Abstract Number: PB0623
Meeting: ISTH 2022 Congress
Background: Acquired autoimmune FXIII deficiency, due to autoantibodies against FXIII, is a rare but life-threatening bleeding disorder that is extremely difficult to manage, that involves immunosuppressive therapy over a long time, and the outcome is poor or even fatal in many cases. Novel treatment options are needed. FXIII has a crucial function in clot formation and stabilisation, but it also contributes to extracellular matrix formation, wound healing and tissue regeneration, a function it shares with transglutaminase 2 (TG2). Whether TG2 may also have a role in haemostasis has not been studied in detail.
Aims: To study the role of TG2 in clot formation and haemostasis and explore TG2 as a potential novel treatment option in autoimmune FXIII deficiency.
Methods: We studied fibrin crosslinking by TG2 with gel electrophoresis and incorporation assays. Effects of TG2 on clot formation and lysis in plasma (FXIII-depleted plasma and plasma from a patient with autoimmune FXIII deficiency) were assessed with a turbidimetric assay and rotation thrombelastometry (ROTEM). We used specific TG2 and FXIII substrates and inhibitors in our microvascular whole blood flow model to monitor TG2 during clot formation in realtime.
Results: TG2 crosslinks fibrin and exhibits transglutaminase activity towards fibrinogen/fibrin and small substrates in a purified and plasma environment. In plasma, TG2 promotes clot formation, stabilises clots and prolongs fibrinolysis. TG2 even supports clot formation and prolongs lysis in the presence of a FXIII autoantibody. Preliminary experiments with our microvascular whole blood flow model suggest that TG2 may be active during clot formation and incorporate a TG2-specific substrate into the clot.
Conclusion(s): Our results suggest that TG2 can indeed support clot formation and haemostasis. Further experiments are underway to explore TG2 as a novel treatment option for patients with autoimmune FXIII deficiency.
To cite this abstract in AMA style:Li B, Suzuki R, Golomingi M, Hitomi K, Schroeder V. Role of Transglutaminase 2 in Haemostasis and as a Novel Treatment Option for Acquired Autoimmune Factor XIII Deficiency [abstract]. https://abstracts.isth.org/abstract/role-of-transglutaminase-2-in-haemostasis-and-as-a-novel-treatment-option-for-acquired-autoimmune-factor-xiii-deficiency/. Accessed November 30, 2023.
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