Hemoglobinopathies – Thalassemia and Abnormal Hemoglobins

Background and Request for Testing

Worldwide, approximately 5% of the population are carriers of hemoglobinopathies. Due to the ongoing migration situation, they are now playing an increasingly relevant role in hematology practice. Thalassemia has now become a frequent differential diagnosis in patients with a corresponding genetic background when it comes to clarifying the cause of microcytic hypochromic anemia. Together with abnormal hemoglobins, these are among the most common hereditary disorders. Over the past years, we have also regularly received requests for to carry out diagnostics in these areas.

In order to provide our colleagues with a central point of contact for this disease complex, which is growing increasingly relevant and frequent, we have expanded our range of tests at MLL to include complete diagnostics for the identification and characterization of hemoglobinopathies.

They can be requested using a special test order process. 1 x 3 ml EDTA blood (standard blood count tube), 1 x 7.5 ml EDTA blood, 1 x 7.5 ml of serum, and the patient’s consent to allow the conducting of genetic analyses according to the Genetic Diagnostics Act are required.

Typical indications for testing for hemoglobinopathy include the following:

  • Hypochromia and/or anemia after iron deficiency has been excluded
  • Chronic hemolytic anemia
  • Vascular occlusions of unknown origin
  • Recurrent pain crises
  • Unexplained severe infections
  • Hydrops fetalis syndrome
  • Positive family history

Classification of hemoglobinopathies

Hemoglobinopathies include congenital quantitative (thalassemia) or qualitative (abnormal hemoglobins) disorders of the hemoglobin chain synthesis. The most common forms of thalassemia are α-thalassemia and β-thalassemia. The clinical spectrum ranges from blood count changes without clinical symptoms to transfusion dependency. Among the abnormal hemoglobins, HbS is of particular importance, as it is the basis for sickle cell disease. This is associated with chronic hemolytic anemia, recurrent vaso-occlusive pain crises, and resultant organ damage. Other regularly occurring hemoglobin structural variants are HbC, HbE, and HbD.

Diagnostic Methods

If hemoglobinopathy is suspected, staged diagnosis consisting of blood count, iron status, hemoglobin differentiation using capillary electrophoresis, and other staged diagnostic methods, depending on the findings, are recommended:

  • Hemoglobin differentiation: High-resolution capillary electrophoresis is used to separate and quantify the different hemoglobin fractions. This produces evidence of disorders in the β-globin gene complex or severe forms of α-thalassemia.
  • Molecular genetics: Molecular genetic methods based on the findings are then employed to confirm the suspected diagnosis. Deletion-specific PCR is used to detect α-thalassemia, while abnormal hemoglobins or β-thalassemia are confirmed with next-generation sequencing (NGS). Rare forms like (γ)δβ-thalassemia are caused by large deletions. In these cases, multiplex ligation-dependent probe amplification (MLPA) is used.

Tests Offered at MLL

All of the above methods are now routinely offered at MLL. We hope that this will satisfy the wishes of colleagues who make requests from us. If you have any questions on this topic or the diagnostic procedure, please contact Dr. Dr. med. Armin Piehler.

The author

»Do you have questions about the article, the diagnostic procedure or would you like more information about hemoglobinopathies?Please feel free to send me an e-mail.«

Dr. Dr. med. Armin Piehler, PhD MM

Head of benign hematology

T: +49 89 99017-357