ArticleHaemophilia : the official journal of the World Federation of Hemophilia2020
A new paradigm for personalized prophylaxis for patients with severe haemophilia A.
Article in Haemophilia : the official journal of the World Federation of Hemophilia, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 26 citations in OpenAlex.
- Personalized prophylactic therapy optimization in hemophilia A using a hybrid PK-PD-TTE model and deep RL.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Measuring FVIII Activity and Thrombin Generation Simultaneously With a Novel Point of Care Platform (EnzySystem HemA): Qualitative Usability Evaluation.JMIR formative research · 2025Article
- Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B.Research and practice in thrombosis and haemostasis · 2024Article
- Pharmacokinetic-Pharmacodynamic Modelling in Hemophilia A: Relating Thrombin and Plasmin Generation to Factor VIII Activity After Administration of a VWF/FVIII Concentrate.European journal of drug metabolism and pharmacokinetics · 2024Article
- Blood-Induced Arthropathy: A Major Disabling Complication of Haemophilia.Journal of clinical medicine · 2023Review
- In patients with hemophilia, a decreased thrombin generation profile is associated with a severe bleeding phenotype.Research and practice in thrombosis and haemostasis · 2023Article
- Area under the curve: Comparing the value of factor VIII replacement therapies in haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2023Article
- Combining factor VIII levels and thrombin/plasmin generation: A population pharmacokinetic-pharmacodynamic model for patients with haemophilia A.British journal of clinical pharmacology · 2022Article
- Thrombin generation for monitoring hemostatic therapy in hemophilia A: A narrative review.Journal of thrombosis and haemostasis : JTH · 2022Review
- Thrombin generation assays to personalize treatment in bleeding and thrombotic diseases.Frontiers in cardiovascular medicine · 2022Review
- Use of population PK/PD approach to model the thrombin generation assay: assessment in haemophilia A plasma samples spiked by a TFPI antibody.Journal of pharmacokinetics and pharmacodynamics · 2021Article
- Pharmacodynamic monitoring of factor VIII replacement therapy in hemophilia A: Combining thrombin and plasmin generation.Journal of thrombosis and haemostasis : JTH · 2020Article
- A new paradigm for personalized prophylaxis for patients with severe haemophilia A.Haemophilia : the official journal of the World Federation of Hemophilia · 2020Article
- Assessing the Performance of Extended Half-Life Coagulation Factor VIII, FC Fusion Protein by Using Chromogenic and One-Stage Assays in Saudi Hemophilia A Patients.Advances in hematology · 2020Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimFor patients with severe haemophilia A, guidelines recommend prophylactic treatment with FVIII, with dose calculations targeting a predetermined FVIII trough level. However, this pharmacokinetic (PK) approach is suboptimal, with some patients experiencing breakthrough bleeds. We aimed to improve FVIII dosing by incorporating the thrombin generation assay, a global haemostasis assay whose main pharmacodynamic (PD) parameter, endogenous thrombin potential (ETP), predicts spontaneous bleeding risk.
methodsWe performed post hoc combined PK-PD modelling using data from 66 adults who received human-cl rhFVIII (Nuwiq
resultsNinety-one spontaneous bleeds occurred in 20/66 patients. The relationship between FVIII:C and ETP was non-linear, and the sigmoid Emax model adequately described the data. Individual PK-PD Bayesian estimation significantly improved predictive performance. Simulations showed that the mean spontaneous annual bleeding rate decreased with increasing baseline ETP or dosing: with ETP values of 200, 400 and 600 (nmol/L)·min annual bleeding rates were 2.36, 1.25 and 0.66, respectively, on 40 IU/kg human-cl rhFVIII every 3 days; and annual bleeding rates were 2.09, 1.10, and 0.60, respectively, on 60 IU/kg every 3 days.
conclusionProphylactic FVIII dosing is more clinically meaningful when incorporating ETP alongside FVIII level. For the first time, FVIII dosing can be personalized with the aim of eliminating spontaneous breakthrough bleeds.
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