[Current recommendations for the treatment of iron deficiency anemia]. / Recommandations actuelles pour le traitement de l'anémie ferriprive.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/ epoetin alfa) in severe cases. Iron saccharate (VENOFER) is commercially available in Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

[The iron letter--an update on the treatment of iron deficiency anemia]. / Eisenbrief--Aktuelle Empfehlungen zur Therapie der Eisenmangelanämie.

Iron deficiency is a frequent complication in chronically ill patients and in pregnant women. Iron status can now be characterised precisely and relatively easily by determining serum ferritin, transferritin saturation and if necessary hypochromic erythrocytes and the haemoglobin content of erythrocytes (CHr). Oral iron replacement is usually restricted by limited absorption and low tolerability. Intravenous iron therapy is possible in such cases and can be combined with rHuEPO (e.g. EPREX/Epoetin alfa) in severe cases. Iron saccharate Switzerland and this permits high dose iron replacement without any danger of anaphylaxis or acute iron toxicity.

Effect of postpartum iron supplementation on red cell and iron parameters in non-anaemic iron-deficient women: a randomised placebo-controlled study.

OBJECTIVE: To investigate the effect of oral iron on postpartum red cell and iron parameters in non-anaemic women with iron deficiency. DESIGN: Randomised study of supplementation with oral iron sulphate 80 mg daily or placebo for 12 weeks starting 24-48 hours after delivery, with visits antepartum and 1, 4, 6 and 12 weeks postpartum. SETTING: Swiss university hospital obstetric unit. PARTICIPANTS: Fifty-two women with antenatal iron deficiency (serum ferritin <15 microg/L) and no antenatal or postnatal anaemia (haemoglobin >11 g/dL up to 48 hours before delivery, and >10 g/dL postpartum), divided into two groups comparable in antenatal iron status. METHODS: Supplementation was started 24-48 hours after delivery (visit 1:V1). Additional tablets were issued one week after V1 (V2), four weeks after V1 (V3) and six weeks after V1 (V4). The last visit took place 12 weeks after visit 1 and 6 weeks after visit 4 (V5). Patients were required to return blisters and boxes whether they were used and unused at each visit and compliance was assessed by counting the tablets. Blood samples for haematology and iron status testing were taken before delivery and at each visit. MAIN OUTCOME MEASURES: Iron status (serum ferritin, hypochromic red cells, iron, transferrin saturation, soluble transferrin receptor concentration); erythropoiesis (standard parameters, including reticulocyte indices); and inflammatory response (serum neopterin, C-reactive protein, white cell count) in five-datapoint profiles. RESULTS: Increased ferritin (P= 0.0004) and transferrin saturation (P= 0.03), decreased soluble transferrin receptors (P= 0.02); increased haemoglobin (P= 0.02) and decreased hypochromic red cells (P= 0.04) compared with placebo at 12 weeks, with no differences in other red cell or reticulocyte parameters. There was a positive correlation between C-reactive protein and postpartum ferritin. No correlation was observed in the puerperium between C-reactive protein and hypochromic red cells or soluble transferrin receptors. CONCLUSIONS: Haemoglobin levels and iron stores in women with term gestational iron deficiency benefit significantly from iron supplementation compared with placebo, even in an industrialised population.

Efficacy and safety of intravenously administered iron sucrose with and without adjuvant recombinant human erythropoietin for the treatment of resistant iron-deficiency anemia during pregnancy.

OBJECTIVE: This study was undertaken to determine the efficacy and safety of intravenously administered iron sucrose with versus without adjuvant recombinant human erythropoietin in the treatment of gestational iron-deficiency anemia resistant to therapy with orally administered iron alone. STUDY DESIGN: Forty patients with gestational iron-deficiency anemia were randomly assigned to receive intravenously iron sucrose plus recombinant human erythropoietin or iron sucrose alone twice weekly. Target hemoglobin value was 11.0 g/dL. Efficacy measures were reticulocyte count, increase in hematocrit, and time to target hemoglobin level (treatment duration in weeks and need for continued therapy after 4 weeks). RESULTS: Both regimens were effective, but with adjuvant recombinant human erythropoietin the reticulocyte counts were higher from day 4 (P<.01), increases in hematocrit were greater from day 11 (P <.01), and the median duration of therapy was shorter (18 vs 25 days), with more patients reaching the target hemoglobin level by 4 weeks of treatment (n = 19 vs. n = 15). The groups did not differ with respect to maternal-fetal safety parameters. CONCLUSION: Adjuvant recombinant human erythropoietin safely enhanced the efficacy of iron sucrose in the treatment of gestational iron-deficiency anemia resistant to orally administered iron alone.

Gustatory and olfactory function in the first trimester of pregnancy.

OBJECTIVE: To investigate gustatory and olfactory sensitivity in the first trimester of pregnancy using validated test kits. DESIGN: Prospective study. SETTING: Department of Obstetrics, University Hospital Zurich, Switzerland. POPULATION: Total 53 pregnant women and 59 controls in a known phase of the menstrual cycle. METHOD: Gustatory sensitivity was assessed by requiring subjects to discriminate between four basic-taste tablets ('sweet', 'salty', 'sour', and 'bitter'). Olfactory testing was performed using the 'Sniffin' sticks' kit. Subjects rated the intensity and hedonic tone of the four tastants and of 10 common odors. RESULTS: Pregnant women had significantly lower overall gustatory sensitivity scores. There were no differences in olfactory sensitivity. However, pregnant women rated the odors 'rum', 'cigarette' and 'coffee' as more aversive than did non-pregnant women. CONCLUSION: Our data do not support the hypothesis of a generalized increase in chemosensitivity in early pregnancy. In terms of adaptive changes of the olfactory system may act as a sentinel to potentially harmful chemicals. In contrast, the gustatory system appears to retreat to allow a greater intake of electrolytes and a more widely sourced diet.

[Anemia in pregnancy]. / Anämie in der Schwangerschaft.

Pregnancy and postpartum anaemia occurs worldwide, particularly in developing countries where it accounts for substantial maternal and infant morbidity and mortality. The main cause is iron deficiency, primarily of dietary origin: 20% of the world population are estimated to have some degree of trace element deficiency. Even in industrialized countries iron deficiency anaemia is common in pregnancy due to the negative iron balance created by the high fetal demand for iron. It is compounded by blood loss during and after delivery, particularly in the absence of adequate prevention and treatment. The main effects of pregnancy and postpartum anaemia (defined by the WHO as hemoglobin values < 110 g/l and < 100 g/l, respectively) present for the mother an increased susceptibility to infection and premature delivery and for the baby intrauterine growth retardation and the consequences of prematurity. Diagnosis and differential diagnosis are thus a major obstetric concern. Iron deficiency can be particularly difficult to diagnose in postpartum anaemia because ferrritin is often falsely elevated due to concurrent infection. Prevention with oral iron + folic acid supplementation has proven effective, as has intravenous iron in more severe cases, while the addition of recombinant erythropoietin augments the effect of iron alone.

Induction of fetal hemoglobin synthesis with recombinant human erythropoietin in anemic patients with heterozygous beta-thalassemia during pregnancy.

OBJECTIVE: Recombinant human erythropoietin (rhEPO) increases fetal hemoglobin synthesis in nonpregnant thalassaemic patients. We used rhEPO in 4 pregnant patients with heterozygous beta-thalassemia and anemia to study its effect on erythropoiesis, F cell production, and HbF synthesis. METHODS: Patients were treated with a combination therapy of rhEPO and iron. The effect on HbF synthesis was assessed by the percentage of F reticulocytes, F cells, and total HbF, erythropietis by reticulocyte count, and hemoglobin measurements and iron status by ferritin levels, transferrin saturation, and percentage of hypochromic red cells. RESULTS: RhEPO caused an increase of F reticulocytes (1.5 to 10.5 fold), F cells (5.0 to 7.7 fold), and HbF (1.4 to 2.2 fold). All patients showed an increase of young, immature reticulocytes and had elevated reticulocytes at the end of therapy. Hemoglobin increased with a range from 0.3 to 1.5 g/dL. Transferrin saturation and ferritin levels were normal at the end of the study. There was an increase of the percentage of hypochromic red cells, indicating functional iron deficiency after rhEPO administration despite supplemental iron. CONCLUSIONS: RhEPO stimulates both HbF synthesis and erythropoiesis in pregnant patients with heterozygous beta-thalassemia and anemia. Since it is known that high HbF levels ameliorate thalassemia symptoms in nonpregnant patients, use of rhEPO for the treatment of severe anemia in thalassaemic patients during pregnancy might be further evaluated.

Optimal timing of repeated rh-erythropoietin administration improves its effectiveness in stimulating erythropoiesis in healthy volunteers.

We studied the effect of recombinant human erythropoietin (rhEPO) on erythropoiesis when given at different time intervals to healthy adults. 15 volunteers were randomly selected to receive rhEPO (2 x 300 U/kg) and parenteral iron (2 x 200mg) either within a 24 h or 72 h interval. Controls received parenteral iron only. Maximum EPO levels were found 24 h after the first intravenous injection (day 1) with a mean value of 364 and 390 U/l for the rhEPO-treated groups. When second rhEPO administration was after 72 h (group III), volunteers showed significantly higher absolute reticulocyte counts and a higher percentage of young RNA-rich reticulocytes (HFR ratio) over several days compared to those who received rhEPO within a 24 h interval (group II). Both rhEPO-treated groups showed an increase in the mean reticulocyte cell volume. Reticulocyte haemoglobin concentration was inversely correlated with the increasing cell size with a nadir on day 8. Reticulocyte haemoglobin content showed a significant decrease in group II after day 5. Serum ferritin levels showed an inverse pattern to the rate of erythropoiesis. After an initial rise, the serum ferritin decrease was most pronounced in group III. Contrary to previous reports with oral iron supplementation, functional iron deficiency was not seen during rhEPO stimulation, due to parenteral iron administration. Our data suggest that the time has interval between repeated administrations of rhEPO has an important influence on its pharmacodynamics. rhEPO given within an interval of 72 h was more effective in stimulating erythropoiesis than administration within 24 h interval for the same total dose.

rhEPO treatment of postpartum anemia.

Postpartum hemorrhage is a continuing problem occurring in 5-10% of all deliveries. Due to recent problems with blood transfusion, heterologous blood is nowadays restricted to life-threatening indications. As a consequence the clinician is faced with many patients suffering from overt symptoms of anemia. We therefore investigated the effect of recombinant human erythropoietin (rhEPO) in combination with adequate iron supplementation as an alternative for blood transfusion in postpartum anemia. In a pilot study we could show that rhEPO can enhance the effect of endogenous erythropoietin on erythropoiesis. These data could be confirmed in a larger randomized trial. In another study we could show that rhEPO given s.c. is as effective as i.v. Measurement of the iron stores, however, demonstrated low values at the end of pregnancy indicating that iron is a limiting factor for erythropoiesis in postpartum anemia. In a next study i.v. iron combined with rhEPO showed a greater increase in Hb compared to i.v. iron alone. The chosen dose of i.v. iron, however, was too small as shown by the low ferritin levels. We concluded from these previous studies that rhEPO enhances endogenous erythropoiesis, but so far the effect was only slight (ca 1 g/dl within 14 days); all treated patients developed overt iron deficiency in terms of low ferritin levels despite oral and i.v. iron supplementation; no major side-effects were seen. A further study in healthy non pregnant volunteers demonstrated an effect on erythropoiesis lasting for 3-4 days after a single dose of 300 U/kg rhEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Recombinant human erythropoietin and parenteral iron in the treatment of pregnancy anemia: a pilot study.

Our aim was to correct severe iron deficiency anemia during pregnancy by using a combination therapy of recombinant human erythropoietin and parenteral iron. Eleven anemic pregnant women were treated once weekly until a hemoglobin value of 11.0 g/dl was reached. Red blood cell production was monitored by reticulocyte flow cytometry and hemoglobin increase. Iron status was assessed by serum ferritin values and transferrin saturation values. 8/11 patients showed an immediate response, noted by a continuous increase of reticulocytes, high fluorescent reticulocyte ratio and hemoglobin levels. Three patients who had lower serum ferritin values, low transferrin saturation and a lower reticulocyte count before treatment showed little response. The combination of rhEPO and parenteral iron is effective in stimulating erythropoiesis and in treating certain pregnancy anemias. This therapy could be an alternative for patients refusing blood transfusions or who are resistant to iron alone. Poor response to the treatment can be due to insufficient iron supplementation during therapy with rhEPO or due to factors that inhibit erythropoiesis during pregnancy, such as undetected infections.

rHuEPO in the treatment of postpartum anemia: subcutaneous versus intravenous administration.

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.

Recombinant human erythropoietin in the treatment of postpartum anemia.

Postpartum maternal anemia (hemoglobin concentration below 10 g/dL) is a common problem in obstetrics. Human recombinant erythropoietin, which has been shown to correct the anemia of end-stage renal disease and eliminate the need for transfusions, was used in a comparative study of women with postpartum hemoglobin concentrations below 10 g/dL. Five daily doses of 4000 IU were given. Hematologic and clinical data were compared on days 5, 14, and 42 after therapy in the treated women and in untreated women. Both groups received the same iron and folic acid supplements. Significantly greater increases in reticulocytes, hemoglobin, and hematocrit were seen by day 5 for the treated subjects compared with controls. Ferritin levels were significantly lower in the therapy group than in controls. No differences were seen between the groups in the platelet counts or clinical characteristics. No negative side effects were observed. As in other studies in populations without renal disease, recombinant human erythropoietin enhanced endogenous erythropoiesis over and above the normal physiologic recovery rate.

[The critical hemoglobin/hematocrit value in obstetrics]. / Der kritische Hämoglobin-/Hämatokritwert in der Geburtshilfe.

During pregnancy, there are characteristics changes in the hemoglobin and hematocrit values. Compared with the norm for nonpregnant women, there is an increase in the total number of erythrocytes and in the plasma volume. An overproportional increase of the latter results in hydremia. The normal physiologic range for hemoglobin during pregnancy is 11.5-13.0 (13.5) g/dl; anemia is, by definition, present when the values are under 11 g/dl and is quite common in pregnancy. Since it is caused almost exclusively (95%) by iron deficiency, iron therapy or routine iron supplementation can influence its incidence. Values outside the norm range are associated with complications during pregnancy and with growth retardation of the fetus.

Transcutaneous pO2 of volunteers during hyperbaric oxygenation.

Continuous transcutaneous pO2 measurements (tcPO2 measurements) were performed in healthy volunteers who were breathing air and oxygen under hyperbaric conditions (max. 4 ata). The results show a close correlation of PO2 values measured by the noninvasive method, in blood from discret arterial punctures, chamber PO2, respectively, the PO2 of the inspiratory gas mixture which was checked up to maximal values of 2,200 mm Hg. The PO2 in the arterial blood samples was measured immediately after the puncture insight the hyperbaric chamber using a specially designed through electrode.