rh‐Erythropoietin stimulates immature reticulocyte release in man

Abstract

The pharmacodynamics of single intravenous dosing with recombinant human erthropoietin (rhEPO) was investigated in eight healthy volunteers (150 U/kg, n = 2; 300 U/kg, n = 6) with respect to reticulocyte subdivisions (by fluorescence flow cytometry) and serum ferritin over 6.5 d. The present study shows that bolus rhEPO injection produces an immediate release of high and middle fluorescence (immature) reticulocytes with a high RNA content from the marrow into the circulation, whereas the low fluorescence (more mature) reticulocytes were at first not affected. Serum ferritin decreased markedly within 24 h, reaching a nadir 50% of baseline after 120 h (5 d), with no increase in haemoglobin. Our data suggests that rhEPO triggers premature expulsion of immature reticulocytes from the bone marrow into the circulation independent of its effect in stimulating erythropoiesis and that rhEPO has an effect on serum ferritin concentration which in this dynamic situation is dependent not only on the iron stores.

Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia

“…We could show, that under dynamic conditions, ferritin levels do not reflect iron stores but might well reflect the rate of synthesis in the reticuloendothelial system with its rapid changes under rhEPO therapy [28]. Lower increase of ferritin levels and the steep decrease of transferrin levels until day 4 might reflect the dynamic changes in the transferrin-iron pool, which are most pronounced in group III.…”

“…HFR reticulocytes are the first young and immature reticulocytes to be released from the bone marrow after administration of rhEPO [28]. The increase of the HFR ratio in groups II and III reflects the additional and persistent effect of rhEPO in stimulating erythropoiesis.…”

“…HFR reticulocytes are young and immature reticulocytes with a high RNA content that are prematurely released from the bone marrow following stimulus of erythropoiesis, e.g. after rhEPO administration, and that change to mature reticulocytes circulating in the blood [28][29][30][31].…”

Dose-related Differences in the Pharmacodynamic and Toxicologic Response to a Novel Hyperglycosylated Analog of Recombinant Human Erythropoietin in Sprague-Dawley Rats with Similarly High Hematocrit

“…However, it is unclear whether these processes surrounding increased splenic erythropoiesis directly influenced thrombosis in the high-dose group. During stress erythropoiesis, increased numbers of reticulocytes as well as subpopulations of increasingly immature stress reticulocytes within are released proportional to the increased concentration of EPO (Al-Huniti et al 2005;Bugelski et al 2008;Major et al 1994;Wiczling and Krzyzanski 2008;Wiczling, Ait-Oudhia, and Krzyzanski 2009). Overall, newly released ''stress'' reticulocytes are more prothrombotic than reticulocytes produced during basal erythropoiesis.…”

The effect of intravenous iron on the reticulocyte response to recombinant human erythropoietin

“…Simple blood removal (350 ml over 7 d) in the absence of r-HuEPO treatment leads to slight reductions in ferritin levels (Major et al, 1994). A disproportionate decrease in serum ferritin was observed after stimulation of erythropoiesis with r-HuEPO in volunteers and haemodialysed patients (Brugnara et al, 1994a;Major et al, 1994;Barosi et al, 1993).…”