Clinical trial NCT02540187: 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hemophilia
Keywords: haemophilia
TFPI
thrombin generation
hemorrhagic score
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2015-09-03
Enrollment: 164
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease

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.


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).

Primary outcomes:
measure: Comparison for TFPI level between Haemophilia A and Haemophilia B
timeFrame: day 1
measure: Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B
timeFrame: Day 1
measure: Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B
timeFrame: Day 1
Secondary outcomes:
measure: Correlation between free TFPI and hemorrhagic score
timeFrame: day 1
measure: Correlation between TFPI activity and hemorrhagic score
timeFrame: day 1
measure: Correlation between Endogenous Thrombin Potential (ETP) and free TFPI
timeFrame: day 1
measure: Correlation between Lag Time and free TFPI
timeFrame: day 1
measure: Correlation between Peak value and free TFPI
timeFrame: day 1
measure: Correlation between Time to Peak and free TFPI
timeFrame: day 1
measure: Correlation between ETP and hemorrhagic score
timeFrame: day 1
measure: Correlation between Lag Time and hemorrhagic score
timeFrame: day 1
measure: Correlation between Peak Value and hemorrhagic score
timeFrame: day 1
measure: Correlation between Time to Peak and hemorrhagic score
timeFrame: day 1
measure: Comparison for ETP between haemophilia A et Haemophilia B
timeFrame: Day 1
measure: Comparison for lag time between haemophilia A et Haemophilia B
timeFrame: Day 1
measure: Comparison for Peak Value between haemophilia A et Haemophilia B
timeFrame: Day 1
measure: Comparison for Time to Peak between haemophilia A et Haemophilia B
timeFrame: day 1
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU Lille
city: Lyon
country: France
facility: HCL
city: Marseille
country: France
facility: AP-HM
city: Nancy
country: France
facility: Chu Nancy
city: Reims
country: France
facility: Chu Reims
city: Saint-Etienne
country: France
facility: CHU Saint-Etienne
city: Tours
country: France
facility: Chu Tours
Study officials:
References: