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| Name | Class |
|---|---|
| Pfizer | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| haemophilia A |
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| |
| Haemophilia B |
|
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood specimen | Other |
|
| Measure | Description | Time Frame |
|---|---|---|
| Comparison for TFPI level between Haemophilia A and Haemophilia B | Comparison for TFPI level between Haemophilia A and Haemophilia B | day 1 |
| Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B | Comparison for TFPI level between severe Haemophilia A and severe Haemophilia B | Day 1 |
| Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B | Comparison for TFPI level between moderate or mild Haemophilia A and moderate or mild Haemophilia B | Day 1 |
| Measure | Description | Time Frame |
|---|---|---|
| Correlation between free TFPI and hemorrhagic score | Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score (HSS). It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations |
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Inclusion Criteria:
Exclusion Criteria:
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Haemophilia A and B patients between 18 and 65 years old, whatever the severity of their disease
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU Lille | Lille | France | ||||
| HCL |
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| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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blood specimen
| day 1 |
| Correlation between TFPI activity and hemorrhagic score | Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. TFPI activity will be measured according to the technique described and modified by Sandset | day 1 |
| Correlation between Endogenous Thrombin Potential (ETP) and free TFPI | Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations | day 1 |
| Correlation between Lag Time and free TFPI | Lag time (min) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations | day 1 |
| Correlation between Peak value and free TFPI | Peak Value (PV, nmol thrombin) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations | day 1 |
| Correlation between Time to Peak and free TFPI | Time to Peak (TTP, min) of the thrombin Generation curve is measured by thromboplastin Generation Test (TGTs) Free TFPI levels will be measured by ELISA according to the manufacturer's recommendations | day 1 |
| Correlation between ETP and hemorrhagic score | Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. | day 1 |
| Correlation between Lag Time and hemorrhagic score | Lag time (min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. | day 1 |
| Correlation between Peak Value and hemorrhagic score | Peak Value (PV, nmol thrombin) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. | day 1 |
| Correlation between Time to Peak and hemorrhagic score | Time to Peak (TTP, min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) Hemorrhagic score is established on the 5 to 10 last years. For severe hemophilic patients: it will use a composite scoring system designed to reflect the clinical severity of haemophilia and named HSS for Haemophilia Severity Score. It consists in the sum of three components: annual incidence of joint bleeds, orthopedic joint score and annual factor utilization. The orthopedic joint score combines pain and physical examination scores as recommended by the orthopedic Advisory Committee of the World Federation of Haemophilia. For mild or moderate hemophilic patients, HSS is not suitable. A composite measure will be used and consist in all bleeding events and consumption of factor concentrate in surgical situation. | day 1 |
| Comparison for ETP between haemophilia A et Haemophilia B | Endogenous Thrombin Potential (i.e. the aera under the thrombin generation curve, nM.min) is measured by Thromboplastin Generation Test (TGTs) | Day 1 |
| Comparison for lag time between haemophilia A et Haemophilia B | Lag time (min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) | Day 1 |
| Comparison for Peak Value between haemophilia A et Haemophilia B | Peak Value (PV, nmol thrombin) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) | Day 1 |
| Comparison for Time to Peak between haemophilia A et Haemophilia B | Time to Peak (TTP, min) of the thrombin generation curve is measured by thromboplastin Generation Test (TGTs) | day 1 |
| Lyon |
| France |
| AP-HM | Marseille | France |
| Chu Nancy | Nancy | France |
| Chu Reims | Reims | France |
| CHU Saint-Etienne | Saint-Etienne | 42055 | France |
| Chu Tours | Tours | France |
| D020147 | Coagulation Protein Disorders |
| D006474 | Hemorrhagic Disorders |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |