eMedicine Specialties > Hematology > Red Blood Cells and Disorders
Thalassemia, Beta: Treatment & Medication
Updated: Aug 24, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
Patients with thalassemia minor usually do not require any specific treatment. Treatment for patients with thalassemia major includes chronic transfusion therapy, iron chelation, splenectomy, and allogeneic hematopoietic transplantation.- Thalassemia minor
- Patients in the heterozygous state usually do not require treatment.
- Inform patients that their condition is hereditary and that physicians sometimes mistake the disorder for iron deficiency.
- Some pregnant patients with the beta thalassemia trait may develop concurrent iron deficiency and severe anemia; they may require transfusional support if not responsive to iron repletion modalities.
- Thalassemia major
- The goal of long-term hypertransfusional support is to maintain the patient's Hb at 9-10 g/dL, thus improving the patient's sense of well-being while simultaneously suppressing enhanced erythropoiesis. This strategy not only treats the anemia, but also suppresses endogenous erythropoiesis so that extramedullary hematopoiesis and skeletal changes are suppressed.
- Patients receiving transfusion therapy also require iron chelation with desferrioxamine.
- Blood banking considerations for these patients include completely typing their erythrocytes prior to the first transfusion. This procedure helps future crossmatching processes.
- Allogeneic hematopoietic transplantation may be curative in some patients with thalassemia major. An Italian group led by Lucarelli has the most experience with this procedure.1 This group's research documents a 90% long-term survival rate in patients with favorable characteristics (young age, HLA match, no organ dysfunction).
Surgical Care
Patients with thalassemia minor rarely require splenectomy, although the development of bilirubin stones frequently leads to cholecystectomy.
Diet
- Drinking tea may help to reduce iron absorption through the intestinal tract.
- Vitamin C may improve iron excretion in patients receiving iron chelation. Anecdotal reports suggest that large doses of vitamin C can cause fatal arrhythmias when administered without concomitant infusion of deferoxamine.
Activity
Activity may be limited secondary to severe anemia.
Medication
Medical therapy for beta thalassemia primarily involves iron chelation. Deferoxamine is the intravenously administered chelation agent currently approved for use in the United States. Deferiprone is an oral chelation agent, recently approved for use in Europe. While the results of studies on this oral agent are encouraging, complications of hepatic fibrosis may develop.2 Deferiprone currently is not approved for use in the United States. Deferasirox is an orally administered chelation agent approved for use by the US FDA in 2005. The drug was undergoing review or investigation in other countries as of 2005.
Additional treatments under development are experimental protocols to manipulate globin gene expression using gene therapy or using drugs that activate gamma-globin genes. Since fetal globin gene expression is associated with a milder phenotype, approaches to enhance intracellular Hb F levels (by activating gamma-globin gene expression) are under investigation. The 2 most widely studied drugs in this area are butyrates and hydroxyurea.
In a small study, Italia et al evaluated the clinical and hematologic response to hydroxyurea in 79 beta-thalassemia patients in western India with variable clinical severity and correlated the findings with genetic factors.16 One group consisted of 38 beta-thalassemia intermedia patients, and a second group consisted of 41 beta-thalassemia major patients. Both groups were administed hydroxyurea therapy and followed up for 20-24 months. Findings consisted of the following16 :
- Fifty-eight percent of the frequently transfused patients in the beta-thalassemia intermedia group became transfusion independent. Sixteen percent demonstrated a 50% reduction in post-therapy transfusions versus 32% in the beta-thalassemia major group, both correlating with a greater mean fold increase in HbF and gamma mRNA expression levels.
- Forty-one percent of the beta-thalassemia intermedia group also had associated alpha-thalassemia, and 72.7% were XmnI (+/+).
- Of beta-thalassemia intermedia patients who had a clinical and hematologic response to hydroxyurea therapy, 41% had a link to haplotype (- + + - + + - - +) as opposed to haplotype (+ - - - - - - - +), which was more common in patients without such a response. However, response was not associated with the beta-thalassemia mutations.
- Both beta-thalassemia groups showed a significant decrease in serum ferritin.
Overall, the investigators found that clinical response to hydroxyurea in the beta-thalassemia intermedia group was better in patients with alpha-thalassemia, XmnI (+/+), and a higher mean fold increase in gamma mRNA expression.16 In those with beta-thalassemia major, one third showed a partial response.
Obstacles in gene therapy include inability to express high levels of the beta-globin gene in erythroid cells and inability to transduce hematopoietic pluripotent stem cells at high efficiency.
Chelating agents
These agents bind iron and promote excretion.
Deferoxamine (Desferal)
Usually administered as slow subcutaneous infusion through portable pump. Freely soluble in water. Approximately 8 mg of iron bound by 100 mg of deferoxamine. Agent is excreted in bile and urine, resulting in red discoloration. Readily chelates iron from ferritin and hemosiderin but not from transferrin. Most effective when administered as continuous infusion.
Adult
20-40 mg/kg/d SC infused over 8-12 h; may be administered IV/IM if necessary
Pediatric
Administer as in adults
Coadministration of vitamin C improves iron chelation (vitamin C is contraindicated in patients with heart failure because it may exacerbate cardiac dysfunction)
Documented hypersensitivity; patients who do not have acute iron poisoning; severe renal disease and anuria (consider dose reduction after the loading dose)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Compliance may be poor, especially in adolescent children; follow efficacy by monitoring ferritin levels; tachycardia, hypotension, and shock may occur in patients receiving long-term therapy, and could add to the cardiovascular collapse resulting from iron toxicity; GI adverse effects include abdominal discomfort, nausea, vomiting, and diarrhea, which may add to the symptoms of acute iron toxicity; flushing and fever are reported
Deferasirox (Exjade)
Tab for oral susp. Oral iron chelation agent demonstrated to reduce liver iron concentration in adults and children who receive repeated RBC transfusions. Binds iron with high affinity in a 2:1 ratio. Approved to treat chronic iron overload due to multiple blood transfusions. Treatment initiation recommended with evidence of chronic iron overload (ie, transfusion of about 100 mL/kg packed RBCs, about 20 U for 40-kg person, and serum ferritin level is consistently >1000 mcg/L). Serum ferritin should be monitored qmo and dosage adjusted q3-6mo based on ferritin measurements in increments of 5 or 10 mg/kg. If ferritin consistently falls below 500 mcg/L, consider holding drug. Dose should not exceed 30 mg/kg/d.
Adult
Initial: 20 mg/kg PO qd on empty stomach 30 min ac; calculate dose to nearest whole tab
Maintenance: Adjust dose by 5- to 10-mg/kg/d
Note: Dissolve tab completely in water, orange juice, or apple juice, then immediately drink susp; resuspend any remaining residue in small volume of liquid and swallow
Pediatric
<2 years: Not established
>2 years: Administer as in adults
Data limited; do not take with aluminum-containing antacids
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Common adverse effects include diarrhea, nausea, abdominal pain, headache, pyrexia, cough, and rash; may increase serum creatinine and hepatic enzyme levels; decrease dose with persistent elevation of serum creatinine level; may cause auditory and visual disturbances; slight decreases in serum copper and zinc levels may occur; dissolve tab completely in water, orange juice, or apple juice and drink resulting susp immediately (do not swallow tab whole, do not chew or crush)
More on Thalassemia, Beta |
| Overview: Thalassemia, Beta |
| Differential Diagnoses & Workup: Thalassemia, Beta |
 Treatment & Medication: Thalassemia, Beta |
| Follow-up: Thalassemia, Beta |
| Multimedia: Thalassemia, Beta |
| References |
| Further Reading |
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References
Lucarelli G, Galimberti M, Polchi P. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med. Sep 16 1993;329(12):840-4. [Medline]. [Full Text].
Olivieri NF, Brittenham GM, McLaren CE, et al. Long-term safety and effectiveness of iron-chelation therapy with deferiprone for thalassemia major. N Engl J Med. Aug 13 1998;339(7):417-23. [Medline]. [Full Text].
Cohen AR, Galanello R, Pennell DJ, et al. Thalassemia. In: Hematology (Am Soc Hematol Educ Program). 2004:14-34.
Forget BG. Thalassemia Syndromes. In: Hematology: Basic Principles and Practice. 2000:485-509.
Fucharoen S, Winichagoon P. Clinical and hematologic aspects of hemoglobin E beta-thalassemia. Current Opinion in Hematology. 2000;7:106-112. [Medline].
Hoffbrand AV, AL-Refaie F, Davis B. Long-term trial of deferiprone in 51 transfusion-dependent iron overloaded patients. Blood. 1998;91:295-300. [Medline].
Ikuta T, Atweh G, Boosalis V. Cellular and molecular effects of a pulse butyrate regimen and new inducers of globin gene expression and hematopoiesis. Ann N Y Acad Sci. 1998;850:87-99. [Medline].
Koshy M, Dorn L, Bressler L. 2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. Blood. 2000;96:2379-2384. [Medline].
Malik P, Arumugam PI. Gene Therapy for {beta}-Thalassemia. In: Hematology (Am Soc Hematol Educ Program). 2005:45-50.
May C, Rivella S, Callegari J. Therapeutic haemoglobin synthesis in beta-thalassaemic mice expressing lentivirus-encoded human beta-globin. Nature. 2000;406:82-86. [Medline].
Perrine SP. Fetal Globin Induction--Can It Cure {beta} Thalassemia?. In: Hematology (Am Soc Hematol Educ Program). 2005:38-44.
Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. Sep 15 2005;353(11):1135-46. [Medline].
Schrier SL, Angelucci E. New strategies in the treatment of the thalassemias. Annu Rev Med. 2005;56:157-71. [Medline].
Thein SL. Pathophysiology of {beta} Thalassemia--A Guide to Molecular Therapies. In: Hematology (Am Soc Hematol Educ Program). 2005:31-7.
Weatherall DJ, Clegg JB. Genetic disorders of hemoglobin. Semin Hematol. Oct 1999;36(4 Suppl 7):24-37. [Medline].
Italia KY, Jijina FJ, Merchant R, et al. Response to hydroxyurea in beta thalassemia major and intermedia: experience in western India. Clin Chim Acta. Sep 2009;407(1-2):10-5. [Medline].
Tan JA, Tan KL, Omar KZ, et al. Interaction of Hb South Florida (codon 1; GTG-->ATG) and HbE, with beta-thalassemia (IVS1-1; G-->A): expression of different clinical phenotypes. Eur J Pediatr. Sep 2009;168(9):1049-54. [Medline].
Galanello R, Sanna S, Perseu L, et al. Amelioration of Sardinian beta-zero thalassemia by genetic modifiers. Blood. Aug 20 2009;epub ahead of print. [Medline].
Further Reading
- Cooley Anemia
- Hematologic Disease and Pregnancy [in the Obstetrics and Gynecology section]
- Hemoglobin H Disease [in the Pediatrics: General Medicine section]
- Iron Deficiency Anemia
- Thalassemia [in the Pediatrics: General Medicine section]
- Thalassemia [in the Radiology section]
- Thalassemia, Alpha
- Thalassemia Intermedia [in the Pediatrics: General Medicine section]
Clinical Trials
- Assess the Feasibility and Safety of Granulocyte Colony Stimulating Factor (GCSF) Mobilization of CD34+ Hematopoietic Progenitor Cells in Patients With Betathalassemia Major
- Evaluating the Efficacy of Deferasirox in Transfusion Dependent Chronic Anaemias (Myelodysplastic Syndrome, Beta-Thalassaemia Patients) With Chronic Iron Overload
- Evaluating the Safety of G-CSF Mobilization in Individuals With Beta Thalassemia Major
- Genetic Factors Affecting the Severity of Beta Thalassemia
- Phase 1/2 Study of HQK-1001 in Patients With Beta Thalassemia
- Stem Cell Transplant in Sickle Cell Disease and Thalassemia
National Guideline Clearinghouse
- Carrier screening for thalassemia and hemoglobinopathies in Canada. Society of Obstetricians and Gynaecologists of Canada - Medical Specialty Society. 2008 Oct. 10 pages. NGC:006773
- Hemoglobinopathies in pregnancy. American College of Obstetricians and Gynecologists - Medical Specialty Society. 2007 Jan. 9 pages. NGC:005700
- Screening for iron deficiency anemia - including iron supplementation for children and pregnant women. United States Preventive Services Task Force - Independent Expert Panel. 1996 (revised 2006). 12 pages. NGC:004965
- Surgical treatment of disease and injuries of the spleen. Society for Surgery of the Alimentary Tract, Inc - Medical Specialty Society. 2004 Feb 21. 3 pages. NGC:003836
Keywords
beta-thalassemia, beta thalassemia syndromes, Cooley anemia, Mediterranean anemia, thalassemia major, thalassemia intermedia, thalassemia minor, erythroblastic anemia, thalassemia trait, hemoglobin E, hereditary disorder
