Iron Overload Remains Prevalent in Individuals with Sickle Cell Disease Despite Guidelines

Although condition is very treatable, less than half of patients receive chelation

(ORLANDO – December 6, 2025) — New research presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, finds that iron overload is a prevalent problem for individuals receiving blood transfusions to treat their sickle cell disease. These findings are based on data from the ASH Research Collaborative (ASH RC) Data Hub and suggest a lack of adherence to screening and management guidelines.

“Transfusions are an effective treatment for managing sickle cell disease, but iron from frequent transfusions can accumulate in the body and cause substantial organ damage or even death,” said lead study author, Samuel R. Wilson, MD, MSCR, assistant professor of medicine in the Division of Hematology at the University of North Carolina School of Medicine in Chapel Hill. “Iron overload has been very clearly linked to morbidity and mortality in other diseases like beta-thalassemia, but it’s more difficult to untangle these patterns in sickle cell disease, given that transfusions (which can cause iron overload) are most frequently given to the sickest patients who are already at higher risk for adverse effects.”

For this study, Dr. Wilson and his research team sought to determine the prevalence of iron overload in individuals with sickle cell disease, as well as screening and diagnosis practices as compared to guideline recommendations. Using 2024 data from the ASH RC Data Hub, they identified 3,723 individuals with a confirmed sickle cell disease diagnosis and sufficient follow up for analysis. All study participants were 18 years or older and had at least one year of follow up. In the absence of liver iron concentration data, the researchers determined iron overload using the lowest annual ferritin value with cutoffs derived from their prior study: unlikely (ferritin <1000 ng/mL or not reported), possible (ferritin 1000 – 2500 ng/mL), or probable (ferritin>2500 ng/mL).

Of the total study cohort, 378 (10%) were classified as probable iron overload, 328 (8.8%) as possible, and 3,017 (81%) as unlikely. Those with the more common subtype of sickle cell disease, hemoglobin SS (HbSS), who made up 64% of the overall cohort (n = 2,394), had the highest prevalence for possible iron overload (11.7%, n=281) and probable iron overload (14.5%, n=347). Altogether, individuals with possible or probable iron overload presented more frequently to the emergency department and had higher rates of hospital admissions during the study period.

“We found that over a quarter of individuals with the HbSS type of sickle cell disease had probable or possible iron overload,” said Dr. Wilson. “This is a common problem that needs to be addressed.”

Recent guidelines recommend evaluating for liver iron overload with an MRI of the abdomen rather than measuring ferritin levels, which tend to be less reliable. However, Dr. Wilson and his team found that abdominal MRIs were obtained in only 27.8% (n=105) of the probable group, 22.9% (75) of the possible group, and 2.7% (82) of the unlikely group. Additionally, iron chelation, the therapy used to reduce iron in the body, was prescribed to only 43.9% (n=166) of those with probable iron overload, 31.7% (n=104) of those with possible, and 2.7% (n=82) of those with unlikely.

“This is a very treatable condition, with three available therapies approved by the U.S. Food and Drug Administration,” said Dr. Wilson. “Patients with iron overload likely won’t experience any symptoms until there is more significant organ damage from chronic iron overload, so following guidelines is essential to ensure that patients are routinely monitored, receive a timely diagnosis, and undergo appropriate treatment prior to the development of complications.”

Given the study’s retrospective nature, it has some limitations, including selection bias (only sites with more than 50% of patients with ferritin values were included), the use of ferritin as a surrogate measure of liver iron concentration, and the cross-sectional analysis, which limits the ability to investigate whether iron chelation therapy improves outcomes.

Dr. Wilson and his team plan to do some longitudinal to investigate whether the treatment of iron overload improves clinical outcomes in this patient population. He noted that more work is needed to understand and address barriers that prevent individuals at risk from being screened, diagnosed, and treated for iron overload.
“The decision to get a blood transfusion can be very nuanced for individuals with sickle cell disease, and data like these can help empower these patients to decide whether it’s the right option for them,” he said.

The American Society of Hematology (ASH) (hematology.org) is the world’s largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. Since 1958, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. Join the #Fight4Hematology by visiting hematology.org/fight4hematology. 

The Blood journals (https://ashpublications.org/journals) are the premier source for basic, translational, and clinical hematologic research. The Blood journals publish more peer-reviewed hematology research than any other academic journals worldwide. 

Contact: 
Claire Whetzel, 202-629-5085
cwhetzel@hematology.org