Sickle Cell Disease

Vasoocclusive crisis

Osteomyelitis

Avascular necrosis

transfuse goal

Spelnic sequestration versus aplastic anemia

acute chest syndrome

What type of hemoglobin is present in sickle cell disease?

HbS

Describe the mutation in sickle cell disease

Glutamic acid -> valine mutation in beta globin gene (chromosome 11)

How does the glutamic acid to valine mutation in HbS affect its behavior?

Increased hydrophobic interactions -> polymerization

What kind of Hemoglobin S is most likely to polymerize and sickle?

Deoxy-HbS

What are 3 conditions that promote sickle cell formation?

1) Hypoxia

2) Dehydration

3) Acidosis

What consequence occurs in RBCs in sickle cell disease following multiple polymerization-depolymerization cycles?

Irreversible damage -> persistent sickling

How many days do sickled RBCs survive compared to normal RBCs?

Sickled ~20 day lifespan

Normal ~120 day lifespan

Persistently sickled cells become stiff and undergo what kind of hemolysis?

Extravascular hemolysis (some minor intravascular as well)

What is the genetic inheritance pattern of sickle cell disease?

Autosomal recessive

Describe the genotypes of sickle cell trait vs sickle cell disease

Trait: 1 HbS allele, 1 normal HbA allele

Disease: 2 HbS alleles

Describe the symptoms of sickle cell trait

Usually asymptomatic, but significant sickling can occur under extreme circumstances

Why can sickle cell anemia lead to vaso-occlusion?

Sickle cells adhere to each other

Describe the changes in the spleen of sickle cell patients in childhood vs adulthood

Childhood: splenomegaly

Adult: Splenic fatigue -> autosplenectomy

What peripheral blood smear finding is seen in sickle cell disease due to splenic fatigue?

Howell Jolly Bodies

Due to splenic fatigue in sickle cell disease, what preventative measures should be taken? (2)

1. Daily penicillin prophylaxis (up to age 5)

2. Vaccinations for encapsulated bacteria

In sickle cell disease, splenic sequestration can cause what symptoms? (2)

1. Anemia

2. Hypotension

Splenic sequestration occurs when a large blockage in the splenic circulation causes the spleen to swell with blood. Dangerous condition with up to 10% mortality. Occurs in children only as adult spleens will be fibrosed and shrunken.

Parvovirus B19 can lead to what complication in patients with sickle cell disease?

Aplastic crisis

How can aplastic crisis vs splenic sequestration be differentiated?

Aplastic crisis: low reticulocyte count

Splenic sequestration: high reticulocyte count

What are the symptoms of sickle cell disease? (7)

1. Pain

2. Dactylitis (hand-foot syndrome, can lead to permanent deformity)

3. Avascular necrosis of femoral head

4. Acute chest syndrome

5. Ischemic stroke

6. Priapism

7. Chronic kidney disease and hematuria