Measurement of the Plasmatic TFPI Level in Haemophilia Patients and Correlation With Thrombin Generation Assay (TGA) Parameters

The goal of this study is to measure the TFPI plasma level, a molecule involved in the regulation of the coagulation system, in haemophilia patients. The second objective is to assess the effects of TFPI inhibition on thrombin generation. Indeed, there is sparse data on the physiological and pathological changes of TFPI levels in human and particularly in hemophilia patients. Yet, TFPI inhibitors may become one of the new by-passing treatments of haemophilia. Until now, published data mainly reports in vitro pharmacodynamics and pharmacokinetics of TFPI inhibitors. Hence, in vivo effects of TFPI inhibition remain unclear, especially in haemophilia patients.

The clinical development of such molecules requires a dedicated biological monitoring. Thrombin Generation Assay (TGA) in Poor Platelets Plasma (PPP) is a good candidate since it is sensitive to Factor VIII and Factor IX deficiencies as well as to TFPI. However, TGA results are very dependent on experimental conditions (i. e. Tissue Factor and phospholipids concentrations) and the relationship between TFPI plasma level and TGA parameters has not been studied yet. This study should provide with original data on TFPI plasma levels and the effect of TFPI on thrombin generation in haemophilia patients. This should help to define the monitoring of TFPI inhibitors in Haemophilia.