The Paradox of 'Non-Severe' Haemophilia: Qualitative Analysis of Treatment Disparities and Quality of Life Impacts from the Learning to Live Study

Background: Non-factor replacement therapies and gene therapy for severe haemophilia convert the bleeding phenotype to mild or moderate. People with haemophilia (PwH) who transition to a milder phenotype as a result of their treatment may require a greater degree of ongoing care and support than those with genetically mild or moderate haemophilia, due to previous bleeding episodes. Assessing the subjective experiences of PwH with genetically mild or moderate haemophilia compared to those converted to a milder phenotype enables a comparison of expectations across the spectrum of the disease. Understanding the lived experience of genetically mild and moderate haemophilia can therefore inform the anticipated care needs of the growing group whose treatment converts a severe phenotype to a non-severe one. Methods: Qualitative interviews were undertaken as part of a mixed-methods study examining the lived experience of non-severe haemophilia. Forty-four men with haemophilia (15 mild, 10 moderate, 11 severe, 8 post-gene therapy) aged 16-76 years were interviewed between January and August 2023. Interviews were recorded, transcribed, and thematically analysed using NVivo software, with cross-validation by two researchers. Analysis followed a grounded theory-informed approach. Results: Five main themes emerged within the overarching theme of Ability vs. Disability: 1) Acceptance vs. Rejection, 2) Benefits vs. Burdens, 3) Control vs. Uncertainty, 4) Freedom vs. Constraint, 5) The Future vs. the Past. Participants with genetically non-severe haemophilia reported significant treatment disparities compared to those with severe haemophilia, including delayed diagnosis, inability to self-treat, and limited access to prophylaxis. Despite higher factor levels, individuals with non-severe haemophilia and those who had transitioned to a non-severe phenotype experienced similar issues with regard to bleeding episodes. Paradoxically, while participants reported their condition did not significantly impact daily life, they described constant background concerns about injuries and activity limitations. Conclusions: PwH of all severities experience similar quality of life impacts, particularly during bleeding episodes. Treatment disparities must be addressed to improve outcomes for those with non-severe haemophilia, including individuals on phenotype-altering treatments. Recommendations include facilitating self-infusion and home treatment for all severity levels, ensuring rapid access to bleed assessment and follow-up regardless of primary diagnosis, and addressing the mixed messaging from healthcare teams regarding activity restrictions and treatment protocols.