. We have previously shown that cellular FXIII (factor XIII-A [FXIII-A]), which is abundant in the platelet cytoplasm, is externalized onto the activated membrane and cross-links extracellular substrates. The contribution of cellular FXIII-A to platelet activation and platelet function has not been extensively studied | ||
| 520 | |a Objectives: This study aims to identify the role of platelet FXIII-A in platelet function | ||
| 520 | |a Methods: We used 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 | ||
| 520 | |a 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 and aggregation 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. Our data demonstrate that platelet FXIII-A is important for clot retraction where clots formed in its absence retracted to a lesser extent | ||
| 520 | |a Conclusion: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a clot retraction | |
| 650 | 4 | |a factor XIII | |
| 650 | 4 | |a fibrinogen | |
| 650 | 4 | |a fibrinolysis | |
| 650 | 4 | |a platelet | |
| 650 | 4 | |a platelet activation | |
| 700 | 1 | |a Little, Gemma |e verfasserin |4 aut | |
| 700 | 1 | |a Bye, Alexander P |e verfasserin |4 aut | |
| 700 | 1 | |a Gaspar, Renato S |e verfasserin |4 aut | |
| 700 | 1 | |a Unsworth, Amanda J |e verfasserin |4 aut | |
| 700 | 1 | |a Kriek, Neline |e verfasserin |4 aut | |
| 700 | 1 | |a Sage, Tanya |e verfasserin |4 aut | |
| 700 | 1 | |a Stainer, Alexander |e verfasserin |4 aut | |
| 700 | 1 | |a Sangowawa, Ibidayo |e verfasserin |4 aut | |
| 700 | 1 | |a Morrow, Gael B |e verfasserin |4 aut | |
| 700 | 1 | |a Bastos, Ricardo N |e verfasserin |4 aut | |
| 700 | 1 | |a Shapiro, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Desborough, Michael J R |e verfasserin |4 aut | |
| 700 | 1 | |a Curry, Nicola |e verfasserin |4 aut | |
| 700 | 1 | |a Gibbins, Jonathan M |e verfasserin |4 aut | |
| 700 | 1 | |a Whyte, Claire S |e verfasserin |4 aut | |
| 700 | 1 | |a Mutch, Nicola J |e verfasserin |4 aut | |
| 700 | 1 | |a Jones, Christopher I |e verfasserin |4 aut | |
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