Sickle Cell Disease



  • Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy characterized by abnormal hemoglobin (HbS) which polymerizes under stress and deforms RBCs, resulting in hemolysis, vaso-occlusion, and subsequent tissue ischemia/infarction
  • HbS production secondary to a single amino acid substitution in hemoglobin gene
  • Occurs in people of African, Mediterranean, Middle Eastern, and Asian descent; areas where malaria is endemic
  • Severity variable even among the same phenotype
  • Genotypes and severity in African Americans:
    • HbSS, severe
    • HbSC, mild to moderate severity
    • HbSβ-thalassemia, mild to moderate severity
    • HbAS, sickle cell trait:
      • No manifestation of disease
      • At risk for sudden death with extreme physical exertion, severe hypoxia, severe dehydration, or maternal labor
  • Chronic hemolytic anemia associated with progressive vasculopathy manifests as disease in virtually all organ systems
  • The clinical hallmark of SCD is acute, episodic pain
  • Acute vaso-occlusive crisis (VOC) or pain crisis
    • Vaso-occlusion of bone microvasculature causes infarction
    • Long bones, ribs, sternum, spine, and pelvis affected
    • Dactylitis, or “hand–foot syndrome,” occurs at ages 6–24 mo
  • Acute chest syndrome:
    • Vaso-occlusion of pulmonary vasculature
    • Fat embolism from infarcted bone marrow and/or infections (viral or bacterial) may contribute
    • Associated Chlamydia pneumoniae and Mycoplasma pneumoniae isolated in sputum and Streptococcus pneumoniae bacteremia
    • High mortality (2–14%)
    • 50% of sickle cell patients will experience at least 1 episode
    • Radiographic pulmonary infiltrate with fever and respiratory symptoms makes it difficult to distinguish from pneumonia
    • More common in children
  • Splenic sequestration:
    • Splenic sinusoids become congested with sickled RBCs, obstructing outflow
    • Estimated 6–17% of SCD deaths
    • Circulatory collapse may be rapidly fatal
    • More common in children <5 yr old
  • Aplastic crisis:
    • Bone marrow suppression usually occurs secondary to viral infection, most commonly Parvovirus B19
    • Hallmark acute anemia with low reticulocyte count
    • Acute bone marrow suppression significantly worsens chronic anemia
    • Generally self-limited
    • More common in children
  • Cerebrovascular accident/transient ischemic attack (CVA/TIA):
    • Secondary to vaso-occlusion by sickled cells and thromboembolism in children and older patients, respectively
    • Children with SCD have a 300-fold increased risk of CVA/TIA
      • Most events occur before the age of 10 and after the age of 29 yr
  • Bacterial infection:
    • Sepsis is the leading cause of death in patients with SCD
    • Increased risk of bacteremia, meningitis, and osteomyelitis
    • Impaired splenic function impairs ability to fight encapsulated organisms
    • S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Escherichia coli, and Salmonella are leading organisms
    • Children <5 yr of age have 400-fold increase in pneumococcal infections
  • Priapism:
    • Painful, sustained, unwanted erection >3 hr
    • More commonly low-flow (ischemic) priapism than high-flow (nonischemic)

Pediatric Considerations
  • Acute sickle cell complications in children carry high morbidity and should be screened for aggressively
  • Infections commonly precipitate crisis
  • Confirm immunization history (pneumococcal and H. influenzae type b)
  • Determine if child is receiving prophylactic penicillin, normally indicated in children ≤5 yr old
  • Overwhelming infection highest in children <3 yr of age

Pregnancy Considerations
  • Variable frequency of crisis episodes, not uncommon for increased frequency
  • Anemia is more profound
  • Increased rates of hypertensive disorders of pregnancy, asymptomatic bacterial infections, UTI, and pyelonephritis leading to septicemia
  • Increased risk of spontaneous abortions, antepartum bleeding, and premature rupture of membranes
  • Increased risk of preterm labor, intrauterine growth restriction, and low birth weight


Common crisis precipitants:
  • Infection (bacterial and viral)
  • Dehydration
  • Hypoxemia
  • Acidosis
  • Emotional stress
  • Surgery/trauma
  • Weather changes
  • Pregnancy
  • Toxins

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