Sickle Cell Disease

Sickle cell disease (SCD) is an autosomal recessive hemoglobinopathy caused by a point mutation in the beta-globin gene (chromosome 11), substituting valine for glutamic acid at position 6, producing abnormal hemoglobin S (HbS). Under conditions of deoxygenation, acidosis, or dehydration, HbS polymerizes into rigid rod-like structures that deform erythrocytes into the characteristic sickle shape. These sickled cells are rigid, adhesive, and have a shortened lifespan (10-20 days vs. normal 120 days), causing chronic hemolytic anemia with reticulocytosis. The hallmark pathophysiology is vaso-occlusion: sickled cells and activated endothelium obstruct microvasculature, causing tissue ischemia and infarction (vaso-occlusive crisis/VOC). Acute complications include acute chest syndrome (ACS — the leading cause of death: new pulmonary infiltrate + respiratory symptoms, caused by fat embolism from bone marrow infarction, infection, or in situ thrombosis), splenic sequestration (rapid splenic trapping of sickled cells causing acute splenomegaly, anemia, and hypovolemic shock — medical emergency in children), aplastic crisis (parvovirus B19 infection halting erythropoiesis — sudden severe anemia with absent reticulocytes), and stroke (11% by age 20 without screening). Chronic complications include functional asplenia (autosplenectomy from repeated splenic infarction...