Splenic Complications in Sickle Cell Disease: A Retrospective Cohort Review

Splenic dysfunction, particularly acute splenic sequestration crisis (ASSC), is a leading cause of death in the first decade of life of patients with sickle cell disease (SCD). Despite the severity of splenic disease in SCD, few large-scale studies have been performed to assess the natural progression of splenic complications, particularly in the less common sickle cell genotypes and with the onset of early use of hydroxyurea.

We performed a retrospective chart review of patients with SCD born between January 2011 and December 2018 and treated at the Texas Children's Hospital Sickle Cell Center. We extracted data from our electronic medical record system to identify patients with documented splenic complications based on ICD9 and ICD10 codes. We then reviewed charts for these patients to confirm diagnoses and obtain additional information about these complications.

We identified 688 patients treated for SCD at our center during the study period. Of these, 113 (16.4%) were diagnosed with one or more splenic complications. The overall prevalence of splenic complications was highest in patients with hemoglobin Sβ ⁰ thalassemia (Sβ ⁰) at 50.0%, compared to 20.7% in hemoglobin SS (SS) patients, 6.9% in hemoglobin SC (SC) patients, and 0% in hemoglobin Sβ ⁺ (Sβ ⁺) patients and patients with other genotypes (Table 1). ASSC and splenectomy were likewise most prevalent in Sβ ⁰, less so in SS, and rare in SC, Sβ ⁺, and other genotypes.

To further delineate the incidence of ASSC, we performed an in-depth analysis of patients from our cohort for whom detailed information was available. Compared to patients with the SS genotype, the incidence rate ratio (IRR) for ASSC was significantly higher for Sβ ⁰ patients and significantly lower for SC patients (Table 2). The mean age of onset of ASSC was similar between SS, Sβ ⁰, and SC patients, but survival curves for time to the first event differed significantly between genotypes.

We examined the association between early hydroxyurea therapy and ASSC in SS and Sβ ⁰ patients by comparing patients who initiated hydroxyurea therapy by the age of two years to those who initiated therapy after this age. ASSC were more frequent among patients initiated on hydroxyurea by the age of two years (Table 3, upper panel). We also compared patients on hydroxyurea to those not on this therapy and found a similar effect, with ASSC occurring more frequently among patients on hydroxyurea (Table 3, lower panel). Survival curves for time to first ASSC also diverged significantly between these groups of patients.

Our data indicate that the prevalence and severity of splenic problems vary widely between different sickle cell genotypes in the first decade of life, with SC patients having relatively mild complications while Sβ ⁰ patients have the most severe and frequent complications. The association between hydroxyurea use and incidence of ASSC also suggests that hydroxyurea therapy may increase the risk of this complication of SCD, particularly when initiated before two years of age.

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Figure 1

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