In Vitro Correction of Thrombin Generation by Concizumab (Anti-TFPI) for Severe Hemophilia Patients

Study Overview
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Brief Summary
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Studies have shown, in haemophilia patients, the effectiveness of Anti TFPI antibody (aTFPIAb) to prevent joint and muscular bleeding (tissues poor in Tissue Factor (TF)). However, cases of cerebral thrombosis (tissues rich in TF) have been observed in some patients treated with this antibody. Because an inter-individual variation in thrombin generation correction by aTFPIAb, an aTFPIAb concentration effective at low TF concentration could be at the same time thrombogenic at high TF concentration.

Detailed Description
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The aim of this study is to determine, for each patient, the minimum concentration of aTFPIAb necessary to restore thrombin generation in the presence of low (1pM) TF concentration and to evaluate at this concentration of aTFPIAb a potential thrombogenic effect in the presence of a high (10pM) TF concentration.

Official Title
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Tissue Factor Pathway Inhibitor (TFPI) and Haemorrhagic Manifestations in Haemophilia A and B Patients

Conditions
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Hemophilia

Intervention / Treatment
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* Other: thrombin generation measurement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe or moderate haemophilia A or B patient with FVIII or FIX <5% with or without prophylaxis Affiliated or beneficiary of a social security regimen Signature of consent Exclusion Criteria: Haemophilia patients aged 12 years or less with a weight less than 30 kg (taking into account the volume of blood collection). Patients who received factor VIII concentrates less than 48 hours or factor IX concentrates less than 96 hours prior to the routine blood draw at the Hemophilia Clinic. 96 hours prior to the routine blood draw at the Hemophilia Centre

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Severe and/or moderate haemophilia A and B<br>At the end of the consultation and follow-up of the disease, an additional blood sample of 35 ml (8 tubes) will be taken | Other: thrombin generation measurement<br>* Thrombin generation will be measured in Platelets rich plasma induced either by 1 pM TF or 10 pM TF concentration in presence of different aTFPIAb concentrations (0; 0.5 µg/ml; 0.75 µg/ml; 1.0 µg/ml; 2.0 µg/ml; 4.0 µg/ml)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| minimum concentration of anti-TFPI antibody | Determine the minimum concentration of anti-TFPI antibody (µg/ml) that normalizes the peak to 1 pM FT | day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of the clot structure | Measurement of the clot structure (density fibers in g/cm3) by scanning electron microscopy | day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anti-TFPI antibody, thrombin generation, tissue factor concentration