Hemolytic Anemias-Hemoglobinopathies (Chapter 11)

Hemoglobinopathies

A group of genetic disorders caused by structural abnormalities in the hemoglobin

What is the frequent cause of Hemoglobinopathies?

Single amino acid substitutions in the globin chains

There are _____ hemoglobin variants

1,000

The majority of hemoglobin variants are clinically _______

Insignificant

There are ___ known polypeptide chains that make up the different globin portions of the hemoglobin molecule

Six

Hemoglobinopathies do not have an amino acid substitution or deletion

False, hemoglobinopathies do have an amino acid substitution/deletion

Hgb A is:

A normal Hgb allele

Hgb S is:

An abnormal Hgb allele

Hgb C is:

An abnormal Hgb allele

Most hemoglobinopathies result from:

β-chain abnormalities

What causes Hemoglobin S (HbS) to occur?

Position 6 of the β chain, valine replaces glutamic acid

What causes Hemoglobin C (HbC) to occur?

At position 6 of the β chain, lysine replaces glutamic acid

Sickle cell disease (SCD)

Group of genetic disorders characterized by the production of abnormal HbS

Sickle cell anemia (HbSS disease)

Most common type of sickle cell disease; most severe form

What represents the homozygous form of sickle cell, in which the individual inherits a double dose of the abnormal gene that codes for HbS?

Sickle cell anemia (HbSS disease)

Sickle cell trait (HbAS)

Occurs when a person inherits one HbS gene and one normal HbA gene (heterozygous)

Which sickle cell is usually asymptomatic, but may have mild symptoms under extreme stress

Sickle cell trait (HbAS)

When properly oxygenated, HbS should usually does not cause any issues

True

HbS is soluble

True

What occurs when oxygen tension decreases (low O₂ environment)?

HbS molecules to stick together when they release O₂, forming long, rigid rods

Causes the RBC to deform into the characteristic sickle shape

What triggers an aplastic crisis?

Usually viral infections (especially parovirus B19)

What effect does an aplastic crisis have?

Temporary suppression of erythropoiesis (bone marrow stops making new RBCs)

What triggers a hemolytic crisis?

• Medications

• Autoimmune disorders

• Viral infections

• Low O₂ state

• Acidosis

• Cold exposure

The lab findings for an individual going through a hemolytic crisis shows ______ H&H and _____

Decreased, jaundice

Lab findings for a patient experiencing hemolytic crisis would show ______ reticulocyte count

Increased

A patient experiencing a hemolytic crisis would have what kind of symptoms?

• Sudden weakness

• Rapid pulse

• Faintness

• Pallor (lips & mucous membranes)

• Abdominal fullness from splenic enlargement

What is the most common type of sickle crisis?

Vaso-occulsive crisis (pain crisis)

Which sickle crisis is associated with severe pain, caused by occlusion (blockage) of small blood vessels?

Vaso-occulsive crisis (pain crisis)

Dactylitis (painful swelling of the hands/feet is more common in ____ & ________ with HbSS anemia?

Infants & young children

What is the major cause of morbidity and mortality for those with HbSS anemia?

Serious bacterial infections

____ occurs in up to 22% of patients with HbSS anemia?

Stroke

How is sickle cell trait inherited?

One normal β-globin gene (HbA) + one sickle β-globin gene (HbS)

Individuals with HbS trait are usually ______

Asymptomatic

Individuals with sickle cell trait produce both HbA and HbS in a ratio of __:__ (HbA, HbS)

60,40

Newborns suspected of HbS in the U.S. and territories are routinely screened

False, every newborn is screened regardless of race or ethnicity

What is the gold standard for confirming HbS?

Hemoglobin electrophoresis (performed on cellulose acetate and citrate agar)

Hemoglobin electrophoresis

Separates hemoglobin types based on their charge

Sickle cell anemia (HbSS) & stickle cell trait are most commonly found in populations with ancestry from?

Regions where malaria is or was historically prevalent

What is in the center of this slide?

HbC crystals “bar of gold”

Hemoglobin C Disease and traits are almost exclusive to:

African & African American populations

HbC disease presents with:

• Normocytic & Normochromic or hyperchromic anemia

• HbC crystals “bars of gold”

Electrophoresis results:

• 95% Hbc (dominant form)

• Some HbA₂ present

• <7% HbF

What could these results indicate?

Hemoglobin C Disease/trait

Hemoglobin Disease/Trait is more common in

Asian populations

• Especially SE Asia

What kind of cells would an individual with Hemoglobin E disease/trait have?

Microcytosis, target cells

What protective effect does Hemoglobin E disease/trait have?

HbE alters the RBC environment, making it less favorable for Plasmodium falciparum

• As a result, the parasite multiplies more slowly in HbAE (trait) or HbEE (disease) cells

HbD

Non-sticking soluble hemoglobin

Hemoglobin D Disease/Trait

• Causes mild hemolytic anemia

• Has variations (name may include area of prevalence)

Hemoglobin O_Arab Disease/Trait

• Exhibits a mild hemolytic anemia with slight splenomegaly & target cells

• Has a distinct electrophoresis pattern

• Those with the trait are asymptomatic

What could this indicate?

Hemoglobin SC disease

The gene for HbS and HbC are inherited from one parent only in the case of Hemoglobin SC disease

False, the gene for HbS is inherited from one parent and HbC from the other

Hemoglobin SD disease

Combination of HbS and HbD disease, rare

How does hemoglobin SD disease present a diagnostic problem?

Hemoglobin migrates together at alkaline pH, the electrophoretic pattern is similar to that of HbSS disease; alternative testing is needed

Thalassemia

Decrease in Hgb production due to decrease production of globin chains

HbS/β⁰ thalassemia

Severe condition that clinically resembles sickle cell anemia (Zero = no synthesis of beta chains)

HbS/β⁺ thalassemia

Generally milder clinical presentation (plus = reduced synthesis of beta chains)

Unstable hemoglobins may cause Hgb to ____ & precipitate in RBCs as _______

Denature, Heinz bodies

Isopropanol stability/Heat stability testing

Detects unstable Hgbs (also, gene sequencing)

Unstable hemoglobins are not hemoglobin variants

False, they are