Ongoing Projects

Role of transglutaminase 2 (TG2) in haemostasis

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 and tissue transglutaminase 2 (TG2). FXIII has a crucial function in clot formation and stabilisation and 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 and involves immunosuppressive therapy over a long time, and the outcome is poor or even fatal in many cases. Novel treatment options are needed.

The aims of this project are

1.         to investigate the role of TG2 in clot formation and haemostasis.

2.         to investigate TG2 as a potential novel treatment option in autoimmune FXIII deficiency.

This project is funded by the Swiss National Science Foundation.

Minimum FXIII levels required for haemostasis

Deficiency of FXIII is associated with severe bleeding complications. Congenital FXIII deficiency is a rare inherited disease, acquired FXIII deficiency can be caused by consumption of FXIII or autoantibodies against it. In the treatment of patients with FXIII deficiency with plasma-purified or recombinant FXIII or FXIII-containing blood products, it is not known what minimum FXIII plasma level is safe to prevent potentially severe bleeding complications. It is almost impossible to study this question in patients since it is of course unethical to withhold FXIII substitution and wait for bleeding complications to happen, and retrospective FXIII analysis after bleeding has already occurred is biased by the bleeding event itself which causes further consumption of FXIII.

The aims of this project are

1. to investigate the effects of FXIII level on clot formation, clot structure and incorporation of blood cells and physiological FXIII substrates into the clot by using our microvascular bleeding model.
2. to define a minimum FXIII level that can prevent serious bleeding complications.

Characterisation of patients with congenital deficiency in Pakistan

We have a longstanding collaboration with Prof. Dr. Munira Borhany, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan.

In our current project we perform a comprehensive evaluation of coagulation and fibrinolysis parameters in patients with congenital factor XIII deficiency in Pakistan.

The aims of this project are

1. to investigate whether there are any changes in the coagulation and fibrinolytic system as a compensation mechanism of congenital FXIII deficiency.
2. to study if any changes in the coagulation and fibrinolytic system are related to the severity of bleeding complications or other medical conditions.

This project is supported by an SSC grant from the ISTH (International Society on Thrombosis and Haemostasis).