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.
Study Type
OBSERVATIONAL
Enrollment
11
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.
Groupement hospitalier Est Hôpital Cardilogique Service d'hémostase clinique
Bron, France
RECRUITINGCentre de Référence Hémophilie et autres déficits rares en protéine de la coagulationCentre de Traitemendes Hémophiles F. Josso
Paris, France
NOT_YET_RECRUITINGDevelopment 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).
Time frame: At time of sample analysis (single visit; Day 0)
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.
Time frame: Day 0
Identification of Optimal TGA Parameters for Monitoring Anti-TFPI Effect
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.
Time frame: 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.
Time frame: 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.
Time frame: Day 0
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