HP and thalassemia: Because Hp levels become depleted in the presence of large amounts of free Hb, decreased Hp is a marker of hemolysis.16 Plasma Hp depletion had been attributed mainly to the direct release of free Hb into the circulation during intravascular hemolysis.17 Even in disorders with predominantly extravascular hemolysis like thalassemia, Hb release from macrophages in the reticuloendothelial system (RES), may account for the observed Hp decrease.