SUMMARY:

Sickle cell disease is a common genetic condition that affects the function of adult hemoglobin. It has a high prevalence in people with African, Middle Eastern, and West Indian ancestry. Any pregnant woman who reports a high-risk ethnicity should be screened with hemoglobin electrophoresis, which is highly accurate in detecting carriers of sickle cell trait. Many reproductive carrier screening genetic panels also include screening for sickle cell carrier status. (For more on screening, see ‘Related ObG Topics’ below).

Background and Genetics 

• Sickle cell disease is caused by a single point mutation within the HBB gene
• RBCs have a “sickled” shape and decreased ability to carry oxygen
• Autosomal recessive
• Hemoglobin electrophoresis is recommended for diagnosis and carrier screening
  • Confirmed by the presence of Hemoglobin S (HbS)
  • Other hemoglobin variants (HbC, HbE, beta thalassemia) can cause disease when inherited with a sickle cell mutation

Symptoms 

Sickle Cell Disease / Sickle Cell Anemia

• Abnormally shaped RBCs aggregate and block small blood vessels (microvascular occlusions)
• Intermittent episodes of acute pain (sickle cell crisis)
• Organ damage and risk of stroke
• Swelling of hands and feet
• Chronic hemolysis
• High risk of infection (septicemia, meningitis)

Sickle Cell Trait / Sickle Cell Carrier

• Generally asymptomatic
• Normal CBC
• Hb electrophoresis shows 40-50% HbS
• May experience vaso-occlusive events with extreme dehydration, physical exertion, or high altitude

Management

• Prophylactic antibiotics to manage risk of infection
• Symptom-based therapies for pain and other complications
• Hydroxyurea may be used to increase the amount of functional HbF in the blood
• Severe cases may require RBC transfusions or bone marrow transplantation
• Recent trials using the latest gene therapy techniques show promise to treat sickle cell disease (see ‘Learn More – Primary Sources’ below for more detail)
  • Gene addition: Adding a therapeutic beta-globin gene)
  • Gene editing: Correction of the mutated β-globin gene

KEY POINTS:

• Prevalence
  • Approximately 10% of Black Americans are carriers of sickle cell disease
  • Highest incidence in West Africa: 1 in 4 individuals are carriers
• In addition to symptom-based therapy, treatment may include RBC transfusions or bone marrow transplantation
  • Recent trials with gene addition and gene editing techniques are an important area of research
• Prenatal diagnosis via CVS or amniocentesis is available for at-risk pregnancies
  • Molecular testing is required for fetal diagnosis
  • There are no fetal ultrasound findings typically associated with this diagnosis
• Pregnant patients with sickle cell disease may experience complications such as thrombosis, infections, preterm birth, preeclampsia, and cardiac failure
  • Refer to Maternal Fetal Medicine and Hematology
  • Review vaccinations, including pneumococcal, meningococcal and Haemophilus influenzae

Learn More – Primary Sources:

ACOG Committee Opinion 691: Carrier Screening for Genetic Conditions

GeneReviews: Sickle Cell Disease

Hematopoietic Stem Cell Gene-Addition/Editing Therapy in Sickle Cell Disease

Locate a Genetic Counselor or Genetics Services: 

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC 

Genetic Services Locator-CAGC 

Locate a Maternal Fetal Medicine Specialist:

Maternal Fetal Medicine Specialist Locator-SMFM

Locate a Hematologist:

American Society of Hematology

Related ObG Topics: