What are the causes of elevated Hemoglobin (Hb) electrophoresis results?

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From the Guidelines

Elevated hemoglobin (Hb) electrophoresis results are primarily caused by hemoglobinopathies, which are genetic disorders affecting the structure or production of hemoglobin molecules. The most common causes include beta-thalassemia trait, which shows increased hemoglobin A2 (typically 3.5-8%) 1; hemoglobin S trait (sickle cell trait), with hemoglobin S levels of 35-45% 1; and hemoglobin C trait, showing hemoglobin C levels of 30-40%. Other causes include:

  • Hemoglobin E trait
  • Hereditary persistence of fetal hemoglobin (HPFH) with elevated hemoglobin F in adults
  • Homozygous conditions like sickle cell disease (predominantly hemoglobin S) or hemoglobin C disease Certain acquired conditions can also affect results, such as recent blood transfusions which may show mixed hemoglobin patterns 1. Laboratory errors during sample collection, processing, or analysis can occasionally lead to falsely elevated results. Understanding these causes is important for proper diagnosis and management of hemoglobinopathies, as they have varying clinical implications ranging from asymptomatic carrier states to severe hematological disorders requiring specific treatments and genetic counseling 1.

It is essential to consider the clinical context and perform a thorough evaluation to determine the underlying cause of elevated Hb electrophoresis results, as some conditions may require specific treatments or genetic counseling 1. In some cases, additional testing such as iron studies or molecular analysis may be necessary to confirm the diagnosis 1. By prioritizing the diagnosis and management of hemoglobinopathies, healthcare providers can improve patient outcomes and reduce the risk of complications associated with these conditions.

From the Research

Causes of Elevated Hb Electrophoresis

Elevated Hb electrophoresis results can be caused by various factors, including:

  • Hemoglobinopathies, such as sickle cell disease and beta-thalassemia 2, 3, 4, 5
  • Abnormal hemoglobin variants, such as HbS and HbE 4, 5, 6
  • Red blood cell transfusions, which can lead to delayed hemolytic transfusion reactions (DHTR) and hyperhemolysis syndrome (HHS) 2
  • Inheritance of multiple alleles, such as HbS and beta-thalassemia, which can result in sickle cell syndrome 5
  • Point mutations, such as the mutation responsible for HbS, and deletions or insertions, such as those found in beta-thalassemia 5

Hemoglobinopathies and Electrophoresis

Hemoglobin electrophoresis is a useful tool in diagnosing hemoglobinopathies, including:

  • Sickle cell disease, which can be diagnosed by the presence of HbS 4
  • Beta-thalassemia, which can be diagnosed by the presence of abnormal hemoglobin variants, such as HbA2 3, 5
  • HbE syndromes, which can range from asymptomatic to severe and require distinction from other hemoglobinopathies 6

Clinical Implications

Accurate diagnosis of the cause of elevated Hb electrophoresis results is crucial for:

  • Prompt management and decrease morbidity and mortality 2
  • Genetic counseling for families affected by hemoglobinopathies 5
  • Monitoring and treatment of complications, such as thromboembolism and iron overload, in patients with HbE syndromes 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Utility of hemoglobin electrophoresis to distinguish between severe delayed hemolytic transfusion reaction versus hyperhemolysis syndrome.

Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis, 2024

Research

[Sickle cell disease: laboratory and hemoglobin study].

Bulletin de la Societe de pathologie exotique (1990), 2001

Research

Hemoglobin e syndromes.

Hematology. American Society of Hematology. Education Program, 2007

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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