From the Guidelines
Elevated transferrin saturation (TSAT) is primarily caused by iron overload conditions, with hereditary hemochromatosis being the most common genetic cause, as stated in the 2022 EASL clinical practice guidelines on haemochromatosis 1.
Causes of Elevated TSAT
The causes of elevated TSAT can be categorized into several groups, including:
- Iron overload conditions, such as hereditary hemochromatosis, which is characterized by increased transferrin saturation and liver iron overload, in the absence of anemia and/or reticulocytosis 1
- Repeated blood transfusions
- Excessive oral iron supplementation
- Certain liver diseases, such as alcoholic liver disease, hepatitis C, and non-alcoholic steatohepatitis
- Ineffective erythropoiesis conditions, like thalassemia and sideroblastic anemia
- Some medications, particularly those containing iron
- Inflammatory states, which may occasionally cause elevated TSAT through increased hepcidin production, altering iron metabolism
- Rare causes, including aceruloplasminemia and atransferrinemia
Diagnosis and Treatment
When elevated TSAT is detected, further evaluation with serum ferritin testing is typically recommended, and values above 45% in women or 50% in men warrant investigation 1. Genetic testing for HFE gene mutations may be indicated if hereditary hemochromatosis is suspected, especially with TSAT values exceeding 60%. Treatment depends on addressing the underlying cause, which may include phlebotomy for iron overload conditions or discontinuation of unnecessary iron supplements. According to the 2022 EASL clinical practice guidelines on haemochromatosis, treatment targets for phlebotomy are ferritin <50 µg/L during the induction phase and <100 µg/L during the maintenance phase 1.
Key Considerations
It is essential to note that transferrin saturation can also be increased in patients with advanced cirrhosis, low transferrin, acute liver failure, acute liver injury, and may be confused with a predisposition to hemochromatosis 1. Therefore, a careful assessment of the underlying cause of elevated TSAT is crucial to provide appropriate treatment and prevent complications. The stage of liver fibrosis and other end-organ damage should be carefully assessed at diagnosis, as they determine disease management 1. Patients with advanced fibrosis should be included in a screening program for hepatocellular carcinoma.
Monitoring and Follow-up
Regular monitoring of serum ferritin and transferrin saturation is necessary to assess the effectiveness of treatment and adjust it as needed. Other methods to confirm increased iron deposits include liver biopsy, Magnetic Resonance Imaging (MRI), and spectroscopy or Subsequent Quantum Interference Device (SQUID) 1. However, these methods may have limitations, and the choice of method depends on the individual patient's circumstances and the availability of resources.
From the Research
Causes of Elevated TSAT
- Elevated TSAT levels can be caused by various factors, including hereditary hemochromatosis, transfusional siderosis, and other refractory anemias 2.
- Ineffective erythropoiesis, which is characterized by the accumulation of ring sideroblasts in the bone marrow, can also lead to elevated TSAT levels 3.
- Regular transfusions of packed red cells can cause iron overload, leading to elevated TSAT levels 4.
- Disorders such as thalassemia and myelodysplastic syndromes (MDS) can also cause elevated TSAT levels due to increased duodenal uptake of iron and chronic transfusion dependence 5.
Treatment-Related Causes
- Phlebotomy and iron chelation therapy are common treatments for iron overload, but they can also affect TSAT levels 6, 2.
- Erythrocytapheresis has been shown to reduce treatment duration and TSAT levels in patients with hereditary hemochromatosis compared to phlebotomy 6.
- Iron chelation therapy with deferasirox has been shown to improve hematopoiesis and reduce TSAT levels in patients with aplastic anemia 4.