Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD), but causes significant iron overload. Iron overload is anticipated in patients on chronic transfusion and treatment is more likely to be prescribed. In chronically transfused patients, red cell exchange transfusion significantly reduces iron loading; however, if the patient is already significantly iron overloaded, chelation will have to be added.

In contrast to many inherited anemias, in SCD, **iron overload does not occur without blood transfusion**.[4] The rate of iron loading in SCD **depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major**, but **iron loading can be minimal with automated erythrocyte apheresis**.[4] Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at **controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma**.[4]

Patients with sickle cell disease who receive blood transfusions are also at risk of organ damage due to transfusional iron overload, even though this may be less severe than in patients with thalassaemia major. The primary goal of iron chelation therapy is to prevent iron overload and subsequent tissue damage from free iron, thereby reducing morbidity and mortality. Long-term transfusion therapy for conditions such as sickle cell disease can therefore result in significant iron accumulation and necessitates regular monitoring and chelation when thresholds are exceeded.

New research presented at the 2025 ASH Annual Meeting and Exposition found that iron overload is a prevalent problem for individuals receiving blood transfusions to treat their sickle cell disease. The article states that "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."

"Patients with sickle cell disease (SCD) often require blood transfusion starting in early childhood. Multiple blood transfusions on a chronic basis lead to excessive accumulation of iron, especially in adults with sickle cell anemia (SS) that is progressively increasing in size." "The majority of adults with SS, however, require episodic blood transfusions on a chronic basis and, hence, are at risk to develop iron overload." "Taken together, the data indicate that ... a significant number of adults with SS have iron overload; and (3) iron overload seems to be a predisposing factor of disease severity."

The study notes that blood transfusions in sickle cell disease are associated with complications including iron overload, and states that "the major and unavoidable complication of blood transfusions in SCD is systemic iron overload." It also says patients with transfusion-dependent anemia can develop fatal cardiac and endocrine toxicities from iron overload.

Sickle cell disease is a frequent indication for chronic transfusion, which can cause iron overload. The article further notes that excess iron often affects the liver, but not the heart, in many patients with sickle cell disease.

"SCD patients often require chronic RBC transfusion therapy which can result in complications, such as iron overload, alloimmunization and infection." "Chronic transfusion therapy is used to prevent stroke and manage other severe SCD complications, but this benefit must be balanced against transfusion-related harms including transfusional iron overload."

In this study we examined the **extent of iron overload** as well as the presence of liver injury and the predictive value of ferritin in estimating iron overload in patients with sickle cell disease receiving **chronic red blood cell transfusion therapy**.[6] The severity of iron overload was assessed by measuring **liver iron concentration (LIC)** and serum ferritin…[6] Patients with sickle cell disease undergoing **chronic transfusion therapy accumulate substantial iron stores**, often in the range seen in other transfusion-dependent anemias.[6]

"Iron overload indices rise linearly with transfusion rate in patients with sickle cell disease." "The resultant significant increase in survival uncovers new complications due to much longer exposure to anemia and to iron, which must be considered in long-term therapeutic strategies." "Severe iron overload still causes significant morbidity and mortality in many parts of the world."

Chronic transfusion therapy is being used more frequently to prevent and treat the complications of sickle cell disease. Previous studies have shown that the iron overload that results from such therapy in other patient populations is associated with significant morbidity and mortality. In this study we examined the extent of iron overload as well as the presence of liver injury in children with sickle cell disease who receive chronic red blood cell transfusions. Quantitative liver iron was highly correlated with the months of transfusion (R = 0.795, P < .001).

"Accumulation of excess body iron can result from ... chronic transfusion therapy for anemia in patients with ineffective erythropoiesis, ineffective hemoglobin production, or chronic hemolysis, such as those with b-thalassemia, sickle cell disease, or myelodysplastic syndromes." "Patients receiving regular RBC transfusions, however, unavoidably and invariably develop cumulative iron overload and therefore are at risk for iron toxicity." "In transfusional iron overload, free iron from erythrophagocytosis of transfused RBCs accumulates in macrophages after iron storage proteins become saturated."

This clinical trial enrolled patients with sickle cell anemia and transfusional iron overload, defining overload in part by a lifetime history of many blood transfusions or elevated liver iron and ferritin. The study’s purpose was to test whether treating iron overload in repeatedly transfused sickle cell patients could reduce morbidity.

"In contrast to thalassemia patients who require routine transfusion, most patients with sickle cell disease are iron overloaded because of intermittent transfusions throughout their life." "No evidence suggests that sickle cell disease patients should be spared the fatal consequences of iron overload. Therefore, a comprehensive program designed to monitor and treat iron overload is necessary." "Iron overload in sickle cell patients is often undetected and/or not treated."

"The excess iron from the transfused erythrocytes gradually accumulates in various tissues, causing morbidity and mortality." "Transfusion-induced iron overload is a common iatrogenic problem in patients who require chronic blood transfusions for the treatment of congenital and acquired anemias, including sickle cell disease."

Build-up of **extra iron can damage the liver, heart, and endocrine system.** The risk of life-threatening complications increases as iron builds up in the organs.[2] The death rate is **3× higher** among people with sickle cell disease and transfusion-dependent thalassemia with **transfusional iron overload** compared with those without overload.[2] Based on a study of people who were **currently on or had received regular transfusion therapy and confirmed to have iron overload** (liver iron concentration >10 mg/g dry weight or ferritin ≥2,000 ng/mL), including 199 people with sickle cell disease who received **regular transfusions** and 64 sickle cell disease controls who did not receive transfusions.[2]

In this study, transfusion-dependent children with sickle cell disease demonstrated increased iron deposition with duration of transfusion, despite chelation. The severity of iron overload correlated with the cumulative duration of chronic transfusion therapy. These findings confirm that long-term regular transfusions in sickle cell disease are associated with progressive iron accumulation that requires monitoring and management.

Transfusion-induced iron overload is a systemic iron excess that **results from repeated blood transfusions**, commonly seen in patients with chronic anemias including sickle cell disease.[9] Patients with sickle cell disease who receive **chronic red blood cell transfusion therapy** are at risk for developing significant **iron overload**, necessitating monitoring of ferritin and liver iron and the use of **iron chelation therapy**.[9] The article discusses management of transfusion-induced iron overload, citing data on **severity of iron overload in patients with sickle cell disease receiving chronic transfusions**.[9]

Chronic RBC transfusions play a prominent role in the treatment of this disease by improving oxygenation through addition of normal RBC. The document focuses on preventative measures and earlier intervention against iron overload in chronically transfused sickle cell patients.

People with sickle cell disease can develop iron overload, and it can also happen after a high number of blood transfusions. Iron chelation therapy is a common way to reduce iron overload during chronic blood transfusions.

"Brittenham describes the management of iron overload in patients with sickle cell anemia who undergo transfusions." "Transfusional iron overload remains a major complication in patients with sickle cell anemia who receive chronic transfusion therapy and requires effective iron-chelating strategies to prevent organ damage."

The article explains that iron overload is a recognized complication of frequent transfusion therapy in sickle cell disease and that chelation or exchange transfusion may be needed to prevent or treat excess iron accumulation.

Clinical guidelines and expert reviews on sickle cell disease consistently note that chronic or regular transfusion therapy (such as for stroke prevention) leads to progressive iron accumulation because each unit of transfused red cells contains about 200–250 mg of iron and humans have no active mechanism to excrete excess iron. Over years, this transfusional iron overload in sickle cell patients can cause organ damage (liver, heart, endocrine glands) unless managed with chelation or exchange transfusion.