UK guidelines on the management of iron deficiency in pregnancy

Iron deficiency is the most common deficiency state in the world, affecting more than 2 billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion. The objective of this guideline is to provide healthcare professionals with clear and simple recommendations for the diagnosis, treatment and prevention of iron deficiency in pregnancy and the postpartum period. This is the first such guideline in the UK and may be applicable to other developed countries. Public health measures, such as helminth control and iron fortification of foods, which can be important to developing countries, are not considered here. The guidance may not be appropriate to all patients and individual patient circumstances may dictate an alternative approach.     

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.     

A prospective randomized,controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy

Abstract. Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, Ball MJ, Seaton D, Brain T, Rasko JEJ Launceston General Hospital (LGH), Australia; University of Tasmania, Australia; and Centenary Institute, University of Sydney, NSW, Australia) A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268 : 286–295. Background. Iron deficiency anaemia is the most common deficiency disorder in the world, affecting more than one billion people, with pregnant women at particular risk. Objectives and design. We conducted a single site, prospective, nonblinded randomized‐controlled trial to compare the efficacy, safety, tolerability and compliance of standard oral daily iron versus intravenous iron Subjects. We prospectively screened 2654 pregnant women between March 2007 and January 2009 with a full blood count and iron studies, of which 461 (18%) had moderate IDA. Two hundred women matched for haemoglobin concentration and serum ferritin level were recruited. Interventions. Patients were randomized to daily oral ferrous sulphate 250 mg (elemental iron 80 mg) with or without a single intravenous iron polymaltose infusion. Results. Prior to delivery, the intravenous plus oral iron arm was superior to the oral iron only arm as measured by the increase in haemoglobin level (mean of 19.5 g/L vs. 12 g/L; P < 0.001); the increase in mean serum ferritin level (222 μg/L vs. 18 ug/L; P < 0.001); and the percentage of mothers with ferritin levels below 30 μg/L (4.5% vs. 79%; P < 0.001). A single dose of intravenous iron polymaltose was well tolerated without significant side effects. Conclusions. Our data indicate that intravenous iron polymaltose is safe and leads to improved efficacy and iron stores compared to oral iron alone in pregnancy‐related IDA.     

Low-dose oral iron absorption test in anaemic patients with and without iron deficiency determined by bone marrow iron content.

The low-dose oral iron absorption test (OIAT) was performed in 85 consecutive anaemic patients referred for bone marrow examination in order to investigate the ability of the test to predict bone marrow iron stores and to differentiate between different categories of anaemia. Eight patients were excluded for technical reasons. Test results from 77 patients are presented as Cmax (micromol/l): the maximum increase in S-iron measured during a 3 h period after administration of 10 mg oral iron sulfate. Iron deficiency was defined as the absence of stainable iron in bone marrow aspirates. Cmax was higher in 46 iron deficient patients [3 (median); 0 and 13 (1st and 3rd quartiles); 0-40 (range)] than in 31 non-iron-deficient patients (0; 0 and 2; 0-4) (P<0.01). 27 patients had primary bone marrow disease, 25 patients had absent bone marrow iron stores accompanied by inflammation, 17 patients had anaemia of chronic disease (ACD) and 8 patients had uncomplicated iron deficiency anaemia (IDA). Patients with IDA had higher Cmax (15; 13 and 28; 6-40) than patients with ACD (1; 0 and 2; 0-3), and than the 69 non-IDA patients (1; 0 and 3; 0-19) (P<0.001). Cmax values above 5 micromol/l always indicated absent bone marrow iron stores.     

The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis

Intragumtornchai T, Rojnukkarin P, Swasdikul D, Israsena S (Division of Haematology, and Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand). The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. J Intern Med 1998; 243 : 233–41.

Objectives

.To determine the diagnostic values of serum ferritin and other conventional laboratory tests in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis.

Design

.Cross-sectional study for diagnostic tests.

Setting

.University hospital.

Subjects

.Seventy-two consecutive patients with liver cirrhosis in whom the haemoglobin level was less than 13.0 g dL^?1 for men and 12.0 g dL^?1 for women. The diagnosis of liver cirrhosis was based on characteristic clinical and hepatic ultrasonographic findings.

Main outcome measures

.By using absence of bone marrow iron as the standard criterion, the diagnostic powers of mean corpuscular volume, transferrin saturation, serum ferritin and the presence of hypochromic red cells in the diagnosis of iron deficiency were compared by analysing the likelihood ratios, the area under the receiver operating curves (ROC) and the stepwise logistic regression associated with each test.

Results.<

> Twenty-nine patients (40.3%) demonstrated no stainable iron in the bone marrow. The likelihood ratios, the area under the ROC and the stepwise logistic regression indicated that serum ferritin was the most powerful test predictive of iron deficiency. Other tests added little further diagnostic values. The likelihood ratios associated with the serum ferritin levels were as follows: <50 μg L^?1, 22.3; 51–200 μg L^?1, 1.5–1.8; 201–400 μg L^?1, 1.0; > 400 μg L^?1, <1. These results indicate that serum ferritin level <50 μg L^?1 depict a very high probability of iron deficiency anaemia (0.83–0.99) irrespective of the patient's pre-test probability.

Conclusion

.Serum ferritin is the most powerful non-invasive test for the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. It should be the primary test of choice in patients suspected of having the disease. When the level was less than 50 μg L^?1, iron supplement may be prescribed without necessitating bone marrow aspiration.

     

An inappropriate erythropoietic response to iron deficiency anaemia in the elderly

Summary This study was carried out to clarify the features of iron deficiency anaemia in the elderly. Subjects were chosen from residents undergoing an annual health check in a home for the aged and the features of anaemia in the elderly were compared with those in middle-aged adults under 60 years old. The red cell count, red cell size and haemoglobin content in an elderly group with iron-deficiency anaemia did not differ from those in middle-aged adults. No significant differences of the serum ferritin and iron levels were noted between the two groups. Total iron binding capacity was higher in the middle-aged adults than in the elderly, while the reticulocyte count was significantly lower in the elderly group. Immature reticulocytes showing a considerable amount of residual RNA by flow cytometry with fluorescent staining were also lower in the elderly group than in the middle-aged adults. Serum erythropoietin levels in both groups were significantly higher than in non-anaemic age-matched controls and no difference in erythropoietin levels was noted between them. The ratio of the reticulocyte count to the log-transformed erythropoietin level was low in the elderly group with iron-deficiency anaemia compared with the middle-aged adults with iron deficiency anaemia. The same result was seen when the immature reticulocyte count was related to the log-transformed erythropoietin level. These findings suggest that the red cell production response to erythropoietin in the elderly with iron-deficiency anaemia might be inappropriate compared with both non-anaemic and anaemic middle-aged adults.     

Ferritin in bone marrow and serum in iron deficiency and iron overload

Summary Nonheme iron and ferritin in the bone marrow and serum ferritin was investigated in patients with iron deficiency anaemia or iron overload. As controls served patients without any disturbance of the iron metabolism.There is a precise correlation between the nonheme iron and ferritin in the bone marrow of patients with and without disturbance of iron metabolism. A correlation was also found between the ferritin in the bone marrow and the serum. Nonheme iron and ferritin in the bone marrow and serum ferritin was decreased in patients with iron deficiency anaemia. Conversely, the same parameters were increased in patients with iron overload.     

Blood counts in adult and elderly individuals: defining the norms over eight decades of life

The blood count is one of the most common tests used for health assessment. In elderly individuals, selection of a ‘healthy’ reference population for laboratory assessment is difficult due to the high prevalence of chronic morbidities, leading to uncertainty regarding appropriate reference intervals. In particular, age-specific lower haemoglobin reference limits to define anaemia are controversial. Here, we applied a data mining approach to a large dataset of 3 029 904 clinical routine samples to establish blood count reference intervals. We excluded samples from units/specialists with a high proportion of abnormal blood counts, samples from patients with an unknown or decreased estimated glomerular filtration rate, and samples with abnormal test results in selected other analytes. After sample exclusion, 566 775–572 060 samples from different individuals aged 20–100 years were available for analysis. We then used an established statistical algorithm to determine the distribution of physiological test results and calculated age- and sex-specific reference intervals. Our results show substantial trends with age in haematology analytes' reference intervals. Most notably, haemoglobin and red cell counts decline in men with advanced age, accompanied by increases in red cell volume in both sexes. These findings were confirmed in an independent dataset, and suggest an at least partly physiologic cause.     

Mass spectrometry evaluation of the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients

In this study, mass spectrometry was used to evaluate the hepcidin‐25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients using the absence of stainable bone marrow iron as the gold standard criterion for iron deficiency (ID). In addition, correlation coefficients for hepcidin‐25 vs. haematimetric and biochemical iron parameters, and C‐reactive protein (CRP) were determined. The optimal cut‐off for hepcidin‐25 was 31.5 ng/mL corresponding to a sensitivity and specificity of 82% and 95%, respectively, for ID. For ferritin, a sensitivity and specificity of 70% and 100%, respectively, correspond to an optimal cut‐off of 41.5 μg/L. Receiver operating characteristics curve analysis revealed that mass spectrometry analysis of hepcidin‐25 does not appear to be superior to ferritin in the diagnosis of ID in elderly anaemic patients with concurrent inflammation. Hepcidin‐25 shows a strong positive correlation with ferritin, and also correlates positively with CRP, in this patient population.     

A pilot iron substitution programme in female blood donors with iron deficiency without anaemia

Background and objectives Blood donation can contribute to iron deficiency. The possibly resulting anaemia importantly affects donor return rate. The determination of serum ferritin levels revealed iron deficiency in many non‐anaemic premenopausal female blood donors at our Institution. We started an iron substitution programme targeting this donor group to prevent anaemia and enhance donor retain. Materials and methods Women aged ≤50 with haemoglobin levels adequate for donation and serum ferritin ≤10 ng/ml were offered iron supplementation. Substitution lasted 16 weeks and the donation interval was extended. History collection including iron deficiency–related symptoms, whole blood count and serum ferritin determination was performed at baseline and after 2 and 6 months. Data were recorded prospectively and compared with those of 108 female controls with iron deficiency not receiving iron substitution (retrospective data). Results Of the 116 participating subjects, 60% completed the programme. Significant results were serum ferritin increase (from a mean value of 7·12 to 25·2 ng/ml), resolution of prostration, fatigue, sleep disturbances, tension in the neck, hair loss and nail breakage. No case of anaemia occurred. Sixty per cent of the women completed the programme and donated blood again. Conclusions Targeted iron substitution prevents the development of anaemia and enhances donation return in premenopausal female blood donors with iron deficiency.     

Human transferrin G277S mutation: a risk factor for iron deficiency anaemia

Numerous polymorphisms of the transferrin gene result in a range of electrophoretic variants. We show that one of these mutations has a functional consequence. A G-->A mutation at cDNA nucleotide 829 (G277S) was associated with a reduction in total iron binding capacity (TIBC). In menstruating white women, the G277S genotype was a risk factor for iron deficiency anaemia: iron deficiency anaemia was present in 27% of homozygous G277S/G277S women, 10% of G277G/G277S heterozygous women and 5% of homozygous wild-type G277G/G277G women.     

Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: a Korean Association for the Study of Intestinal Disease Study

Background: Although endoscopy is recommended for patients with iron deficiency anaemia, there is, currently, no consensus on the role of endoscopy for iron‐deficient patients without anaemia. The goal of this study was to determine the prevalence of serious gastrointestinal (GI) lesions, identified by endoscopy in patients with iron deficiency and anaemia compared with patients with iron deficiency without anaemia. Methods: One thousand five hundred and eighteen patients with a ferritin value of ≤50 ng/mL and a total iron‐binding capacity ≥300 mg/dL were retrospectively investigated using oesophagogastroduodenoscopy and colonoscopy between January 2005 and September 2006. The lesions identified were classified as clinically important according to standard predetermined criteria. Results: Among the 1518 cases, 749 patients had anaemia and 769 had normal haemoglobin levels. Clinically important lesions were identified in 24.6% of the patients with anaemia and in 22.8% of the patients without anaemia (P > 0.05). The frequency of lower GI tract lesions (13.6 vs 11.4%, P > 0.05) and upper GI tract lesions (11.9 vs 12.5%, P > 0.05) was similar in the comparisons between the two groups. However, the frequency of malignant GI lesions was higher in the patients with anaemia (5.1 vs 0.7%, P < 0.01). In addition, the patients without anaemia were significantly more likely to have early‐stage neoplasia (adenoma, early gastric cancer and Dukes’ A and B colon cancer) than were the patients with anaemia (98.4 vs 52.5%, P < 0.01). Conclusion: The results of this study suggest that patients with iron deficiency should undergo endoscopic evaluation of the GI tract, irrespective of whether they have anaemia. The endoscopic evaluation of the GI tract in patients with iron deficiency without anaemia could provide an opportunity for the detection of early‐stage neoplasia at a curable stage.