Which of the following is the primary mechanism of hemolysis in sickle cell disease?

Question

Accepted Answer

C. Polymerization of deoxygenated hemoglobin S leading to RBC rigidity and splenic sequestration. ## 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.

Answer

A. Osmotic lysis due to increased intracellular sodium

Answer

B. Complement-mediated destruction of RBCs

Answer

D. Antibody-dependent cellular cytotoxicity against abnormal hemoglobin

Which of the following is the primary mechanism of hemolysis in sickle cell disease?

Explanation

Primary Mechanism of Hemolysis in Sickle Cell Disease

Pathophysiology of HbS Polymerization

Sequence of Events

Types of Hemolysis

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Mechanism	Location	Contribution
Splenic sequestration	Extravascular	Majority of hemolysis
Direct polymerization injury	Intravascular	Minor component
Oxidative stress	Both	Accelerates hemolysis