What is the main genetic abnormality in sickle cell disease? Describe why patients with sickle cell disease are at risk of vascular crises.
Sickle cell disease includes all conditions associated with hemolytic anemia and vaso-occlusive pain. Over 20% of people in equatorial Africa are heterozygous for the sickle gene, as it is believed to offer protection against malaria. The pathophysiology arises from an amino acid switch in the 6th position (11th chromosome) from glutamic acid to valine.
When hemoglobin S encounters a deoxygenated state, the hemoglobin is less soluble and the Hb S tetramers aggregate or polymerize. The sickled RBCs adhere to the vascular surface, causing occlusion and an increased hypercoagulable state.
Not surprisingly, sickle cell disease patients have the potential for many co-morbidities:
- Vaso-occlusive crises including chest crises
- Pulmonary hypertension
- Splenic sequestration crises
- Growth retardation
- Avascular necrosis
- Increased risk of infection from encapsulated organisms