Reduction in the Frequency of Emergency Department Visits for Complications Related to Sickle Hemoglobinopathies: Effects of Aggressive Hydroxyurea Therapy
Authors: Raj Ashok , Panigrahi Arun Ranjan , Myers Scott N. , Mullinax Jennifer , Myers John A , Padmanabhan Pradeep 
Published: October 2019

Abstract
Context
Early and aggressive use of hydroxyurea (HU) in sickle hemoglobinopathies has been in practice at our comprehensive sickle cell center since 2012 when standardized protocols were still evolving. The consensus treatment protocol for hydroxyurea therapy in sickle cell disease (SCD) documented in the "Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014" has authenticated our clinical practice.
Objectives
Although emergency departments play an important role in providing acute and urgent care for patients with SCD, the frequency of visits by patients can possibly be reduced by increased use of sickle-directed therapies in the outpatient setting. The objective of this study was to determine the impact of aggressive HU therapy, including shared decision making with parents for early use of HU and dose escalation up to the maximum tolerated dose, on the frequency of emergency department (ED) visits for patients with sickle hemoglobinopathies.
Methods
ED visits by patients with sickle hemoglobinopathies (HbSS disease, Hb S beta zero thalassemia, HbSC disease, Hb S beta plus thalassemia) were identified using ICD-9-CM diagnosis codes of 282.6, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, 282.69, 282.41, and 282.42. From visits having one or more of these diagnoses, cases that had indicated that the visit was related to an injury, poisoning, or adverse effect of medical treatment were excluded to form the study group of emergency department visits by patients. However, if the ED visit was for HU complications/side effects, they were included. Data from 2010-2015 was collected from the ED of Kosair Children's Hospital and affiliated hospitals in Louisville, which are the community-wide and primary locations where pediatric patients with sickle hemoglobinopathies are evaluated for disease-related complications requiring emergency management including pain crises, fever episodes, acute chest syndrome, etc.
To determine if aggressive use of HU was associated with adecrease in the frequency of ED visits, segmented linear regression techniques were used to compare the mean monthly rates of ED visits before and after implementation of this treatment strategy.
Results: The rate of sickle hemoglobinopathies seen in the ED significantly decreased after implementation of the aggressive HU treatment protocol (β=2.48 vs. β=-3.91, p=0.003). After implementation of the aggressive HU protocol, there has been a 55% decrease in the monthly rate of sickle hemoglobinopathies seen in the ED (21.0 vs. 9.5, p<0.001) from the peak monthly rate seen in 2012, which is a 40% reduction since the start of the study period [15.8 vs. 9.5, p=0.011]).
Conclusion: Substantial reduction in the frequency of ED visits occurred in children with sickle hemoglobinopathies with the simple intervention of early and aggressive usage of HU and its dose escalation to the maximally tolerated dose. The findings of this study suggest that improving the process of prescribing HU as outlined in the "Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014" reduced the complications of sickle hemoglobinopathies requiring emergency care management and is an indicator of the enhanced quality of health care in sickle hemoglobinopathies.
Figure 1. The average monthly rate of sickle hemoglobinopathies seen in the ED stratified by year. --- = reference point in which aggressive HU was implemented. Figure 1. The average monthly rate of sickle hemoglobinopathies seen in the ED stratified by year. --- = reference point in which aggressive HU was implemented.

Disclosures
No relevant conflicts of interest to declare.