Assessment of End-Organ Damage Among Elderly Patients with Sickle Cell Anemia: A Single-Center Retrospective Study

Background: The cause of death in adulthood for patients with sickle cell anemia (SCA) is often end organ damage leading to multiorgan failure. The expected lifespan for patients is over two decades less than that of the general population. With continuing advancements in SCA disease-modifying therapies (DMTs), more patients are surpassing this threshold. However, little is known about the characteristics of patients in this unique age cohort. This retrospective study assesses the severity of end-organ damage among SCA patients living beyond the expected lifespan.

Methods: This retrospective single-center study reviewed all patients ≥ 60 years old with SCA genotype HbSS treated at the UT Physicians Comprehensive Sickle Cell Center between January and June 2024. A total of 16 patients were included in this study. The most recently recorded demographic, clinical, and laboratory data were collected and analyzed using descriptive statistics. Laboratory values were compared to corresponding normal ranges published by the Centers for Disease Control and Prevention (CDC). Mean hemoglobin, total bilirubin, and reticulocyte count were used to assess SCA severity. ALT was included to assess liver function. Creatinine was used to assess kidney function. Chamber dilation, maximum tricuspid regurgitation velocity (TRV max), and ejection fraction (EF) were collected from echocardiograms to assess heart function. Five patients had a brain MRI from which significant findings were collected to assess ischemic changes. Medical history was reviewed to collect information on co-morbidities and further assess end-organ damage.

Demographic Results: This study included 16 SCA patients ≥ 60 years old, of which 15 were female (94%) and one was male. The average age of patients was 67.7 ± 2.1 years. All patients included in this study were of African and/or African American ethnicity. 56% of patients had never used tobacco products, while 31% were former smokers and 13% were current smokers. 69% of patients had used at least one of three DMTs (hydroxyurea, Oxbryta, L-glutamine), while the remaining 31% managed their disease without DMT. 73% of patients on a DMT used hydroxyurea. Three patients were prescribed Oxbryta, but two discontinued due to intolerance. 25% of patients had chronic transfusions. All patients who did not use DMT had hereditary persistence of fetal hemoglobin (HPFH).

Clinical Results: The average BMI for patients included in this study was 23.48 ± 2.61 kg/m². 63% of patients had chronic kidney disease (CKD), and 56% of patients had hypertension. 44% of patients had a history of at least one thromboembolic event. 38% of patients had a history of heart failure/arrhythmias. 31% of patients had a history of stroke and/or transient ischemic attack. 6% had a history of diabetes mellitus.

Laboratory Results: Mean hemoglobin was below normal limits, averaging 7.48 ± 0.60 Hg. Total bilirubin was above normal limits with a reported average of 2.38 ± 0.67 mg/dL. Reticulocyte count was above normal limits, averaging 9.1 ± 3.19 mg/dL. ALT was within normal limits, averaging 18.0 ± 2.7 U/L. Creatinine was elevated, averaging 1.2 ± 0.34 mg/dL. 69% of patients had mild to severe chamber dilation. Average TRV max noted on ECG for this patient group was slightly elevated above normal limits with an average of 2.82 ± 0.34 m/s. EF was within the normal range for 81% of patients, averaging 57.5 ± 3.77% overall. MRI findings ranged from mild diffuse volume loss to advanced chronic microangiopathic changes.

Conclusion: Our comprehensive sickle cell center has a cohort of HbSS patients maintaining good health at age 60 and older. This cohort is disproportionately more female (94%) than male. Patients ≥ 60 years old with SCA have evidence of end-organ damage affecting multiple systems. However, our study suggests that these end-organ outcomes are well managed among this cohort with DMT or HPFH. For example, the patients have good liver function, and while 63% of patients reported a history of CKD, none were on hemodialysis and 44% had normal creatinine levels. 38% of patients reported a history of heart failure/arrhythmias with good control. It must be acknowledged that our outpatient population has access to a comprehensive medical specialist team. Thus, these findings may not be generalizable to the overall SCA population. Future research can evaluate the effect of various DMTs on multiorgan function of a larger cohort of older SCA patients.

Idowu:Forma: Research Funding; Agios Pharmaceuticals, Inc.: Research Funding; Alexion: Research Funding; bluebird bio Pharmaceuticals: Consultancy; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novo Nordisk: Consultancy, Other: Advisory board or panel, Research Funding; Novartis: Consultancy, Research Funding; GBT: Consultancy, Other: Advisory board or panel, Research Funding, Speakers Bureau; Vertex: Consultancy.