What is thalassemia trait?

Thalassemia Trait: Clinical Overview

Thalassemia trait (also called thalassemia minor) is an inherited carrier state characterized by microcytic anemia with normal or elevated red blood cell count, typically asymptomatic, and distinguished from iron deficiency anemia by normal RDW (≤14.0%) and normal or elevated ferritin levels. 1, 2

Definition and Genetics

Thalassemia trait represents the carrier state of thalassemia, an autosomal recessive hemoglobinopathy affecting the production of either alpha or beta globin chains that comprise hemoglobin. The condition results from:

• Alpha thalassemia trait: Mutations or deletions in one or two of the four alpha-globin genes on chromosome 16
• Beta thalassemia trait: Mutations in one of the two beta-globin genes on chromosome 11 1, 2

These genetic alterations lead to reduced (but not absent) production of the respective globin chains, causing mild imbalance in globin chain synthesis.

Laboratory Characteristics

Thalassemia trait can be identified by several key laboratory findings:

• Microcytosis: MCV <80 fL (hallmark finding)
• Normal or elevated RBC count (distinguishes from iron deficiency)
• Normal RDW (≤14.0%) (whereas iron deficiency typically shows elevated RDW >14.0%) 1
• Normal or slightly decreased hemoglobin levels
• Normal or elevated ferritin levels (key distinguishing feature from iron deficiency anemia) 2

Diagnostic Approach

The American College of Medical Genetics recommends the following diagnostic approach 1:

1. Initial screening: Complete blood count (CBC) with red blood cell indices
2. Secondary testing: If microcytosis with normal/elevated RBC count is found, proceed with:
   • Hemoglobin electrophoresis or
   • High-performance liquid chromatography (HPLC)
3. Confirmatory testing: Molecular genetic testing to identify specific mutations

Clinical Significance

• Asymptomatic presentation: Most individuals with thalassemia trait are clinically asymptomatic 2, 3
• Misdiagnosis risk: Often misdiagnosed as iron deficiency anemia, leading to unnecessary iron supplementation
• Genetic counseling importance: Carriers should receive genetic counseling, especially if their partner is also a carrier 1
• Normal life expectancy: Individuals with thalassemia trait have a normal life expectancy 3

Population Distribution

Thalassemia trait is most common in individuals with ancestry from:

• Mediterranean region
• Middle East
• Africa
• Southeast Asia 1, 4

Common Pitfalls and Caveats

• Misdiagnosis as iron deficiency: The microcytic anemia of thalassemia trait is often mistaken for iron deficiency, leading to inappropriate iron therapy
• Coexisting conditions: Thalassemia trait can coexist with iron deficiency, making diagnosis more challenging
• Pregnancy considerations: Women with thalassemia trait who become pregnant should be monitored closely, as they may be more susceptible to anemia during pregnancy
• Genetic implications: Individuals with thalassemia trait who have children with another carrier have a 25% chance of having a child with thalassemia major, which can be severe 1, 4

Importance of Screening

The Centers for Disease Control and Prevention and American College of Medical Genetics recommend targeted screening for:

• Individuals with unexplained microcytic anemia
• Those with family history of thalassemia
• Individuals from high-risk ethnic backgrounds
• Partners of known carriers for genetic counseling purposes 1