Thalassemia Intermedia Differential Diagnoses

  • Author: Hassan M Yaish, MD; Chief Editor: Robert J Arceci, MD, PhD  more...
Updated: Oct 01, 2015

Diagnostic Considerations

In prenatal diagnosis of thalassemia intermedia, DNA probes of known genotypes are usually used. Because this condition varies significantly in severity (despite the misleading name), a milder form of disease may be anticipated in a baby who turns out to be affected by a more severe form of the disease. For this reason, parents should be informed in advance that testing may help rule out the possibility of severe disease (such as when a heterozygous condition is diagnosed) or may confirm severe disease when a homozygosity or heterozygosity for 2 severe mutations is confirmed. However, intermediate cases may be misleading, and the predictability of severity has been less accurate until recently, when a new study showed 83.2% accuracy in predicting disease severity when the patient is tested for the presence or absence of 5 predetermined genetic modifiers of severity.[24]

Other problems that should be considered during the evaluation of a patient with suspected thalassemia intermedia include the following:

  • Acute leukemias
  • Hemolytic anemias (autoimmune, metabolic)
  • Hemophagocytosis
  • Hypersplenism
  • Beta thalassemia major
  • Thalassemia traits
  • Thrombocytopenia, associated with splenomegaly in various clinical entities
  • Anemia, hypochromic and microcytic

The severe anemia, if associated with thrombocytopenia, hypersplenism, and the immature leukocytes often observed on peripheral blood films, raises the question of acute leukemia or metastatic lymphoma. Milder cases, on the other hand, must be differentiated from thalassemia trait or even anemias related to iron deficiency or chronic inflammation. Unlike the intermedia forms, β thalassemia trait rarely produces an Hb level less than 9 g/dL, nor is it associated with enlarged spleen, the presence of nucleated RBCs, or significant anisocytosis and poikilocytosis on peripheral blood smear examination. Iron deficiency anemia is characterized by a normal Hb electrophoresis pattern and abnormal iron study results.

Differential Diagnoses

Contributor Information and Disclosures

Hassan M Yaish, MD Medical Director, Intermountain Hemophilia and Thrombophilia Treatment Center; Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology, Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center

Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, New York Academy of Sciences, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD Director, Children’s Center for Cancer and Blood Disorders, Department of Hematology/Oncology, Co-Director of the Ron Matricaria Institute of Molecular Medicine, Phoenix Children’s Hospital; Editor-in-Chief, Pediatric Blood and Cancer; Professor, Department of Child Health, University of Arizona College of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.


James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

J Martin Johnston, MD Associate Professor of Pediatrics, Mercer University School of Medicine; Director of Pediatric Hematology/Oncology, Backus Children's Hospital; Consulting Oncologist/Hematologist, St Damien's Pediatric Hospital

J Martin Johnston, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Pharmacy Editor, eMedicine

Disclosure: Nothing to disclose.

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Peripheral blood film in thalassemia intermedia.
Basophilic stippling in thalassemia intermedia.
Nucleated red blood cell in thalassemia intermedia.
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