Haemophilia Carriers Experience Study (CARES): A mixed method exploration into the experience of women who are carriers of Haemophilia.

INTRODUCTION: Haemophilia research has traditionally focused on patients diagnosed with haemophilia and although research priorities are rapidly changing, there is still a lot more we need to understand about the experiences and psychosocial issues facing women who are diagnosed as carriers of haemophilia (Haemophilia, https://doi.org/10.1111/hae.14043). One study noted that the understanding of carriers' experience of bleeding by healthcare professionals is limited and that many women have had negative experiences of healthcare (Haemophilia, 17, 2011, 237). The carrier population does not typically receive much support for themselves as individuals as they are often not registered at Haemophilia Centres in their own right. AIM: This study aimed to look at the emotional wellbeing of carriers in more detail. METHOD: This was initially investigated through the use of focus groups and individual interviews with 16 participants (Stage 1) and then widening the study using an online questionnaire battery developed from the themes identified from these interviews (Stage 2). The questionnaire battery was completed by 226 participants. RESULTS: Descriptive statistics are reported on the endorsement of themes identified in Stage 1 and around participants' experiences of their carriership and healthcare. Results demonstrated that the participants have had a number of difficulties with accessing helpful information and support during key times in their lives, for example, at diagnosis and when deciding whether to start a family. They also showed that although participants endorsing a higher number of bleeding symptoms scored statistically significantly higher in measures of depression, anxiety and negative affect, this difference was not clinically significant. CONCLUSION: These results lend support to the growing evidence base that women who are carriers of haemophilia have a distinct set of (currently unmet) needs that need assessing and treating.

Adenovirus-associated antibodies in UK cohort of hemophilia patients: A seroprevalence study of the presence of adenovirus-associated virus vector-serotypes AAV5 and AAV8 neutralizing activity and antibodies in patients with hemophilia A.

BACKGROUND: Current treatment for severe hemophilia A is replacement of deficient factor. Although replacement therapy has improved life expectancy and quality, limitations include frequent infusions and high costs. Gene therapy is a potential alternative that utilizes an adeno-associated virus (AAV) vector containing the human genetic code for factor 8 (FVIII) that transduces the liver, enabling endogenous production of FVIII. Individuals with preexisting immunity to AAV serotypes may be less likely to benefit from this treatment. OBJECTIVES: This study measured seroprevalence of antibodies to AAV5 and 8 in an UK adult hemophilia A cohort. PATIENTS/METHODS: Patients were recruited from seven hemophilia centres in the UK. Citrated plasma samples from 100 patients were tested for preexisting activities against AAV5 and 8 using AAV transduction inhibition and total antibodies assays. RESULTS: Twent-one percent of patients had antibodies against AAV5 and 23% had antibodies against AAV8. Twenty-five percent and 38% of patients exhibited inhibitors of AAV5 or AAV8 cellular transduction respectively. Overall seroprevalence using either assay against AAV5 was 30% and against AAV8 was 40% in this cohort of hemophilia A patients. Seropositivity for both AAV5 and AAV8 was seen in 24% of participants. CONCLUSIONS: Screening for preexisting immunity may be important in identifying patients most likely to benefit from gene therapy. Clinical studies may be needed to evaluate the impact of preexisting immunity on the safety and efficacy of AAV mediated gene therapy.