P1488: ASSOCIATION BETWEEN HEMOGLOBIN LEVELS AND END-ORGAN DAMAGE IN SICKLE CELL DISEASE: A RETROSPECTIVE LINKED PRIMARY AND SECONDARY CARE DATABASE ANALYSIS IN ENGLAND

Abstract

Background: Sickle cell disease (SCD) is a chronic, multifaceted blood disorder that affects the oxygen-carrying protein hemoglobin (Hb). Along with chronic hemolysis and vaso-occlusion that often accompanies SCD, low Hb levels may contribute to downstream end-organ damage (EOD). Emerging evidence suggests an association between chronic hemolytic anemia in SCD and both short-term and long-term adverse outcomes, including EOD. Therefore, treatments that directly increase Hb may improve patients’ acute symptoms while reducing the risk for long-term disease-related effects known to contribute to morbidity and mortality. Aims: This study aims to ascertain the association between Hb level variation and EOD and clinical conditions typically associated with SCD (stroke, pulmonary hypertension, chronic kidney disease [CKD], end-stage renal disease [ESRD], leg ulcers, and pneumonia) in a real-world data set. Methods: The Clinical Practice Research Datalink (CPRD) and the Hospital Episode Statistics (HES) databases in England were used to retrospectively identify linked Hb data among patients with SCD (1 April 2007 to 31 March 2019). Recurring results in any 90-day period were averaged. Logistic regression adjusted with demographic and clinical variables was used to determine odds ratios (ORs) of developing each EOD outcome or clinical complication. ORs, P values, 95% confidence intervals (CIs), and areas under the receiver operating curve (AUC-ROCs) and corresponding 95% CIs were reported. Results: Of 11,936 patients identified, 5379 (45%) had Hb results recorded in the CPRD. The logistic model for risk assessment of all outcomes studied indicated that an increase in Hb among patients with SCD was associated with a statistically significant (P<0.001) decrease in adjusted ORs per 1 g/dL increase in Hb (Table). Except for ESRD, leg ulcers, and pneumonia, the adjusted models showed statistically significant increases in AUC-ROC compared with the unadjusted models, signifying that the adjusted models were more robust and further verified a statistical OR after adjustment. Increased Hb was associated with decreased risk of respiratory-related events. Pulmonary hypertension had the strongest effect with the most robust model (ORadjusted of 0.66). For pneumonia, ORadjusted was 0.77. For renal insufficiency, ORs for developing CKD or ESRD were significantly lower than 1 (ORadjusted=0.73 and ORadjusted=0.75, respectively). After adjusting for clinical and demographic factors, the model predicted a lower risk for stroke (ORadjusted=0.89). The estimated AUC-ROCs suggest that the adjusted model is more robust in stroke, hypertension, and CKD. These findings did not change when testing for other covariates such as deep vein thrombosis. Image:Summary/Conclusion: Among patients with SCD, an increase in Hb of 1 g/dL was associated with a statistically significant reduction in risk for 6 common EOD outcomes and clinical conditions. The results were more pronounced after adjusting for demographic and clinical covariates (based on clinical opinion and literature review) and further assessed with a bivariate analysis. The results were obtained from a representative real-world evidence dataset analyzed over a 12-year period, which was sufficient to observe EOD events, and are generalizable to the UK and similar populations. Our findings support the use of therapeutics that increase Hb in patients with SCD to protect against deleterious organ damage.