VWF-ADAMTS13 axis dysfunction in children with sickle cell disease treated with hydroxycarbamide vs blood transfusion.

Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention in SCD, the biological mechanisms underpinning its improved efficacy compared with hydroxycarbamide are not fully understood. We hypothesized that the improved efficacy of blood transfusion might relate to differences in VWF-ADAMTS13 axis dysfunction. In total, 180 children with a confirmed diagnosis of SCD (hemoglobin SS) on hydroxycarbamide (n = 96) or blood transfusion (n = 84) were included. Despite disease-modifying treatment, plasma VWF and VWF propeptide were elevated in a significant proportion of children with SCD (33% and 47%, respectively). Crucially, all VWF parameters were significantly higher in the hydroxycarbamide compared with the blood transfusion cohort (P < .05). Additionally, increased levels of other Weibel-Palade body-stored proteins, including factor VIII (FVIII), angiopoietin-2, and osteoprotegerin were observed, indicated ongoing endothelial cell activation. Children treated with hydroxycarbamide also had higher FVIII activity and enhanced thrombin generation compared with those in the blood transfusion cohort (P < .001). Finally, hemolysis markers strongly correlated with VWF levels (P < .001) and were significantly reduced in the blood transfusion cohort (P < .001). Cumulatively, to our knowledge, our findings demonstrate for the first time that despite treatment, ongoing dysfunction of the VWF-ADAMTS13 axis is present in a significant subgroup of pediatric patients with SCD, especially those treated with hydroxycarbamide.

Adherence to hydroxyurea, health-related quality of life domains and attitudes towards a smartphone app among Irish adolescents and young adults with sickle cell disease.

INTRODUCTION: SCD patients experience declines in health-related quality of life (HRQOL) domains compared with healthy controls. Despite evidence supporting the benefits of hydroxyurea, medication non-adherence remains problematic, especially in adolescents and young adults (AYA). Adherence barriers include forgetfulness and lack of knowledge. Recently, increased interest in technology-based strategies to improve medication adherence has emerged. No data currently exists on hydroxyurea adherence, HRQOL or perceptions of technology-based tools in the Irish SCD population. METHODS: In order to interrogate these domains among Irish AYA SCD patients we administered an anonymous survey at two tertiary referral centres in Dublin, Ireland, in July 2019. RESULTS: Sixty-three patients participated; 63% female and 37% male, with a median and mean age of 17 and 19 years, respectively. Average monthly adherence was 76% using a visual analogue scale. Recall barriers were present in 62% while 26% omit hydroxyurea for reasons other than forgetting. Reviewing HRQOL; only 36.5% felt always physically able to engage in recreational activities, while 51% experienced disruption to school/college/work due to pain. Eighty-one percent reported that anxiety about health interferes with their lives and non-adherence correlated with worse HRQOL outcomes. Interest in a smartphone app was expressed by the majority, with daily medication reminders being the most popular feature. Sharing adherence data with doctors and discussion forums were less appealing. CONCLUSIONS: Representing over 10% of the Irish SCD population, our survey provides novel and valuable insights into medication adherence and HRQOL domains. Preferred app features may inform future technology-based interventions to improve medication adherence in SCD and other chronic health conditions.