Background: Acute splenic sequestration is a potentially life-threatening complication in patients with sickle cell disease. It is the second leading cause of death in young children with hemoglobin SS/Sβ0 thalassemia (SCD). The incidence approaches 35% during the first two years of life in SCD. Although splenic sequestration can occur in patients with any sickle phenotype, patients with SCD tend to be significantly younger when compared to patients with hemoglobin SC disease. Splenic function may be preserved in children treated with hydroxyurea. We recommend hydroxyurea for all SCD patients diagnosed via newborn screening, with a goal of starting therapy before 12 months of age. With this aggressive approach and potential for maintaining some splenic function, this study evaluates acute splenic sequestration in this young cohort and compares this to institutional and historical controls

Methods: We performed a retrospective search of electronic medical records at Children's Minnesota from 1/1/1999 through 12/31/2019 to identify patients with SCD and splenic sequestration. We used a broad array of ICD-9 an ICD-10 codes in order to capture all appropriate patients. Following this initial search, in-depth chart review was performed to identify patients with SCD and confirmed splenic sequestration. Data collected includes age, sex, hydroxyurea use, splenectomy, and hematologic results including hemoglobin F percentage, if available. Student t-tests for independent samples were performed to compare cohorts. This study was granted exemption by our Institutional Review Board.

Results: Over this 21 year period, the initial search revealed 151 patients. Of those, 74 had SCD. In-depth chart review found 38 (24M, 14F) of these children were confirmed to have splenic sequestration. Twelve patients started hydroxyurea before 2 years of age at a mean age of 12.6 months, median 11 months (cohort A). Of these, six started hydroxyurea during infancy at a mean and median age of 6.5 months (cohort B). The remaining 26 patients were not on hydroxyurea at the time of splenic sequestration (cohort C). Children in cohorts A and B were significantly older at the time of splenic sequestration compared to patients in cohort C (mean 58 and 45.8 months vs. 14.9 months, p< 0.0001).

Conclusions: Children with SCD who start hydroxyurea at a young age may develop splenic sequestration much later in life than previously expected. More study is needed to confirm this finding. It will be important to educate families and healthcare providers about this potential unintended consequence of early hydroxyurea use.

Disclosures

No relevant conflicts of interest to declare.

OffLabel Disclosure:

Hydroxyurea use in children with sickle cell disease < 2 years of age

Author notes

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Asterisk with author names denotes non-ASH members.