Age Ranges Identified for Onset of Acute Splenic Sequestration Crisis

Mariane de Montalembert, MD, PhD

Results from an analysis of the onset age of acute splenic sequestration crisis (ASSC) in sickle cell disease patients given hydroxyurea (HU) found that 45% of ASSC cases were in patients ages 5.7 to 17.9 years and 32% were in patients 1 to 5 years.

ASSC involves sudden spleen enlargement along with an acute drop in Hb levels >2g/dL, and it is the result of large amounts of red blood cells being trapped in the spleen. The study investigators note that the trapping of red blood cells is a consequence of low velocity of blood in the splenic red pulp’s open circulation.

The study was led by Mariane de Montalembert, MD, PhD, from Pediatrics at the Hospital Necker, Paris, France. The study results were presented at the American Society of Hematology (ASH) Annual Meeting and Exposition.

“We observe that ASSC appeared in this cohort of patients treated with HU later than in previous publications in which a minority of children received HU,” Montalembert and colleagues wrote. “Various studies in the literature have evaluated the effect of HU on spleen function in SCD patients.”

Background and Research

The study became known as the European Sickle Cell Disease Cohort – Hydroxyurea (ESCORT-HU), and was a non-interventional prospective cohort study conducted in SCD patients treated with HU

The investigators recruited 1906 patients, with 45% being children, in several European countries. The follow-up meetings had a median duration of 45 months.

The investigators also included a retrospective study assessing 190 children diagnosed at birth with the HbSS and HbS/β0thalassemia genotypes. They noted that splenic sequestration issues are usually some of the earliest major manifestations for patients with these genotypes.

Study Results

The study investigators noted that in 32% of ASSC episodes (10), patients were found to be in the age range of 1 to 5 years. They found that 45% (14) of episodes were in patients in the range of 5.7 to 17. 9 years, and 19.3% (6) were found to be in patients ages 26.6 to 64.

Each of these ASSC episodes were also determined by the research team to have been disease-related and unrelated to treatment with HU.

The investigators’ retrospective study which followed 190 children in the Paris metropolitan area between the years of 2000 and 2009, reported that the childrens’ median age by the first episode of ASSC was 1.4 years.

They noted that 33 ASSC episodes were reported in 11 male patients and 12 female patients (23 in total), with each of these patients possessing the HbSS genotype. The team also noted that the mean duration of HU treatment was 4.2 ± 3.9 years.

“We hypothesize that the later age at which HU patients experience ASSC is a consequence of improved splenic perfusion,” they wrote. “A positive consequence is better protection against overwhelming infections, but physicians should be aware of the increased period at risk for ASSC, well beyond the 6-7 year age limit usually reported in HbSS and Sβ0 genotypes.”

The study, “Hydroxyurea Is Associated with Later Onset of Occurrence of Acute Splenic Sequestration Episodes in Sickle Cell Disease: Lessons from the European Sickle Cell Disease Cohort – Hydroxyurea (ESCORT-HU) Study,” was presented at ASH 2022.