Biomarkers in Hemophilia: Diagnostic, Prognostic, and Treatment-Selection Utility: A Narrative Review of the Literature

Abstract

Background: Hemophilia A and B are inherited bleeding disorders in which outcomes are shaped by factor levels, inhibitor development, inter-individual pharmacokinetics, and progressive joint disease. With the emergence of extended half-life therapies, non-factor therapies, and gene therapy, there is an increasing need for biomarkers to support diagnosis, risk stratification, treatment selection, and monitoring. Methods: We conducted a narrative review of English-language studies indexed in PubMed, Scopus, Web of Science, and Google Scholar (January 2000 to October 2025). We prioritized primary studies, trials, registries, and assay-validation reports on diagnostic, prognostic, predictive, or monitoring biomarkers in hemophilia A/B; guidelines were used for context. Results: Established biomarkers include FVIII/FIX activity assays, inhibitor testing (Bethesda/Nijmegen-modified), F8/F9 genotyping, and imaging-based joint assessment. Emerging candidates include global hemostasis assays (thrombin generation, viscoelastic testing), PK/PD metrics for prophylaxis individualization, and exploratory inflammatory/angiogenic and tissue-turnover markers linked to arthropathy. Conclusions: Evidence for biomarkers in hemophilia is heterogeneous, and many non-traditional markers remain exploratory; standardized assays and prospective multicenter validation with clinically meaningful endpoints are needed before routine adoption. Limitation: This narrative synthesis was conducted in English and did not include a formal risk-of-bias assessment.