Revisiting Spleen Function and Pneumococcal Risk in Children with Hemoglobin SC Disease

Spleen dysfunction and susceptibility to pneumococcal infection is a well known feature in homozygous sickle cell disease (HbSS), whilst to date splenic function in hemoglobin SC disease (HbSC) has been poorly investigated. The aim of this study was to analyze spleen function in children with HbSC disease using a high-throughput validated method (1) and to examine if the current recommendations regarding pneumococcal risk are appropriate in this population. Spleen function was evaluated using a flow cytometry quantification of red blood cells (RBCs) with Howell-Jolly bodies (HJBs), in a cross-sectional study of patients at steady state during an outpatient visit in an expert center. Quantification of HJB-RBCs was performed in children with HbSC disease aged < 10 years and compared to children with HbSS disease or healthy children of the same age groups, or splenectomized children. Additional exploratory analysis was performed according to age (under or above the age of 5 years old) and treatment group (hydroxyurea). The median (Q1-Q3) HJB-RBCs count was 16 (11-28.25) /100.000 RBCs in 40 HbSC children (Figure 1). This result was not statistically different from the control group of 22 healthy children (p=0.96) nor in subgroups < or ≥ 5 years old, indicating that children with HbSC under 10 years have a preserved splenic function. Expectedly, the HJB-RBCs counts differed significantly from splenectomized children (419 (296-489)/100.000 RBCs, n=15, p<0.0001). By contrast, among the 53 HbSS children, the median HJB-RBCs count was 134 (29-216) /100.000 RBCs, differing significantly from HbSC children (p<0.0001). In HbSS children, HJB-RBCs counts increased significantly with age (r=0.30, p=0.03), showing important variability among subjects but did not reach the level found in splenectomized patients suggesting that complete loss of spleen function occurs presumably later in a majority of children in this population. Treatment with hydroxyurea did not significantly impact HJB-RBCs counts in a subgroup analysis in HbSS children. The result of this study suggests that spleen function in children under 10 years old with HbSC is not altered. The routine administration of prophylactic penicillin to young children with SC disease may therefore be questioned. Similarly, fever in children with HbSC under 3 years old may not require parenteral antibiotics as it is generally currently recommended by analogy to children with HbSS. Functional or anatomical asplenia in children with HbSC is delayed compared to those with HbSS at least after the first decade of life. Future large cohort studies using similar methodology will allow better evaluation of the pneumococcal risk in adolescents and adults with Hb SC disease. Bibliography (1) El Hoss S, Dussiot M, Renaud O, Brousse V, El Nemer W. A novel non-invasive method to measure splenic filtration function in humans. Haematologica. oct 2018;103(10):e436-9. Figure 1 Figure 1. Disclosures El Nemer: Hemanext: Consultancy.

Experience with clinical pathway for management of high grade blunt splenic injuries: a prospective study in adults at two tertiary trauma centers

Background: There is ambiguity regarding anatomical site of embolization, frequency of follow-up scans and splenic function following angioembolisation in the management of high grade blunt splenic injury. A splenic salvage pathway in patients who are hemodynamically stable or resuscitated to stability was introduced across two trauma centres. The aims of this project were: to develop a clinical pathway to manage hemodynamically stable blunt splenic injury patients and to determine rates of splenic salvage for patients with high grade splenic injury, assess complications and splenic function following completion of the pathway.Methods: Prospective study over a period of 24 months. Data was collected to evaluate rates of splenic salvage, complications and function of the spleen following angioembolisation.Results: Thirty-three patients, predominantly males (n=29) between the ages of 14-85 years, were included in the study. Three (9%) with grade V injury, underwent angioembolization on admission but required splenectomy as an inpatient. On day 14, all patients (n=30) with splenic salvage underwent blood tests, with 3 patients (9%) receiving vaccination for altered red cell morphology. The introduction of clinical pathway led to an increase in our splenic salvage rate to 91%.Conclusions: We believe that introduction of proposed clinical pathway may result in increased rates of splenic salvage with preservation of function following angioembolisation.

Late Splenic Sequestration: A Consequence of Early Hydroxyurea Use?

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

Insights into determinants of spleen injury in sickle cell anemia

Spleen dysfunction is central to morbidity and mortality in children with sickle cell anemia (SCA). The initiation and determinants of spleen injury, including acute splenic sequestration (ASS) have not been established. We investigated splenic function longitudinally in a cohort of 57 infants with SCA enrolled at 3 to 6 months of age and followed up to 24 months of age and explored the respective contribution of decreased red blood cell (RBC) deformability and increased RBC adhesion on splenic injury, including ASS. Spleen function was evaluated by sequential 99mTc heated RBC spleen scintigraphy and high-throughput quantification of RBCs with Howell-Jolly bodies (HJBs). At 6 and 18 months of age, spleen filtration function was decreased in 32% and 50% of infants, respectively, whereas the median %HJB-RBCs rose significantly (from 0.3% to 0.74%). An excellent correlation was established between %HJB-RBCs and spleen scintigraphy results. RBC adhesion to laminin and endothelial cells increased with time. Adhesion to endothelial cells negatively correlated with splenic function. Irreversibly sickled cells (ISCs), used as a surrogate marker of impaired deformability, were detected at enrollment and increased significantly at 18 months. %ISCs correlated positively with %HJB-RBCs and negatively with splenic uptake, indicating a relationship between their presence in the circulation and spleen dysfunction. In the subgroup of 8 infants who subsequently experienced ASS, %ISCs at enrollment were significantly higher compared with the asymptomatic group, suggesting a major role of impaired deformability in ASS. Higher levels of %HJB-RBCs were observed after the occurrence of ASS, demonstrating its negative impact on splenic function.