Trends of Splenectomy in Pediatric Patients with Immune Thrombocytopenia before and after the ASH 2011 Evidence-Based Practice Guidelines
Authors: Bhatt Neel S , Bhatt Parth , Donda Keyur , Dapaah-Siakwan Fredrick , Batalahally Sunil Kumar , Linga Vijay , Lekshminarayan Anusha , Chaudhari Riddhi , Zaid Kalyani Samer , Bhaskaran Smita 
Published: April 2021

Abstract
Background: Immune thrombocytopenia (ITP) is an autoimmune disorder which affects 1 in 10,000 children. Thrombocytopenia occurs largely due to rapid destruction of antibody sensitized platelets in the reticuloendothelial system. While spontaneous resolution is commonly seen in acute ITP, treatment of chronic or persistent ITP is controversial and could pose as management challenges for clinicians. Splenectomy increases platelet survival by removing a common site of platelet destruction and has a 70-80% response rate, however, published literature is conflicting regarding its ideal timing. Furthermore, it is an invasive procedure with significant risk of infections, venous thromboembolism. In 2011, the American Society of Hematology (ASH) published revised clinical practice guidelines for the management of ITP (Neunert C et al. Blood 2011). Splenectomy was recommended in patients with severe symptomatic ITP with significant or persistent bleeding refractory to intravenous immunoglobulin (IVIG), corticosteroids, and anti-D therapy. It is unclear if the rates of splenectomy have changed since the publication of these guidelines. Using a large population-based estimate, we aimed to study the trends of splenectomy in pediatric patients with ITP, and the factors predicting the procedure in this population.
Methods: We used discharge data from the National (Nationwide) Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality (AHRQ). Pediatric patients (age ≤ 18 years) hospitalized with ITP from 2005-2014 were identified using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD9-CM) code 287.31. Cases of total splenectomy were identified using ICD9-CM procedure code '41.50'. To calculate estimated trends of splenectomy, Cochran-Armitage trend test was used. Chi-square test, Mann-Whitney U test, survey logistic regression and hierarchal regression were used for analyses. Weights provided by NIS were used to calculate national estimates. A p-value &lt; 0.05 was considered significant. All analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).
Results: The NIS data included 62 million weighted pediatric hospitalizations between 2005 and 2014 (unweighted admissions n=13 million). After excluding patient transfers, a total of 40,998 weighted hospitalizations with ITP occurred during this time-period. Total splenectomy was performed in 1,009 patients. Splenectomy rate showed a decline prior to revised guidelines: 3.3% (2005-06) to 2.3% (2011-12). It continued to decline further after the publication: 1.6% (2013-14), p &lt;0.0001. Similar trend was noted for patients &lt; 5 years of age: 10.6% (2005-06), 5.2% (2011-12), and 3.5% (2013-14), p &lt;0.001. None of the other patient ages (5-10, 11-15, and 16-18), gender, or hospital regions showed consistent splenectomy trend in either direction. Multivariable analysis showed one year increase in patient age significantly increased adjusted odds of having splenectomy (odds ratio, OR 1.18, 95% confidence interval, CI 1.14-1.22, p &lt;0.0001). Having an intracranial bleed also significantly predicted splenectomy (OR 5.16, 95% CI 1.96- 13.61, p=0.0009). Splenectomy was more commonly done in patients from Midwest (OR 2.83, 95% CI 1.19-6.74, p= 0.02) and South region (OR 1.89, 95% CI 1.02-3.51, p=0.04) compared to Northeast region. Mortality rate was similar between patients who received splenectomy and who did not.
Conclusion: Overall, splenectomy rates showed consistently downward trend in pediatric patients with ITP between 2005 and 2014. Reduction in splenectomy rates in children &lt;5 years of age could be due to increasing awareness for sepsis secondary to asplenia. Presence of severe bleeding (e.g. intracranial bleeding) in patients with ITP predicted splenectomy, which is consistent with ASH recommendations. Declining splenectomy rates in last 3 years since ASH guidelines release could mean that more patients receive medical management initially as recommended by ASH. However, due to possible under-coding for IVIG, corticosteroids, and anti-D and lack of longitudinal data, we were unable to study the association between prior treatment and splenectomy. Future studies should revisit the role of splenectomy in ITP with advent of novel therapeutic options such as thrombopoietin receptor agonists.

Disclosures
No relevant conflicts of interest to declare.