Rheological Characteristics of Elderly Individuals with Sickle Cell Disease Compared with an Adult Sickle Cell Population
Authors: Yoo Justin J , Zgodny Jordan , Hernandez Britney , Darazim Jawa , Patel Ashwin P , El Rassi Fuad , Yu G. Karen , Potdar Alka A , Sheehan Vivien A. 
Published: December 2023

Introduction: Individuals with sickle cell disease (SCD) have a shorter life expectancy (median age 43 years in the US) compared with the general population. However, a subset of patients with SCD live ≥60 years. Prior case series examining conventional laboratory values found no significant differences between elderly and adult populations with SCD. Red blood cell (RBC) function, which is affected by RBC deformability and density, is abnormal in SCD, but the degree of impairment varies greatly among patients. Oxygen gradient ektacytometry measures RBC deformability as an elongation index (EI) under conditions of oxygenation (EI max) and deoxygenation (EI min). The oxygen partial pressure at which RBC deformability decreases is the point of sickling (PoS), and a higher PoS is associated with greater likelihood of a pain crisis. % dense RBCs (%DRBC), defined as RBCs containing &gt;1.11 g/dL of hemoglobin (Hb), are associated with an increased likelihood of clinical complications. We hypothesized improved RBC function contributes to the longevity of patients with SCD and in this analysis we compared the RBC function of elderly patients with SCD vs an unselected adult cohort with SCD aged ≤45 years.

Methods: Peripheral blood samples (transfused samples excluded) and clinical data were collected from consenting patients with SCD treated at Grady Memorial Hospital, Atlanta, GA, from August 2022 to June 2023. Patients were assigned to groups by age (elderly, ≥60 years; controls, 18-45 years) and genotype (HbSS or HbSC). Complete blood count, absolute reticulocyte count (ARC), and %DRBC were determined using an ADVIA hematology analyzer. EI max, EI min, and PoS were measured using a Laser Optical Rotational Red Cell Analyzer. Tests were performed within 24 h of blood collection. Hydroxyurea (HU) use and % fetal Hb were collected via chart review.

Results: Thirteen elderly patients (HbSS, median age 63 years; 61.5% using HU) were compared with 78 control patients (HbSS, median age 28 years; 75.6% using HU). Apart from median ARC and absolute neutrophil count (ANC), which were significantly lower in the elderly group, all hematological parameters were comparable between HbSS groups (Table). The RBCs of the HbSS elderly group had improved deformability compared with the RBCs of the HbSS control group with a higher EI max (0.506 vs 0.410; P=0.001) and EI min (0.203 vs 0.125; P&lt;0.001; Figure). PoS and %DRBC were significantly lower in the HbSS elderly group vs the HbSS control group (PoS: 20.48 mmHg vs 32.40 mmHg; %DRBC: 3.0% vs 7.4%; each P&lt;0.001). Eleven elderly patients (HbSC, median age 64 years; 9.1% using HU) and 37 control patients (HbSC, median age 29 years; 18.9% using HU) were compared. Apart from median Hb, ANC, and mean corpuscular Hb concentration, which were significantly lower in the HbSC elderly group, all hematological parameters were comparable between HbSC groups (Table). Although there were no significant differences in EI max, EI min, or PoS between HbSC groups, %DRBC was significantly lower in the HbSC elderly group (8.5% vs 14.4%; P=0.003).

Conclusions: This is the first study to compare rheology as well as hematologic parameters between elderly patients with SCD and control patients with SCD aged ≤45 years to determine if RBC function contributes to longevity. Significantly lower %DRBC in HbSS and HbSC elderly groups, vs respective control cohorts, may contribute to improved rheology as denser RBCs have higher concentrations of HbS and are more prone to sickle. In the elderly groups, %DRBC was numerically higher in the HbSC group vs the HbSS group, and significantly lower vs respective control groups, emphasizing the dehydrating effects of HbC and supporting phlebotomy to reduce %DRBC in HbSC disease. Only the HbSS elderly group demonstrated better RBC deformability regardless of oxygen conditions and a lower PoS, indicating less HbS polymerization at lower oxygen levels and suggesting increased relevance of deformability to pathophysiology and outcomes in HbSS vs HbSC disease. Even outside of SCD, older age is associated with more dehydrated, less deformable RBCs, and the reversal of this trend in HbSS groups is remarkable. Use of HU, a modifier of RBC function, was comparable between HbSS groups and cannot account for our findings. Overall, our results support the clinical relevance of RBC function testing and its potential role in assessing genotype-specific disease severity and expected longevity.