Abstract Objective Mean platelet volume is arousing increasing interest as a new independent cardiovascular risk factor. Large platelets are likely to be more reactive. If mean platelet volume would drop after LDL-lowering therapy, decreased MPV could be one of the markers of successful therapy. Therefore, we investigated mean platelet volume after extracorporeal LDL-cholesterol elimination. Methods Mean platelet volume was investigated in patients with severe familial hypercholesterolemia long-term treated (3–12 years) by LDL-apheresis (immunoapheresis) or cascade filtration. Plasma was obtained by centrifugation. Adsorbers Lipopak 400 were used for immunoapheresis and filters Evaflux 4A were used for cascade filtration. 95 pair samples were measured (before and after the procedures) in a group of 12 patients – each patient 8 times in 4 years. Results Mean platelet volume before the procedures was 10.891 fl, CI 10.25–11.53. Mean platelet volume after the procedures decreased – 10.478 fl, CI 09.84–11.11. The difference is statistically significant (p = 0.036). Mean platelet volume did not correlate with age, sex, platelet count, duration of therapy. At the same time, we used rheohemapheresis in the therapy of 40 patients with age-related macular degeneration. But mean platelet volume was not changed. Conclusion Mean platelet volume is easily available and is often disregarded, and sometimes may suggest the need for a careful assessment in patients with familial hypercholesterolemia. Mean platelet volume could be one of the markers of therapeutic efficacy in patients with familial hypercholesterolemia treated by extracorporeal LDL-cholesterol elimination that is simple and inexpensive.