Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
During the development of anti-TFPI antibodies, thrombin generation assay (TGA) was employed using both in vitro measurements (antibodies added to blood samples) and ex vivo approaches (blood samples from patients in phase II and III trials). While a significant improvement in thrombin generation was observed in all samples from patients with severe hemophilia, no correlation with clinical outcomes could be established. Notably, thrombin peak levels were consistently improved even in patients who experienced bleeding episodes. These measurements were conducted in platelet-poor plasma (PPP) with standard reagents, which may not adequately reflect the hemostatic efficacy of anti-TFPI antibodies given their mechanism of action. It is hypothesized that optimizing reagents and utilizing more appropriate biological materials could enhance TGA sensitivity, as previously demonstrated for monitoring emicizumab.
The absence of a laboratory assay to monitor anti-TFPI (tissue factor pathway inhibitor) antibodies poses a significant challenge for managing patients in surgical settings and treating acute severe bleeding. This study aims to develop a reliable assay to evaluate the hemostatic efficacy of anti-TFPI antibodies and their combined procoagulant effect with factor concentrates (FVIII or FIX) or bypassing agents.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Severe adult haemophilia A or B patient with factor levels ≤2% |
|
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| blood sampling | Biological | One-time peripheral blood draw (10.8 mL total, 4 citrated tubes) collected during a routine clinical visit for thrombin generation testing on platelet-rich and platelet-poor plasma. No additional medical procedures or treatments are involved in the study. |
| Measure | Description | Time Frame |
|---|---|---|
| Development of a Laboratory Assay to Assess Hemostatic Efficacy of Anti-TFPI Antibodies | Assessment of the thrombin generation assay's ability to evaluate the procoagulant effect of anti-TFPI antibodies alone and in combination with factor concentrates (FVIII or FIX) or bypassing agents (rFVIIa, aPCC). | At time of sample analysis (single visit; Day 0) |
| Measure | Description | Time Frame |
|---|---|---|
| Analytical Sensitivity of TGA to Anti-TFPI Antibodies | Evaluate the effect of different TGA conditions (e.g., low TF concentration, use of PRP, CTI) to enhance sensitivity to anti-TFPI antibodies. | Day 0 |
| Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect |
Not provided
Inclusion Criteria :
Exclusion Criteria :
Not provided
Not provided
Not provided
Potentials patients for this study will be identified within the department of clinic hemostasis at Louis Pradel Hospital and Necker Hospital during their routine visit. Hemophila patients are coming regularly to the hospital for their consultaion and a blood drawn
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yesim DARGAUD, Pr | Contact | 0472118822 | +33 | gamze.dargaud@chu-lyon.fr |
| Sandra DURANTEL | Contact | 0472118819 | +33 | sandra.durantel@chu-lyon.fr |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Groupement hospitalier Est Hôpital Cardilogique Service d'hémostase clinique | Recruiting | Bron | 69677 | France |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006467 | Hemophilia A |
| ID | Term |
|---|---|
| D025861 | Blood Coagulation Disorders, Inherited |
| D001778 | Blood Coagulation Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
Not provided
Not provided
Not provided
Not provided
Not provided
The specific types of samples that will be retained include platelet-rich plasma (PRP) and platelet-poor plasma (PPP) derived from citrated whole blood.
During a routine visit, four citrate tubes of 2.7 mL each (totaling 10.8 mL) will be collected per patient. PRP is prepared by centrifugation at 150 × g for 10 minutes at 18°C within 30 minutes of collection. The plasma is carefully transferred to avoid leukocyte contamination and adjusted to a standardized platelet count if necessary.
These samples will be used for thrombin generation testing, specifically via the Calibrated Automated Thrombogram (CAT) method, and will not be stored for long-term use-no long-term storage is planned.
|
Determine which parameters (e.g., thrombin peak, ETP, lag time, velocity, time to peak) best reflect the action of anti-TFPI antibodies under optimized assay conditions. |
| Day 0 |
| Correlation Between TGA Parameters and Clinical Use of Anti-TFPI Therapies | Compare TGA results from 5 patients treated with marstacimab and 3 patients with concizumab to assess correlation with clinical treatment exposure. | Day 0 |
| Detection of Hypercoagulability from Combined Therapy in TGA | In vitro testing of anti-TFPI antibodies in combination with FVIII, FIX, rFVIIa, or aPCC to assess risk of excessive thrombin generation. | Day 0 |
| Centre de Référence Hémophilie et autres déficits rares en protéine de la coagulationCentre de Traitemendes Hémophiles F. Josso | Not yet recruiting | Paris | 75015 | 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 |