Alexander Krafft

Characteristics and determinants of restless legs syndrome in pregnancy A prospective study

Objective: 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. Methods: 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. Results: 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 IRLSS >20 and 100% had a PSQI >5. Hemoglobin levels <11 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. Conclusion: 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.

Selective Use of Recombinant Human Erythropoietin in Pregnant Patients with Severe Anemia or Nonresponsive to Iron Sucrose Alone

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 <10.0 g/dl and ferritin ≤15 μg/l. Patients with an Hb level ≥9.0 g/dl and <10.0 g/dl received 200 mg iron sucrose intravenously twice weekly. If response to therapy was poor, patients additionally received 10,000 U rhEPO twice weekly. Patients with an Hb level <9.0 g/dl primarily received iron sucrose and rhEPO likewise. 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 <9.0 g/dl. The overall Hb level after therapy was 11.0 g/dl (±0.5, range 10.0–12.6 g/dl). Mean duration of therapy was 3.5 weeks (7 infusions). 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.

Impact of parturition on iron status in nonanaemic iron deficiency

Background  Iron‐deficient nonanaemic parturients risk underdiagnosis as a result of the reliance on postpartum ferritin and haemoglobin as markers of iron status. Ferritin is an acute‐phase protein whose levels increase during the inflammatory response, as occurs after delivery. Our aims were to evaluate the impact of parturition on iron status, erythropoiesis and the inflammatory response, and identify the optimal parameters and timing for diagnosing iron deficiency in the presence of postpartum inflammation.

Intravenous iron sucrose in two pregnant women with inflammatory bowel disease and severe iron deficiency anemia

In chronic inflammatory bowel disease (IBD), the iron deficiency anemia caused by intestinal blood loss and chronic inflammation is associated with decreased quality of life and increased morbidity and mortality (1–3). Since IBD typically develops in a woman’s fertile years, it is a potential complication in pregnancy. Management today is improved by the new generation of sophisticated flow cytometry hematology analyzers which provide detailed information about reticulocytes and red cells (4). Following the successful use of intravenous iron sucrose in anemic non-pregnant patients with IBD (2), and of parenteral iron in pregnancy and postpartum anemia (5, 6), we present two cases of IBD (ulcerative colitis and Crohn’s disease, respectively) with severe pregnancy anemia treated successfully with intravenous iron sucrose.

Open-label study of the efficacy and safety of intravenous ferric carboxymaltose in pregnant women with restless legs syndrome

OBJECTIVE 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). PATIENT AND METHODS Nineteen women in the third trimester of pregnancy with moderate-to-severe RLS and serum ferritin levels <35 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. RESULTS 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. CONCLUSIONS 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.

Iron sucrose with and without recombinant erythropoietin for the treatment of severe postpartum anemia: A prospective, randomized, open‐label study

Aim:  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.

Screening for β-Thalassaemia Trait in Anaemic Pregnant Women

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.

Effect of altitude on thrombopoietin and the platelet count in healthy volunteers

Although 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-exposure increases in TPO (57.9 vs 37.1 U/l; P=0.0006), platelet count (219.1 vs 208.0 x 10(3)/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.

Impact of the time window on plasma volume measurement with indocyanine green

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; p < 0.05 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.

Manual removal of the placenta after vaginal delivery: an unsolved problem in obstetrics.

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.