Erythropoetin treatment can increase 2,3-diphosphoglycerate levels in red blood cells

Some patients experience an improved well-being during treatment with recombinant human erythropoietin even with an unchanged Hb level. We have hypothesized that this may not be only a placebo effect. 2,3-diphosphoglycerate (2,3-DPG) in red blood cells increases in response to anaemia/hypoxia and causes a shift of the oxygen dissociation curve, allowing a more effective oxygen delivery. We have investigated red cell 2,3-DPG concentrations during erythropoietin treatment in healthy volunteers as a mediator of a possible physiological explanation. Thirteen healthy subjects with no iron deficiency were recruited and randomly assigned to a treatment group comprising five males and three females and a control group including three males and two females. The treatment group was treated with erythropoietin (Recormon(R)), 20 IE/kg subcutaneously three times/week for 4 weeks. Blood samples were collected at each injection day and 10 days after the last injection and at corresponding times in the control group. B-Hb, red cell 2,3-DPG and P50 were measured by standard techniques and oxygen-releasing capacity was calculated. Results: due to the sampling (26ml each time, three times/week) the mean Hb level was lowered from 140.5 +/-5.9 to 128.6 +/- 10.4 g/L in the control group whereas the erythropoietin treatment group maintained a mean Hb level of about 142g/L (p<0.002). The 2,3-DPG mean level curve as well as that for oxygen releasing capacity also differed significantly between the two groups (p<0.002), the treatment group showing higher levels. Conclusion: treatment with erythropoietin causes an increase in red cell 2,3-DPG levels.