A blood processing system for collecting and exchanging blood components includes a venous-access device for drawing whole blood from a subject and returning blood components to the subject. The system may include three lines connecting the venous access device to a blood component separation device and an anticoagulant source. A blood draw line fluidly connects to the venous-access device to the blood component separation device. An anticoagulant line introduces anticoagulant into the drawn whole blood. A return line, fluidly connected to the venous-access device and the blood component separation device, returns uncollected blood component to the subject. Each line may have a pump that controls flow through the line. The blood component separation device separates the drawn blood into a first blood component and a second blood component, and may be configured to send the first blood component to a first blood component bag.