What is the diagnosis for a patient with thalassemic (a genetic disorder that affects the production of hemoglobin) red cell indices, elevated Hemoglobin A2 (HbA2) and Hemoglobin F (HbF) levels, and mild hypochromic microcytic anemia?

From the Guidelines

Beta thalassemia trait is indeed diagnosed by finding elevated HbA2 and HbF levels in a patient with thalassemic red cell indices, and the most recent and highest quality study suggests that these patients should be reassured about the benign nature of their condition but informed that it's hereditary 1. The characteristic laboratory findings include microcytic (small) and hypochromic (pale) red blood cells, with an MCV often below 75 fL and MCH below 27 pg.

• The elevated HbA2 (typically 3.5-7%) and sometimes elevated HbF (1-5%) result from reduced beta-globin chain production, causing a relative increase in other hemoglobin types.
• Patients with beta thalassemia trait usually have mild anemia with hemoglobin levels around 10-12 g/dL, though some may have normal hemoglobin.
• Iron supplementation should be avoided unless true iron deficiency is confirmed, as it provides no benefit and may cause harm, as suggested by studies on iron deficiency and thalassemia minor 1.
• Genetic counseling is recommended for family planning, as having children with a partner who also carries a hemoglobinopathy can result in more severe disease in offspring. The management of beta thalassemia trait should focus on preventing complications and providing genetic counseling, rather than treating the condition itself, as it is typically asymptomatic and requires no specific treatment 1.
• The use of hematopoietic stem cell transplantation is not recommended for beta thalassemia trait, as it is a curative option only for more severe forms of thalassemia, such as thalassemia major 1.
• The diagnosis and management of beta thalassemia trait should be guided by clinical and molecular insights, and should avoid unnecessary delay, invasive or costly diagnostic tests, and harmful treatments 1.

From the Research

Beta Thalassemia Trait Diagnosis

• The diagnosis of beta thalassemia trait is typically made based on the finding of raised HbA2 and HbF values, in combination with thalassemic red cell indices 2.
• Patients with beta thalassemia trait are usually asymptomatic, but may experience a mild decrease in hemoglobin 2.
• The condition is caused by a partial or complete deficiency in the synthesis of β-globin chains, which is often the result of one or more mutations in the corresponding genes 2.

HbA2 and HbF Levels

• Increased HbA2 levels are a characteristic feature of β-thalassemia carriers, but some carriers may have borderline HbA2 levels, which can make diagnosis more challenging 3.
• Borderline HbA2 levels may occur as a result of mild β-thalassemia mutations, co-inherited β-thalassemia and α- or δ-thalassemia, or iron deficiency anemia 3.
• Exceptionally high HbA2 levels have been reported in patients with beta-thalassemia intermedia, and may be related to mutations in the beta-gene promoter 4.

Discrimination from Other Conditions

• δβ-Thalassemia trait can be discriminated from β-thalassemia trait and iron deficiency anemia based on differences in classic hematologic parameters and RBC subpopulations, including RDW and HbF levels 5.
• Red cell indices, such as Srivastava Index and Mentzer Index, can be used to differentiate between β-thalassemia trait and iron deficiency anemia, as well as between homozygous sickle cell disease and sickle cell thalassemia 6.
• The use of these indices can help to improve the accuracy of diagnosis and reduce the need for more complex and expensive testing 6.