Sickle Cell, and iron overload

Living with Sickle Cell Disease means that every treatment comes with its own side effects. Today, we will focus on the dangers of blood exchange or transfusion and the risk of iron overload.

In conditions like Sickle Cell Disease, regular blood transfusions or exchanges are used to replace damaged red blood cells with healthy ones. This process helps prevent complications such as pain crises, strokes, and organ damage caused by the sickling of red blood cells.

However, every unit of transfused or exchanged blood introduces approximately 200–300 mg of iron into the body. The human body has no natural mechanism for actively excreting excess iron, meaning that, with every transfusion, iron gradually accumulates.

Normally, the body maintains a delicate iron balance through dietary intake and regulated absorption in the small intestine. Any excess iron absorbed or ingested is stored in the liver, spleen, and bone marrow. In a healthy individual, iron homeostasis is tightly regulated, allowing the body to absorb only the amount needed for normal functions.

In individuals undergoing repeated blood exchanges or transfusions, however, the amount of iron introduced into their bodies far exceeds what the body can handle. As each transfusion adds more iron, it begins to accumulate in the liver, heart, pancreas, and other organs. Over time, this leads to a condition called secondary iron overload, where toxic levels of iron are stored in tissues throughout the body.

 While iron is essential for life, in high concentrations, it becomes highly toxic to cells and tissues. Excess iron deposits in organs can lead to oxidative stress, damaging cellular components such as lipids, proteins, and DNA. Over time, this can result in permanent organ damage and impaired function in several critical systems of the body.

Liver damage (Hepatic iron overload)

The liver is the primary organ responsible for storing excess iron, making it particularly vulnerable to iron toxicity. Hepatic iron overload can cause inflammation of liver cells (hepatitis), leading to fibrosis (scarring) and eventually cirrhosis, where healthy liver tissue is replaced by scar tissue, impairing liver function. If left untreated, this condition can progress to liver cancer or liver failure.

Cardiac complications (Cardiac iron overload)

Iron deposits in the heart can lead to serious cardiac conditions, including cardiomyopathy, where the heart muscle becomes weakened or enlarged. This can progress to heart failure or arrhythmias (irregular heartbeats). Iron-induced cardiomyopathy is one of the leading causes of death in patients with transfusion-related iron overload if left unchecked.

Endocrine dysfunction

Excess iron can accumulate in glands such as the pancreas, leading to conditions like diabetes mellitus due to impaired insulin production. It can also affect the thyroid, pituitary, and adrenal glands, resulting in various hormonal imbalances. In women, it may impair ovarian function, contributing to infertility and other reproductive health issues.

Skin and joint problems

Iron deposits can lead to a darkening of the skin, known as bronzing, and contribute to joint issues, as excess iron can accumulate in the joints, causing arthritis-like symptoms.

Given the dangers of iron overload, managing excess iron in patients undergoing regular blood exchanges is critical. Iron chelation therapy, which uses specific medications, is the primary treatment for iron overload.

Chelating agents such as deferoxamine, deferasirox, or deferiprone bind to excess iron in the bloodstream, allowing it to be excreted from the body through urine or faeces. This helps reduce iron levels and minimise organ damage. Regular monitoring of iron levels through serum ferritin tests or liver biopsy ensures that chelation therapy is working effectively.

Some common chelating agents include:

Deferoxamine (Desferal)

Administered via injection (subcutaneous or intravenous), it is effective for chronic iron overload but requires continuous infusion, which can be inconvenient.

Deferasirox (Exjade, Jadenu)

Administered orally (tablet or granules dissolved in water), this is a more convenient option for many patients.

Deferiprone (Ferriprox)

Administered orally (tablet or liquid), it is often used for patients who cannot tolerate other chelators or require additional chelation support.

In addition to chelation therapy, managing iron overload involves careful monitoring and potentially limiting the number of transfusions when medically feasible. For patients with Sickle Cell Disease (SCD), alternative treatments such as hydroxyurea or haematopoietic stem cell transplantation may reduce the need for regular transfusions. Emerging therapies, such as gene therapy, also hold promise for reducing reliance on transfusions and, by extension, the risk of iron overload.

Psychological and quality-of-life considerations:

The dangers of iron overload extend beyond physical health. The need for regular chelation therapy, combined with the chronic nature of diseases like SCD, can lead to psychological distress. Patients may experience feelings of frustration or anxiety due to the invasive and lifelong nature of treatment. Additionally, iron overload can diminish the overall quality of life, as managing the condition requires frequent hospital visits, ongoing medication, and significant lifestyle changes.

While blood transfusions or exchanges are life-saving treatments for many patients with Sickle Cell Disease and other chronic conditions, they carry the significant risk of iron overload. The of iron, over time, can lead to serious, potentially fatal organ damage, particularly in the liver, heart, and endocrine system. Managing iron overload is a critical aspect of care for these patients, with iron chelation therapy serving as the primary defence against its harmful effects.

With emerging therapies and improved management strategies, there is hope that the risks of iron overload can be minimized, improving the long-term health and quality of life for affected individuals. However, ongoing awareness, research, and patient education are essential in addressing this complex and life-threatening issue.

Until next time.

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