CH. 24 - Hemoglobinopathies

mama mo mukhang sickle cell

Hemoglobinopathies

Results from a genetic mutation in one or more genes that affect hemoglobin synthesis

Qualitative Hemoglobinopathies

The hemoglobin molecule has an altered amino acid sequence within the globin chains

Quantitative Hemoglobinopathies

Thalassemias result in a reduced rate of hemoglobin synthesis but do not affect the amino acid sequence of the affected globin chains.

Point Mutation

• The most common type of genetic mutation

• Replacement of one original nucleotide in the normal gene with a different nucleotide.

Gene fusions

Occurs when two normal genes break between nucleotides, switch positions, and anneal to the opposite gene

Zygosity

Refers to the association between the number of gene mutations and the level of severity of the resultant genetic defect

Sickle Cell Disease (SCD)

This is the most common form of hemoglobinopathy

Hb S

• Type of Hb in which sickling occurs when a solution of RBCs is deficient in oxygen.

• Resistant against infection with P. falciparum

Reversible Sickle Cells

• RBCs that change shape in response to oxygen tension.

• Circulate as normal biconcave disc.

• Able to travel into the microvasculature.

Irreversible Sickle Cells

• RBCs do not change their shape.

• Seen as elongated sickle cells with a point at each end.

• Recognized as abnormal by the spleen and removed from circulation

Hemoglobin solubility test

The most common screening test for Hb S.

Alkaline hemoglobin electrophoresis

Based on the separation of hemoglobin molecules in an electric field, the result of differences in total molecular charge

High-Performance Liquid Chromatography (HPLC)

• Used to confirm hemoglobin variants.

• More automated

• Separates hemoglobin types in a cation exchange columns

• Best used in the diagnosis of thalassemia.

Capillary Electrophoresis

• Separates hemoglobin types based on charge in an alkaline buffer

• Use smaller volumes and produce better separation than traditional agarose electrophoresis

Isoelectric focusing

It is a confirmatory technique that is expensive and complex, requiring well-trained and experienced laboratory personnel

Hb C-Harlem

• Type of Hb that has a Double - Substitution on the Beta Chain.

• The substitution of valine for glutamic acid at position 6 of the beta chain and the substitution at position 73 of aspartic acid for asparagine

Hb S-β-Thalassemia

Type of Hb that resembles mild or moderate SCD

Hb S-Korle Bu

It is a rare hemoglobin variant with substitution of aspartic acid for asparagine at position 73 of the b chain

Hb M

The mutation in the Alpha, Beta, and Gamma Globin Genes results in the production of this Hb.

It also causes blood specimens to appear brown

Cyanosis

This is produced when iron in the ferric state is unable to carry oxygen.

Hb Köln

This is the most prevalent unstable hemoglobin

Plasmodium falciparum

This parasite is most associated with SCD

Vasoocclusive crisis

This is the hallmark of SCD

Spleen sequestration

This is characterized by a sudden trapping of blood in the spleen, which leads to a rapid decline in hemoglobin

Autosplenectomy

Gradual loss of splenic function is referred to as?

Fat embolism syndrome (FES)

A rare but often fatal sequalae of SCD

Aplastic episodes

The most common life-threatening hematologic complications and are usually associated with infection, particularly parvovirus infection

Megaloblastic episodes

These episodes result from the sudden arrest of erythropoiesis caused by folate depletion

Avascular necrosis (AVN)

Impaired blood supply to the head of the femur and humerus results in a condition called

Hand-foot syndrome

This is characterized by pain and swelling in the hands and feet of children younger than 3 years

Hb C

Type of Hb that is found primarily in people of African descent

Decreased production of a globin chain

REVIEW QUESTION:

A qualitative abnormality in hemoglobin may involve all of the following except:

Polymerizes to form tactoid crystals

REVIEW QUESTION:

The substitution of valine for glutamic acid at position 6 of the b chain of hemoglobin results in hemoglobin that:

Higher levels of Hb F are present

GUIDE QUESTIONS:

Patients with SCD usually do not exhibit symptoms until 6 months of age because:

Folic acid

Megaloblastic episodes in SCD can be prevented by prophylactic administration of:

Hemoglobin electrophoresis at acid pH

Which of the following is the most definitive test for Hb S?

Substitution of lysine for glutamic acid at position 6 of the b chain

REVIEW QUESTION:

A patient presents with mild normochromic, normocytic anemia. On the peripheral blood film, there are a few target cells, rare nucleated RBCs, and hexagonal crystals within and lying outside of the RBCs. Which abnormality in the hemoglobin molecule is most likely?

The patient has Hb M.

REVIEW QUESTION:

A well-mixed specimen obtained for a CBC has a brown color. The patient is being treated with a sulfonamide for a bladder infection. Which of the following could explain the brown color?

25%

REVIEW QUESTION:

Through routine screening, prospective parents discover that they are both heterozygous for Hb S. What percentage of their children potentially could have sickle cell anemia (Hb SS)?

Vasoocclusion

REVIEW QUESTION:

Painful crises in patients with SCD occur as a result of:

Are insoluble in reduced, deoxygenated form

REVIEW QUESTION:

The screening test for Hb S that uses a reducing agent, such as sodium dithionite, is based on the fact that hemoglobins that sickle:

Homozygous/disease

REVIEW QUESTION:

DNA analysis documents a patient has inherited the sickle mutation in both b-globin genes. The two terms that best describe this genotype are:

Sub-Saharan Africa

REVIEW QUESTION:

In which of the following geographic areas is Hb S most prevalent?

Hb E

REVIEW QUESTION:

Which hemoglobinopathy is more common in Southeast Asian patients?

Hb SG

REVIEW QUESTION:

Which of the following Hb S compound heterozygotes exhibits the mildest symptoms?

Only homozygotes are symptomatic

REVIEW QUESTION:

Unstable hemoglobins exhibit all of the following findings except: