Sickle Cell Disease

Sickle cell disease (SCD) is a group of inherited red-blood-cell disorders caused by a mutation in the HBB gene encoding beta-globin. Normal red blood cells are flexible discs that glide easily through blood vessels; in SCD, cells become rigid, crescent-shaped, and prone to clumping. That clumping obstructs blood flow, triggering pain crises, progressive organ damage, stroke, and hemolytic anemia. SCD is the most common inherited blood disorder in the United States, affecting approximately 100,000 Americans — more than 90 percent of whom are Black. The mutation confers partial protection against Plasmodium falciparum malaria, which drove its prevalence in populations from sub-Saharan Africa, the Caribbean, and the Mediterranean over centuries.

• Severe pain crises, most often in the back, chest, limbs, or abdomen
• Fatigue and chronic anemia
• Swelling of hands and feet (dactylitis), especially in infants and young children
• Fever above 101°F, which is a medical emergency in SCD
• Yellowing of the eyes and skin (jaundice)
• Vision disturbances or sudden vision loss
• Delayed growth and puberty
• Frequent bacterial infections, especially pneumococcal

Newborn screening for SCD is mandatory in all 50 U.S. states and detects disease before symptoms appear, enabling penicillin prophylaxis to begin by 3 months of age. Adults of African, Mediterranean, Middle Eastern, South Asian, or Caribbean descent who were not screened as newborns may request a hemoglobin electrophoresis test — particularly important before planning a family. Sickle cell trait carriers (HbAS) generally do not have disease but can pass the gene to children. When both parents have trait, each pregnancy has a 1-in-4 chance of SCD.

Disease-modifying therapies include hydroxyurea (reduces pain crises by increasing fetal hemoglobin), L-glutamine, voxelotor, and crizanlizumab. Chronic transfusion programs prevent stroke in high-risk children identified by transcranial Doppler. Opioids, NSAIDs, and nerve blocks manage acute pain crises. Allogeneic bone marrow or stem cell transplantation is curative for children with matched sibling donors. The 2023 FDA-approved gene therapies Casgevy and Lyfgenia reprogram a patient's own hematopoietic stem cells and represent the first potential functional cure available to patients without a matched sibling donor, though access is currently limited by cost and center availability. The ASH 2020 guidelines and NHLBI 2014 Evidence-Based Management Report remain the primary clinical references.