Correlation of Genetic Mutation With Outcomes in Children With Hereditary Spherocytosis Undergoing Partial Splenectomy: A Multicentre Study

Abstract

Purpose

Hereditary Spherocytosis (HS) is a common genetic hematological disorder causing a life-long hemolytic anemia, with sequela of hemolysis. Children with severe HS commonly undergo partial or total splenectomy (PS, TS); PS confers the theoretical advantage of maintaining splenic immune function, but may be associated with regrowth, ongoing hemolysis, and need for completion splenectomy. HS can be caused by 5 different pathogenic gene variants. A rare and severe form is caused by homozygous/compound heterozygous mutations in the SPTA1 gene, coding for alpha spectrin. We hypothesized this form of HS is associated with worse outcomes following PS.

Methods

Following REB approval, a retrospective chart review of children with HS undergoing PS between 2000 and 2023 was conducted across 7 sites in the USA and Canada. Pre- and post-operative hematological values and need for completion splenectomy were analyzed. P < 0.05 was significant.

Results

Of 51 eligible patients, 10 had SPTA and 41 had non-SPTA1 HS. The SPTA1 group underwent PS at a younger age to non-SPTA1 (5.1 vs 9.6 yr, p = 0.003), and had lower pre-operative hemoglobin (86.2 vs 98.8 g/L, p = 0.04). There were no differences between groups regarding peri-operative surgical or hematological outcomes. The SPTA1 group required completion splenectomy at a higher rate than the non-SPTA1 group (70.0 % vs 24.4 %, p = 0.01).

Conclusion

Children with SPTA1 HS are more likely to require completion splenectomy following PS than children with other HS-causing mutations. These results support the role of genetic testing to permit an evidence-based individualized approach to patient selection for partial vs. total splenectomy.

Level of evidence

III.