PB2305 HIGH HEMOGLOBIN F IN SICKLE CELL DISEASE: WANING PROTECTION WITH AGE
Authors: Tolu S. , Gil M. Reyes , Ogu U. , Choudhuri J. , Fecher R. , Thomas M. , Crouch A. , Minniti C. 
Published: June 2019

Background:

Sickle cell disease (SCD) is a monogenetic inherited disorder with pleomorphic clinical manifestations. Hemoglobin F (Hb F) concentration is the major genetic modifier of clinical expression and levels between 10% and 20% have been found to lead to improved survival and fewer vaso‐occlusive complications. Most of this data was collected from children and young adults at a time when life expectancy was significantly shorter. However, recent data suggest that individuals with the Arab‐Indian haplotype and/or HbS‐δβ thalassemia, who typically have Hb F of 15% to 25%, still suffer from vaso‐occlusive complications (VOCs). Persistence of SCD complications may be due to the heterocellular distribution of Hb F among red blood cells in these patients. Survival for patients with SCD has increased dramatically in the past 20 years, and we hypothesized that SCD related complications may increase with age, even in “high F” individuals. We report a case series of adults with HbSS/Sβ0 and high levels of Hb F who are hydroxyurea naïve or have been treated for ≤ 6 months, and their respective complication profile.

Aims:

To report a case series of adults with HbSS/Sβ0 with high levels of Hb F and their respective complication profile.

Methods:

After obtaining IRB approval, we performed a comprehensive chart review of 10 patients with SCD and Hb F levels > 15%, who had never been on hydroxyurea, or were treated for ≤6 months. Electronic medical records were reviewed for VOCs, chronic opioid therapy, ACS, AVN, retinopathy, pneumonia, leg ulcers, splenomegaly/infarction, pulmonary hypertension, cardiomyopathy/infarction, and chronic kidney disease. All events were confirmed by supportive laboratory or imaging data. Available Hb F levels were averaged for each patient from all hemoglobin electrophoresis studies recorded in the patient's electronic medical record (EMR) and are presented as mean ± SD. Laboratory values are a mean of up to three values obtained at steady state. In a subset of patients, cellular distribution of Hb F by flow cytometry was performed following fixation and permeabilization of RBCs and incubation with an antibody against Hb F directly conjugated with FITC.

Results:

Our cohort consisted of 10 patients, 4 men and 6 women, age range from 23 to 72 years.Genotypes included 9 patients with HbSS, and 1 with HbS/β0. Available data in the EMR ranged from 3 to 11 years. Mean Hb F levels ranged from 14.80% to 29.50%, SD ± 4.76. Clinical data shows increasing complications with age in Table 1. Of note, 9/10 patients were taking chronic opioids for pain management and four had leg ulcers. Patients 3 and 5 for which flow cytometry data is available, revealed heterocellular distribution of Hb F. Laboratory data notable for minimal levels of hemolysis in most patients.

Summary/Conclusion:

Most individuals with SCD living in in high resources countries now reach adulthood. Therefore the disease profile that was previously studied and reported mostly in the pediatric population is evolving. High levels of Hb F appear to delay the onset of complications, but do not completely prevent them, perhaps due to a heterocellular distribution of Hb F in some patients. Therefore, even with Hb F concentration of as high as ∼30 %, some patients still suffer from chronic pain, frequent hospitalizations for VOC's, and vasculopathic changes, such as leg ulcers. The number of complications increases with age. Therefore, additional therapy and close vigilance may be necessary when treating sickle cell patients with high levels of Hb F, especially with increasing age.

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