TGA (Thrombin Generation Assay) and Prophylaxis in Haemophilia

Not Applicable

Brief Summary: Haemophilic arthropathy is one of the major complications of severe haemophilia. In order to maintain plasma clotting factor activity levels above 1% and avoid spontaneous joint bleeds and other serious bleeding events, prophylactic factor replacement therapy is used. Because of the high cost and limited availability of clotting factor concentrates, dosing is a crucial issue for prophylaxis therapy. Several studies reported a better correlation between clinical bleeding tendency of patients with haemophilia and thrombin generation assay results compared to FVIII/FIX levels. However there is no specific data showing that thrombin generation may be a better indicator of the clinical efficacy of prophylaxis compared to the conventional FVIII measurement.

The main objective of this open, multicentre, prospective study is to compare trough thrombin generation capacity and FVIII levels in severe haemophilia patients and compare these two laboratory results with:

* the number of spontaneous haemarthroses and other spontaneous serious bleeds occurred in the last 6 months

* the number of additional FVIII units used in the last 6 months

This project requires no change in term of type of treatment : During the study, each patient will be treated by his usual clotting factor at the usual regimen (frequency and dosage).

The clinical outcome with the usual prophylaxis regimen will be correlated to TGA results

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Age <2 and >45 years
Haemophilia A with documented inhibitor in the last 12 months
Clinically symptomatic liver disease (historical evidence documented in patient's medical file)
Platelet count < 100x109/l
Poor venous access
Presence of a documented target joint
Subject under legal protection measure.

Arm && Interventions

Group	Intervention	Description
One arm: patients with severe haemophilia A on prophylaxis	Thrombin generation measurement.	Patients with severe haemophilia A (FVIII \< 1 IU/dl), currently on prophylactic therapy , having the same prophylaxis regimen in the last six months, aged between 2 (with a body weight ≥12.5 kg ) and 45 years , with adequate venous access, having patient's diary or equivalent regularly completed and able to give informed consent

Primary Outcome Measures

Name	Time	Method
The correlation between the trough TGA (ETP) results of severe haemophilia patients who are on prophylaxis and the clinical efficacy of the ongoing prophylaxis regimen will be studied	The clinical efficacy of prophylaxis will be evaluated on the basis of the number of spontaneous joint bleeds the number of other relevant spontaneous bleeds and the consumption of clotting factor concentrate in the last 6 months prior to TGA.

Secondary Outcome Measures

Name	Time	Method
The correlation between the trough FVIII:C results of severe haemophilia patients who are on prophylaxis and the clinical efficacy of the ongoing prophylaxis regimen will be studied	The clinical efficacy of prophylaxis will be evaluated on the basis of the number of spontaneous joint bleeds the number of other relevant spontaneous bleeds and the consumption of clotting factor concentrate in the last 6 months prior to FVIII.

Locations (7): Hôpital Pellegrin
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Bordeaux, France
Unité d'Hémostase Clinique Centre Régional de Traitement des Hémophiles Centre de Référence de Maladies Hémorragiques Hôpital Cardiologique Louis Pradel
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Bron, France
CH Metropole Savoie site de Chambéry
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Chambéry, France
CHU Dijon Bourgogne Hôpital François Mitterrand
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Dijon, France
Chu Timone
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Marseille, France
CHU Saint Etienne - Hôpital Nord
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Saint-Étienne, France
CHU de Nantes
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Nantes, France