| dc.description.abstract | Haemophilia is an inherited bleeding disorder caused by a deficiency in procoagulant Factor VIII (Haemophilia A) or Factor IX (Haemophilia B). Disease severity is stratified according to basal clotting factor levels, as severe (<1%), moderate (1-5%) or mild (>5-<40%) haemophilia. People with haemophilia (PwH), predominantly those with moderate and severe haemophilia (PwMSH), may experience traumatic or spontaneous bleeding into joints and muscles, resulting in significant pain and functional disability. Repetitive joint bleeding in the long-term causes synovitis and osteochondral destruction, resulting in a chronic, degenerative joint disease known as ?haemophilic arthropathy?. PwH who have a severe bleeding tendency are typically treated using regular intravenous administration of replacement clotting factor concentrates in a treatment regimen known as ?prophylaxis?. Prophylactic treatment in PwMSH aims to prevent bleeding and the development or further deterioration of arthropathy. Haemophilic arthropathy causes significant pain and physical disability, which significantly impacts on the quality of life of affected PwH. This particularly affects older adults who had less access to effective treatment as children, in comparison to children and younger adults with haemophilia in the present day who may have better access to improved treatments earlier in life.
PwMSH used to be discouraged from participating in physical activity (PA) due to the increased risk of bleeding and potential joint injury. The improvements in haemophilia treatment over recent decades, however, have enabled PwMSH to become more physically active. PA, with certain considerations for the safety of activity, is now strongly encouraged amongst the haemophilia population due to the numerous health benefits associated with it. PA is beneficial for cardiorespiratory fitness, muscle strength and bone health. It is also associated with a reduced risk of all-cause mortality, obesity and many chronic diseases, such as cardiovascular disease and certain types of cancer. PwMSH may, however, face significant challenges in achieving regular PA due to significant pain and physical disability caused by bleeds and haemophilic arthropathy. They may, therefore, be at an increased risk of various unfavourable health outcomes in the long-term.
The overarching aim of this PhD was to undertake a detailed examination of PA, physical health and clinical phenotype in adult PwMSH in Ireland. To begin, a systematic review is presented in Chapter 1. This review identified variable levels of PA amongst heterogeneous samples of PwH. The majority of studies assessed PA using self-report methods, which are inherently affected by response and recall bias. Furthermore, the relationship between bleeds and PA was difficult to elucidate due to significant heterogeneity amongst study methodologies, as well as incomplete reporting of bleeding phenotype and treatment regimen.
The primary aim of Study I (Chapter 3), was to determine PA in adult PwMSH using combined objective and self-report methods. PA was measured using an accelerometer and a questionnaire. Additional aims were to examine the relationship between PA and age, as well as PA and clinical phenotypic parameters, such as bleeding rate, joint health and treatment regimen. Lower levels of moderate to vigorous PA (MVPA) were demonstrated in PwMSH compared to controls of a similar age. Participation in various types of PA and sport were reported by both groups. Participation in childhood PA and sport was significantly lower in adult PwMSH compared to controls. No significant relationships were demonstrated between MVPA with bleeding rate, joint health or the age at which prophylactic treatment was commenced.
Considering regular PA is associated with better physical fitness and cardiometabolic health, Study II (Chapter 4) aimed to determine levels of physical fitness and cardiometabolic health risk in PwMSH. Functional aerobic capacity, grip strength and balance were significantly lower in PwMSH compared to controls. Higher rates of abdominal obesity were also identified in PwMSH. There were no significant differences in blood pressure or aortic arterial stiffness between PwMSH and controls, although combined aortic and peripheral arterial stiffness was significantly higher in PwMSH. Lastly, the prevalence of hypertension, insulin resistance and hyperlipidaemia was relatively higher in PwMSH compared to controls.
In light of the findings from Studies I and II regarding lower levels of PA and physical fitness, and increased cardiometabolic risk amongst PwMSH compared to controls, Study III (Chapter 5) was undertaken to explore barriers to PA in PwMSH. Lack of willpower, lack of energy and lack of time were the most common barriers to PA in PwMSH and controls. Lack of resources, fear of injury, lack of skill and social influences were less common barriers to PA in both study groups, although lack of willpower, lack of skill, social influences and fear of injury were more frequently reported by PwMSH. Furthermore, acute pain, chronic pain, frequent analgesia requirements and functional disability were highly prevalent in PwMSH. PA was not significantly associated with pain but age, bleeding rate and the age at which prophylactic treatment was commenced were all significantly increased in PwMSH who reported to have chronic pain. Adults who reported to have functional difficulties were significantly older and less physically active compared to those who denied having functional difficulties.
Lastly, after a period of postponed research activity due to the Covid-19 pandemic, Study IV (Chapter 6) aimed to conduct a follow-up assessment of PA in PwMSH. The impact of the Covid-19 pandemic on PA, function, mobility and pain was also examined. No significant differences in PA measured using accelerometry were found between the original and follow-up time-points. Since the original assessment, the majority of participants reported an increased awareness of PA and a desire to become more physically active. Knowledge of PA guidelines was low, but similar to national average rates. Compared to normal levels of PA engagement, trends in self-reported PA during the consecutive phases of lockdown and eased restrictions throughout the pandemic were variable. PA was reduced compared to normal during the third wave of lockdown, but PA increased in the majority of participants during the third wave of eased restrictions. Pain, access to exercise resources, and maintaining or increasing PA were commonly reported concerns for PA beyond the pandemic.
To conclude, the findings of this thesis highlight that despite a uniform diagnosis, ageing PwMSH present with considerable variation in their physical health profile, potential for multi-morbidity, as well as barriers to PA. In light of this evidence, a ?one-size-fits-all? approach to health interventions to address chronic health risk factors may not suffice. Personalised, multi-disciplinary approaches to health interventions to address lower levels of PA and physical fitness, as well as cardiometabolic risk factors are therefore warranted in future studies in order to optimally improve chronic health risk and quality of life amongst the ageing haemophilia population. | en |
