Laboratory Studies

Initial workup

The initial workup for a patient with suspected thalassemia should include a complete blood count (CBC), review of the blood smear, and iron studies, as follows:

CBC - Thalassemia involves microcytic anemia with a high red blood cell count, with the high count possibly helping to distinguish between thalassemia and iron deficiency ^[1]
Peripheral smear - Review of the peripheral smear reveals hypochromasia and microcytosis; more severely affected patients can demonstrate poikilocytosis, with target cells, teardrop cells, and cell fragments ^[1](see the image below)
Iron studies - Iron studies should be obtained to differentiate iron deficiency anemia from thalassemia and also to monitor for ongoing iron overload in patients with an established diagnosis of thalassemia; in thalassemia intermedia, iron studies reveal a normal to high ferritin level, elevated serum iron, and elevated transferrin saturation ^[1]

Ancillary laboratory studies may include analyses for hemolytic anemia, such as Coombs testing, haptoglobin, lactate dehydrogenase, and indirect bilirubin. Study results found in thalassemia—including negative Coombs testing, low haptoglobin, elevated lactate dehydrogenase, and elevated indirect bilirubin—are also derived in nonimmune hemolytic anemia.

Peripheral blood film in thalassemia intermedia.

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Confirmatory testing

Thalassemia is diagnostically confirmed via hemoglobin analysis and genetic testing.^[1]

Hemoglobin analysis

High-performance liquid chromatography (HPLC) or hemoglobin electrophoresis is used in the execution of hemoglobin analysis.^[1]In beta thalassemia intermedia, hemoglobin analysis reveals elevated levels of HbF and HbA2. However, beta thalassemia may still exist when the HbA2 level is normal, with such concentrations dropping into the normal range in the presence of conditions such as concomitant iron deficiency and delta-chain mutations.^[1]

Genetic testing

The diagnosis of beta thalassemia intermedia does not always require DNA-based genotyping, but such analysis may aid in recognizing complex thalassemias such as delta-beta and gamma-delta-delta thalassemia.^[1]Genetic analysis may also help to differentiate thalassemia intermedia from thalassemia major. For example, the presence of IVSI‐5 homozygous with Xmn‐1 is a strong indicator of thalassemia intermedia, but genetic heterogeneity means that this method is not in routine use.^[15]

Routine Monitoring

Using the following studies, patients with beta thalassemia intermedia can be monitored for complications during routine health visits with a specialist^[1]:

CBC, reticulocyte count, hepatic panel, and renal function
Iron studies
Baseline cardiac magnetic resonance imaging (MRI) with iron deposition quantification
Echocardiographic evaluation
Liver iron concentration assessed via magnetic resonance evaluation
Dual-energy radiographic absorptiometry (DRA) scan or skeletal survey for pediatric patients
Screens for thyroid dysfunction, diabetes mellitus, gonadal dysfunction (in the presence of delayed puberty), hypoparathyroidism, growth hormone deficiency (in the presence of failure to thrive), and adrenal insufficiency

Treatment & Management

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Media Gallery

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

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Author

May C Chien, MD Clinical Assistant Professor, Department of Medicine, Division of Hematology, Clinical Assistant Professor, Department of Pediatrics, Division of Hematology and Oncology, Associate Director, Hematology Block, Science of Medicine Course, Stanford University School of Medicine

May C Chien, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Coauthor(s)

Clara Yeong-Yi Lo, MD Clinical Assistant Professor, Department of Pediatric Hematology/Oncology, Lucile Packard Children’s Hospital at Stanford Medical Center

Clara Yeong-Yi Lo, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) Professor Emeritus of Pediatrics, Albany Medical College; Chief of Pediatric Oncology, Homi Bhabha Cancer Hospital, Varanasi, India

Vikramjit S Kanwar, MBBS, MBA, MRCP(UK) is a member of the following medical societies: Children's Oncology Group, Indian Academy of Pediatrics, International Society of Pediatric Oncology

Disclosure: Nothing to disclose.

Additional Contributors

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, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Acknowledgements

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.