Diagnostics

• In infants (usually aged 6–24 months): Consider beta-thalassemia major.

• In children (usually aged 2–6 years): Consider beta-thalassemia minor or alpha/beta-thalassemia intermedia.

• Demographic factors

  • Family history of thalassemia

  • Asian, African, or Mediterranean ancestry

• Incidental diagnostic findings

  • Microcytic hypochromic anemia not explained by other causes or not responsive to supplemental iron

  • Antenatal ultrasound showing hydrops fetalis

  • Detection of abnormal hemoglobin chains in newborn screening

• Characteristic finding: microcytic hypochromic anemia (i.e., MCV < 80 fL, MCH < 27 pg/cell) present regardless of Hb level

• Hb levels: variable depending on the subtype

• Other red cell indices

  • Normal RDW [11]

  • Higher RBC count than iron deficiency anemia

CBC parameters can help differentiate thalassemia minor/trait from iron deficiency anemia. IDA is frequently associated with a high RDW, low RBC count, and low MCV typically occurring once the Hb is < 10 g/dL. In thalassemia, microcytosis is always present regardless of the Hb level, the RDW is typically normal, and compared to IDA, the RBC count is higher and the MCV is lower.

Low ferritin suggests iron deficiency anemia and patients should receive iron supplementation. Suspect thalassemia if there is no significant response after three months

nonimmune-mediated hemolytic anemia

• Coombs test: negative

• ↓ Haptoglobin, ↑ LDH, ↑ reticulocytes

• Liver chemistries: hyperbilirubinemia (indirect)

• Iron studies (particularly ferritin) : expected to be normal in thalassemia

• HbH inclusion bodies

• Target cells

• Teardrop cells

• Anisopoikilocytosis

• Erythroblasts

• Detection of hemoblobin variants (Hb-electrophoresis)

• Genetic studies

• Bone marrow aspiration

• Hb-electrophoresis (qualitative analysis)

• Automated HPLC (qualitative and quantitative analysis)

• Findings (vary depending on the subtype)

  • Hemoglobin A (and subtypes): hemoglobin A2 values are helpful to determine the diagnosis (i.e., to distinguish alpha from beta thalassemia)

  • Hemoglobin F: may be elevated in some children and adults with thalassemia

• Genetic studies (PCR-based): to determine specific diagnosis and mutations

• Bone marrow aspiration (not routinely indicated)

  • Usually performed to rule out other hematologic conditions

  • Findings in thalassemia are nonspecific (e.g., reactive hyperplasia).

• Skull x-ray (AP and lateral)

  • Indication: assessment of craniofacial abnormalities

  • Findings include:

    • High forehead

    • Prominent zygomatic bones and maxilla (referred to as “chipmunk facies”)

    • Hair-on-end (also known as “crew cut”) sign

• CXR

  • Indication: suspected extramedullary hematopoiesis in the thorax

  • Findings include:

    • Mediastinal or pulmonary masses

    • Subperiosteal extension in the ribs (also known as “rib within a rib”)

• MRI spine: helpful to evaluate mass effect symptoms due to extramedullary hematopoietic pseudotumors