Diagnostics

Hemoglobin E (Hb E)

Request forms

Method:
Anticoagulant:
Recommendation:

Method:

Blood Count
Anticoagulant:

EDTA*
Recommendation:

obligatory

Method:

Hemoglobin Differentiation
Anticoagulant:

EDTA*
Recommendation:

obligatory

Method:

Iron Status
Anticoagulant:

Serum**
Recommendation:

Dep. on Blood Count

Method:

Molecular genetics
Anticoagulant:

EDTA***
Recommendation:

once

^{*3 ml EDTA blood (blood count tube), **7.5 ml serum, ***7.5 ml EDTA blood (extra tube)}

Overview
Diagnosis

Hemoglobin E: Overview

Hemoglobin E (Hb E) is a common hemoglobin variant in Southeast Asia. Hemoglobin E is based on the exchange of amino acid 27 of the β-globin chain from glutamate to lysine (HBB:c.79G>A, p.Glu27Lys, HbVarID 277). This sequence variant activates an additional splice site, which leads to reduced expression of the affected β-globin gene and thus shows some thalassemic features. Heterozygous carriers exhibit slight hypochromia and a normal to slightly reduced hemoglobin concentration.

In patients with Hb E disease (homozygous form of Hb E), hypochromic microcytic anemia is found. If Hb E occurs in combination with β-thalassemia, the clinical picture is similar to that of β-thalassemia major. Since hemoglobin E is unstable, hemolysis can be triggered by viral infections and medication.

Hemoglobin E: Diagnosis

The diagnosis or the exclusion of Hb E disease or a carrier status of Hb E is carried out by a combination of blood count, iron status, hemoglobin differentiation, and molecular genetic tests in the case of abnormal findings to confirm the diagnosis.

In the case of heterozygous carriers, there is usually a slight hypochromia (MCH approx. 25 pg) with normal to slightly reduced hemoglobin. Patients with Hb E disease often show anemia with a hemoglobin of 10 - 14 g/dl, erythrocytosis, MCH at approx. 20 pg and MCV at approx. 65 fl. Due to the thalassemic blood count changes in presence of Hb E, simultaneously occurring α-thalassemia cannot be ruled out with certainty based on the blood count. Molecular genetic testing is therefore necessary for reliable detection of concurrently inherited α-thalassemia, which occurs in up to 30% of Hb E cases.

Iron status is usually normal in Hb E disease and heterozygous Hb E carriers.

In HbE disease, hemoglobin differentiation typically shows >95% Hb E, with Hb A2 accounting for approximately 2.5% and Hb F <3% of total hemoglobin.

In heterozygous carriers, the proportion of Hb E is about 25-35% of the total hemoglobin; lower values indicate the simultaneous presence of α-thalassemia or iron deficiency.

At initial diagnosis, the Hb E causing mutation (HBB:c.79G>A p.Glu27Lys, HbVarID 277) is confirmed by sequencing of the β-globin gene HBB. Moreover, in Hb E disease molecular genetic deletion analyzes (MLPA) of the β-globin gene complex are used to differentiate between Hb E homozygosity and a combination of Hb E and β-thalassemia.

Bain BJ. Haemoglobinopathy Diagnosis. Wiley-Blackwell 2020;3. Edition.

Busse B et al. Stufendiagnostik der Hämoglobinopathien. LaboratoriumsMedizin 2015;39(5):335-341.

Kohne E. Hemoglobinopathies. Deutsches Ärzteblatt international 2011;108(31-32):532-540.

Thomas L 2022 Labor und Diagnose. www.labor-und-diagnose-2020.de. Ausgabe 30.06.2022.

Status: April 2024

You may also be interested in

Career

As a rapidly growing, innovative medical laboratory, we are always looking for bright minds to help us bring new and more effective therapies to patients around the world.

Learn more

Services

Do you have questions about sample submission, analyses performed or findings? Here you will find contact details, contact persons and our most frequently asked questions (FAQs).

Learn more

Quality management

We have been certified according to national and international standards since 2009 and have successfully maintained these accreditations.

Learn more