TFPI Levels in Haemophilia A and B Patients
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Reims, France
- Recruiting
- Damien JOLLY
-
Contact:
- Philippe NGUYEN
- Phone Number: 0033 03 26 78 80 74
- Email: pnguyen@chu-reims.fr
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
inclusion criteria :
- Men, adult (≥ 18 years old), haemophilia A or B disease (whatever the severity)
- Follow-up consultation in our center
- Blood samples collection planed during the consultation exclusion criteria :
- Children (< 18 years old), women
- No blood samples collection planed during the follow-up consultation
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Adult haemophilia patients
Adult (≥ 18 years old) haemophilia patients, only men
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NON INTERVENTIONAL
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Concentration of TFPI plasma level
Time Frame: Day 1
|
Correlation coefficient between concentration of TFPI inhibitor and parameter of thrombin generation
|
Day 1
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ANTICIPATED)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- PO19085
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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