eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Thalassemia, Beta: Differential Diagnoses & Workup

Author: Kenichi Takeshita, MD, Adjunct Associate Professor, Department of Medicine, Division of Hematology, New York University School of Medicine; Medical Director, Clinical Research and Development, Celgene
Contributor Information and Disclosures

Updated: Aug 24, 2009

Differential Diagnoses

Lead Nephropathy

Other Problems to Be Considered

Additional causes of microcytic anemia:

Workup

Laboratory Studies

  • The diagnosis of beta thalassemia minor usually is suggested by the presence of an isolated, mild microcytic anemia, target cells on the peripheral blood smear, and a normal red blood cell count. An elevation of Hb A2 (2 alpha-globin chains complexed with 2 delta-globin chains) demonstrated by electrophoresis or column chromatography confirms the diagnosis of beta thalassemia trait. The Hb A2 level in these patients usually is approximately 4-6%. In rare cases of concurrent severe iron deficiency, the increased Hb A2 level may not be observed, although it becomes evident with iron repletion. The increased Hb A2 level also is not observed in patients with the rare delta-beta thalassemia trait.
  • An elevated Hb F level is not specific to patients with the beta thalassemia trait.
  • Free erythrocyte porphyrin (FEP) tests may be useful in situations in which the diagnosis of beta thalassemia minor is unclear. FEP level is normal in patients with the beta thalassemia trait, but it is elevated in patients with iron deficiency or lead poisoning.
  • Alpha thalassemia is characterized by genetic defects in the alpha-globin gene, and this variant has features similar to beta thalassemia. Patients with this disorder have normal Hb A2 levels. Establishing the diagnosis of the alpha thalassemia trait requires measuring either the alpha-beta chain synthesis ratio or performing genetic tests of the alpha-globin cluster (by Southern blot or polymerase chain reaction tests).
  • Iron studies (iron, transferrin, ferritin) are useful in excluding iron deficiency and the anemia of chronic disorders as the cause of the patient's anemia.
  • Patients may require a bone marrow examination to exclude certain other causes of microcytic anemia. Physicians must perform an iron stain (Prussian blue stain) to diagnose sideroblastic anemia (ringed sideroblasts).
  • The Mentzer index is defined as mean corpuscular volume per red cell count. An index of less than 13 suggests that the patient has the thalassemia trait, and an index of more than 13 suggests that the patient has iron deficiency.
  • Prenatal diagnosis is possible (see Other Tests).

Imaging Studies

  • The skeletal abnormalities observed in patients with thalassemia major include an expanded bone marrow space, resulting in the thinning of the bone cortex. These changes are particularly dramatic in the skull, which may show the characteristic hair-on-end appearance. Bone changes also can be observed in the long bones, vertebrae, and pelvis.
  • The liver and biliary tract of patients with thalassemia major may show evidence of extramedullary hematopoiesis and damage secondary to iron overload resulting from multiple transfusion therapy. Transfusion also may result in infection with the hepatitis virus, which leads to cirrhosis and portal hypertension. Gallbladder images may show the presence of bilirubin stones.
  • The heart is a major organ that is affected by iron overload and anemia. Cardiac dysfunction in patients with thalassemia major includes conduction system defects, decreased myocardial function, and fibrosis. Some patients also develop pericarditis.

Other Tests

Molecular diagnostic tests can precisely determine whether a mutation is present any time after approximately 8 weeks of gestation. The physician can establish the diagnosis in utero using DNA obtained from amniocentesis or by chorionic villus sampling. In most laboratories, the DNA is amplified using the polymerase chain reaction technique and then is analyzed for the presence of the thalassemia mutation using a panel of oligonucleotide probes corresponding to known thalassemia mutations.

Procedures

  • Physicians often use splenectomy to decrease transfusion requirements. Because postsplenectomy sepsis is possible, defer this procedure until the patient is older than 6-7 years. In addition, to minimize the risk of postsplenectomy sepsis, vaccinate the patient against Pneumococcus species, Meningococcus species, and Haemophilus influenzae. Also, administer penicillin prophylaxis to children after splenectomy.
  • Patients with thalassemia minor may have bilirubin stones in their gall bladder and, if symptomatic, may require treatment. Perform a cholecystectomy using a laparoscope or at the time of the splenectomy.

Histologic Findings

The peripheral blood smear shows microcytic hypochromic red cells with target cells and anisopoikilocytosis.

Peripheral smear in beta-zero thalassemia minor s...

Peripheral smear in beta-zero thalassemia minor showing microcytes (M), target cells (T), and poikilocytes.

[ CLOSE WINDOW ]
Peripheral smear in beta-zero thalassemia minor s...

Peripheral smear in beta-zero thalassemia minor showing microcytes (M), target cells (T), and poikilocytes.



Peripheral smear from a patient with beta-zero th...

Peripheral smear from a patient with beta-zero thalassemia major showing more marked microcytosis (M) and anisopoikilocytosis (P) than in thalassemia minor. Target cells (T) and hypochromia are prominent.

[ CLOSE WINDOW ]
Peripheral smear from a patient with beta-zero th...

Peripheral smear from a patient with beta-zero thalassemia major showing more marked microcytosis (M) and anisopoikilocytosis (P) than in thalassemia minor. Target cells (T) and hypochromia are prominent.

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
[ CLOSE WINDOW ]

References

  1. 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].

  2. 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].

  3. Cohen AR, Galanello R, Pennell DJ, et al. Thalassemia. In: Hematology (Am Soc Hematol Educ Program). 2004:14-34.

  4. Forget BG. Thalassemia Syndromes. In: Hematology: Basic Principles and Practice. 2000:485-509.

  5. Fucharoen S, Winichagoon P. Clinical and hematologic aspects of hemoglobin E beta-thalassemia. Current Opinion in Hematology. 2000;7:106-112. [Medline].

  6. 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].

  7. 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].

  8. Koshy M, Dorn L, Bressler L. 2-deoxy 5-azacytidine and fetal hemoglobin induction in sickle cell anemia. Blood. 2000;96:2379-2384. [Medline].

  9. Malik P, Arumugam PI. Gene Therapy for {beta}-Thalassemia. In: Hematology (Am Soc Hematol Educ Program). 2005:45-50.

  10. 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].

  11. Perrine SP. Fetal Globin Induction--Can It Cure {beta} Thalassemia?. In: Hematology (Am Soc Hematol Educ Program). 2005:38-44.

  12. Rund D, Rachmilewitz E. Beta-thalassemia. N Engl J Med. Sep 15 2005;353(11):1135-46. [Medline].

  13. Schrier SL, Angelucci E. New strategies in the treatment of the thalassemias. Annu Rev Med. 2005;56:157-71. [Medline].

  14. Thein SL. Pathophysiology of {beta} Thalassemia--A Guide to Molecular Therapies. In: Hematology (Am Soc Hematol Educ Program). 2005:31-7.

  15. Weatherall DJ, Clegg JB. Genetic disorders of hemoglobin. Semin Hematol. Oct 1999;36(4 Suppl 7):24-37. [Medline].

  16. 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].

  17. 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].

  18. 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].

[ CLOSE WINDOW ]

Further Reading

Related eMedicine Topics

Clinical Trials

National Guideline Clearinghouse

[ CLOSE WINDOW ]

Keywords

beta-thalassemia, beta thalassemia syndromes, Cooley anemia, Mediterranean anemia, thalassemia major, thalassemia intermedia, thalassemia minor, erythroblastic anemia, thalassemia trait, hemoglobin E, hereditary disorder

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Kenichi Takeshita, MD, Adjunct Associate Professor, Department of Medicine, Division of Hematology, New York University School of Medicine; Medical Director, Clinical Research and Development, Celgene
Kenichi Takeshita, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Wadie F Bahou, MD, Chief, Division of Hematology, Hematology/Oncology Fellowship Director, Professor, Department of Internal Medicine, State University of New York at Stony Brook
Wadie F Bahou, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Marcel E Conrad, MD, (Retired) Distinguished Professor of Medicine, University of South Alabama
Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group
Disclosure: No financial interests None None

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.