Targeting TFPI With Concizumab to Improve Haemostasis in Glanzmann Thrombasthenia Patients: an in Vitro Study

Overview

Glanzmann thrombasthenia is a rare genetic disorder caused by the absence or the dysfunction of the main receptor present on the surface of platelets, integrin αIIbβ3 or GPIIb-IIIa. The lack of this protein on the surface of platelets no longer allows these blood cells to bind to each other. This binding corresponds to the process of platelet aggregation. Generally, local measures will control nasal and superficial bleeding whereas platelet transfusions are used to control or prevent life-threatening. The main complication of this treatment is the risk of developing anti-αIIbβ3 antibodies directed against the absent protein and platelet transfusion therapy can become ineffective. Activated recombinant factor VII (rFVIIa) provides an alternative treatment for GT patients who develop such antibodies. However, this therapy has a short duration of efficacy, requiring repeated intravenous administrations every 2 to 3 hours. There is a new treatment, Concizumab, which has not yet been marketed. This treatment acts on TFPI (tissue factor pathway inhibitor). TFPI is a protein that occurs naturally in the body and prevents blood cells from binding to each other. Concizumab works by blocking TFPI, which may allow sufficient clotting to prevent bleeding. This treatment could replace recombinant activated factor VII (rFVIIa) because it has the advantage of a much longer duration of efficacy (about 3 days) and is administered subcutaneously.

This is in vitro research. The treatment will be tested on blood samples. This will allow us to evaluate in vitro the ability of Concizumab to restore coagulation compared to the usual treatments of platelet transfusions and recombinant activated factor VII (rFVIIa). This is a single-center study conducted at the Bordeaux University Hospital, which included 10 with Glanzmann thrombasthenia patients and 10 healthy donors over a period of 12 months.