Prevalence and Predictors of Steady-State Hypoxemia in Sickle Cell Disease.
Authors: Quinn Charles T. , Ahmad Naveed 
Published: October 2019

Abstract
Individuals with sickle cell disease (SCD) may have arterial oxygen desaturation during the steady-state that is mainly due to a right shift of the oxyhemoglobin dissociation curve. This right shift has both non-specific causes (increased concentration of 2,3-DPG due to chronic anemia) and SCD-related causes (an effect of the intracellular concentration of hemoglobin (Hgb) S and an enhanced Bohr effect). Another possible cause is chronic cardiopulmonary disease that may be related to past acute chest syndrome (ACS). We aimed to describe the distribution of steady-state peripheral oxygen saturation (SpO2) in a large population of children with SCD and to determine whether any simple laboratory or clinical features were predictive of SpO2. We hypothesized that most of the variation in SpO2 was not explained by steady-state Hgb alone, and that a history of ACS could explain some of this variability. Using our center’s comprehensive database we identified all subjects with sickle cell anemia (SS), sickle-hemoglobin C disease (SC), sickle-β+-thalassemia (Sβ+), or sickle-β0-thalassemia (Sβ0) who had been evaluated within the past 5 years for whom steady-state Hgb concentration, reticulocyte count (retic), and SpO2 were available. All steady-state values are rolling averages calculated at routine well clinic visits. SpO2 was determined by pulse oximetry in room air. Individuals receiving chronic transfusions were excluded. Lifetime rates of ACS were known for a subset of subjects with SS and Sβ0. A standard multiple regression analysis was performed between steady-state SpO2 as the dependent variable, and steady-state Hgb and retic, age, and sex as independent variables. 585 subjects were analyzed (390 SS/Sβ0, 195 SC/ Sβ+; 47% female, 53% male). Mean age was 9.4 years (SD 5.6, range 0.2 – 19.7). Mean SpO2 was 96.3% (SD 3.0) for SS/Sβ0 and 98.7% (SD 1.7) for SC/ Sβ+ subjects. The percentage of subjects with SpO2 <96% and <90% was 33.1 and 2.8 for SS/Sβ0 and 3.6 and 0.5 for SC/ Sβ+. Bivariate analyses showed no correlation between Hgb and SpO2 for SC/ Sβ+ subjects (N=195, Pearson R=0.024, P=0.74) and no correlation between ACS rate and SpO2 in those with SS/Sβ0 (N=183, Pearson R=−0.043, P=0.56). Thus, only the 390 subjects with SS/Sβ0 were included in the multivariate analysis, and ACS rate was not included in the model as an idependent variable. All 4 independent variables (Hgb, retic, age, and sex) contributed significantly to prediction of SpO2. Altogether, about 45% (adjusted 44%) of the variability in SpO2 was explained by the model. Multiple correlation coefficient (R = 0.67) showed a significant linear relationship between independent variables and SpO2 (F = 78.07, p < 0.001). The estimated model can be given as: SpO2 = 94.24 + (0.58 * Hgb) − (0.16 * Age in years) + (0.64 * Female sex) − (0.20 * Retic in %). In summary, steady-state hypoxemia is common among individuals with SS and Sβ0, in whom decreased steady-state SpO2 is related to decreased steady-state Hgb, increased steady-state retic, increased age, and male sex. This relationship was not found for individuals with SC and Sβ+. Only 5% of the variation in SpO2 was explained by Hgb while controlling for other variables, and ACS rate was not associated with SpO2. We conclude that most steady-state hypoxemia in individuals with SCD is explained by factors other than chronic anemia, and that hypoxemia appears to be unrelated to prior episodes of ACS.