Vaso-occlusive painful episodes (VOE) are the most common clinical manifestation of sickle cell disease (SCD) and the primary reason for hospitalizations and emergency visits.

This project aims to identify the clinical predictors of VOE hospitalization in adult participants of the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) Brazil SCD Cohort.

The REDS-III Brazil SCD Cohort enrolled participants from 2013 to 2015 who were followed until 2018. Participants were randomly selected as eligible from public blood centers in 6 cities. Medical records were reviewed to abstract clinical data including the indications for all hospitalizations that occurred from one year prior to enrollment through the end of follow up. Adult cohort participants with 3+ hospitalizations per year due to VOE (cases) were compared to controls with less frequent VOE admissions to identify predictors of frequent VOE.

Of the 2793 participants enrolled in the cohort, 184 (6.7%) had 3+ VOE admissions per year (5.5% of 1330 children <18yr and 7.5% of 1453 adults). Compared to adults with <3 VOE admissions/ year, the adults with frequent VOE had higher white blood cell counts (11,566 vs. 98,659 cells/uL), platelet counts (389,500 vs 357,333 cells/uL) and lower hemoglobinF (4.4% vs 6.9%) and were more likely to have received red blood cell transfusions (80% vs. 41%) and hydroxyurea (60% vs. 49%) in the past year. Acute chest syndrome, bacteremia, and asthma were also more common in adult cases compared to controls (83% vs 61%, 16% vs 8% and 17% vs 8%, respectively). Independent predictors of 3+ VOE admissions/year in multivariable models included higher white blood cell (OR 1 [1.000-1.001], history of acute chest syndrome (OR 2.8 [1.581-5.202] and treatment with hydroxyurea (OR 1.8 [1.123-3.038].

Frequent hospitalizations due to VOE are a marker of severe SCD used to identify patients for disease modifying therapy or even curative therapies such as bone marrow transplant. Understanding the significant predictors of frequent VOE in adults may identify other surrogate markers of severe disease that can be used to target therapies for high risk individuals.

In this multi institutional cohort of SCD, white blood cell count and a history of acute chest syndrome were identified as significant independent predictors of frequent VOE while the association of hydroxyurea likely reflects treatment with this disease modifying therapy for frequent pain. Individuals with high white blood cell counts and acute chest syndrome should have close follow up to be monitored frequently and considered for early and aggressive treatment of pain as well as other disease modifying therapies.