Here are the open-access results of a study testing the efficacy of a novel intrinsic trigger reagent (platelet-poor plasma [PPP] Reagent INT) for monitoring emicizumab and octocog alfa: Urlings EH, Heubel-Moenen FCJI, van Oerle R, et al. Intrinsic activated thrombin generation for treatment efficacy and monitoring of octocog alfa and emicizumab in severe hemophilia A. Res Pract Thromb Haemost. 2026 Apr 30;10(4):106627. doi: 10.1016/j.rpth.2026.106627. PMID: 42254461; PMCID: PMC13241885.
Essentials
- Monitoring patients with SHA on treatments such as emicizumab is challenging.
- The intrinsic pathway TGA reagent PPP Reagent INT was developed.
- PPP Reagent INT was sixfold more sensitive to emicizumab than tissue-factor-based reagents.
- PPP Reagent INT is a promising tool for personalized monitoring of SHA patients on therapy.
Abstract
Background
Monitoring patients with severe hemophilia A (SHA) receiving nonfactor replacement therapies such as emicizumab presents significant challenges, because conventional activated partial thromboplastin time-based assays are subject to interference from these treatments. Therefore, we hypothesized that an intrinsic activated thrombin generation assay (TGA) could be an improved alternative.
Objectives
To investigate the sensitivity and applicability of intrinsic activated TGA compared with extrinsic activated assays for monitoring SHA patients on factor (F)VIII (
FVIII) and non-
FVIII replacement products.
Methods
We developed a novel intrinsic trigger reagent (platelet-poor plasma [
PPP] Reagent INT) and compared it with tissue factor (
TF) reagents, as well as an
FXIa-based reagent, using the Calibrated Automated Thrombography method. Thrombin generation was measured in deficient plasmas, healthy volunteers (
n = 103),
FVIII-deficient plasma spiked with octocog alfa or emicizumab, and plasma from SHA patients on emicizumab (
n = 22).
Results
PPP Reagent INT specifically activated the intrinsic pathway, showing minimal thrombin generation in
FXII– and
FXI-deficient plasma, and no thrombin generation in
FIX– and
FVIII-deficient plasma, whereas activation occurred independently of prekallikrein. Linear regression analysis showed superior sensitivity for
PPP Reagent INT triggered thrombin generation in
FVIII-deficient plasma spiked with octocog alfa or emicizumab. In plasma from SHA patients,
PPP Reagent INT demonstrated sixfold and fourfold greater sensitivity to emicizumab level changes compared with
TF-based reagents.
Conclusion
Intrinsic activated TGA using
PPP Reagent INT provides enhanced sensitivity for monitoring SHA patients on both
FVIII and non-
FVIII replacement products compared with
TF-based triggers, representing a promising tool for personalized monitoring.
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