Similarly, acute destruction or loss can likewise reduce the number of red cells in the blood stream. Since the spleen is the major filter of the red cells, any inappropriate increase in splenic function will result in unusually high destruction of the red cells. Increased splenic function (or hypersplenism) may be caused by a primary splenic disease or secondary to the complications of other disease states. Other major mechanisms for red cell destruction will include infective causes (eg malaria), self-destructive causes (eg autoimmune hemolytic anemia), hereditary disorders (eg paroxysmal nocturnal hemoglobinuria), and physical agents (eg burns). Furthermore, in any situations where there is significant bleeding, the number of red cells can also decrease accordingly.