Long-Term Risks of Thalassemia

Introduction to Thalassemia Complications

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, 2

Heart disease is the predominant cause of death in β-thalassemia major, accounting for approximately 70% of deaths in transfusion-dependent patients 3, 4
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) 5, 6
Heart failure can develop as iron accumulates in cardiac tissue, particularly in patients with abnormal cardiac MRI results 5
Cardiac complications during pregnancy range from 1.1% to 15.6% in women with thalassemia 5, 7

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
Growth hormone deficiency, hypothyroidism, and decreased adrenal reserve are common and may exacerbate heart failure 1

Liver disease is frequent due to transfusion-transmitted hepatitis and iron overload 2
The prevalence of cirrhosis in adult thalassemia major patients ranges from 10% to 20% 2
Hepatocellular carcinoma risk is increasing in the thalassemia population, particularly in patients with cirrhosis 2
Even in low amounts, iron may amplify and propagate the initial toxic effects of other liver toxins, accelerating fibrotic response in the liver 8

Various abnormalities of renal function, including both glomerular and tubular dysfunction, have been reported in thalassemia patients 2
Acute kidney injury can occur due to prerenal causes from sepsis or complications of heart failure 2
Labile iron may lead to acute kidney injury 2
Iron chelators can cause renal side effects in some patients 2

Impaired fertility is common in women with thalassemia major due to hypogonadism 5, 7
Spontaneous miscarriage and fetal loss have been reported in 9% to 33.3% of pregnancies in women with thalassemia 5, 7
Obstetric complications including gestational diabetes, preeclampsia, and hypertension are frequently reported 5, 7

Sepsis is the second-leading cause of death in thalassemia major patients 1
Splenectomized patients are vulnerable to severe infections by encapsulated organisms 1

Before the introduction of chelation therapy, patients with transfused but unchelated β-thalassemia typically died by age 10 4
With improved chelation therapy, the median age at death improved to 35 years by 2000 in the UK 4
Recent advances in management have substantially reduced complications and improved quality of life and life expectancy 5

Severe pre‑conception iron overload can impair placental perfusion and limit fetal growth. 9
Transfusion needs rise during pregnancy to keep hemoglobin near 10 g/dL; stopping chelation worsens iron overload and may further compromise fetal growth. 9
The incidence of preterm delivery is approximately three‑fold higher than in the general obstetric population, with a rise in both early‑preterm and very‑preterm births. 9
Spontaneous miscarriage and fetal loss are reported in roughly 9 %–33 % of pregnancies affected by thalassemia. 9
Gestational diabetes, preeclampsia, and hypertension occur more frequently in thalassemia pregnancies than in non‑affected pregnancies. 9
The likelihood of cesarean delivery is increased by about 30 % (adjusted OR 1.30, 95 % CI 1.03‑1.63), with reported rates ranging from 24 % to 100 % across series due to fetopelvic disproportion, osteoporosis, or maternal complications. 9

Cardiac complications develop in 1.1 %–15.6 % of thalassemia pregnancies; heart disease accounts for roughly 70 % of deaths among transfusion‑dependent thalassemia patients. 9

Mandatory pre‑conception evaluation should include cardiac MRI T2* for iron quantification, comprehensive echocardiography, and assessment of hepatic iron burden. 9
Women with severe cardiac or hepatic iron overload are advised to intensify chelation therapy before attempting conception. 9
Throughout pregnancy, hemoglobin should be maintained around 10 g/dL via transfusion; for patients with severe iron overload threatening cardiac function, deferoxamine chelation may be re‑initiated in the late second trimester. 9

Prophylactic anticoagulation with unfractionated heparin or low‑molecular‑weight heparin is recommended, especially for splenectomized patients and those with thalassemia intermedia. 9

Management by a multidisciplinary team at a specialized thalassemia‑expert center is essential to optimize maternal and fetal outcomes. 9