Which hemoglobin variant polymerization leads to sickling under deoxygenated conditions?

Which hemoglobin variant polymerization leads to sickling under deoxygenated conditions?

• A. HbA
• B. HbS
• C. HbF
• D. HbA2

Answer: (B)

Sickling under low oxygen is caused by polymerization of deoxygenated HbS inside red blood cells. The HbS variant has a mutation in the beta-globin chain that substitutes valine for glutamic acid at position 6, creating a hydrophobic patch that promotes polymer formation when oxygen is released. These long HbS fibers distort the cell into a rigid, sickle shape and can block small vessels. Normal hemoglobin A does not polymerize under deoxygenation, and the fetal form HbF along with HbA2 do not form the damaging polymers; HbF can even help reduce polymerization. So the polymerization-driven sickling under deoxygenated conditions is characteristic of HbS.

Sickling under low oxygen is caused by polymerization of deoxygenated HbS inside red blood cells. The HbS variant has a mutation in the beta-globin chain that substitutes valine for glutamic acid at position 6, creating a hydrophobic patch that promotes polymer formation when oxygen is released. These long HbS fibers distort the cell into a rigid, sickle shape and can block small vessels. Normal hemoglobin A does not polymerize under deoxygenation, and the fetal form HbF along with HbA2 do not form the damaging polymers; HbF can even help reduce polymerization. So the polymerization-driven sickling under deoxygenated conditions is characteristic of HbS.