Haemophilia A and B Clinical Trial
Official title:
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.
This study is a single-institution cohort study. Patients will be informed during their
follow-up consultation. If the patient agrees to participate to this study, a non-opposition
form will be signed.
If blood tests are prescribed during the consultation, the unused plasma samples that are not
required to perform the prescribed analyses will be collected and anonymized in order to
measure the TGA and TFPI levels.
TFPI plasmatic level and TFPI activity measurements will be performed by a quantitative ELISA
assay (Total TFPI ELISA kit®, R&d Systems) and a chromogenic assay (Actichrom TFPI®, Cryopep)
respectively.
TGA will be performed on a Fluoroskan® machine using 3 different levels of Tissue Factor
(TF): 1, 5 and 20 pM. In order to study the relation between different levels of TFPI
inhibitors and TGA parameters, TGA will also be performed by spiking blood samples with
several concentrations of TFPI inhibitor. For each TGA performed, ETP (Endogenous Thrombin
Potential, nM/min), peak (nM) and lagtime (min) will be analyzed.
Clinical data will be collected from the computerized patient record: date of birth, age,
gender, haemophilia type (A or B) and its severity, ongoing treatments and deficient factor
level.
The goal of this study is to measure the TFPI plasma level in haemophilia patients. The
second objective is to assess the effects of TFPI inhibition on thrombin generation. 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.
There is no additional risk for the patient since only unused blood samples, not needed for
the prescribed blood tests, will be collected.
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