Question 2: At what age do children with SCA become functionally asplenic?

The spleen is important in the removal of encapsulated organisms in young children who have not developed antibodies to pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, and Salmonella species.¹ Early studies regarding splenic dysfunction involved radio-labeled technetium-99 and demonstrated diminished uptake within the first six to 12 months of life, suggesting splenic dysfunction.² While this study showed diminished uptake of a radio-labeled substance, it still didn’t necessarily mean that the child demonstrated either total or clinically significant dysfunction of the spleen. A later prospective study included 694 children with sickle cell disease at 19 U.S. pediatric sickle cell centers and suggested poor splenic function in 94 percent of sickle cell anemia (SCA) patients by 5 years of age; 28 percent of children had poor splenic function at 1 year of age and the authors noted that initial splenic dysfunction rose sharply after 6 months of age.³ While functional asplenia may occur by 5 years of age, these studies suggest that splenic dysfunction begins as early as the first year of life.

But what if we could measure a patient’s spleen via ultrasound in the emergency department (ED) to guide specific patient care? Is there a correlation? Practitioners have looked at splenic size on ultrasound and its association with splenic dysfunction. A multi-institutional, randomized, double-blinded, placebo-controlled trial (the BABY HUG trial) evaluated spleen size as well as serum labs and splenic dye uptake of technetium-labeled sulfur colloid.⁴ This study served to report baseline data for a future randomized controlled trial on hydroxyurea in patients with SCA. A total of 203 infants, ranging from 7.5 to 18 months of age, were evaluated for baseline data. Of these children, 12 percent had normal uptake, 74 percent had present but decreased uptake, and 14 percent had absent uptake. There was no correlation between spleen volume and function assessed by dye study, suggesting that that measurement of the spleen is not a method that can be utilized for assessment of splenic dysfunction. It also suggests that there is a portion of infants and toddlers that already demonstrate very poor splenic function even at this young age. Another similar study of 100 children aged 7 months to 16 years evaluated ultrasound-measured spleen size and splenic function.⁵ While the splenic sizes varied between these two studies in regard to the age of splenic auto-infarction, they found that spleen size did not predict splenic function. This would suggest that measuring the spleen via ultrasound is not a reliable method to predict splenic function in the ED setting.

As might reasonably be expected with splenic dysfunction, the prevalence of bacteremia in children with SCA appears to be higher. Occult bacteremia in healthy children aged 3 to 36 months in the ED setting was found to be 0.25 percent in the post-pneumococcal-conjugate-vaccine era.⁶ A retrospective study of all pediatric patients less than 18 years old with SCA at a single institution (outpatient, emergency, and inpatient) who had blood cultures drawn yielded a true bacteremia rate of 1 percent which is significantly higher.⁷ Clinically, a febrile patient with SCA should be evaluated for bacteremia via blood culture, and according to the 2014 National Heart, Lung, and Blood Institute treatment guidelines, pediatric patients with sickle cell anemia presenting with fever should receive empiric parenteral antibiotics.⁸

Summary

Splenic dysfunction appears to develop within 6 to 12 months of age in pediatric patients with sickle cell anemia and functional asplenia should be assumed in all SCA patients. In febrile children with SCA, physicians should evaluate for bacteremia via blood culture and consider empiric antibiotics.

Dr. Jones is assistant professor of pediatric emergency medicine at the University of Kentucky in Lexington.

Dr. Cantor is professor of emergency medicine and pediatrics, director of the pediatric emergency department, and medical director of the Central New York Regional Poison Control Center at Upstate Medical University in Syracuse, New York.

References

1. Cober MP, Phelps SJ. Penicillin prophylaxis in children with sickle cell disease. J Pediatr Pharmacol Ther. 2010;15(3):152-9.
2. Pearson HA, Gallagher D, Chilcote R, et al. Developmental pattern of splenic dysfunction in sickle cell disorders. Pediatr. 1985;76(3):392-7.
3. Brown AK, Sleeper LA, Miller ST, et al. Reference values and hematologic changes from birth to 5 years in patients with sickle cell disease. Cooperative study of Sickle cell disease. Arch Pediatr Adolesc Med. 1994;148:(8):796-804.
4. McCarville MB, Luo Z, Huang X, et al. Abdominal ultrasound with scintigraphic and clinical correlates in infants with sickle cell anemia: baseline data from the BABY HUG trial. Am J Roentgenol. 2011;196(6):1399-404.
5. Nardo-Marino A, Glenthoj A, Brewin JN, et al. The significance of spleen size in children with sickle cell anemia. Am J Hematol. 2022;97(12):1520-1528.
6. Wilkinson M, Bulloch B, Smith M. Prevalence of occult bacteremia in children aged 3 to 36 months presenting to the emergency department with fever in the post-pneumococcal conjugate vaccine era. Acad Emerg Med. 2009;16(3):220-5.
7. Yee ME, Lai KW, Bakshi N, et al. Bloodstream infections in children with sickle cell disease: 2010-2019. Pediatr. 2022;149(1):e2021051892.
8. US Department of Health and Human Services. Appropriate emergency department fever management for children with sickle cell disease (AHRQ Publication No. 14). Agency for Healthcare Research and Quality website. Published February 2018. Accessed August 10,

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