Characteristics and Trends of Hospitalizations for Sickle-Cell Related Complications
Authors: Chennapragada Suma Sri , Thevuthasan Sindhu , Savani Saloni , Goyal Shriya , Singh Vaishnavi , Ramphul Kamleshun , Sakthivel Hemamalini , Sharma Shivani , Pramudita Arcita Hanjani , Ramadas Poornima 
Published: December 2023

Introduction
There are approximately 100,000 people living with sickle cell disease (SCD) in the United States. As per the Center for Disease Control estimates, almost all patients with SCD will require hospitalization more than once a year and visit the emergency department at least 2-3 times a year on average. Previous studies have shown that SCD hospitalization trends are steadily increasing in the country. In November of 2019, two new drugs, crizanlizumab (to decrease the frequency of vaso-occlusive crises) and voxelotor (to increase hemoglobin response), were approved by the Food and Drug Administration (FDA) for the treatment of sickle cell disease. Around the same time, the entire health care system experienced disruption in the form of the COVID-19 pandemic. Hence, we conducted this retrospective study to assess SCD hospitalization trends from 2016-2020 and stratified them across various demographic factors to analyze the underlying causes.
Methods
We conducted a retrospective study from the National Inpatient Sample (NIS), which is a large all-payer database created by the Health Care Cost and Utilization Project (HCUP). We included all adult patients with a diagnosis of SCD (HbSS, HbSC, Sickle/b thal, and other variants) and identified their trends of hospitalizations for various SCD-related complications like vaso-occlusive crises, heart failure exacerbation, acute kidney injury, stroke, sepsis with and without septic shock, bacteremia, pneumonia, osteomyelitis, acute chest syndrome, splenic sequestration, and priapism. We then did a linear-to-linear analysis and ANOVA test to stratify these trends across various age, gender, income, and location groups. SPSS was used for the statistical analysis.
Results
Our study included a total of 19,250 patients who had at least one admission for sickle cell-related complications during 2016-2020. The average number of admissions for sickle cell pain crisis steadily increased from 10.2 per 100,000 in 2016 to 14.7 in 2019 and then decreased to 13.9 in 2020. Priapism steadily declined from 2.3% in 2016 to 1.4% in 2020 (p&lt;0.001). Acute kidney injury complicated 4.9% of admissions in 2016 and steadily rose to 5.2% of admissions in 2020 (p = 0.88). Admissions complicated by bacteremia peaked in 2017 (0.9%) but have since been on a decline (0.5% in 2020) (p-0.02). Admissions complicated by pneumonia showed a steady decline from 6% in 2016 to 4.3% in 2020 (p&lt;0.001). Admissions with osteomyelitis, splenic sequestration, acute chest syndrome, heart failure exacerbation, stroke, and sepsis complicated &lt;1% of all admissions and were not statistically relevant.
When stratified by age, it was noted that the age group of 18-39 had the most admissions. Females consistently had more admissions than males. Medicaid was the predominant insurance among all the admissions, followed by Medicare. Around 50% of the patients admitted for SCD-related complications were in the 0-25th percentile of median household income quartiles. The majority of admissions were seen in urban teaching hospitals. The majority of these admissions were also seen in the Southern regions.
Conclusion
Our results show that female patients in the age group 18-39 years, those covered by Medicaid and Medicare, and those in lower income quartiles comprised the majority of admissions for SCD-related complications. This demonstrates disparities in SCD care, wherein patients in lower socio-economic strata may not have access to newer advances in SCD treatment. Although it is optimistic to note that admissions for pain crises had a significant decline from 2019-2020, it remains to be seen whether these numbers are due to new therapies or due to the disruption of healthcare services caused by the pandemic. Analyzing more long-term trends after the year 2020 will help us understand this impact. The overall trend of infections and sepsis has been low, likely due to widespread vaccinations and early antibiotic treatments. It is interesting to note that although there was a downtrend for the majority of SCD complications, the incidence of AKI during admissions is steadily rising, validating the need to focus more on renal care in sickle cell patients.