ArticleHaematologica2020
Relationship between factor VIII activity, bleeds and individual characteristics in severe hemophilia A patients.
Article in Haematologica, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- Efanesoctocog Alfa Population Pharmacokinetics and Repeated Time-To-Event Analysis of Bleeds in Adults, Adolescents, and Children with Severe Hemophilia A.Journal of clinical pharmacology · 2025Trial
- Population repeated time-to-event analysis of exacerbations in asthma patients: A novel approach for predicting asthma exacerbations based on biomarkers, spirometry, and diaries/questionnaires.CPT: pharmacometrics & systems pharmacology · 2021Trial
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- Use of PopPK and E-R Analyses toward Explaining Causal Link Between ADAMTS13 in Recombinant vs. Plasma-Based Therapies and Clinical Effects in cTTP.Clinical pharmacology and therapeutics · 2025Article
- Relationship between Dose, Factor IX Activity Levels and Bleeding Probability for rIX-FP Prophylaxis in Hemophilia B: A Repeated Time-to-Event Analysis.Clinical pharmacology and therapeutics · 2025Article
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- Anesthetic considerations for joint replacement surgery in hemophilic arthropathy: a comprehensive review.Anesthesia and pain medicine · 2024Review
- Predictive performance of pharmacokinetic-guided prophylactic dosing of factor concentrates in hemophilia A and B.Research and practice in thrombosis and haemostasis · 2024Article
- Pharmacokinetics of recombinant factor VIII in adults with severe hemophilia A: fixed-sequence single-dose study of octocog alfa, rurioctocog alfa pegol, and efanesoctocog alfa.Research and practice in thrombosis and haemostasis · 2023Article
- Relationship between factor VIII levels and bleeding for rFVIII-SingleChain in severe hemophilia A: A repeated time-to-event analysis.CPT: pharmacometrics & systems pharmacology · 2023Article
- Association between Sports Participation, Factor VIII Levels and Bleeding in Hemophilia A.Thrombosis and haemostasis · 2023Observational
- Pharmacokinetic parameter driven outcomes model predicts a reduction in bleeding events associated with BAY 81-8973 versus antihemophilic factor (recombinant) plasma/albumin-free method in a Chinese healthcare setting.BMC medical research methodology · 2022Article
- SYMPHONY consortium: Orchestrating personalized treatment for patients with bleeding disorders.Journal of thrombosis and haemostasis : JTH · 2022Article
- Mobile Health Technology for the Personalized Therapy of Hemophilia.Frontiers in medicine · 2021Review
- Population Pharmacokinetics of Clotting Factor Concentrates and Desmopressin in Hemophilia.Clinical pharmacokinetics · 2021Review
- Bayesian Forecasting Utilizing Bleeding Information to Support Dose Individualization of Factor VIII.CPT: pharmacometrics & systems pharmacology · 2019Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pharmacokinetic-based prophylaxis of replacement factor VIII (FVIII) products has been encouraged in recent years, but the relationship between exposure (factor VIII activity) and response (bleeding frequency) remains unclear. The aim of this study was to characterize the relationship between FVIII dose, plasma FVIII activity, and bleeding patterns and individual characteristics in severe hemophilia A patients. Pooled pharmacokinetic and bleeding data during prophylactic treatment with BAY 81-8973 (octocog alfa) were obtained from the three LEOPOLD trials. The population pharmacokinetics of FVIII activity and longitudinal bleeding frequency, as well as bleeding severity, were described using non-linear mixed effects modeling in NONMEM. In total, 183 patients [median age 22 years (range, 1-61); weight 60 kg (11-124)] contributed with 1,535 plasma FVIII activity observations, 633 bleeds and 11 patient/study characteristics [median observation period 12 months (3.1-13.1)]. A parametric repeated time-to-categorical bleed model, guided by plasma FVIII activity from a 2-compartment population pharmacokinetic model, described the time to the occurrence of bleeds and their severity. Bleeding probability decreased with time of study, and a bleed was not found to affect the time of the next bleed. Several covariate effects were identified, including the bleeding history in the 12-month pre-study period increasing the bleeding hazard. However, unexplained inter-patient variability in the phenotypic bleeding pattern remained large (111%CV). Further studies to translate the model into a tool for dose individualization that considers the individual bleeding risk are required. Research was based on a
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