What are the variants of hemoglobin (Hb) associated with sickle cell disorders and what is the purpose and interpretation of hemoglobin electrophoresis in diagnosing these conditions?

From the Guidelines

For STEP 3, it is crucial to understand that sickle cell disorders involve abnormal hemoglobin variants, and hemoglobin electrophoresis is essential for identifying and quantifying these variants, with the most recent guideline from the Association of Anaesthetists in 2021 1 providing a comprehensive overview of the common forms of sickle cell disease and related haemoglobinopathies. The variants of hemoglobin seen with sickle cell disorders include HbS, HbC, HbE, and HbF (fetal hemoglobin), with HbS being the most common variant, resulting from a point mutation in the beta-globin gene causing valine to replace glutamic acid, as described in the guideline from the Association of Anaesthetists in 2021 1. Hemoglobin electrophoresis is a diagnostic test that separates these hemoglobin variants based on their electrical charge, allowing for identification and quantification of abnormal hemoglobins, and is a critical tool in the diagnosis and management of sickle cell disorders, as outlined in the 2021 guideline 1. When interpreting hemoglobin electrophoresis, the following patterns are typically seen:

• Normal adults: predominantly HbA (95-98%) with small amounts of HbA2 (2-3%) and HbF (<1%)
• Sickle cell trait: both HbA and HbS, with HbS usually comprising 35-45%
• Sickle cell disease (HbSS): predominantly HbS (>80%) with absence of HbA
• Other hemoglobinopathies: characteristic patterns, such as HbSC disease showing approximately equal amounts of HbS and HbC, while beta-thalassemia variants show altered ratios of normal hemoglobins, as described in the guideline from the Association of Anaesthetists in 2021 1. Understanding these patterns is crucial for diagnosing specific hemoglobinopathies and determining appropriate management strategies for patients with sickle cell disorders, and the 2021 guideline from the Association of Anaesthetists 1 provides a comprehensive overview of the common forms of sickle cell disease and related haemoglobinopathies. Key points to consider when interpreting hemoglobin electrophoresis include:
• The percentage of HbS, which can indicate the severity of the disease
• The presence of other hemoglobin variants, such as HbC or HbF, which can affect the disease course
• The absence of HbA, which can indicate a more severe form of the disease, as outlined in the 2021 guideline from the Association of Anaesthetists 1. By understanding the variants of hemoglobin and the interpretation of hemoglobin electrophoresis, healthcare providers can provide accurate diagnoses and develop effective management plans for patients with sickle cell disorders, as recommended in the 2021 guideline from the Association of Anaesthetists 1.

From the Research

Variants of Hemoglobin in Sickle Cell Disorders

• Hemoglobin S (Hb S) is the most common variant associated with sickle cell disease, which can lead to a range of clinical manifestations from asymptomatic to severe 2.
• Other variants, such as Hemoglobin E (Hb E), can also contribute to sickle cell disease, particularly when combined with Hb S (Hb SE) 2.
• The clinical course of sickle cell disease can be influenced by various genetic modifiers, including the type of beta-thalassemia mutation, Hb F levels, and co-inheritance of alpha-thalassemia 2, 3.

Purpose of Hemoglobin Electrophoresis

• Hemoglobin electrophoresis is a diagnostic tool used to identify and quantify different hemoglobin variants, including those associated with sickle cell disease and beta-thalassemia 4, 5.
• The purpose of hemoglobin electrophoresis is to distinguish between different hemoglobin variants, which is essential for diagnosing and managing hemoglobinopathies 2, 4.

Interpretation of Hemoglobin Electrophoresis

• Hemoglobin electrophoresis can separate and identify over 45 commonly encountered hemoglobin variants, including Hb S, Hb E, and Hb F 4.
• The results of hemoglobin electrophoresis can be used to diagnose hemoglobinopathies, such as sickle cell disease and beta-thalassemia, and to monitor the effectiveness of treatment 4, 5.
• Accurate interpretation of hemoglobin electrophoresis requires expertise in the field, as the results can be complex and influenced by various factors, including the type of hemoglobin variant and the presence of other genetic modifiers 2, 3.