In sickle cell disease, which of the following does not influence the degree of sickling of red cells?
Intake of primaquine acts as a trigger for hemolysis in G6PD deficiency, and not related to sickle cell disease/sickling. Sickle cell disease Caused by a point mutation in which there is replacement of glutamic acid by valine at position 6 of the beta chain generating a sticky patch on the surface of HbS. The sticky patch on the surface of adjacent HbS molecules cause their polymerization resulting in formation of long fibrous precipitates. HbA, HbF can also weakly interact with HbS & prevent its polymerization (HbF >> HbA), therefore individuals with co-inherited condition of hereditary persistence of fetal Hb (HPFH) have less severe due to reduced sickling. Intracellular dehydration, increases the MCHC, facilitates sickling. Condition reducing MCHC also lead to less severe disease, eg. individual who is homozygous for HbS also has coexistent a-thalassemia, which reduces Hb synthesis and leads to milder disease. A decrease in intracellular pH reduces the oxygen affinity of hemoglobin, thereby increasing the fraction of deoxygenated HbS at any given oxygen tension and augmenting the tendency for sickling.
Hereditary persistence of fetal hemoglobin
Intracellular pH
Intake of primaquine
Co-existing a-thalassemia
Hemoglobinopathies: Sickle cell anemia