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

Abstract

Richard Gooding,1 Jecko Thachil,2 Jayanthi Alamelu,3 Jayashree Motwani,4 Pratima Chowdary5 1Leicester Haemophilia Centre, Haemostasis & Thrombosis Unit, Leicester Royal Infirmary, Leicester, UK; 2Haematology Department, Manchester Royal Infirmary, Manchester, UK; 3Haemophilia Department, Evelina Children’s Hospital – St Thomas’ Hospital, London, UK; 4Haemophilia Comprehensive Care Centre, Birmingham Children’s Hospital, Birmingham, UK; 5Katharine Dormandy Haemophilia Centre, Royal Free Hospital, London, UKCorrespondence: Richard GoodingLeicester Haemophilia Centre, Haemostasis & Thrombosis Unit, Level 2, Osborne Building, The Leicester Royal Infirmary, Infirmary Square, Leicester, LE1 5WW, UKTel [phone]Fax [phone]Email [email protected]: 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

Keywords

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