Coagulation Profile to Present Abstract on Intrinsic Thrombin Generation at EAHAD in Milan on February 5th 2025 Congress
In a collaboration between Maastricht University Medical Center+ and Coagulation Profile B.V., Dr. Floor Heubel-Moenen will present the abstract "Intrinsic Activated Thrombin Generation for Efficacy and Monitoring of Factor VIII Replacements and Mimetics" at the EAHAD 2025 Congres in Milan, Italy, om February 5th 2025 (18:30-19:30). The abstract, selected by the conference organisers for a poster presentation, is available below.
Dr. Floor Heubel-Moenen, Haematologist at Maastricht University Medical Center+, will present the new reagent (PPP Reagent INT) for intrinsic activation of thrombin generation by means of the Calibrated Automated Thrombogram (CAT) method. The PPP Reagent INT demonstrated increased sensitivity compared to the tissue factor triggers in factor VIII deficient plasma treated with Emicizumab.
For further information, please contact:
Coagulation Profile B.V.
Henri Spronk, CEO
Abstract
Introduction: Conventional laboratory tests are unreliable for monitoring the effect of emicizumab, an alternative for the treatment of severe hemophilia A (SHA) patients, on coagulation in acute settings or bleeding. Global Thrombin Generation Assay (TGA) has the potential to be a useful tool for monitoring efficacy of various FVIII and non-FVIII replacement products, and the present study aims to investigate the applicability of intrinsic activated thrombin generation (TG) in comparison to the accepted extrinsic activated assay.
Methods: Normal pool plasma or factor VIII deficient plasma spiked with clinically relevant concentrations of octocog alfa or emicizumab and citrated plasma of 25 patients (steady state) on emicuzimab were tested. Emicizumab levels were determined using Siemens reagents on CS2500. TG was assessed by means of the CAT assay, optimized, and validated for the new PPP Reagent INT (contact activator, 4 μM phospholipids) for increased sensitivity towards octocog alfa and/or emicizumab. In parallel, TG was also measured using extrinsic activated PPP Reagent LOW, PPP Reagent, and PPP Reagent HIGH (data only shown for PPP Reagent LOW).
Results: TG in normal plasma triggered by PPP Reagent INT (36 replicates) was characterized by a lag time of 5.39±0.22 min, an ETP of 1451±38 nM×min, a peak height of 420±9 nM and a velocity index of 254±25 nM/min. The overall variability of the assay was <10% coefficient of variation for all parameters, with a within-run and between-day variation <5%. PPP Reagent INT failed to induce TG in plasmas deficient for FXII, FXI, FIX, or FVIII, whereas normal profiles were obtained for FVII deficient plasma. Addition of octocog alfa or emicizumab dose dependently increased TG when triggered with PPP Reagent INT. Both PPP Reagent LOW (low) and PPP Reagent (mid tissue factor) displayed poor sensitivity for the two replacement products. No dose dependent correlation was found between plasma emicizumab levels and extrinsic triggered TG in plasma from SHA subjects (n=58) treated with emicizumab. In contrast, maximum thrombin (peak height) from the intrinsic activated TGA correlated with plasma emicizumab levels.
Discussion/conclusion: Intrinsic activated thrombin generation may be used for efficacy and monitoring of different Hemophilia A replacement therapies. Future applicability for this PPP Reagent INT assay in monitoring SHA patients must be studied in more detail.
Comentarios