Hydroxyurea Dose and Adherence Affect Hematologic Outcomes in Children With Sickle Cell Disease

Hydroxyurea Dose and Adherence Affect Hematologic Outcomes in Children With Sickle Cell Disease 1024 683 JoAnna Pendergrass, DVM
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Optimal hydroxyurea dosing and medication adherence can improve hematologic outcomes for children with sickle cell anemia.


For pediatric patients with sickle cell anemia, hydroxyurea is highly effective at reducing disease complications. However, it can be challenging for these patients to take hydroxyurea for the long term.

“There are many barriers to medication adherence in pediatric patients with sickle cell anemia. The number one barrier is forgetting to take the medication,” says Susan Creary, MD, a pediatric hematologist at Nationwide Children’s Hospital and associate professor of pediatrics at The Ohio State University College of Medicine.

In the first study of its kind, Dr. Creary and her research team evaluated how prescribed hydroxyurea dose and medication adherence affect hematologic outcomes in pediatric patients with sickle cell anemia. The study demonstrated that, in a high-income setting, patients with high levels of hydroxyurea exposure had improved hematologic outcomes. Results were published in Pediatric Blood & Cancer.

The researchers performed a secondary data analysis of two studies that evaluated hydroxyurea adherence in 45 pediatric patients with sickle cell anemia. The first study was conducted at Nationwide Children’s, and the second study was conducted at Ann & Robert H. Lurie Children’s Hospital of Chicago.

Adherence in the two studies was assessed using smartphone-based video directly observed therapy (VDOT) and electronic pill bottles. The study cohort at Nationwide Children’s used VDOT, while the cohort at the Children’s Hospital of Chicago used electronic pill bottles. The patients’ medical records were used to determine the average prescribed hydroxyurea dose.

“Very few interventions to improve medication adherence have been studied in patients with sickle cell anemia,” notes Dr. Creary.

For the data analysis, average daily hydroxyurea exposure was calculated by dividing the number of hydroxyurea exposure days (confirmed by VDOT or electronic pill bottle) by the number of days in the intervention period. Using this calculation, patients were classified as either “higher exposure” (> 20 mg/kg/day) or “lower exposure” (≤ 20 mg/kg/day).

Hematologic outcomes were assessed by measuring fetal hemoglobin (HbF) and mean corpuscular volume (MCV).

The researchers observed that the average daily hydroxyurea exposure was similar between the study cohorts (VDOT: 20.5 mg/kg/day, electronic pill bottles: 19.4 mg/kg/day).

The average prescribed hydroxyurea dose was higher in higher-exposure patients (27.2 mg/kg/day) than in lower-exposure patients (24.4 mg/kg/day). Medication adherence was also higher in the higher-exposure group, evidenced by a higher proportion of hydroxyurea exposure days (0.92 vs. 0.71) and higher average daily hydroxyurea exposure (23.6 mg/kg/day vs. 16.1 mg/kg/day).

HbF and MCV levels were highest in the higher-exposure group.

Given the study’s reported findings, Dr. Creary explains that physicians should recognize how prescribing dose and medication adherence affect hematologic outcomes in pediatric patients with sickle cell anemia.

Extra consideration may be needed for patients with low medication adherence. One potential solution is to increase the prescribing dose to compensate for the low adherence, but the safety of this approach is not yet known, Dr. Creary notes.

Non-technological interventions can also be used, such as having a parent or caregiver provide medication reminders and positive reinforcement.

“Overall, it is important to identify and find the right intervention for the right patient,” she says.

Future research is needed to determine whether the improved hematologic outcomes due to higher hydroxyurea exposure leads to enhanced clinical outcomes.

“Although we ultimately want to have more treatments to treat sickle cell anemia,” Dr. Creary says, “the current focus is to use the current treatments most effectively.”



Creary SE, Beeman C, Stanek J, King K, McGann PT, O’Brien SH, Liem RI, Holl J, Badawy SM. Impact of hydroxyurea dose and adherence on hematologic outcomes for children with sickle cell anemia. Pediatric Blood Cancer. 2022 Apr 4:e29607.

About the author

JoAnna Pendergrass, DVM, is a veterinarian and freelance medical writer in Atlanta, GA. She received her veterinary degree from the Virginia-Maryland College of Veterinary Medicine and completed a 2-year postdoctoral research fellowship at Emory University’s Yerkes Primate Research Center before beginning her career as a medical writer.

As a freelance medical writer, Dr. Pendergrass focuses on pet owner education and health journalism. She is a member of the American Medical Writers Association and has served as secretary and president of AMWA’s Southeast chapter.

In her spare time, Dr. Pendergrass enjoys baking, running, and playing the viola in a local community orchestra.