Such changes are caused by either structural or quantitative defects. Structural abnormalities are due to alterations in the polypeptide sequence changing the molecular structure and, often, the function of the globin chains.
Quantitative abnormalities are secondary to decreased rates of globin chain synthesis.
Sickle cell disease and trait will be discussed in the following cards where the discussion focuses on structural defects. Hb S is poorly soluble in low oxygen tension situations, forming a gel and polymerizing into fibrilary structures or tactoids. This distorts the red cells causing them to become rigid and sickled. The normal glutamate is tucked inside the tetramer. The PBS chacteristically shows sickle cells or drepanocytes.