Systems and methods are provided for automatically adjusting the operational parameters of a blood separation procedure. A blood separation device has an inlet for passing fluid thereinto and an outlet for removing fluid therefrom. A pump system is provided for moving fluid into and out of the device. In use, blood is conveyed into the device, where platelets are separated from at least a portion of the blood. A controller determines the amount of platelets in the device. Based at least in part on the amount of platelets in the device, corrective action is taken to avoid platelet aggregation in the device. The corrective action may be conveying an elevated amount of anticoagulant into the blood and/or the device and may be initiated when the determined amount of platelets approaches, meets, or exceeds a threshold predicted likelihood of platelet aggregation.