Evidence map›Paper›PMID 42254461›Full record

ArticleResearch and practice in thrombosis and haemostasis2026

Intrinsic activated thrombin generation for treatment efficacy and monitoring of octocog alfa and emicizumab in severe hemophilia A.

Emma H Urlings, Floor C J I Heubel-Moenen, René van Oerle, Dave L S Hellenbrand, Paola E J van der Meijden, Tilman M Hackeng, Hugo Ten Cate, Magdolna Nagy, Yvonne M C Henskens, Henri M H Spronk

Abstract readComparative Study
In one paragraph

Article in Research and practice in thrombosis and haemostasis, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Emma H UrlingsInternal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
Floor C J I Heubel-MoenenInternal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.
René van OerleBiochemistry, Maastricht University, Maastricht, The Netherlands.
Dave L S HellenbrandCentral Diagnostic Laboratory, Maastricht University Medical Center+, Maastricht, The Netherlands.
Paola E J van der MeijdenCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Tilman M HackengCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Hugo Ten CateCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Magdolna NagyCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Yvonne M C HenskensCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.
Henri M H SpronkCardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 ( 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.

Indexed as

Antibodies, BispecificAntibodies, Monoclonal, HumanizedDrug MonitoringFactor VIIIFactor VIIIaHemophilia AThrombinBlood CoagulationBlood Coagulation TestsHumansMalePartial Thromboplastin TimeThromboplastinTreatment OutcomeAntibodies, BispecificAntibodies, Monoclonal, HumanizedemicizumabFactor VIIIFactor VIIIaThrombinThromboplastinemicizumabhemophilia Aintrinsic coagulation pathwaymonitoringthrombin generation assay

Identifiers

PMID42254461
PMCPMC13241885

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.