Implementation of near‐universal hydroxyurea uptake among children with sickle cell anemia: A single‐center experience

Abstract

Background Without early initiation of disease‐modifying therapy, the acute and chronic complications of sickle cell anemia (SCA) begin early in childhood and progress throughout life. Hydroxyurea is a safe and effective medication that reduces or prevents most SCA‐related complications. Despite recommendations to prescribe hydroxyurea for all children with SCA as young as 9 months, utilization remains low. Procedure We completed a retrospective review of hydroxyurea‐prescribing practices and associated clinical outcomes at our institution over a 10‐year period before and after the 2014 National Heart, Lung, and Blood Institute (NHLBI) recommendations to use hydroxyurea for all children with SCA. Results Hydroxyurea use more than doubled within our pediatric SCA population from 43% in 2010 to 95% in 2019. The age of hydroxyurea initiation was significantly younger during 2014–2019 compared to 2010–2013 (median 2 years vs. 6 years, p ≤ .001). With this change in clinical practice, nearly all (69/71 = 97%) children born after 2013 received disease‐modifying therapy by the end of 2019, primarily hydroxyurea (93%). Concurrently, the number of SCA‐related admissions significantly decreased from 67/100 patient‐years in 2010 to 39/100 patient‐years in 2019 (p < .001). Conclusion The early and universal prescription of hydroxyurea for children with SCA is the standard of care. Here, we demonstrate that a careful and deliberate commitment to follow this guideline in clinical practice is feasible and results in measurable improvements in clinical outcomes. Our approach and improved outcomes can serve as a model for other programs to expand their hydroxyurea use for more children with SCA.

How I approach disease‐modifying therapy in children with sickle cell disease in an era of novel therapies

“…In addition, routine weight‐based dose adjustments are critical to maintain a stable milligram per kilogram dose; the availability of compounding pharmacies for a liquid hydroxyurea formulation allows for flexibility in dose titration (Figure 1). In contrast to concerns regarding dose‐limiting neutropenia, 6,7,26 and although limited to our single‐center experience, we have found no increase in bacteremia even after lowering our dose‐limiting absolute neutrophil cutoff to 750/μl from the NHLBI guidelines’ recommendation of 1250/μl 11,20 …”

“…However, further studies investigating the long‐term effects of hydroxyurea upon reproductive and other organs are needed, particularly in children who began hydroxyurea at an early age 19 . Importantly, as we have demonstrated, the conversation about hydroxyurea must begin early with its introduction as a medication prescribed to prevent acute and chronic complications of SCA and to allow for a high quality of life 20 . These conversations must also directly address the misinformation that parents often find from internet searches, social media, or older members of the sickle cell community.…”

“…19 Importantly, as we have demonstrated, the conversation about hydroxyurea must begin early with its introduction as a medication prescribed to prevent acute and chronic complications of SCA and to allow for a high quality of life. 20 These conversations must also directly address the misinformation that parents often find from internet searches, social media, or older members of the sickle cell community. This contrasts with the previous approach, which cautiously introduced hydroxyurea as a medication with an unknown side effect profile used only in the setting of frequent or severe complications.…”

Ten‐year longitudinal analysis of hydroxyurea implementation in a pediatric sickle cell program

“…During preparation of this manuscript, Karkoska et al 30 published a 10‐year retrospective analysis of HU prescription practice at Cincinnati Children's Hospital reporting similar excellent results. Data presented here were prospectively gathered with slightly longer follow‐up after HU implementation, and our report offers the novel aspect of dosing HU to target a high Hgb F level.…”

“…Another potential limitation is that fewer patients were tracked in the baseline interval, which could have biased rate calculations, but the absolute numbers of hospitalizations and transfusions decreased after initiation of HU implementation even as patient numbers increased. Adherence monitoring was not direct, as no plasma HU levels were measured, but Hgb F served as a reliable indicator.During preparation of this manuscript, Karkoska et al30 published a 10-year retrospective analysis of HU prescription practice at Cincinnati Children's Hospital reporting similar excellent results. Data presented here were prospectively gathered with slightly longer followup after HU implementation, and our report offers the novel aspect of dosing HU to target a high Hgb F level.…”