What are the long-term complications of thalassemia?

Long-Term Risks of Thalassemia

Iron overload is the primary cause of long-term complications in thalassemia, leading to significant morbidity and mortality through damage to multiple organ systems, particularly the heart, liver, and endocrine glands. 1

Cardiovascular Complications

• Heart disease is the predominant cause of death in β-thalassemia major, accounting for approximately 70% of deaths in transfusion-dependent patients 1, 2
• Iron cardiomyopathy is the most feared complication but is potentially reversible with proper iron chelation therapy 1
• Arrhythmias are common in patients with severe iron overload, with atrial fibrillation being the most frequent type (occurring in up to 14% of patients with severe iron overload) 1
• Heart failure can develop as iron accumulates in cardiac tissue, particularly in patients with T2* values <6 ms on cardiac MRI 1
• Cardiac complications during pregnancy range from 1.1% to 15.6% in women with thalassemia 1

Endocrine Complications

• Multiple endocrine glands are affected by iron overload, including the pancreas, pituitary, thyroid, parathyroid, and adrenal glands 1
• Hypogonadotropic hypogonadism is the most common endocrinopathy in thalassemia major 1
• Diabetes mellitus and insulin resistance are strongly associated with cardiac iron deposition 1, 3
• Growth hormone deficiency, hypothyroidism, and decreased adrenal reserve are common and may exacerbate heart failure 1
• The risk of developing a new endocrine complication within 5 years is approximately 9.7% in patients on deferasirox therapy 4
• Endocrine complications are more prevalent in patients with very high liver iron concentration (>30 mg Fe/g dry liver) 3

Hepatic Complications

• Liver disease is frequent due to transfusion-transmitted hepatitis and iron overload 1
• The prevalence of cirrhosis in adult thalassemia major patients ranges from 10% to 20% 1
• Hepatocellular carcinoma risk is increasing in the thalassemia population, particularly in patients with cirrhosis 1
• Even in low amounts, iron may amplify and propagate the initial toxic effects of alcohol and viruses, accelerating fibrotic response in the liver 1
• Hepatitis C positivity has been reported in approximately 20.8% of patients with severe iron overload 3

Renal Complications

• Various abnormalities of renal function, including both glomerular and tubular dysfunction, have been reported in thalassemia patients 1
• Acute kidney injury can occur due to prerenal causes from sepsis or complications of heart failure (cardiorenal syndrome) 1
• Labile iron may lead to acute kidney injury 1
• Iron chelators (deferoxamine and deferasirox) can cause renal side effects in some patients 1

Reproductive Complications

• Impaired fertility is common in women with thalassemia major due to hypogonadism 1
• Spontaneous miscarriage and fetal loss have been reported in 9% to 33.3% of pregnancies in women with thalassemia 1
• Obstetric complications including gestational diabetes, preeclampsia, and hypertension are frequently reported 1

Other Complications

• Sepsis is the second-leading cause of death in thalassemia major patients 1
• Splenectomized patients are vulnerable to severe infections by encapsulated organisms 1
• Chronic transfusion therapy leads to alloimmunization in approximately 10-20% of patients 5
• Adverse transfusion reactions occur in approximately 50% of patients 5
• Pain (25%-69%) and psychiatric disorders (25%-30%) significantly impact quality of life 5

Monitoring and Management Considerations

• Regular assessment of cardiac iron by T2* MRI is essential for early detection of cardiac iron overload 6
• Liver iron concentration (LIC) correlates significantly with serum ferritin levels and can predict risk of complications 3
• Iron chelation therapy is crucial to prevent and treat iron-related complications 2, 7
• Available chelators include deferoxamine, deferiprone, and deferasirox, each with different efficacy profiles 2, 7
• Despite improvements in transfusion practices and iron monitoring, patients with transfusion-dependent thalassemia remain at increased risk for early mortality 5

Prognosis

• Before the introduction of chelation therapy, patients with transfused but unchelated β-thalassemia typically died by age 10 2
• With improved chelation therapy, the median age at death improved to 35 years by 2000 in the UK 2
• Recent advances in management have substantially reduced complications and improved quality of life and life expectancy 1, 7