Congratulations to Nancy Crego, assistant professor, who has received an award from the NHLBI funded Functional and Translational Genomic (FTG) of Blood Disorders-PRIDE Small Research Program administered by Augusta University for her proposal entitled “Exploring Predictors of Fetal Hemoglobin Responsiveness to Hydroxyurea in Adults with Sickle Cell Disease.” This award is for a 1- year period with a start date of November 15, 2019.
Fetal Hemoglobin (HBF) level is an important disease modifier in Sickle Cell Disease (SCD). Low levels of HBF have been associated with increased illness severity, while elevated HBF levels are correlated with reductions in early mortality and SCD complications. However, the exact mechanism by which Hydroxyurea (HU) induces HBF production is not fully understood and there is great variability in HBF concentrations among SCD patients. Long-term management of SCD includes treatment with HU, a daily oral medication that induces production of HBF. HBF responsiveness to HU varies greatly but is highly associated with adherence to the medication regime. Although effectiveness and safety of HU for treatment of SCD has been established, medication adherence is poor (30-50%) and is lowest in adults. Contributors to poor HU adherence include negative patient beliefs about medication efficacy and a perceived lack of benefit as a result of the lengthy period (3-6 months) before the patient experiences clinical benefit. Furthermore, lack of adherence to HU is the most cited reason health care providers’ use for not prescribing HU when it was otherwise indicated. Current strategies to increase HU adherence target improving patient medication knowledge, medication tracking and reminders through devices such as mobile phones but have had limited success. However, interventions that incorporate individualized feedback (e.g. progress toward achieving therapeutic drug levels) with graphic representations improved medication adherence and prevent worsening adherence of adults with other chronic illnesses. The objective of the proposed research is to explore the relationship of HBF responsiveness to HU in adults with SCD. An understanding of this relationship will provide preliminary data for development of individualized models of HBF responsiveness that can be incorporated into future HU adherence interventions that provides visual feedback for SCD patients. This novel patient-centered proactive approach to HU adherence could impact patient perceptions of the value and effectiveness of HU until optimal dosing is achieved and the patient experiences clinical benefits, when treatment is initiated. We will test the hypothesis that that childhood predictors of HBF responsiveness: hemoglobin (HGB), reticulocyte count (RC), white blood cell count (WBC) and mean corpuscular volume (MCV) are associated with HBF responsiveness to HU in adults with SCD. The long-term-goal of this research is to develop models of HBF responsiveness in adults with SCD HU adherence. Results of this study could shift the current paradigm in the field of HU adherence and strategies for self-management in SCD patients adding visual feedback and educational information about HU via a digital platform.