Rise in RBC aggregability and concomitant decrease in blood pressure 10 days after injection of the long acting erythropoietin analogue methoxy polyethylene glycol-epoetin-β (MIRCERA®)

Abstract

Erythropoietin (EPO) is a major regulator of blood viscosity. Its long lasting action analogue methoxy polyethylene glycol-epoetin-β (MIRCERA®) seems to be also employed in modern doping. We took the opportunity of a study aiming at developing a detection of recent MIRCERATM injection in the context of doping detection to assess the effects of this EPO analogue on red blood cells (RBC) aggregation. A single dose 200 μg of MIRCERA® was injected to 10 male volunteers and blood samplings were drawn over 24 days. After injection a decrease in mean corpuscular volume at day 2 (p < 0.01) and day 10 (p < 0.02), a rise in reticulocyte count (p < 0.001) between day 4 and day 17 and a decrease in ferritin a day 5 (p < 0.05) was observed. Hemoglobin decreased at day 4 (p < 0.005). Hematocrit was unchanged. There was a dramatic (+67%) increase in RBC aggregation index "M" (from 9.49±1.01 to 17.66±1.8, p < 0.01). A decrease in systolic blood pressure was observed during the period from day 4 to day 17 (at day 10: -11.90±2.28 mmHg, p < 0.001; at day 17: -15.80±2.83, p < 0.001). There was also a decrease in diastolic blood pressure, mean and pulse pressure. Correlations between this decrease in blood pressure and "M" did not reach significance but pulse pressure was positively correlated to "M" (r = 0.743, p < 0.05).These data show that the long acting erythropoietin analogue MIRCERA® strongly increases RBC aggregation parallel to a decrease in blood pressure, but a possible causative link between the two events is not clearly evidenced.

Keywords: Blood viscosity; erythrocyte deformability; exercise; hematocrit.