Use of recombinant human erythropoietin in combination with parenteral iron in the treatment of postpartum anaemia. rHuEPO in the treatment of postpartum anemia: subcutaneous versus intravenous administration. Does recombinant human erythropoietin not only treat anemia but reduce postpartum (emotional) distress as well? [Anemia in puerperium; parenteral iron substitution renders erythropoietin therapy dispensable]. 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.
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. The aim of this study was to determine whether single-shot therapy with recombinant human erythropoietin (rHuEPO) is as effective as divided dosing in postpartum anemia for both subcutaneous and intravenous administration. In a randomized prospective study we treated 95 women with postpartum anemia (Hb < 10 g/dl) within 72 h after delivery with rHuEPO (total dose 300 U/kg body weight) and oral iron supplementation in four treatment groups: group A rHuEPO 150 U/kg s.c. once daily for two consecutive days; group B rHuEPO 150 U/kg i.v. once daily for two consecutive days; group C rHuEPO 300 U/kg s.c. once only; group D rHuEPO 300 U/kg i.v. once only. No significant intergroup differences were found in the mean increase of hemoglobin (P = 0.93 for a difference of 1 g/dl). The mean increase in the single-shot groups was 3 g/dl in 14 days. There was a significant reduction of iron stores in all groups. We conclude that single-shot rHuEPO 300 U/kg body weight corrects anemia just as effectively as divided doses on both intravenous and subcutaneous administration. The overall increase in Hb is only slight but preliminary results indicate that the effect can be enhanced by administrating iron intravenously and by an interval therapy with high-dose rHuEPO. Based on the established rhEPO treatment of anemia in endstage renal failure, which results in improved quality of life, and on the clinical observation that patients with postpartum anemia treated with rhEPO seemed to gain a more stable mood, we inferred that there is a beneficial side-effect of rhEPO on postpartum blues. The aim of this study was to test the hypotheses 1) that postpartum anemia aggravates, and 2) that treatment of postpartum anemia with rhEPO reduces maternity blues. The results show that on the fifth day postpartum anemic patients score consistently worse than nonanemic women on the Symptom Checklist SCL-90-R, indicating more symptoms and distress in general, and also more symptoms characteristic of maternity blues (p < 0.05). On a "Blues Questionnaire," postpartum anemia expresses itself with a reduced "well-being" (p < 0.001). Thus, our first hypothesis was verified. There were no differences by the fifth day postpartum between anemic patients receiving either rhEPO or placebo. Our second hypothesis was thus not confirmed within this limited time. We conclude as clinicians that postpartum anemia should be treated effectively to reduce distress and hence the risk for postpartum affective disorders. Follow-up studies after rhEPO treatment beyond the first week post partum are needed. In addition, in investigations on postpartum affective disorders, the hemoglobin concentration should be considered. 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 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.
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.]