Asymptomatic Joint Bleeding and Joint Health in Hemophilia: A Review of Variables, Methods, and Biomarkers

Abstract

Joint health is a key contributor to quality of life in patients with hemophilia. However, variables that impact long-term joint outcomes have not been comprehensively defined. A systematic literature search identified publications relating to joint health in patients with hemophilia. Studies clearly show that early, sustained prophylaxis with factor replacements improves long-term joint outcomes. However, a subset of patients appear to develop arthropathy despite maintaining excellent bleeding outcomes, which suggests possible recurrent asymptomatic bleeding into the joints in these patients. Furthermore, limited data are available on how long-acting factor VIII and factor IX replacement therapies could impact long-term joint outcomes. Many variables were identified as potential indicators that a patient may develop hemophilic arthropathy, including genetic mutations, endogenous factor VIII and IX levels, bone health, and physical activity levels. Tools for the diagnosis and monitoring of hemophilic arthropathy are critical to detect early joint damage, so that management can be adjusted accordingly. Imaging techniques, particularly magnetic resonance imaging, can detect synovial changes, a strong predictor for the future development of hemophilic arthropathy. In addition, several biomarkers associated with cartilage and bone formation, vascularization, and angiogenesis could potentially identify the onset and progression of early joint damage. Since the development of hemophilic arthropathy is complex, a comprehensive therapeutic approach is necessary for the effective prevention of arthropathy in patients with hemophilia.

Keywords:

• hemophilia
• asymptomatic bleeding
• joint disease
• hemarthrosis
• hemophilic arthropathy
• hemarthropathy

Abbreviations

BMD, bone mineral density; FVIII, factor VIII; FIX, factor IX; HJHS, Hemophilia Joint Health Score; MRI, magnetic resonance imaging; ROM, range of motion; SNP, single nucleotide polymorphism.

Acknowledgments

Medical writing assistance was provided by Anna Mestres-Missé of Meridian HealthComms Ltd (Plumley, UK) in accordance with Good Publication Practice (GPP3) guidelines, funded by CSL Behring.

Disclosure

Dr Richard Gooding reports personal fees from CSL Behring, during the conduct of the study. Dr Jecko Thachil reports personal fees from CSL Behring, Takeda, Shire, Roche Chugai, and Sobi, during the conduct of the study. Professor Pratima Chowdary reports non-financial support from CSL Behring, during the conduct of the study; grants from and advisory committee for Pfizer, Bayer, CSL Behring, Freeline, Novo Nordisk, Sobi, Chugai, Roche, Takeda, Sanofi, and Spark; personal fees from BioMarin and UniQure, outside the submitted work. The authors report no other conflicts of interest in this work.

Additional information

Funding

The authors received no specific funding for this work.