## Primary Mechanism of Hemolysis in Sickle Cell Disease ### Pathophysiology of HbS Polymerization **Key Point:** The hemolysis in sickle cell disease is primarily **intravascular and extravascular** due to polymerization of deoxygenated HbS, which causes RBC rigidity, vaso-occlusion, and splenic sequestration. ### Sequence of Events 1. **Deoxygenation** of HbS → polymerization into long, rigid fibers 2. **RBC deformation** into sickle shape → loss of deformability 3. **Vaso-occlusion** → tissue ischemia and pain crises 4. **Splenic sequestration** → extravascular hemolysis 5. **Membrane damage** → intravascular hemolysis (less common) ### Types of Hemolysis | Mechanism | Location | Contribution | |-----------|----------|---------------| | Splenic sequestration | Extravascular | Majority of hemolysis | | Direct polymerization injury | Intravascular | Minor component | | Oxidative stress | Both | Accelerates hemolysis | **High-Yield:** The spleen is the primary organ responsible for removing sickled RBCs, leading to functional asplenia in chronic SCD ("autosplenectomy"). **Clinical Pearl:** Hemoglobin F (HbF) does NOT polymerize with HbS, which is why patients with hereditary persistence of fetal hemoglobin (HPFH) or β-thalassemia/sickle cell disease have milder disease.
Sign up free to access AI-powered MCQ practice with detailed explanations and adaptive learning.