[Anemia in puerperium; parenteral iron substitution renders erythropoietin therapy dispensable]. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia. Effectiveness of recombinant erythropoietin and iron sucrose vs. iron therapy only, in patients with postpartum anaemia and blunted erythropoiesis. Recombinant human erythropoietin treatment of postpartum anemia. Preliminary results. Perisurgical erythropoietin application in anemic patients with colorectal cancer: A double-blind randomized study.
In a double-blind, randomised study we treated 36 women in the puerperium with haemoglobin concentration below 9 g/dl with 400 mg Fe . 20 women received 20,000 IE erythropoietin (rHuEPO) i.v. in addition, 12 women received placebos. In both groups there were no differences in the haematological and iron parameters in the first 4 weeks after delivery. The results show that the additional therapy with rHuEPO in postpartum anaemia is not justified. The limiting factor in a quick correction of the postpartum anaemia is the insufficient presence of iron at the end of pregnancy. The therapy of choice for quick and safe correction of p.p. anaemia is the effective intravenous iron supplementation. To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.
                A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.
                At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.
                In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity. The authors compared the effect of recombinant human erythropoietin (rhEPO) in combination with iron with that of iron therapy only in the treatment of postpartum anaemia. Ninety patients (30 patients/group) received either rhEPO (300 U kg-1, i.v. or s.c., once) and iron (parenteral and oral), or iron therapy only. Erythropoiesis was assessed by haemoglobin and haematocrit increase, absolute reticulocyte counting and reticulocyte flow cytometry. Ferrokinetics was assessed by serum ferritin, transferrin and transferrin saturation measurements. There was no difference before therapy for baseline haematological values or iron status. Patients with endogenous EPO levels below 145 mU mL-1 had a significant benefit from intravenous rhEPO administration with highest haematocrit and haemoglobin levels 4 and 14 days after therapy. rhEPO-treated groups showed a higher absolute reticulocyte count 1 and 4 days after therapy and an elevated percentage of high fluorescent reticulocytes (HFRs). Parenteral iron therapy caused a significant increase of ferritin and transferrin saturation, while transferrin concentration decreased. Ferritin and transferrin levels were lowest after i.v. administration of rhEPO, 1 and 4 days after therapy. C-reactive protein concentration was highest in patients who underwent caesarean section until the end of the observation period. A single dose of rhEPO in combination with iron was more effective in treating postpartum anaemia than iron therapy only, in patients who had low EPO levels despite peripartal blood loss. Postpartum low endogenous EPO levels might be a consequence of inhibiting inflammatory cytokines that are released after spontaneous or operative deliveries. To compare efficacy between recombinant human erythropoietin (rhEPO) plus parenteral iron vs. iron alone (parenteral vs. oral) in postpartum anaemia.
                Sixty patients (haemoglobin 8.6 +/- 1.1 g dL-1) were randomized to rhEPO plus intravenous (i.v.) iron sucrose (group 1), rhEPO placebo plus i.v. iron sucrose (group 2), or oral iron alone (group 3), daily for 4 days beginning 48-72 h postpartum. Erythropoiesis and iron status were assessed before, and on 4, 7 and 14 days after, starting therapy.
                On day 7 the group 1 haematocrit increase was 7.7 +/- 3.1% vs. 5.3 +/- 1.9% (group 2, P < 0.01) and 4.4 +/- 3.2% (group 3, P < 0.01), and on day 14, 11.3 +/- 2.9% vs. 9.2 +/- 3.4% (group 2, P < 0.05) and 8 +/- 2.8% (group 3, P < 0.01). The odds of achieving a target haematocrit > 32% on day 7 and > 35% on day 14 were higher on rhEPO (1.5-2.7) than on either iron regimen alone. Group 1 reticulocyte counts were also higher on days 4 (P < 0.05 vs. oral iron) and 7 (P < 0.01 vs. oral and parenteral iron).
                All three regimens were effective in postpartum anaemia, but the haematocrit and reticulocyte responses to rhEPO plus parenteral iron were significantly greater than to iron alone. Benefit was greatest in the blunted erythropoiesis subgroup with elevated post-Caesarean section C-reactive protein levels. The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEpo) in postpartum anemia.
                At the University Hospital of Ioannina, rHuEpo was administrated subcutaneously to twenty anemic women (hemoglobin [Hb]<10 g/dl), for 15 days following delivery; all were given iron and folic acid per os. Twenty other women (the control group) with postpartum anemia (Hb<10 g/dl), received only iron and folic acid. The Mann-Whitney U-test was used for the comparison of hematological indices between the two groups, on days 1, 3, 5, 10, 15 and 40 postdelivery.
                On day 3, reticulocyte counts were significantly higher in the women who received rHuEpo, as compared to the controls (P<0.05). The mean Hb value increased to >2 g/dl in the group undergoing rHuEpo therapy as compared to 0.7 g/dl in the control group on day 5 (P<0.05). Furthermore, two women in the control group required blood transfusions, while no transfusions were required by the rHuEpo group.
                rHuEpo administration is useful for a more rapid amelioration of hematological indices in women with postpartum anemia. Further, the dose given in this study was not associated with significant side-effects. Blood transfusions are associated with higher postoperative morbidity and tumor recurrence rates in colorectal cancer surgery, To reduce the need for transfusions in patients with tumor-induced anemia who are not suitable for autologous blood donation, it was tested whether perisurgical erythropoietin application would be able to stimulate hematopoiesis adequately.
                In a double-blind randomized study 150 IU/kg body weight erythropoietin was given subcutaneously every 2 days beginning 10 days before operation and continuing until postoperative day 2. Twenty patients were randomized into the erythropoietin group with three observed dropouts and 10 patients into the placebo group.
                In the erythropoietin group two episodes of hypertension and one deep venous thrombosis were observed. Preoperative hemoglobin response in the erythropoietin group (p = 0.069) was paralleled by a highly significant reticulocyte increase (p = 0.0004). However, frequency of blood transfusion was not different between both study groups (erythropoietin, 1.82 +/- 0.80 units/ patient; placebo, 1.80 +/- 0.97 units/patient). If iron availability was analyzed, a strong correlation between ferritin blood levels and transferrin iron saturation with hemoglobin response was observed in regression analysis (p < 0.001).
                These results indicate that hematopoiesis in anemic patients with colorectal cancer can be stimulated by erythropoietin; however, clinical efficacy is to be expected only in selected patients with high iron availability, which calls for further studies combining erythropoietin and parenteral iron application.
There is some limited evidence of favourable outcomes for treatment of postpartum anaemia with erythropoietin. However, most of the available literature focuses on laboratory haematological indices, rather than clinical outcomes. Further high-quality trials assessing the treatment of postpartum anaemia with iron supplementation and blood transfusions are required. Future trials may also examine the significance of the severity of anaemia in relation to treatment, and an iron-rich diet as an intervention.
[Note: The 27 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]