2. 2
Outline
1. Introduction
2. Hemoglobinopathy: Basics and Laboratory Testing
3. Common Hemoglobinopathies
4. Thalassemia: Basics and Laboratory Testing
5. Bio-Rad Hemoglobinopathy Education programs
3. 3
Introduction
Hemoglobinopathies:
• Clinical syndromes resulting from disorders of
hemoglobin synthesis.
Thalassemia:
• Failure to synthesize one or more of the globin
chains of hemoglobin at a normal rate
Role of the Medical Technologists
• Performing specialized laboratory tests, ensuring
the accuracy of results, and assisting healthcare
providers in the interpretation of findings.
This Photo by Unknown Author is licensed under CC BY-SA-NC
4. 4
Hemoglobinopathy
Hemoglobinopathies:
• Clinical syndromes resulting from disorders of
hemoglobin synthesis.
• Alteration of structure of Hb because of point
mutation like substitution of amino acid in Beta
chain. (Eg: 6Glu – Val) = HbS
• HbE caused by a base substitution at codon 26
of the β-globin gene, GAG-AAG, which results in
the substitution of lysine for glutamic acid.
• Common Hb variants that have clinical and
genetic significance
• There are also other variant haemoglobins that
are clinically silent
15. 15
Hemoglobinopathy: Basics and Laboratory Testing
• Some structural variants are associated with severe
clinical phenotypes in the homozygous or even in the
double heterozygous state.
• The mutation can change the solubility, stability or
oxygen-binding capability.
• Because the mutation affected the physical or
chemical properties of the hemoglobin.
• Many of these variants are separated by
chromatography technique, but some are not and
remain undetected.
• Variants that are clinical significant like HbS, C, D, E
and OArab are detectable by chromatography
techniques
16. 16
Hemoglobinopathy: Basics and Laboratory Testing
Hb Genotype Name Clinical Problems
S
A/S Sickle cell trait None
S/S Sickle cell anemia Moderate hemolytic anemia, vaso-occlusive episodes
C
A/C C trait None
C/C C disease Occasional mild anemia, increase incidence of gallstones
DPunjab
A/D D trait None
D/D D disease Occasional mild anemia
E
A/E E trait Minimal morphological abnormalities of the red cells and
normal red cell indices
E/E E disease Hypochromic microcytic red cells with significant
morphological abnormalities including increased numbers of
target cells. They are mildly anemic
HbE alone does not cause any significant clinical problems, its interactions with various forms of
α and β thalassemia produce a very wide range of clinical syndromes of varying severity.
Fucharoen S, Weatherall DJ. The hemoglobin E thalassemias. Cold Spring Harb Perspect Med. 2012 Aug 1;2(8):a011734. doi: 10.1101/cshperspect.a011734. PMID: 22908199; PMCID:
PMC3405827.
18. 18
Thalassemia: Basics and Laboratory Testing
Thalassemia:
• Failure to synthesize one or more of the globin chains of
hemoglobin at a normal rate
• Two types of syndromes
• Inadequate production of globin chains
• Unbalance accumulation of one type of globin chain
• Anemia with hypochromia & microcytosis
• Ineffective erythropoiesis and hemolysis
Role of the Medical Technologists
• Performing specialized laboratory tests, ensuring the accuracy
of results, and assisting healthcare providers in the
interpretation of findings.
This Photo by Unknown Author is licensed under CC BY-SA
This Photo by Unknown Author is licensed under CC BY-NC
19. 19
Common Hemoglobinopathies
Chaichompoo, Pornthip, Saovaros Svasti, and Duncan R. Smith. 2022. "The Roles of Mitophagy and Autophagy in Ineffective Erythropoiesis in β-
Thalassemia" International Journal of Molecular Sciences 23, no. 18: 10811. https://doi.org/10.3390/ijms231810811
21. 21
Common Hemoglobinopathies (HbE)
Sikdar, Mithun. (2016). Hemoglobin E in Northeast India: A review on its origin, distribution, migration and health implication.
Anthropological Review. 79. 241-263. 10.1515/anre-2016-0019.
22. 22
Thalassemia: Basics and Laboratory Testing
Thalassemia:
• Many different mutations can cause thalassemia and related disorders.
• More than 200 mutations have been documented with many of them the result of
point mutations affecting the globin gene.
• Certain mutations are particularly common in some communities which helps to
simplify prenatal diagnosis which is carried out by detection or exclusion of a
particular mutation in fetal DNA.
• Effects of different mutations leads to different impacts.
• Some can lead to severe anemia
• Whereas some are mild with normal MCV and HbA2
• Mainly thalassemia will see Hb at low end of normal range with hypochromic &
microcytic and raised HbA2
23. 23
Thalassemia: Basics and Laboratory Testing
Thalassemia major:
• Severe form of anemia
• Transfusion dependent inherited anemia
• Defective production of chain which leads to excess a chains accumulation
• The imbalance a chains will precipitate and affect the RBC production.
• The few cells that leaves the marrow will carry the precipitate which the spleen
will remove them quickly.
• This continuous cycle will stress the bone marrow and result in extramedullary
erythropoiesis.
• If untreated, 80% of children with thalassemia major dies within the first 5 years
of life.
24. 24
Thalassemia: Basics and Laboratory Testing
Thalassemia trait:
• Can have normal Hb value with microcytosis and mild hypochromic anemia.
• HbA2 is elevated and HbF is raised as well.
25. 25
Thalassemia: Basics and Laboratory Testing
a Thalassemia (normal 4 working genes):
• One of the two globin genes on a single chromosome fails to function (a+ )
• Two genes on a single chromosome fails to function (a0 )
• Three genes fail to function (Hb H disease)
33. 33
Reference
Bain, B. J., Bates, I., Laffan, M. A., & Lewis, S. M. (2016, December 22).
Dacie and Lewis Practical Haematology. Elsevier Health Sciences.
Acknowledge:
Marco Flamini - Bio-Rad Global Product Manager for Hemoglobinopathies
PT Diastika
30 minutes
Presentation points for hemoglobinopathy and thalassemia presentation for 30 mins targeting medical technologists
2 mins
Start with an engaging introduction to the importance of hemoglobinopathies and thalassemia in clinical laboratory practice.
Highlight the role of medical technologists in the diagnosis and management of these disorders.
medical technologists play a vital role in the diagnosis and management of hemoglobinopathies and thalassemia by performing specialized laboratory tests, ensuring the accuracy of results, and assisting healthcare providers in the interpretation of findings. Their work is essential in helping patients receive appropriate care and treatment for these genetic blood disorders.
5 mins
Hemoglobinopathy: Basics and Laboratory Testing
Define hemoglobinopathy and its significance.
Explain the structural abnormalities of hemoglobin in these conditions.
Describe the laboratory tests used for diagnosing and characterizing hemoglobinopathies.
Eg: the substitution of valine for glutamic acid in position 6 of the beta chain
"clinically silent" refers to a medical condition, symptom, or abnormality that exists within a person's body but does not produce noticeable or observable clinical signs or symptoms.
5 mins
Discuss common hemoglobinopathies encountered in clinical practice, with a focus on sickle cell disease and hemoglobin C disease.
Explain the genetic basis and laboratory findings associated with each disorder.
Hemoglobin is a complex globular protein. It has a tetrameric structure made of two dissimilar pairs of globin chains: alpha and beta (primarily).
@Its function is to carry oxygen.
Globin chains are polypeptides made of a unique sequence of amino acids.
Amino acid is a polar molecule that can be charged.
@Depending on the unique sequence of amino acids in the chains, and the different assembling, the resulting @ hemoglobin may have different charges.
Later we will review how the charge is used to differentiate and measure the different hemoglobin fractions.
Genes encoding for making globin chains and hemoglobin are on chromosome 16 for the alpha chains , chromosome 11 for the beta (or non-alpha) chains.
The main hemoglobin in adults is HbA (alpha2-beta2)
We will discuss about changes in the glycation dynamic when the beta chain is changed, and substituted with another chain.
Here is the structure of the protein (hemoglobin), from primary to quaternary.
Any change in the gene sequence @ may lead to a different amino acid being added to the polypeptide chain, causing a change @ in protein structure and function. @
In sickle cell anemia, the hemoglobin β chain has a single amino acid substitution, causing a change in both the structure and function of the protein.
We will discuss about the influence of these conformational changes on the glycation process
Here is the structure of the protein (hemoglobin), from primary to quaternary.
Any change in the gene sequence @ may lead to a different amino acid being added to the polypeptide chain, causing a change @ in protein structure and function. @
In sickle cell anemia, the hemoglobin β chain has a single amino acid substitution, causing a change in both the structure and function of the protein.
We will discuss about the influence of these conformational changes on the glycation process
Here is the structure of the protein (hemoglobin), from primary to quaternary.
Any change in the gene sequence @ may lead to a different amino acid being added to the polypeptide chain, causing a change @ in protein structure and function. @
In sickle cell anemia, the hemoglobin β chain has a single amino acid substitution, causing a change in both the structure and function of the protein.
We will discuss about the influence of these conformational changes on the glycation process
Here is the structure of the protein (hemoglobin), from primary to quaternary.
Any change in the gene sequence @ may lead to a different amino acid being added to the polypeptide chain, causing a change @ in protein structure and function. @
In sickle cell anemia, the hemoglobin β chain has a single amino acid substitution, causing a change in both the structure and function of the protein.
We will discuss about the influence of these conformational changes on the glycation process
5 mins
Hemoglobinopathy: Basics and Laboratory Testing
Define hemoglobinopathy and its significance.
Explain the structural abnormalities of hemoglobin in these conditions.
Describe the laboratory tests used for diagnosing and characterizing hemoglobinopathies.
Eg: the substitution of valine for glutamic acid in position 6 of the beta chain
"clinically silent" refers to a medical condition, symptom, or abnormality that exists within a person's body but does not produce noticeable or observable clinical signs or symptoms.
Thalassemia: Basics and Laboratory Testing (5 minutes)
Define thalassemia and its importance in laboratory diagnosis.
Differentiate between alpha and beta thalassemia and their laboratory markers.
Describe the laboratory tests used to identify and categorize thalassemia.
5 mins
Discuss common hemoglobinopathies encountered in clinical practice, with a focus on sickle cell disease and hemoglobin C disease.
Explain the genetic basis and laboratory findings associated with each disorder.
5 mins
Discuss common hemoglobinopathies encountered in clinical practice, with a focus on sickle cell disease and hemoglobin C disease.
Explain the genetic basis and laboratory findings associated with each disorder.
Thalassemia: Basics and Laboratory Testing (5 minutes)
Define thalassemia and its importance in laboratory diagnosis.
Differentiate between alpha and beta thalassemia and their laboratory markers.
Describe the laboratory tests used to identify and categorize thalassemia.
Thalassemia: Basics and Laboratory Testing (5 minutes)
Define thalassemia and its importance in laboratory diagnosis.
Differentiate between alpha and beta thalassemia and their laboratory markers.
Describe the laboratory tests used to identify and categorize thalassemia.
Thalassemia: Basics and Laboratory Testing (5 minutes)
Define thalassemia and its importance in laboratory diagnosis.
Differentiate between alpha and beta thalassemia and their laboratory markers.
Describe the laboratory tests used to identify and categorize thalassemia.
