Sickle Cell Anemia Flashcards
What is sickle cell disease?
A group of conditions characterized by mutations in the HbS genotype that result in phenotypic manifestations
Genotypes of sickle cell disease?
HbSS, HbSβ0thal, HbSβ+thal, HbSC, and rarely, HbSD, and HbSE
What is sickle cell anemia?
The most severe clinical presentation of sickle cell disease
- Genotypes include homozygous HbSS and compound heterozygous HbSβ0thal (a form of sickle beta thalassemia).
What is sickle cell trait?
Refers to the sickle cell carrier genotype (HbAS)
- Not considered a form of sickle cell disease
Which sickle cell anemia genotypes have the most severe clinical presentations?
HbSS and HbSβ0thal
Epidemiology of sickle cell disease?
Predominantly affects individuals of African and Eastern Mediterranean descent
- Africa has the highest prevalence of the disease (30% heterozygote prevalence).
Genetics behind sickle cell disease?
Point mutation in the β-globin gene (chromosome 11) → glutamic acid replaced with valine (single amino acid substitution) → 2 α-globin and 2 mutated β-globin subunits create pathological hemoglobin S (HbS).
1. Heterozygotes (HbAS): carry one sickle allele and one other (usually normal) → sickle cell trait
2. Homozygotes (HbSS): carry two sickle alleles → sickle cell anemia
How do RBCs become sickled?
HbS polymerizes when deoxygenated, causing deformation of erythrocytes (“sickling”).
What triggers the sickling of RBCs?
triggered by any event associated with reduced oxygen tension
1. hypoxia
- In homozygotes, up to 100% of the hemoglobin molecules are affected, leading to sickle cell formation under minimally decreased oxygen tension.
- In heterozygotes, sickling only occurs due to severe reduction in oxygen tension
2. Infections
3. Dehydration
4. Acidosis
5. Sudden changes in temperature
6. Stress
7. Pregnancy
Pathophysiology of sickle cell disease?
- Sickle cells lack elasticity and adhere to vascular endothelium, which disrupts microcirculation and causes vascular occlusion and subsequent tissue infarction.
- Extravascular hemolysis and intravascular hemolysis are common and result in anemia.
- Hemolysis and the subsequent increased turnover of erythrocytes may increase the demand for folate, causing folate deficiency.
- The body increases the production of fetal hemoglobin (HbF) to compensate for low levels of HbA in sickle cell disease
Onset of sickle cell disease?
∼ 30% develop symptoms in the first year of life; > 90% by age 6 years
- Typically manifests after 3–6 months of age as the production of HbF decreases and HbS levels increase
Acute manifestations of sickle cell disease?
- vaso-occlusive events
- infection
- acute hemolytic crisis
What are the vaso-occlusive events of SCD?
- dactylitis
- vasooclusive crises - sickle cell pain crisis
- Acute chest syndrome
- Priapism
- Stroke (common in children)
- Sickle cell hepatopathy
- Organ infarctions (any organ; particularly the spleen)
- Avascular necrosis
What is Dactylitis in SCD?
in children < 5 years of age
- Typically the earliest manifestation of sickle cell disease
- Most common in children between 6 months and 2 years of age; uncommon in older children and adults
What is sickle cell pain crisis?
- Most common acute complication of sickle cell disease
- Characterized by recurrent episodes of severe throbbing or sharp pain
- Typically affects the limbs, chest, and back and lasts for ∼ 7 days
- Often associated with other vasoocclusive events (especially dactylitis in children)
