The objective of this chapter is to provide a systematic overview of current knowledge regarding therapeutic apheresis-primarily therapeutic plateletapheresis (TP)-and to summarize evidence-based practical approaches related to cytapheresis treatment of "hyperthrombocytosis" or "extreme thrombocytosis" (ETC). Our results of platelet (Plt) quantitative/qualitative analyses and evaluation of efficacy of apheresis systems/devices-on the basis of Plt removal and in vivo Plt depletion-will be presented. Our preclinical researches confirmed that in Plt concentrates, the initial ratio of discoid shapes was 70%, spherical 20%, and less valuable (dendritic/balloonized) shapes 10%-with morphological score of platelets (MSP = 300-400). After storage, the ratio of discoid and spherical shapes was decreased, while the less valuable ones progressively increased (MSP = 200). Electron microscopy has shown discoid shapes with typical ultrastructural properties. Spherical shapes with reduced electron density and peripheral location of granules/organelles were detected. Also, dendritic shapes with cytoskeletal "rearrangement," membrane system integrity damages, and pseudopodia formations were documented. Our clinical study demonstrated that TP was useful in ETC treatment and should help prevention of "thrombo-hemorrhagic" events-until chemotherapy, antiplatelet drugs, and other medication take effect. During TP treatment, Plt count and morphology/ultrastructure were examined. Plt functions by multiplate analyzer were evaluated. We concluded that intensive TP was an effective, safe, and rapid cytoreductive treatment for ET.