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Objective.We assess and compare the efficacy of anemia treatment in pregnant women with anemia of chronic disease with true iron deficiency and in women with iron deficiency anemia.Study Design.Fifty patients with moderate anemia (hemoglobin 8.0–9.9 g/dl) and iron deficiency (ferritin < 15 μg/l) were treated in the Anemia Clinic at the Department of Obstetrics.Results.All patients showed stimulation of erythropoiesis as evidenced by an increase in reticulocyte count at day eight of therapy and showed an increase in hemoglobin and hematocrit at the end of therapy (p<0.001). The target hemoglobin (≥10.5 g/dl) was achieved in 45/50 women (90%). 12 patients showed anemia of chronic disease with true iron deficiency (12/50; 24%). Seven women (7/12; 59%) with anemia of chronic disease and iron deficiency responded well to anemia treatment. 50% of women with anemia of chronic disease and iron deficiency (3/6) responded well to intravenous iron, and 67% (4/6) responded well to the combination of intravenous iron and recombinant human erythropoietin.Conclusion.Because of frequent true iron deficiency in pregnant women with anemia of chronic disease, anemia of chronic disease in pregnancy is often falsely diagnosed as iron deficiency anemia.

Erythropoietin (EPO) controls red cell volume (RCV) and plasma volume (PV). Therefore, injecting recombinant human EPO (rhEPO) increases RCV and most likely reduces PV. RhEPO-induced endurance improvements are explained by an increase in blood oxygen (O2) transport capacity, which increases maximum O2 uptake ( $$\dot{V}$$ O2max). However, it is debatable whether increased RCV or $$\dot{V}$$ O2max are the main reasons for the prolongation of the time to exhaustion (t lim) at submaximal intensity. We hypothesized that high rhEPO doses in particular contracts PV such that the improvement in t lim is not as strong as at lower doses while $$\dot{V}$$ O2max increases in a dose-dependent manner. We investigated the effects of different doses of rhEPO given during 4 weeks [placebo (P), low (L), medium (M), and high (H) dosage] on RCV, PV, $$\dot{V}$$ O2max and t lim in 40 subjects. While RCV increased in a dose-dependent manner, PV decreased independent of the rhEPO dose. The improvements in t lim (P +21.4 ± 23.8 %; L +16.7 ± 29.8 %; M +44.8 ± 62.7 %; H +69.7 ± 73.4 %) depended on the applied doses (R 2 = 0.89) and clearly exceeded the dose-independent $$\dot{V}$$ O2max increases (P −1.7 ± 3.2 %; L +2.6 ± 6.8 %; M +5.7 ± 5.1 %; H +5.6 ± 4.3 %) after 4 weeks of rhEPO administration. Furthermore, the absolute t lim was not related (R 2 ≈ 0) to RCV or to $$\dot{V}$$ O2max. We conclude that a contraction in PV does not negatively affect t lim and that rhEPO improves t lim by additional, non-hematopoietic factors.

The main aim of the present study was to quantify the magnitude of differences introduced when estimating a given blood volume compartment (e.g. plasma volume) through the direct determination of another compartment (e.g. red cell volume) by multiplication of venous haematocrit and/or haemoglobin concentration. However, since whole body haematocrit is higher than venous haematocrit such an approach might comprise certain errors. To test this experimentally, four different methods for detecting blood volumes and haemoglobin mass (Hbmass) were compared, namely the carbon monoxide (CO) re-breathing (for Hbmass), the indocyanine green (ICG; for plasma volume [PV]) and the sodium fluorescein (SoF; for red blood cell volume [RBCV]) methods. No difference between ICG and CO re-breathing derived PV could be established when a whole body/venous haematocrit correction factor of 0.91 was applied (p = 0.11, r = 0.43, mean difference -340 ± 612 mL). In contrast, when comparing RBCV derived by the CO re-breathing and the SoF method, the SoF method revealed lower RBCV values as compared to the CO re-breathing method (p

To assess the efficacy of paracetamol (acetaminophen) for neonatal pain relief.Randomized, double-blind placebo-controlled trial in 3 Swiss university hospitals. Term and near-term infants (n = 123) delivered by forceps or vacuum were randomized to receive 2 suppositories with paracetamol (60/80/100 mg in infants3000 g/3000-4000 g/4000 g birth weight) or placebo at 2 and 8 hours of life. Pain and discomfort during the first 24 hours was assessed by the échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] score. The response to the subsequent heel prick for metabolic screening at days 2-3 of life was investigated by the Bernese Pain Scale for Neonates (BPSN).The échelle de douleur et d'inconfort du nouveau né [neonatal pain and discomfort scale] pain scale ratings after assisted vaginal delivery were low and declined within 4 hours of life (P.01) irrespective of paracetamol administration. At 2-3 days of life, BPSN scores after heel prick were significantly higher in infants who had received paracetamol, compared with controls, both when BPSN were scored by nurses at the bedside (median [IQR] 4 [2-7] vs 2 [0-5], P = .017) or off-site from videos (4 [2-8] vs 2 [1-7], P = .04). Thirty-five of 62 (57%) infants treated with paracetamol cried after heel prick, compared with 25 of 61 (41%) controls (P = .086).Infants born by assisted vaginal delivery have low pain scores in the immediate period after birth. Paracetamol given to newborns soon after birth may aggravate a subsequent stress response.

The objective of this study was to test the efficacy and safety of intravenous ferric carboxymaltose (FCM) in pregnant women with restless legs syndrome (RLS) and iron deficiency or anemia. The open-label pilot study (exploratory) was performed at the University Hospital of Zürich and the Neurocenter of Southern Switzerland (Lugano).Nineteen women in the third trimester of pregnancy with moderate-to-severe RLS and serum ferritin levels35 µg/l or hemoglobin (Hb) 11.0 g/dl were included in the study. RLS was graded according to the International Restless Legs Syndrome (IRLS) Study Group rating scale. All participants had a score of ≥20 or had RLS ≥3 times/week. Based on the Hb levels, 500 or 700 mg of FCM was administered over 20 min. The primary end point was a ≥ 50% reduction in the mean IRLS score one week after FCM infusion. The secondary end points included periodic limb movements (PLMs; assessed using nocturnal foot actigraphy), sleep quality (assessed using the Pittsburgh Sleep Quality Index), and safety.The IRLS score decreased from 23 ± 7 (baseline) to 13 ± 7 (P 0.01), whereas the PLM index decreased from 35 ± 26 (baseline) to 25 ± 20 (P 0.001). Significant improvement in sleep quality was also reported (P 0.029), and treatment was well tolerated. Three serious adverse events were reported, but they were considered unrelated to treatment.These data provide promising evidence on the safety and efficacy of FCM for moderate-to-severe RLS in pregnant women with iron deficiency or anemia. Therefore, a future placebo-controlled study is warranted.

Objective: The aim of this study was to determine the response to recombinant human erythropoietin (rhEPO) in anemic pregnant women with heterozygous hemoglobinopathies. Methods: A prospective study including 19 consecutive pregnant women with anemia and heterozygous hemoglobinopathy was performed. Treatment wasdivided into two phases: the initial low-dose phase and the subsequent high-rhEPO phase. In the initial phase, 3 × 10,000 U of rhEPO was administered with intravenous iron sucrose. In patients showing a poor response (Hb increase Results: All patients showed stimulation of erythropoiesis as evidenced by an increase in hemoglobin. In 13 patients, a good response to therapy was observed (mean Hb increase 1.6 ± 0.5 g/dl). In 6 patients, resistance to rhEPO was noted (mean Hb increase 0.5 ± 0.5 g/dl). The mean gestational age at the start of therapy was 28 weeks of gestation and at the end 32 weeks. The mean duration of a complete therapy was 3.5 weeks (range 2–4.5 weeks). If calculated for body weight, the initial low- rhEPO dose of 160.4 ± 30.6 U/kg body weight/treatment was increased to 320.9 ± 61.2 U/kg body weight/treatment in the subsequent phase. Conclusion: Response to rhEPO treatment differs widely in anemic pregnant patients with heterozygous hemoglobinopathy. Resistance was observed in anemic pregnant patients with the β-thalassemia trait originally from the Mediterranean region.

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 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.

Background. The potential benefits of administering a dose of intravenous iron in patients with moderate postpartum anaemia rather than oral iron alone remains unproven.Aims.To determine whether a single injection of intravenous iron followed by a 6-week course of oral iron is as effective over 6 months in restoring normal haemoglobin levels and replenishing iron stores in women with moderate postpartum anaemia as a course of oral iron alone in women with mild postpartum anaemia.Materials and Methods. Retrospective two-arm cohort study in women with mild postpartum anaemia (haemoglobin 9.6–10.5 g/dL) prescribed iron daily for 6 weeks (N=150) and women with moderate postpartum anaemia (haemoglobin 8.5–9.5 g/dL), given a single 500 mg injection of intravenous iron followed by iron daily for 6 weeks (N=75). Haemoglobin and ferritin were measured 6 months postpartum.Results. Haemoglobin returned to similar mean levels in both groups. Ferritin levels were statistically significantly higher in the intravenous + oral group (57.7±49.3 μg/L versus32.9±20.1 μg/L).Conclusions.Despite lower baseline haemoglobin, intravenous iron carboxymaltose was superior to oral iron alone in replenishing iron stores in moderate postpartum anaemia and may prove similarly beneficial in mild postpartum anaemia.

The third stage of labor is associated with considerable maternal morbidity and mortality. The major complication is postpartum hemorrhage (PPH), which is the leading cause of maternal morbidity and mortality worldwide. Whereas in the event of PPH due to atony of the uterus there exist numerous treatment guidelines; for the management of retained placenta the general consensus is more difficult to establish. Active management of the third stage of labour is generally accepted as standard of care as already its duration is contributing to the risk of PPH. Despite scant evidence it is commonly advised that if the placenta has not been expelled 30 minutes after delivery, manual removal of the placenta should be carried out under anaesthesia. Pathologic adhesion of the placenta in the low risk situation usually is diagnosed at the time of delivery; therefore a pre- or intrapartum screening opportunity for placenta accreta would be desirable. But diagnosis of abnormalities of placentation other than placenta previa remains a challenge. Nevertheless the use of ultrasound and doppler sonography might be helpful in the third stage of labor. An improvement might be the implementation of standardized operating procedures for retained placenta which could contribute to a reduction of maternal morbidity.

Objective : To describe hemoglobin (Hb) levels and percentiles for multiple pregnancies and to compare them with reference ranges of singleton pregnancies as published by the Center for Disease Control. Study design : Maternal hemoglobin and red cell indices were compared: (a) between multiple and singleton pregnancies of our hospital and (b) with trimester-specific cut-offs for singleton pregnancies obtained from literature. Results : While early pregnancy hemoglobin values were similar in multiple and singleton pregnancies, second trimester values decreased much faster in multiple pregnancies. Nadir in multiple pregnancies was reached in weeks 24–28 of gestation. In the third trimester mean hemoglobin values were higher in multiple pregnancies, while 5th and 10th percentile were still lower compared to singleton pregnancies at term. The mean whole-pregnancy hemoglobin exceeded the Center for Disease Control (CDC) cut-off for anemia in singleton pregnancies (fifth percentile) and red cell indices remained constant. Conclusion : We conclude that with a significantly lower fifth percentile than introduced by the CDC in all trimesters, there should be different cut-offs for anemia in multiple pregnancies considered. A more pronounced decrease in multiple pregnancy hemoglobin levels seems to be physiological.

The aim of this cohort study was to prospectively assess frequency, characteristics, and determinants of restless legs syndrome (RLS) in pregnancy and its impact on sleep.Pregnant women were prospectively studied in each trimester and 8 weeks postpartum. Assessments included interview about RLS symptoms and sleep disturbances; standardized sleep-wake questionnaires including the International Restless Legs Syndrome Scale (IRLSS) and the Pittsburgh Sleep Quality Questionnaire (PSQI); actigraphic recording of periodic limb movements (PLM); and blood tests including levels of hemoglobin, ferritin, and estrogen.RLS was diagnosed in 58 of 501 women (12%). Positive family history was found in 37% of women with RLS; 59% reported onset of RLS symptoms before the 20th week; 45% had an IRLSS20 and 100% had a PSQI5. Hemoglobin levels11 g/dL were found in 20% of both affected and unaffected women in the third trimester. Women with and without RLS had similar hemoglobin, ferritin, and estrogen levels. IRLSS and PLM in sleep dropped by more than 50% postpartum in women with RLS.We found lower prevalence and earlier onset of symptoms compared to previous studies and confirmed significant improvement after delivery. RLS is clinically relevant due to severe impact on sleep quality. Genetic factors and smoking, but not ferritin, anemia, or estrogen levels, seem to play a role in the pathophysiology of RLS in pregnancy.

At last, benefits on maternal measures and risk of low birth weight are shown In the linked review and meta-analysis of anaemia, prenatal iron use, and the risk of adverse pregnancy outcomes (doi:10.1136/bmj.f3443), Haider and colleagues make a strong case for iron supplementation in pregnancy.1 Iron deficiency is the world’s most common and widespread nutritional disorder. Not only does it affect many women and children in developing countries, it is the one nutritional deficiency that is also highly prevalent in industrialised countries. World Health Organization data indicate that a staggering two billion people—around 30% of the world’s population—may have anaemia, mainly as a result of iron deficiency, often exacerbated in resource poor areas by infectious disease.2 Iron deficiency is thus …

Iron deficiency is still the world's most common nutritional deficiency, and generally, iron deficiency anemia is the most prevalent form of anemia. The major risk groups for iron deficiency include women of childbearing age, pregnant women, and lactating postpartum women. There exist plenty of studies attending and reconfirming this important issue. To combat this problem, different food iron fortification programmes have been implemented in some regions, iron supplementation guidelines have been elaborated in some countries, and iron therapy schemes involving both oral and intravenous administration have been proposed. But despite these efforts and the recommendations by the World Health Organization, the problem concerning iron deficiency and anemia is still unsolved in most parts of the world. Even in many industrialized countries, the topic of iron and pregnancy often stays unattended and there is a lack of consensus concerning guidelines in different countries. Other disorders, such as hemoglobinopathies, also contribute to the high prevalence of anemia worldwide. The prevalence of anemia is influenced by a variety of deficiencies (e.g., folate, vitamin B12, vitamin A, vitamin D, and vitamin C), infectious diseases, parasitic infestations, inflammatory diseases as well as malnutrition. As data for iron are quite profound, these are often scarce if we look on other vitamins and micronutrients, except for folic acid. As we know, periconceptional supplementation with folic acid has the potential to reduce the incidence of neural tube defects (e.g., spina bifida) dramatically. Unfortunately, folic acid prophylaxis is not commonly used for several reasons. By this special issue, our intention was to broaden the perspective on anemia in pregnancy and propose ways to solve the problems. We have chosen three articles concerning the prevention/treatment of iron deficiency anemia in pregnancy/postpartum including papers from Australia, Nigeria, and Denmark. Another Danish study focuses on the prevention of postpartum anemia through hemostatic sealing of the placental bed at caesarean section, thereby reducing perioperative blood losses. A paper from France and Lebanon evaluates the relationship between periconceptional folate deficiency and neural tube defects. A Chinese study addresses the supposed relationship between iron deficiency and postpartum depression. Together, these papers illustrate some of the many facets of the complexity of the prevention and treatment of anemia in pregnant and postpartum women. Alexander Krafft Laura Murray-Kolb Nils Milman

Our aim was to evaluate the clinical impact of routine amniotic fluid and neonatal surface swab microbiology at Caesarean section. Microbiology data from 1 537 neonates delivered by Caesarean section were analysed in the light of clinical outcome. 1 340 (87%) neonates had non-pathogenic bacteria or negative culture results from both amniotic fluid and surface swab samples. Of the 197 (13%) neonates with pathogenic bacteria, 22 (1.4%) were diagnosed with infection, but only in 6 (0.4%) were the bacteria presumed to be responsible for the infection. Amniotic fluid and surface swab culture had sensitivities of 54% and 35%, and positive predictive values of 14% and 17%, respectively, for detecting a neonate at risk of infection. Amniotic fluid and neonatal surface swab microbiology at Caesarean section contributes little if anything to postnatal management and can be safely dropped from operative routine.

Although haematocrit and haemoglobin value are concentrations, they are commonly used to guide clinical decisions involving red cell and plasma volumes. A study challenging this convention systematically co-determined and compared these measures.Using a non-radioactive double-tracer technique to assess blood volume components, measurements were taken once in 46 healthy male endurance athletes. The best predictors of blood composition were derived from the first 36 athletes by automated stepwise forward selection of non-invasive metric parameters (age, weight, height, body surface area and body mass index) and the resulting formulae validated in the remaining ten volunteers. Haematocrit, haemoglobin concentration, red cell volume and plasma volume were measured again 4 weeks later in eight randomly selected volunteers.Red cell volume (2,282±283 mL) did not correlate with either haematocrit (0.42±0.02) or haemoglobin concentration (14.2±0.8, P0.05, resp.), but was predictable from body surface area (red cell volume [mL]=1,547 × body surface area [m2]-723; r=.88, P0.01). A similar accuracy was unobtainable using any potential predictor for plasma or blood volume, haematocrit or haemoglobin concentration. Red cell volume showed high intra-individual stability when measured again after 4 weeks, whereas plasma volume oscillated in both directions by up to 22%.Only red cell volume shows sufficiently stable intra- and interindividual values to be an accurate, objective indicator of normality in blood composition. The measurement technique is feasible in the outpatient setting and this parameter provides effective, robust, and readily available diagnostic information that might be useful in numerous clinical situations. Its clinical significance does, however, remain to be demonstrated.

Purpose The cumulative summation technique (CUSUM) is an innovative method for the quality control of nuchal translucency (NT) measurements. CUSUM allows immediate corrective intervention as soon as an unacceptable tendency is noted. The aim of this study was to implement an objective and dynamic quality control method based on the CUSUM technique for prompt analysis of fetal NT measurement which would be compatible with different standards in routine clinical practice. The findings were compared to the standard NT quality control methods currently in use. Materials and methods Three sets of fetal NT measurements performed by three experienced examiners (I, II and III) were selected for retrospective evaluation. One additional set of NT measurements performed by examiner IV was prospectively assessed to approve the practicability of the method. NT measurements were conducted according to the recommendations of Fetal Medical Foundation (FMF) Germany and London. NT values were converted to Z-scores. For quality and accuracy evaluation, data were fed into the Digisono CUSUM software to create double CUSUM charts of Z-scores. In addition, histograms were composed from the Z-scores of each set of measurements and plotted against a normal Gaussian distribution. Results Three different patterns of retrospective performance and one set of NT measurements that was evaluated prospectively are presented. The full alignment of Z-scores using CUSUM curves reflected exact periods of under- and overestimation of NT measurements. The CUSUM chart of the prospective data set reveals that prompt corrective intervention of poor performance resulted in reconstitution of optimal results and provided sufficient control. In contrast, histograms of NT Z-scores only showed a minor positive or negative shift as compared to the expected values on the basis of Gaussian distribution, but could not identify poor performance. Conclusion Use of the CUSUM technique analysing the quality of sonographic NT measurements provides the possibility to prospectively observe the development of the examiner's skills, to maintain competence and to promptly define the time when inaccurate measurements start to occur.

Postpartum anemia is a common problem in obstetrics. Depending on the severity of anemia, it can cause a wide range of symptoms. Obstetrical management should be focused on avoiding blood transfusion in young and otherwise healthy women. The aim of this study was to examine the effectiveness of recombinant human erythropoietin (rhEPO) combined with iron sucrose compared to iron sucrose alone in patients with severe postpartum anemia.A prospective randomized study was conducted in women with severe postpartum anemia (Hb8.5 g/dL). The first group received 200 mg iron sucrose intravenously daily on days 1-4. The second group received 200 mg iron sucrose plus 10.000E rhEPO in the same regimen. Twenty women were enrolled in each group. The follow-up period was two weeks.Baseline Hb was 7.1 g/dL and 7.5 g/dL, respectively, depending on the subgroup. Hemoglobin values increased close to normal values within two weeks in both groups treated with iron sucrose alone or in combination with rhEPO (10.5 g/dL, 10.7 g/dL, respectively).In general, iron sucrose alone is a sufficient anemia therapy agent. A subgroup of patients (i.e. with a more pronounced inflammatory response after cesarean section) may benefit from additional rhEPO therapy. Despite being severely anemic, none of our patients required transfusion. Iron sucrose as well as rhEPO was very well tolerated. The benefit of the therapy lies in the avoidance of allogenic blood transfusions with their potential side effects. In cases of severe anemia after operative delivery, additional rhEPO therapy can result in a faster Hb increase and, therefore, faster recovery.

Objective: To evaluate the effectiveness of a stepwise use of recombinant human erythropoietin (rhEPO) in pregnant patients with severe anemia or nonresponsive to intravenously administered iron only. Methods: All subjects had iron deficiency anemia, i.e., a hemoglobin (Hb) level Results: Of the 84 patients, 59 had a baseline Hb level between 9.0 and 9.9 g/dl, of whom 32 responded poorly, thus receiving additional rhEPO. Twenty-five patients had a baseline Hb level Conclusion: This study shows an effective treatment regimen for patients with various degrees of anemia in pregnancy. Iron sucrose is a safe and effective treatment option. In cases of severe iron deficiency anemia or poor response to parenteral iron therapy additional administration of rhEPO might be considered. However, the mechanism for not responding to intravenous iron therapy despite iron deficiency anemia still remains unclear to a large extent.

Recent reports have questioned the accuracy of the indocyanine green dilution technique for measuring plasma volume. Our objective was to evaluate the impact of different time windows for monoexponential extrapolation. We retrospectively analysed 31 indocyanine green decay curves to investigate the problem in principle (group 1) and prospectively performed another 21 plasma volume measurements to estimate its practical impact (group 2). To monoexponentially extrapolate back to the specific extinction at the time of dye injection, two different time windows were applied to each decay curve, comparing the plasma volumes resulting from sampling within a short (or=5 min) versus a longer (5 min) period of time. Extrapolating back from the longer period led to a higher apparent plasma volume relative to the shorter period in both groups, the difference being 348 +/- 171 ml (group 1) and 384 +/- 131 ml (group 2; mean +/- SD; p0.05 each). This result was due to a reliable monoexponentiality of decay only up to the 5th min after dye injection. Thus, to estimate the initial distribution space of indocyanine green via monoexponential extrapolation, the first linear kinetic of indocyanine green decay should be taken.

Correspondence to:Alexander Krafft, MDClinic of Obstetrics, Department of Obstetrics and GynaecologyUniversity Hospital Zurich, Frauenklinikstrasse 10CH 8091 Zurich, SwitzerlandTe l.: +41442555148, Fax: +41 44 2554430E-mail: alexander.krafft@usz.chReceived January23, 2008Accepted after minor revision May7,2008Prepublished onlineJune 11, 2008doi:10.1160/TH08-01-0048

The indocyanine green (ICG) dilution technique (DT) is frequently used for plasma volume (PV) measurement. However, because of inadequate knowledge about the properties of this dye, lack of accuracy has been attributed to the method. The aim of this report is to provide physiological background information about the ICG-DT to avoid some profound misunderstandings. When performing tracer dilution, one has to consider the tracer's distribution space before interpreting the result. For ICG, the distribution space is the total PV, i.e., circulating + noncirculating PV, fixed within the endothelial glycocalyx. The distribution space of red blood cells and large molecules, in contrast, is only the circulating part of PV. Therefore, it is erroneous to compare directly PV derived from different tracer dilution methods. The transcapillary escape rate of ICG should not relevantly influence measured PV if the method is performed properly, i.e., if a short time window of measurement is subjected to monoexponential extrapolation. A major problem of PV measurement in general is that the target itself is very inconstant. Thus, checking for constancy of ICG-DT with two consecutive measurements is unreliable. Nevertheless, the ICG-DT is a useful tool for determining PV, provided it is well understood by the investigator to enable correct interpretation of the results.

Aims: To find a clinically practicable parameter for the identification of β-thalassaemia trait (β-TT) in anaemic pregnant women on the basis of routine use of haematological examination. Methods: During 1998–2002, 304 anaemic pregnant women were observed in anaemia consultation hours. A retrospective study was carried out with the aim of finding a screening method for β-TT in anaemic pregnant women. We compared a sensitivity and a specificity of six different parameters for identification of β-TT. On the basis of a sensitivity and a specificity for each parameter, we calculated Youden’s index, the likelihood ratio and determined the receiver-operating curves. The logistic regression of the variables MCV, MCH and microcytosis was accomplished. Results: The analysis using receiver-operating curves as well as a calculation of Youden’s index showed that the best parameter for screening of β-TT in anaemic pregnant women is MCV ≤75 fl. For differentiation between patients with iron deficiency anaemia (IDA) alone and patients with β-TT and concomitant IDA, microcytosis ≥15% was the most sensitive. By using MCH we identified 100% of patients in the group with β-TT but only 67% of patients in the group with IDA. Conclusion: Our results suggest identification of β-thalassaemia on the basis of quantification of HbA2 in all patients with MCV ≤75 fl and normal iron status.

SummaryAlthough there is evidence that altitude increases the platelet count, its effect on the platelet precursor stimulating factor, thrombopoietin (TPO), is unclear. Unlike erythropoietin, TPO appears largely unresponsive to exogenous signals. In a study in 16 healthy volunteers,we report the effects of altitude exposure at between 1000 and 1822 m for 1 or 2 weeks on TPO, the platelet count (+ indices), erythropoietin, hemoglobin, hematocrit and erythrocytes (+ indices).There were significant post-expo-sure increases in TPO (57.9 vs 37.1 U/l; P = 0.0006), platelet count (219.1 vs 208.0 x 103/ml; P = 0.031) and erythropoietin (16.1 vs 9.9 U/l; P = 0.0032).There was a positive correlation between the increases in TPO and platelet count (r = 0.52, P = 0.043). Hemoglobin and hematocrit remained unchanged. Our results provide clear evidence for a relationship, presumably driven by hypoxia, between altitude exposure,TPO production and the platelet count.

I disagree with Steer’s statement that oral iron supplementation in pregnancy has only marginal benefit1 because I think that Haider and colleagues’ study and Pena-Rosas and colleagues’ updated Cochrane review prove the opposite.2 3 4 I do agree, however, that oral iron often has unpleasant side effects and that an entire population should not be exposed to it …

Combined thrombopoietin and platelet response to altitude in a patient with autoimmune thrombocytopenia