https://www.journal-of-hepatology.eu/article/S0168-8278(02)00429-4/pdf

Liver fibrosis – from bench to bedside

Iron-chelating therapy and the treatment of thalassemia

Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload.

Beta-thalassemia

Imaging iron stores in the brain using magnetic resonance imaging.

MRI R2 and R2* mapping accurately estimates hepatic iron concentration in transfusion-dependent thalassemia and sickle cell disease patients

Background and Methods We tested the usefulness of measuring the hepatic iron concentration to evaluate total body iron stores in patients who had been cured of thalassemia major by bone marrow transplantation and who were undergoing phlebotomy treatment to remove excess iron. Results We began treatment with phlebotomy a mean (±SD) of 4.3±2.7 years after transplantation in 48 patients without hepatic cirrhosis. In the group of 25 patients with liver-biopsy samples that were at least 1.0 mg in dry weight, there was a significant correlation between the decrease in the hepatic iron concentration and total body iron stores (r=0.98, P<0.001). Assuming that the hepatic iron concentration is reduced to zero with complete removal of body iron stores during phlebotomy, the amount of total body iron stores (in milligrams per kilogram of body weight) is equivalent to 10.6 times the hepatic iron concentration (in milligrams per gram of liver, dry weight). With the use of this equation, we could reliably estimate tot...

https://www.nejm.org/doi/pdf/10.1056/NEJM200008033430503

Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major

Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation

Marta Ripalti

Papers

Hepatic Iron Concentration and Total Body Iron Stores in Thalassemia Major

Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation

Marrow transplantation for patients with thalassemia: results in class 3 patients.

Persistence of Mixed Chimerism in Patients Transplanted for the Treatment of Thalassemia

Phlebotomy to Reduce Iron Overload in Patients Cured of Thalassemia by Bone Marrow Transplantation