Brief Title
Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
Official Title
Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients
Brief Summary
Haemophilia is a rare and serious congenital defect of blood coagulation due to a genetic
mutation on a sexual chromosome. It affects quasi-essentially the men and it is responsible
for bleeding. There are two types of haemophilia: Haemophilia A, (85 % of cases), due to a
factor VIII (FVIII) deficiency and Haemophilia B (15 % of cases) due to factor IX (FIX)
deficiency. According to the intensity of the defect, there are three forms of haemophilia:
severe (FVIII or FIX lower than 1 %), moderate (factor level between 1 and 5 %), minor
(factor level between 5 and 40 %). For a same level of factor VIII or IX, hemorrhagic
manifestations are variable from one patient to the other. Moreover, several studies showed
that haemophilic B patients bleed less and consume fewer anti-hemophilic concentrate that
haemophilic A patients.
The main inhibitors of the coagulation are antithrombin, Protein C-Protein S-Thrombomodulin
system, and tissue factor pathway inhibitor (TFPI). TFPI is the specific and exclusive
inhibitor of tissue factor pathway that is the main way by which plasmatic coagulation
starts. TFPI is a potent direct inhibitor of factor Xa and Xa-dependent inhibitor of the
VIIa-Tissue Factor (TF) complex. In hemophilic patient, the production of Xa by the
amplification pathway being strongly altered because of factor VIII or IX deficiency,
thrombin generation (via Xa) comes exclusively from TFPI regulated tissue factor pathway. We
can thus say that if haemophilic patients bleed, it is also because of the presence of TFPI
that inhibits at the same time Xa and the complex TF-VIIa as soon as factor Xa is generated.
Study Type
Observational
Primary Outcome
Comparison for TFPI level between Haemophilia A and Haemophilia B
Secondary Outcome
Correlation between free TFPI and hemorrhagic score
Condition
Hemophilia
Intervention
blood specimen
Study Arms / Comparison Groups
haemophilia A
Description: Blood specimen for measuring : Free TFPI and TFPI activity levels Thrombin generation in platelet rich plasma (PRP) and platelet poor plasma (PPP) Thrombin generation assay (TGA) in fresh PRP and frozen PPP Hemorrhage score for each patient
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Other
Estimated Enrollment
164
Start Date
February 2012
Completion Date
February 2016
Primary Completion Date
February 2016
Eligibility Criteria
Inclusion Criteria:
- Haemophilia A and B patients between 18 and 65 years old, whatever the severity of
their disease, who have signed the informed consent form
- On-demand or on prophylactic therapy.
- Regular monitoring in investigator center.
Exclusion Criteria:
- - Haemophilia patients under 18.
- Presence of an inhibitor at any time before or during the study period.
- Patients who received factor VIII concentrate less than 72 hours or factor IX
concentrate less than 96 hours before blood collection
- Patients who refused to sign informed consent
- Patient data over the last 5 years at least not available.
- No regular monitoring in haemophilia center (required at least one visit every 18
months for severe or moderate hemophiliac patients).
Gender
Male
Ages
18 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
, ,
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT02540187
Organization ID
1108164
Responsible Party
Sponsor
Study Sponsor
Centre Hospitalier Universitaire de Saint Etienne
Collaborators
Pfizer
Study Sponsor
, ,
Verification Date
March 2016