Hemolytic Anemias-Thalessemia (Chapter 12)

What is one of the most common genetic disorders in the world?

Thalassemia syndrome

What is the cause of thalassemia?

A reduction or absent production of globin chains

What is the first main type of thalassemia?

Alpha (α) thalassemia

What is the second main type of thalassemia?

Beta (β) thalassemia

What is the cause of alpha thalassemias?

Gene deletions

What is the cause of beta thalassemias?

Various genetic mutations

Decreased production of one globin chain leads to:

• Reduced amounts of normal hemoglobin

• Microcytic, hypochromic anemia (small, pale red cells)

What is the clinical classification of Beta-Thalassemia major?

Homozygous

What is the clinical classification of Beta-Thalassemia intermedia?

Variable (can be homozygous or heterozygous)

What is the clinical classification of Beta-Thalassemia minor?

Trait or heterozygous

Beta thalassemia

Inherited genetic mutations that reduce or eliminate Beta-globin chain production

β⁰ mutations

Cause a complete absence of beta-globin chains

β⁺ mutations

Cause reduced amounts of beta-globin chains

β thalassemia major is also called

Cooley’s Anemia

A patient with β-thalassemia major would have an Hgb typically of:

<7 g/dL

What is the arrow pointing to?

Howell-Jolly body in the hypochromic microcyte

What condition could this smear be showing?

β thalassemia major (Cooley’s anemia)

β thalassemia intermedia

• Appears after age 2

• Patients maintain a higher Hb level

• Variable degrees of symptomatic anemia, jaundice, splenomegaly & some complications of β thalassemia major

• Survive into adulthood without a large blood transfusion requirement

β thalassemia minor

• Usually discovered incidentally

• Mild microcytic, hypochromic anemia

Silent carriers

β thalassemia minor

Why is there such heterogeneity in the clinical presentation of the beta thalassemias?

This is due to a decrease in the production of beta globin chains caused by mutations and several factors

α-thalassemias are based on the:

Number of gene deletions

α-thalassemia major

Occurs when all four alpha-globin genes deleted (no α-chains produced)

In the fetal stage of α-thalassemias what is present?

“Hemoglobin Bart”, which is composed of four gamma globin chains

Hydrops fetalis

Severe edema in unborn/newborn baby

Hemoglobin H Disease

Three alpha-globin genes deleted

Adults have _____% hemoglobin H; have 4 beta chains

5-40%

What is hemoglobin H composed of?

Four β-globin chains

What gives off this “golf ball appearance”?

Hemoglobin H disease

α-thalassemia trait/minor

Occurs when two alpha-globin proteins have been deleted

α-thalassemia silent carrier

Occurs when only one alpha-globin gene is deleted, which can cause children to have hemoglobin H disease

Hemoglobin constant spring (HbCS)

Results of a point mutation in the α₂-globin gene

Hereditary persistence of fetal hemoglobin (HPFH)

A group of conditions with the persistence of fetal hemoglobin synthesis into adult life

How can the automated hematology results, such as the RBC count and RBC indices, be used to aid the diagnosis of thalassemia?

They can be used to check for:

• Normal-to-increased RBC

• Normal to mildly decreased MCHC

• Normal RBC volume distribution width (RDW)

Which types of thalassemias causes elevated (range 1-6 mg/dL), due to hemolysis?

• Major

• Intermedia

In an individual who is a thalassemia carrier, the serum ferritin level is:

Normal/High