MLS 2304 Hematology: Structural Hemoglobinopathies & Sickling Disorders

lesson 1 ppt

What is the predominant adult hemoglobin?

HbA (α₂β₂)

What is the structure of fetal hemoglobin?

HbF (α₂γ₂)

What causes structural hemoglobinopathies?

Altered globin amino acid sequence, such as in HbS and HbC.

What is the primary defect in thalassemia?

Reduced or absent globin-chain synthesis.

Which chromosome contains alpha-like globin genes?

Chromosome 16.

Which chromosome contains beta-like globin genes?

Chromosome 11.

What does heterozygous mean in the context of hemoglobin?

Different alleles at the HBB locus (e.g., AS).

What does homozygous mean in the context of hemoglobin?

Same allele on both HBB copies (e.g., SS).

What is the inheritance pattern of AS × AS?

25% AA, 50% AS, 25% SS.

What amino acid substitution occurs in HbS?

Glutamic acid (Glu) is replaced by Valine (Val) at position β6.

What are the consequences of HbS polymerization?

Deoxygenation leads to sickling, hemolysis, and vaso-occlusion.

What laboratory findings are associated with HbSS?

Chronic anemia, increased reticulocyte response, sickle cells, and target cells.

What is the effect of hydroxyurea in sickle cell disease?

It increases HbF and can alter MCV.

What is the primary characteristic of HbC?

β6 glutamic acid is replaced by lysine, usually causing mild chronic hemolysis.

What defines HbSC disease?

One beta-S allele and one beta-C allele, leading to compound heterozygous sickle cell disease.

What is the sickle solubility principle?

Deoxy-HbS becomes insoluble in concentrated buffer under reducing conditions.

What does alkaline electrophoresis separate?

It separates S/D/G overlap and C/E/O/A2 overlap.

What does acid electrophoresis clarify?

It separates S from D/G and C from E/O.

What is the significance of a transfused HbSS pattern?

It indicates the presence of donor hemoglobins alongside patient hemoglobins.

What does the HPLC chromatogram indicate in sickle trait?

Peaks appear in F, A, A2, and S windows, with integrated peak areas providing reported fractions.

What factors can change hemoglobin patterns?

Age, transfusion, treatment, and underlying conditions like thalassemia or iron deficiency.

What is the typical hemoglobin fraction pattern in a 22-year-old with sickle cell trait?

HbA 58.0%, HbS 38.8%, HbA2 2.8%, HbF 0.4%.

What does a predominant HbS pattern with no HbA suggest?

It is most consistent with HbSS.

What are common clinical complications of sickle cell disease?

Hemolysis, vaso-occlusion, and chronic pain.

What is the role of molecular testing in hemoglobin disorders?

It resolves selected genotypes and clarifies overlapping patterns.

What is the expected reticulocyte response in sickle cell disease?

Increased reticulocyte count due to chronic hemolysis.

What is the clinical significance of target cells in blood films?

They can indicate hemoglobinopathies such as HbC or thalassemia.