Abstract: Blood separation systems and methods utilize a membrane separation device comprising a gap between a microporous membrane and a surface facing the microporous membrane, one of the microporous membrane and the surface being rotatable relative to the other to cause separation of whole blood in the gap into plasma and concentrated red blood cells. The systems and methods include an inlet pump element coupled to the membrane separation device to convey whole blood having a known beginning hematocrit value into the gap for separation. The systems and methods also include a drive element coupled to the membrane separation device to cause rotation of the rotatable one of the microporous membrane and the facing surface. The systems and methods command the inlet pump element and the drive element as a function of the known beginning hematocrit value.