Epidemiology

Etiology

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).
- Heterozygotes (HbAS): carry one sickle allele and one other (usually normal) → sickle cell trait
- Homozygotes (HbSS): carry two sickle alleles → sickle cell anemia
HbS polymerizes when deoxygenated, causing deformation of erythrocytes (“sickling”). This can be triggered by any event associated with reduced oxygen tension.
- Hypoxia (e.g., at high altitudes)
  - 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.
- Infections
- Dehydration
- Acidosis
- Sudden changes in temperature
- Stress
Sickle cells lack elasticity and adhere to vascular endothelium, which disrupts microcirculation and causes vascular occlusion and subsequent tissue infarction.
Hemolysis and the subsequent increased turnover of erythrocytes may increase the demand for folate, causing folate deficiency.
- Can present as macrocytic anemia
Extravascular hemolysis and intravascular hemolysis are common and result in anemia.

Antibiotic prophylaxis against invasive pneumococcal disease until 5 years of age
Hydroxyurea therapy regardless of clinical severity to minimize disease-related complications (First-line)
Annual transcranial doppler to screen for stroke risk from 2 months till 16 years of age

All infants > 9 months, children, and adolescents with sickle cell anemia regardless of symptom severity
Adults with any of the following:
- Frequent (≥ 3 episodes/year) acute pain episodes or other vasoocclusive events
- Severe symptomatic anemia
- History of severe and/or recurrent acute chest syndrome

Stimulation of erythropoiesis and increased fetal hemoglobin

Pathophysiology: splenic vasoocclusion and entrapment and pooling of large amounts of blood in the spleen
Clinical presentation
- Most commonly affects children < 5 years of age
- Acute left upper quadrant pain, splenomegaly
- Hypotension and/or hypovolemic shock, especially in infants
  - Due to the trapping of blood in the spleen
- Symptoms of anemia (e.g., pallor, fatigue)
- Functional asplenia: Increased risk of infection with encapsulated bacteria (Streptococcus pneumoniae (most common), Neisseria meningitis, Haemophilus influenzae type b
Supportive findings
- Anemia (Hb drop of ≥ 2 g/dL) with reticulocytosis
- Thrombocytopenia
Acute management
- Immediate IV fluid resuscitation for hypovolemia
- Simple RBC transfusion in consultation with a sickle cell expert (avoid raising hemoglobin > 8 g/dL)