The impact of HFE mutations on haemoglobin and iron status in individuals experiencing repeated iron loss through blood donation*

Frequent blood donors become iron deficient. HFE mutations are present in over 30% of donors. A 24-month study of 888 first time/reactivated donors and 1537 frequent donors measured haemoglobin and iron status to assess how HFE mutations impact the development of iron deficiency erythropoiesis. Donors with two HFE mutations had increased baseline haemoglobin and iron stores as did those with one mutation, albeit to a lesser extent. Over multiple donations haemoglobin and iron status of donors with HFE mutations paralleled those lacking mutations. The prevalence of HFE mutations was not increased in higher intensity donors. Thus, in general, HFE mutations do not temper donation-induced changes in haemoglobin and iron status. However, in Black donors there was an increase of H63D carriers at baseline, from 3·7% in first time/reactivated donors to 15·8% in frequent donors, suggesting that the relative effects of HFE mutations on iron absorption may vary between racial/ethnic groups. In secondary analyses, venous haemoglobin decreased more slowly in donors with ferritin ≥12μg/l; and haemoglobin recovery time was shorter in donors with reticulocyte haemoglobin (CHr) ≥32·6pg, indicating that these biochemical measures are better indicators of a donor's response to phlebotomy than their HFE mutation status.     

40 mg pantoprazole and 40 mg esomeprazole are equivalent in the healing of esophageal lesions and relief from gastroesophageal reflux disease-related symptoms

BACKGROUND: Proton pump inhibitors are regarded as the most effective class of acid suppressive medication for gastroesophageal reflux disease treatment. There is considerable interest regarding the dose equivalence between various proton pump inhibitors. GOALS: To compare the efficacy of pantoprazole and esomeprazole with regard to healing and relief from gastroesophageal reflux disease-related symptoms. STUDY: Multicenter, randomized, double-blind study. Patients with gastroesophageal reflux disease grades B/C (Los Angeles classification) received 40 mg pantoprazole daily (n = 113) or 40 mg esomeprazole daily (n = 114). Healing (endoscopy) and relief from gastroesophageal reflux disease-related symptoms (direct questioning) were assessed at first and final visit (after 4, 6, 8, or 10 weeks of treatment). RESULTS: Overall healing in both treatment groups was 88% of patients (intention-to-treat population), 95% (pantoprazole), and 90% (esomeprazole) (per-protocol population); statistically, this indicates "at least equivalence" between treatments. Overall relief from gastroesophageal reflux disease-related symptoms was similar for pantoprazole (55%) and esomeprazole (51%, per-protoco). No correlation between healing and symptom relief was seen. The majority of reported adverse events were assessed as "not related" to the study drug. Pantoprazole and esomeprazole have comparably good safety and tolerability. CONCLUSION: In patients with gastroesophageal reflux disease, 40 mg pantoprazole daily and 40 mg esomeprazole daily are equally effective for healing of esophageal lesions and relieving gastroesophageal reflux disease-related symptoms.     

A study of changes in red cell volume and haemoglobin concentration during phlebotomy induced iron deficiency and iron repletion using the Technicon H1

The recently introduced Technicon H1 analyser uses an improved optical principle to measure the size and haemoglobin concentration of erythrocytes. We have made a serial study of ten patients undergoing phlebotomy to induce mild iron deficiency. The instrument showed the early development of anisohypochromia with subsequent fall in the mean cell haemoglobin concentration (MCHC). Cell volume was preserved until relatively late and during early iron deficient erythropoiesis cell volume would appear to be maintained at the expense of haemoglobin concentration. The Technicon H6000 (conventional technology) used in parallel produced contrasting results indicating anisomicrocytosis with preservation of cell haemoglobin concentration until relatively late. Five cases of severe iron deficiency treated with iron were similarly studied and showed comparable changes on both instruments, with characteristically bimodal cell volume histograms and large increases in red cell distribution width. Our results indicate that the new generation of instruments will generate red cell data of additional clinical value.     

Usefulness of measuring reticulocyte hemoglobin equivalent in the management of haemodialysis patients with iron deficiency

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin treatment. The cellular iron status of the patients can be determined from the recently available measurement of reticulocyte hemoglobin equivalent (RET-He). RET-He is measured on the basis of automated fluorescent flow cytometry which in the reticulocyte channel, using a polymethine dye, also measures the mean value of the forward light scatter intensity of mature red blood cells and reticulocytes. These values equate with reticulocyte hemoglobin content. In this study, to clarify the accuracy of RET-He in diagnosing iron deficiency in dialysis patients, we initially compared RET-He with such iron parameters as serum ferritin levels, transferrin saturation and content of reticulocyte hemoglobin (CHr) which has been established as indicators of functional iron deficiency. Secondly, we investigated the changes in RET-He during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 217 haemodialysis patients. Iron deficiency was defined as havsing a transferrin saturation (TSAT) < 20% or serum ferritin < 100 ng/ml. Conventional parameters of red blood cells and RET-He were measured by on a XE-2100 automated blood cell counter (Sysmex). CHr was measured on an ADVIA120 autoanalyser (Siemens). RET-He mean value was 32.4 pg and good correlation (r = 0.858) between RET-He and CHr is obtained in dialysis patients. Receiver operating characteristic curve analysis revealed, values of the area was 0.776 and at a cutoff value of 33.0 pg, a sensitivity of 74.3% and a specificity of 64.9%, were achieved. Iron supplements given to the patients with low TSAT or ferritin, RET-He responded within 2 weeks, and this seemed to be a potential advantage of using RET-He in the estimation of iron status. RET-He is a new parameter, equivalent value to CHr, and is easily measurable on the widely spread and popular blood cell counter and is a sensitive and specific marker of iron status in dialysis patients.     

Indirect estimates of body composition are useful for groups but unreliable in individuals

OBJECTIVE: To assess the usefulness of the body mass index (BMI) in identifying individuals classified as overweight or obese based on estimates of body fat percentage (BF%) obtained by the deuterium dilution (BF%DD) method. In addition, to assess the accuracy of bioelectrical impedance analysis (BIA) and skinfold thickness (SFT) measurements in the estimation of body composition of Australians at the individual and group level. DESIGN: Cross-sectional study. SUBJECTS: One hundred and seventeen healthy Australian volunteers of European descent, comprising of 51 males and 66 females, ranging in age from 19 to 77 y. MEASUREMENTS: BMI was calculated from body weight and height. Fat-free mass (FFM) was estimated from measures of total body water (TBW) using deuterium dilution (FFM(DD)), SFT using the equations of Durnin and Womersley (Br J Nutr 1974; 32: 77-97) (FFM(SFT)), and BIA using the equations of Lukaski et al (J Appl Physiol 1986; 60: 1327-1332) (FFM(Lu)), Segal et al (Am J Clin Nutr 1988; 47: 7-14) (FFM(Se)) and Heitmann (Eur J Clin Nutr 1990; 44: 831-837) (FFM(He)). Estimates of fat mass (FM) were calculated as the difference between body weight and FFM, while BF% was calculated by expressing FM as a percentage of body weight. RESULTS: BMI had poor sensitivity and positive predictive value in identifying individuals as being overweight/obese as classified by BF%DD. Furthermore, estimates of FFM (and hence FM) from BIA or SFT could not be used interchangeably with DD, without the risk of considerable error at the individual level. At the group level errors were relatively smaller, though statistically significant. While FFM(SFT) could be corrected by the addition of the bias (1.2 kg in males and 0.8 kg in females), no simple correction was possible with BIA estimates of FFM for any of the equations used. However, an accurate prediction of FFM(DD) was possible from the combination of FFM(He), biceps SFT and mid-arm circumference in both males and females. The bias of this prediction was small (<0.15 kg), statistically non-significant in both sexes, and unrelated to the mean FFM obtained by the two methods. The revision of Heitmann's estimate of FFM using anthropometric variables described in this study had the best sensitivity (79%), specificity (96%) and positive predictive value (92%) in identifying overweight/obese individuals in comparison to the other equations tested. CONCLUSION: BMI was a poor surrogate for body fatness in both males and females. The currently recommended equations for the prediction of body composition from SFT and BIA provided inaccurate estimates of FFM both at the individual and group level as compared to estimates from DD. However, Heitmann's equations, when combined with measures of the biceps SFT and mid-arm circumference, provided better estimates of FFM both at the individual and group level.     

Relationship of hepatic iron concentration to histochemical grading and to total chelatable body iron in conditions associated with iron overload

A simple method based on atomic absorption spectrophotometry and using protein concentration as the reference standard was used for measuring the total tissue iron concentration in needle liver biopsy specimens from 47 patients with varying levels of body iron stores. The values obtained showed a close correlation over a wide range with measurements of total chelatable body iron stores. A comparison with the histochemical assessment of iron deposition showed that only those with grades 3 and 4 had significant increases in iron concentration which is in accord with other clinical observations in such patients. A liver biopsy can thus be of value in the quantitative determination of total body iron overload as well as in the diagnosis of underlying liver disease.     

Parenteral iron supplementation for the treatment of iron deficiency anemia in children

Iron-deficiency anemia impairs growth and intellectual development in children, which can be reversed only by early diagnosis and iron supplementation. Oral supplementation can efficiently replace stores, but in many cases parenteral iron is needed. Unfortunately some adverse reactions have limited its use in children. We compared the efficacy and safety of intramuscular and intravenous administration in 33 evaluable children with severe iron deficiency and/or iron-deficiency anemia who failed to respond to oral iron supplementation. Nineteen children received intravenous infusion and 14 intramuscular injections. All children showed recovery from iron-deficiency anemia, with statistically similar improvement in hemoglobin levels. The duration of treatment was longer in those receiving intramuscular injection. Parenteral iron therapy for the treatment of iron-deficiency anemia is a rapid, easy, and definitive solution to a long-troubling situation. We suggest the use of parenteral iron, in particular intravenous iron, in children who do not recover from severe iron-deficiency anemia after oral therapy. We should consider the physical and neuropsychological sequelae of long-lasting iron deficiency in children and the fact that oral supplementation is less likely to replace iron stores.     

Estimates of the effect on hepatic iron of oral deferiprone compared with subcutaneous desferrioxamine for treatment of iron overload in thalassemia major: a systematic review

Background  

Beta thalassemia major requires regular blood transfusions and iron chelation to alleviate the harmful accumulation of iron. Evidence on the efficacy and safety of the available agents, desferrioxamine and deferiprone, is derived from small, non-comparative, heterogeneous observational studies. This evidence was reviewed to quantitatively compare the ability of these chelators to reduce hepatic iron.     

Efficacy and safety of IV ferumoxytol for adults with iron deficiency anemia previously unresponsive to or unable to tolerate oral iron

Although oral iron is the initial treatment approach for iron deficiency anemia (IDA), some patients fail to respond to or cannot tolerate oral iron. This double‐blind safety and efficacy study of the intravenous (IV) iron, ferumoxytol, randomized patients with a history of unsatisfactory oral iron therapy, or in whom oral iron could not be used, to ferumoxytol (n = 609) or placebo (n = 203). The proportion of patients achieving the primary endpoint (hemoglobin increase ≥2.0 g/dL at Week 5) was 81.1% with ferumoxytol versus 5.5% with placebo (P < 0.0001). The mean increase in hemoglobin from Baseline to Week 5, a secondary endpoint (also the alternative preplanned primary efficacy endpoint for other health authorities), was 2.7 versus 0.1 g/dL (P < 0.0001). Achievement of a hemoglobin ≥12 g/dL, time to a hemoglobin increase ≥2.0 g/dL, and improvement in the Functional Assessment of Chronic Illness Therapy Fatigue score also significantly favored ferumoxytol over placebo at Week 5 (P < 0.0001). Ferumoxytol treatment‐emergent adverse events were mainly mild to moderate. Ferumoxytol was effective and well tolerated in patients with IDA of any underlying cause in whom oral iron was ineffective or could not be used. This trial was registered at www.clinicaltrials.gov as #NCT01114139. Am. J. Hematol. 89:7–12, 2014. © 2013 Wiley Periodicals, Inc.     

肥胖者胰岛素抵抗与总体脂、局部体脂关系的研究

目的应用扩展高胰岛素-正葡萄糖钳夹技术,研究正常糖耐量中国人中正常体重者及超重/肥胖者胰岛素敏感性的异同,以及体脂含量及分布与胰岛素敏感性的关系.方法对22例居住上海地区中国人,其中正常体重组(BMI＜25kg/m2)9例,超重/肥胖组(BMI≥25kg/m2)13例,进行扩展高胰岛素-正葡萄糖钳夹试验,并应用核磁共振技术(MRI)测定局部体脂.结果(1)超重/肥胖组较之正常体重组胰岛素介导的葡萄糖利用率降低[(3.37±0.15)mg*kg-1*min-1比(5.86±0.65)mg*kg-1*min-1,P＜0.01],以糖原合成障碍为主[(1.51±0.15)mg*kg-1*min-1比(3.17±0.62)mg*kg-1*min-1,P＜0.01].(2)超重/肥胖组胰岛素抑制脂氧化及血游离脂肪酸水平的作用减弱.(3)局部体脂中以腹内脂肪增加对胰岛素敏感性的影响最显著(r=-0.80,P＜0.01).结论中国人正常糖耐量、超重/肥胖个体胰岛素敏感性下降,腹内脂肪增加是胰岛素抵抗的主要原因.     

Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel disease--a randomized, controlled, open-label, multicenter study

OBJECTIVES: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The optimal route for iron supplementation to replenish iron stores has not been determined so far. We therefore evaluated the efficacy and safety of intravenous iron sucrose as compared with oral iron sulfate for the treatment of iron deficiency anemia (IDA) in patients with IBD. METHODS: A randomized, prospective, open-label, multicenter study was performed in 46 patients with anemia and transferrin saturation 相似文献   

Thalassemia and hemoglobinopathies rather than iron deficiency are major causes of pregnancy-related anemia in northeast Thailand

A cross-sectional prevalence study of anemia was undertaken on 412 pregnant women in northeast Thailand during January 2003 to May 2004. With standardized diagnostic protocols and the CDC criteria of anemia [hemoglobin (Hb) < 11 g/dl at < or = 12 weeks of gestation and Hb < 10.5 g/dl at < or = 20 weeks of gestation], 71 (17.2%) subjects were anemic. Of these, 42 (59.2%) subjects had thalassemia, 5 (7.0%) had iron deficiency, 18 (25.4%) had combined thalassemia and iron deficiency and 6 (8.5%) had no thalassemia nor iron deficiency. Adjusted logistic regression analyses indicated that various thalassemia genotypes were significantly related to anemia, while homozygous Hb E had the highest risk with an odds ratio (OR) of 44.8 (95% CI 12.6-159.7). In comparison, iron deficiency demonstrated a much lower risk with OR of 3.1 (95% CI 1.4-6.8). This finding suggests that the contribution of iron deficiency to pregnancy associated anemia in this region is low.     

Inflammation and iron deficiency in the hypoferremia of obesity

CONTEXT: Obesity is associated with hypoferremia, but it is unclear if this condition is caused by insufficient iron stores or diminished iron availability related to inflammation-induced iron sequestration. OBJECTIVE: To examine the relationships between obesity, serum iron, measures of iron intake, iron stores and inflammation. We hypothesized that both inflammation-induced sequestration of iron and true iron deficiency were involved in the hypoferremia of obesity. DESIGN: Cross-sectional analysis of factors anticipated to affect serum iron. SETTING: Outpatient clinic visits. PATIENTS: Convenience sample of 234 obese and 172 non-obese adults. MAIN OUTCOME MEASURES: Relationships between serum iron, adiposity, and serum transferrin receptor, C-reactive protein, ferritin, and iron intake analyzed by analysis of covariance and multiple linear regression. RESULTS: Serum iron was lower (75.8+/-35.2 vs 86.5+/-34.2 g/dl, P=0.002), whereas transferrin receptor (22.6+/-7.1 vs 21.0+/-7.2 nmol/l, P=0.026), C-reactive protein (0.75+/-0.67 vs 0.34+/-0.67 mg/dl, P<0.0001) and ferritin (81.1+/-88.8 vs 57.6+/-88.7 microg/l, P=0.009) were higher in obese than non-obese subjects. Obese subjects had a higher prevalence of iron deficiency defined by serum iron (24.3%, confidence intervals (CI) 19.3-30.2 vs 15.7%, CI 11.0-21.9%, P=0.03) and transferrin receptor (26.9%, CI 21.6-33.0 vs 15.7%, CI 11.0-21.9%, P=0.0078) but not by ferritin (9.8%, CI 6.6-14.4 vs 9.3%, CI 5.7-14.7%, P=0.99). Transferrin receptor, ferritin and C-reactive protein contributed independently as predictors of serum iron. CONCLUSIONS: The hypoferremia of obesity appears to be explained both by true iron deficiency and by inflammatory-mediated functional iron deficiency.     

Pathways for the regulation of body iron homeostasis in response to experimental iron overload

BACKGROUND/AIMS: Secondary iron overload is a frequent clinical condition found in association with multiple blood transfusions. METHODS: To gain insight into adaptive changes in the expression of iron genes in duodenum, liver and spleen upon experimental iron overload we studied C57BL/6 mice receiving repetitive daily injections of iron-dextran for up to 5 days. RESULTS: Iron initially accumulated in spleen macrophages but with subsequent increase in macrophage ferroportin and ferritin expression its content in the spleen decreased while a progressive storage of iron occurred within hepatocytes which was paralleled by a significant increase in hepcidin and hemojuvelin expression. Under these conditions, iron was still absorbed from the duodenal lumen as divalent metal transporter-1 expressions were high, however, most of the absorbed iron was incorporated into duodenal ferritin, while ferroportin expression drastically decreased and iron transfer to the circulation was reduced. CONCLUSIONS: Experimental iron overload results in iron accumulation in macrophages and later in hepatocytes. In parallel, the transfer of iron from the gut to the circulation is diminished which may be referred to interference of hepcidin with ferroportin mediated iron export, thus preventing body iron accumulation.     

A comparison between intravenous iron polymaltose complex (Ferrum Hausmann®) and oral ferrous fumarate in the treatment of iron deficiency anaemia in pregnancy

Abstract: Anaemia is the most common medical disorder in pregnancy with iron deficiency anaemia accounting for the majority of cases. Over 90% of the iron deficiency anaemia is due to red cell iron deficiency associated with depleted iron stores and deficient intake. The two main modalities of treating iron deficiency anaemia are oral or parenteral iron. Ferrous Hausmann® (iron dextrin) is the latest iron preparation which can be used for intravenous parenteral administration as a total dose infusion. This study compares the efficacy of Ferrum Hausmann® with oral ferrous fumarate therapy in the treatment of iron deficiency anaemia in pregnancy. Our study shows that treatment with intravenous Ferrum Hausmann® (iron dextrin) resulted in a significantly better level and rate of increase of haemoglobin (p<0.001). Serum ferritin, which is the best indicator of iron stores, was significantly higher (p<0.001) in the intravenous group. Other indices of iron status such as serum iron, serum transferrin and zinc protoporphyrin also showed a significant improvement in the intravenous group compared to those given oral iron. The results suggest that intravenous iron as a total dose infusion is able to replenish iron stores more efficiently, completely and at a faster rate than oral iron therapy, thus providing the fuel for stimulation of full erythopoiesis compared to oral iron. There were also no reports of any adverse reactions with intravenous iron dextrin, whereas there were a considerable proportion of women on oral iron therapy who reported side effects. In conclusion, intravenous iron therapy with Ferrous Hausmann® (iron dextrin) is a suitable, effective and safe alternative to oral iron therapy in the treatment of iron deficiency anaemia in pregnancy.