Hamostaseologie 2025; 45(S 01): S19
DOI: 10.1055/s-0044-1801567
Abstracts
Topics
T-04 Coagulation and fibrinolysis

Role of Tissue Transglutaminase 2 in Fibrin Formation and Haemostasis

P Stoklosa
1   University of Bern, Department for BioMedical Research (DBMR), Bern, Switzerland
,
M Golomingi
1   University of Bern, Department for BioMedical Research (DBMR), Bern, Switzerland
,
E T Hardy
2   Georgia Institute of Technology, Atlanta, USA
3   Emory University, Atlanta, USA
,
W Lam
2   Georgia Institute of Technology, Atlanta, USA
3   Emory University, Atlanta, USA
,
V Schroeder
1   University of Bern, Department for BioMedical Research (DBMR), Bern, Switzerland
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    Introduction: Transglutaminases are enzymes with pleiotropic functions in the human body. The two most studied members of the transglutaminase family are the A-subunit of coagulation factor XIII (FXIII; FXIII-A) and tissue transglutaminase 2 (TG2). FXIII has a crucial function in clot formation and stabilisation. FXIII also contributes to extracellular matrix formation, wound healing and tissue regeneration, a function it shares with TG2. Whether TG2 may also have a role in haemostasis has never been studied in detail. Acquired autoimmune FXIII deficiency, due to autoantibodies against FXIII, is a rare but life-threatening bleeding disorder that is extremely difficult to manage, it involves immunosuppressive therapy over a long period of time, and the outcome is poor or even fatal in many cases. Novel treatment options are therefore needed. The aim of our project is to study the role of TG2 in clot formation and haemostasis and to investigate TG2 as a potential novel treatment option in autoimmune FXIII deficiency.

    Method: We used a microfluidic endothelialised whole blood bleeding model with confocal microscopy to visualise the presence and effects of TG2 on clot formation at the injury site. We performed turbidity assays and rotational thrombelastometry (ROTEM) to study effects of TG2 on plasma clot formation, structure, and fibrinolysis. Mass spectrometry analysis of pure fibrin and plasma clots is performed to compare crosslinking patterns and protein incorporation mediated by TG2 and FXIII-A.

    Results: Upon vessel injury in the microfluidic whole blood bleeding model, endogenous TG2 could be detected at the injury site. When we added exogenous TG2, it clearly co-localised with the forming fibrin clot. TG2 had no significant effects on the kinetics of plasma clot formation, but it increased maximum clot firmness and prolonged fibrinolysis. Preliminary proteomic analysis of fibrin and plasma clots revealed differences in the crosslinking pattern and protein composition between TG2 and FXIII-A.

    Conclusion: Our data so far suggest that TG2 is present at the site of clot formation upon vessel injury and contributes to fibrin crosslinking and clot stabilisation. Hence TG2 may be able support haemostasis when FXIII-A is absent or cannot function.


     

    Conflict of Interest:

    No conflict of interest.

    Publikationsverlauf

    Artikel online veröffentlicht:
    13. Februar 2025

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