ISTH Congress Abstracts

Official abstracts site for the ISTH Congress

MENU 

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

1University of Birmingham, Birmingham, England, United Kingdom, 2University of Reading, READING, England, United Kingdom, 3St Georges University London, London, England, United Kingdom, 4 Manchester Metropolitan University, Manchester, England, United Kingdom, 5University of Reading, Reading, England, United Kingdom, 6Oxford University Hospitals NHS Foundation Trust, Oxford, England, United Kingdom, 7University of Aberdeen, Aberdeen, Scotland, United Kingdom, 8Institute for Cardiovascular and Metabolic Research, School of Biological sciences, University of Reading, Reading, UK, Reading, England, United Kingdom

Abstract Number: OC 77.3

Meeting: ISTH 2022 Congress

Theme: Platelets and Megakaryocytes » Platelet Function and Interactions

Background: Platelet factor XIII-A (FXIII-A) is externalised upon platelet activation and is functional in cross-linking extracellular fibrin to stabilise thrombi against fibrinolysis. FXIII-A is abundant inside platelets and has many intracellular substrates, suggesting it may be involved in platelet function.

Aims: Determine the role platelet FXIII-A plays in platelet function.

Methods: Platelets were isolated from FXIII-deficient patients and normal donors and assessed using confocal microscopy and flow cytometry. Clots or thrombi under flow were formed from FXIII-depleted plasma with normal healthy or FXIII-deficient platelets. FXIII was inhibited using a cell-permeable transglutaminase inhibitor (TGI).

Results: FXIII-deficient platelets contained no detectable FXIII-A and were not functional in stabilising FXIII-depleted thrombus lysis, compared to the stabilising effect achieved by healthy platelets confirming platelet FXIII-A protects thrombi against fibrinolysis.

Retraction of FXIII-depleted plasma clots was reduced in the presence of FXIII-deficient platelets and platelets with TGI, compared to untreated healthy platelets (P < 0.05) indicating platelet FXIII-A plays roles in driving clot retraction. Fibrinogen binding to FXIII-deficient platelets and platelets treated with TGI (P < 0.0001) was reduced when compared to untreated normal platelets, and FXIII-deficient platelets had reduced sensitivity to CRP-XL and TRAP6 stimulation, suggesting FXIII-A may be involved in the signalling processes that regulate platelet activation. Furthermore, FXIII-A activity co-localized with the platelet cytoskeleton, suggesting FXIII-A may participate cross-link actin. Platelet spreading on collagen (P < 0.01) and fibrinogen (P < 0.05) was attenuated in TGI treated and FXIII-deficient platelets compared to normal platelets. In line with this, FXIII-deficient platelets and TGI-treated normal platelets had reduced adherence to fibrinogen and formed smaller thrombi on fibrinogen under flow.

Conclusion(s): Fibrinogen binding, spreading, platelet sensitivity to agonists and clot retraction are attenuated in TGI treated and FXIII-deficient platelets. These data suggest platelet FXIII-A is actively involved in these processes, possibly by mediating intracellular cytoskeletal rearrangement.

To cite this abstract in AMA style:

Mitchell J, Little G, Bye A, Unsworth A, Gaspar R, Kriek N, Sage T, Stainer A, Sangowawa D, Curry N, Shapiro S, Desborough M, Whyte C, Gibbins J, Mutch N, Jones C. Platelet factor XIII-A regulates platelet function and promotes clot retraction and stability [abstract]. https://abstracts.isth.org/abstract/platelet-factor-xiii-a-regulates-platelet-function-and-promotes-clot-retraction-and-stability/. Accessed October 2, 2023.

« Back to ISTH 2022 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-factor-xiii-a-regulates-platelet-function-and-promotes-clot-retraction-and-stability/