Chapter 104: Sickle Cell Disease

High-Yield Facts

• Sickle cell disease (SCD) is a chronic hemolytic anemia that is most common among African Americans but may occur in children of any ethnic background. Patients with a single abnormal gene for hemoglobin S (Hgb S) have sickle cell trait and remain essentially asymptomatic.

• Acute vasoocclusive events, or painful “crisis,” are the most common complication of SCD and are the most frequent cause of emergency department (ED) visits.

• Patients with SCD presenting with a new infiltrate on chest radiograph and chest pain, fever, and/or respiratory symptoms have acute chest syndrome (ACS) requiring hospitalization.

• A blood culture should be obtained and parenteral antibiotic given to every patient with SCD and fever due to the risk of sepsis from encapsulated bacteria, especially Pneumococcus.

• Splenic sequestration crisis occurs when RBCs become entrapped in the spleen, resulting in a rapidly enlarging spleen and a sudden drop in Hgb.

• Stroke occurs in 11% of patients with sickle cell anemia under 20 years of age. Patients with signs and symptoms concerning for stroke should have neuroimaging performed (preferably MRI and MRA) and consultation with a hematologist as soon as possible.

Hgb S is a variant resulting from a single nucleotide mutation of the β-globin gene leading to the substitution of hydrophobic valine for the normal hydrophilic glutamic acid. SCD occurs when an individual is homozygous for Hgb S or is a compound heterozygote for Hgb S and another interacting β-globin variant. The most common combination of hemoglobins leading to SCD are Hgb SS (sickle cell anemia), Hgb SC (hemoglobin SC disease), and Hgb S-β thalassemia (either β⁰ or β⁺). Although there is wide variability in individual severity of illness, patients with double heterozygous states such as Hgb SC, Hgb Sβ⁺ thalassemia, and are typically less seriously affected than those with Hgb SS or Hgb Sβ⁰ (no hemoglobin A production). Approximately 2600 children are born in North America each year with SCD, most commonly children of African descent.¹ However, Hgb S also occurs in people of Mediterranean, Indian, Central/South American, and Middle Eastern descent.

Patients with a single abnormal gene for HbS have sickle cell trait. The concentration of HbS is typically 40%, and the large percentage of normal hemoglobin allows the patients to remain asymptomatic except under the most severe hypoxic stress. Sickle trait should be considered a benign condition. Patients with SCD experience a number of complications that are likely to bring them to the ED.

Vasoocclusive Crisis

Acute vasoocclusive events, or painful “crisis,” are the most common complication of SCD and are the most frequent cause of ED visits.² Pain episodes result from the obstruction of blood flow in the microcirculation leading to tissue ischemia and microinfarction. Vasoocclusion occurs via a combination of sickle cell interactions with endothelial cells and obstruction from nondeformable sickle cells.

Dactylitis, or hand–foot syndrome, ...