Dr. Suraj Chiraniya Hematologist & BMT Physician

What are the tests for Thalassemia ?

History and physical examination — The history focuses on the following:

• Family history (FH)
• FH of thalassemia can help determine type and severity of thalassemia.
• FH of sickle cell disease or trait or other hemoglobinopathies can suggest compound syndromes.
• The FH may include anemia without a specific diagnosis.
• A negative FH does not eliminate the possibility of thalassemia since both parents may be asymptomatic carriers.
• Age of onset – Onset at or before birth suggests alpha thalassemia major; onset in infancy (6 to 12 months) suggests transfusion-dependent beta thalassemia.

Diagnosis later in life suggests a milder form.

Severity of symptoms

• History of gallstones suggests possible chronic hemolysis.
• History of jaundice or dark urine suggests significant hemolysis.
• Impaired growth or skeletal changes suggest significant extramedullary hematopoiesis.

Examination – Those with severe disease may also have evidence of hemolysis and extramedullary hematopoiesis such as jaundice, skeletal abnormalities, or splenomegaly.

The family or clinician may be contacted with positive results from PRENATAL TESTING or from a newborn screening test. The evaluation of these individuals is the same as for those suspected to have thalassemia based on other information.

WHAT ARE THE LABORATORY TESTS?

• Complete blood count (CBC)
• Review of the blood smear, and iron studies.
• Iron studies are required to evaluate for iron deficiency and iron overload.
• In appropriate patients, hemoglobin analysis and/or genetic testing is appropriate to confirm the diagnosis.
• Bone marrow evaluation is not required, but, if performed, it will reveal hyperplasia that is unusual in the degree to which there is a preponderance of immature erythroblasts.
• There may be bizarre morphology of erythroid progenitors, with poorly hemoglobinized erythroblasts that have inclusion bodies similar to Heinz bodies.
• There may be megaloblastic changes, especially if folate is deficient (due to increased requirements with hemolysis).

CBC and hemolysis testing — The following findings are consistent with thalassemia:

Microcytic anemia – Microcytic, hypochromic anemia is typical in all thalassemia syndromes except asymptomatic carriers .

• In transfusion-dependent beta thalassemia and hemoglobin H (Hb H) disease there is profound hypochromic, microcytic anemia accompanied by bizarre red blood cell (RBC) morphology .
• Mild microcytosis or anemia may be seen in thalassemia minor.
• The CBC may be normal in thalassemia minima/trait.
• Other RBC abnormalities may also be present in more severe disease, including extreme hypochromia, poikilocytosis, target cells, teardrop cells, and cell fragments.

RBC inclusions representing precipitated globin chains may be seen on routine Wright-Giemsa staining and are more easily appreciated using supravital stains such as methyl violet or brilliant cresyl blue .

High RBC count; mildly increased reticulocyte count – The RBC count is increased in thalassemias. This is especially true in more severe disease but may also occur in thalassemia minor.

The reticulocyte count may be slightly increased, but not to the extent that would be expected for the severity of anemia, especially in beta thalassemia. An increased RBC count is often helpful in distinguishing thalassemia from iron deficiency anemia, although other testing is required.

Hemolysis – Testing for hemolysis includes lactate dehydrogenase (LDH), indirect (unconjugated) bilirubin, haptoglobin, and Coombs testing .

• Thalassemia causes non-immune hemolysis, with high LDH, high indirect bilirubin, low haptoglobin, and negative Coombs testing.
• If the diagnosis of thalassemia is very likely, the Coombs testing may be omitted. The other testing for hemolysis (LDH, bilirubin, haptoglobin) is useful as a baseline for monitoring the course of the disease and the response to therapy. In thalassemia minor, evidence of hemolysis is typically absent .

Normal WBC and platelet count – Thalassemia does not directly affect white blood cells (WBCs) and platelets. Leukocytosis may signify an infection. However, many individuals with thalassemia have chronically elevated neutrophil counts for reasons that are not always clear. Some laboratory cell counters will misclassify nucleated red blood cells (NRBCs) as WBCs. Mild cytopenias due to hypersplenism may develop later in the disease course. WBCs, platelets, and NRBCs may increase dramatically after splenectomy.