Overview
Definition
An inherited group of disorders where red blood cells contort into a sickle shape, leading to premature breakdown (hemolysis) and microvascular occlusion.
Epidemiology
Most common inherited blood disorder in the US. Predominantly affects people of African descent.
Etiology & Risk Factors
- Autosomal recessive mutation in the beta-globin gene (point mutation substituting valine for glutamic acid), resulting in Hemoglobin S (HbS). HbS polymerizes under hypoxic conditions, causing the cell to sickle.
Clinical Symptoms
- Vaso-occlusive crises (severe ischemic pain, commonly in back, chest, and long bones)
- Dactylitis (hand-foot syndrome) in infants
- Anemia symptoms (fatigue, pallor)
- Jaundice (due to hemolysis)
Clinical Approach
Diagnosis
- Hemoglobin Electrophoresis (Gold Standard): Shows presence of HbS and absence of HbA
- Peripheral blood smear: Sickled red blood cells, target cells, Howell-Jolly bodies (due to functional asplenia)
Management
- Hydroxyurea (increases Hemoglobin F, which does not sickle, significantly reducing crises)
- Folic acid supplementation
- Pain management during crises (Opioids, IV hydration)
- Prophylactic Penicillin for children < 5 years (due to functional asplenia and high risk of encapsulated bacterial infections)
- Curative: Hematopoietic Stem Cell Transplant (in select patients)
Complications
- Acute Chest Syndrome (leading cause of death)
- Stroke (requires exchange transfusion)
- Avascular necrosis of the femoral head
- Splenic sequestration crisis
- Functional asplenia (susceptibility to encapsulated organisms like Strep pneumoniae)