Alpha Thalassemia Workup

  • Author: Samer A Bleibel, MD; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Jan 10, 2012
 

Laboratory Studies

  • Trait -a/aa
    • Hemoglobin level is within the reference range.
    • Reticulocyte count is normal.
    • Mean corpuscular volume (MCV) ranges between 75 and 85 fL.
    • Mean corpuscular hemoglobin (MCH) is around 26 pg.
  • Alpha1 thalassemia minor
    • Hemoglobin level is within the reference range.
    • Reticulocyte count is normal.
    • MCV is 65-75 fL.
    • MCH is around 22 pg.
  • Hemoglobin H disease
    • Hemoglobin level is 7-10 g/dL.
    • Reticulocyte count is 5-10%.
    • MCV is 55-65 fL.
    • MCH is 20 pg.
    • The peripheral blood smear shows small misshapen red cells, hypochromia, microcytosis, and targeting.
    • Brilliant cresyl blue stain demonstrates hemoglobin H inclusion bodies.
  • Hydrops fetalis
    • Hemoglobin is 4-10 g/dL.
    • MCV is 110-120 fL.
    • The peripheral blood smear shows severe anisopoikilocytosis, severe hypochromia, and nucleated red blood cells.
  • Alpha thalassemia combined with sickle cell anemia causes a higher hemoglobin concentration and improved red blood cell survival. The alpha gene deletion is associated with improved red cell deformability, but the improved rheologic benefits often are overcome by the greater viscosity of a higher hematocrit. Clinically, this is observed as a greater number of painful vasoocclusive crises. Interestingly, however, the incidence of stroke is lower than that in sickle cell disease alone.
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Imaging Studies

  • Imaging studies are not useful in these disorders.
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Other Tests

  • Hemoglobin electrophoresis separates hemoglobin into different types. Hemoglobin Bart is elevated at birth in patients with alpha thalassemia. In hemoglobin H disease, 20-40% of total hemoglobin is of hemoglobin Bart; however, in the silent carrier alpha thalassemia condition, the percentage is only 1-2% with low or normal amounts of hemoglobin A2.[9] Hemoglobin electrophoresis is generally not sufficiently sensitive to diagnose silent carrier alpha thalassemia.
  • The imbalance between the quantities of α- and β-globin chains initially was used to define the thalassemias. β to α synthetic ratios are altered in both alpha and beta thalassemias. Increasing ratios of β- to α-globin chains are observed in alpha-2 thalassemia, alpha-1 thalassemia, and hemoglobin H disease, respectively. Tests are performed by incubation of red blood cells with radiolabeled amino acid and subsequently separating α- and β-globin chains using urea carboxymethyl cellulose (CMC) chromatography.
  • Currently, genetic testing is used to establish the diagnosis in patients with a suggestive family history and/or hematologic findings suggestive of alpha thalassemia.[10, 11, 12]
    • Recombinant DNA technology can be diagnostic but is still a research tool.
    • Gene mapping
    • Polymerase chain reaction (PCR)
    • Restriction endonucleases
    • Anti-L globin monoclonal antibodies
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Procedures

  • Bone marrow aspiration and biopsy are not helpful in establishing the precise diagnosis and are not indicated unless other confounding problems exist.
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Histologic Findings

Peripheral blood smear may reveal target cells, microcytosis, hypochromia, and anisopoikilocytosis. Most individuals with alpha2 thalassemia (trait) have only mild microcytosis, which can be differentiated from other common causes of microcytosis based on serum iron and ferritin concentrations within the reference range.

See the image below.

Peripheral smear from a patient with hemoglobin H Peripheral smear from a patient with hemoglobin H disease showing target cells, microcytosis, hypochromia, and anisopoikilocytosis. Morphological abnormalities are similar to those observed in beta thalassemia. In alpha2 thalassemia (silent trait), only mild microcytosis is observed.
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Contributor Information and Disclosures
Author

Samer A Bleibel, MD  Staff Physician, Department of Internal Medicine, Wayne State University School of Medicine, St John's Hospital and Medical Centers

Samer A Bleibel, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Robert J Leonard, MD  Clinical Assistant Professor, Department of Medicine, Wayne State University School of Medicine

Disclosure: Nothing to disclose.

Jennifer L Jones-Crawford, MD  Fellow, Department of Hematology/Oncology, Medical College of Georgia

Jennifer L Jones-Crawford, MD is a member of the following medical societies: American College of Physicians and American Society of Hematology

Disclosure: Nothing to disclose.

Abdullah Kutlar, MD  Director of Sickle Cell Center, Fellowship Program Director, Professor, Department of Internal Medicine, Section of Hematology and Oncology, Medical College of Georgia

Abdullah Kutlar, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Linda K Hendricks, MD  Assistant Professor, Department of Internal Medicine, Section of Hematology and Oncology, Mercer University School of Medicine

Linda K Hendricks, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

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

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, 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, Jefferson Medical College of 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 Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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Peripheral smear from a patient with hemoglobin H disease showing target cells, microcytosis, hypochromia, and anisopoikilocytosis. Morphological abnormalities are similar to those observed in beta thalassemia. In alpha2 thalassemia (silent trait), only mild microcytosis is observed.
 
 
 
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