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  • Writer's pictureHenri Spronk

Intrinsic Thrombin Generation at EHA 2024

Updated: May 29

Coagulation Profile to Present Abstract on Intrinsic Thrombin Generation at EHA 2024 Congress

Coagulation Profile B.V., will present one abstract at the EHA2024 Hybrid Congres in Montreal, June 13-16, 2024. The abstract, selected by the conference organisers for a poster presentation, is available below.

Henri Spronk, CEO at Coagulation Profile B.V., will present a new reagent (PPP Reagent INT) for intrinsic activation ofhrombin 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


Title: Intrinsic Activated Thrombin Generation For Efficacy And Monitoring Of Factor Viii Replacements And Mimetics

Authors: Henri Spronk, René van Oerle, Floor Heubel-Moenen, Peter Giesen, Dave Hellenbrand, Amaury Monard, Paola van der Meijden, Tilman Hackeng, Hugo ten Cate, Yvonne Henskens

Session: P1712

Date: June 14, 2024

Time: 18.00-19:00 

Background: Traditionally, severe hemophilia A (SHA) patients are treated with intravenous prophylactic FVIII replacement concentrates to prevent spontaneous bleeding. Various extended half-life FVIII products and non-factor (mimetics) agents (such as emicizumab and fitusiran) were introduced as alternatives. Subcutaneous administration of emicizumab may clinically resemble a mild hemophilia, resulting in improvement of quality of life. Conventional laboratory tests are unreliable for monitoring the emicizumab effect 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.

Aims: To investigate the applicability of intrinsic activated thrombin generation (TG) in comparison to the general accepted extrinsic activated assay.

Methods: Normal pool plasma or factor VIII deficient plasma spiked with clinical 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 of5.39±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. However, maximum thrombin (peak height) from the intrinsic activated TGA correlated with plasma emicizumab levels.

Conclusion(s): 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 has to be studied in more detail.

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