Sickle Cell Disease

Description

• 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)

• 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

• 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

Etiology

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