Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2–24.8) mg/l, compared with 6.6 mg/l (11.2–24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.     

Reticulocyte haemoglobin content vs. soluble transferrin receptor and ferritin index in iron deficiency anaemia accompanied with inflammation

Ferritin concentration, as a parameter of iron status that is commonly used in the diagnosis of iron deficiency anaemia (IDA), often has limited values if the iron deficiency is accompanied by inflammatory disease. This study evaluated the value of reticulocyte haemoglobin content (CHr) and soluble transferrin receptor-ferritin index (sTfR/F) in the diagnosis of IDA and differential diagnosis of IDA and anaemia of chronic disease. The study included 66 nonanaemic individuals as controls, 86 patients with IDA divided into noninflammatory and inflammatory subgroups, and 32 patients with anaemia of chronic disease. Blood count, iron, transferrin saturation, total iron binding capacity, ferritin, C-reactive protein, sTfR and CHr were determined. Receiver operator characteristic curve analysis showed very high discriminating power for CHr, soluble transferrin receptor (sTfR) and sTfR/F in the diagnosis of IDA. In patients with anaemia of chronic disease these parameters showed no significant difference from the control. CHr and sTfR enabled recognition of iron deficiency and were not affected by acute phase reaction. They are sensitive markers of body iron status with additional value to conventional tests for the detection of iron deficiency.     

Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Erythropoiesis: Correlations Between Iron Status Markers During Normal Pregnancy in Women with and without Iron Supplementation

The aim was to evaluate relationships between iron status markers (haemoglobin, erythrocyte indices, serum iron, serum transferrin, serum transferrin saturation, serum ferritin) in normal pregnancy. Iron status markers were measured at 4-week-intervals during pregnancy and postpartum in 120 healthy women; 62 had daily treatment with tablets containing 66 mg ferrous iron, 58 were treated with placebo. Placebo-treated: Ferritin displayed positive correlations with transferrin saturation during 2nd and 3rd trimester. There were positive correlations between ferritin, erythrocyte MCV and MCH during 2nd and 3rd trimester and postpartum. Prior to delivery and postpartum, ferritin demonstrated positive correlations with haemoglobin. Transferrin saturation showed positive correlations with MCV, MCH and MCHC during 2nd and 3rd trimester and postpartum. Transferrin saturation displayed positive correlations with haemoglobin prior to delivery and postpartum. Iron-treated: In general, there were no correlations between iron status markers. Positive correlations appeared postpartum between ferritin, transferrin saturation and MCHC but not with haemoglobin. Transferrin saturation showed a positive correlation with MCH postpartum, but not with haemoglobin. Conclusion: The patterns of relationships in placebo-treated women were consistent with iron deficient erythropoiesis.     

Serum soluble transferrin receptor in the diagnosis of iron deficiency in chronic liver disease.

Fifty-one consecutive patients with chronic liver disease (CLD) underwent investigations of their iron status (full blood count, serum iron [Fe], total iron binding capacity [TIBC], transferrin saturation [TS], serum ferritin and serum soluble transferrin receptor [sTfR] level). Twenty-six patients were anaemic; 12 patients had iron deficiency, and 10 had iron deficiency anaemia (IDA). The median (range) sTfR in the IDA patients was 16.6 (11.2-24.8) mg/l. compared with 6.6 mg/l (11.2-24.8) in the 16 patients with anaemia due to other causes (P = 0.01). The sensitivity of sTfR for diagnosing iron deficiency in CLD was 91.6% (100% if only anaemic patients are included) and the specificity was 84.6%. Patients with haemolysis and recent blood loss may have falsely elevated sTfR levels. The results suggest that the sTfR is as useful as serum ferritin in identifying a potentially treatable cause of anaemia in CLD.     

Causes of microcytic anaemia and evaluation of conventional laboratory parameters in the differentiation of erythrocytic microcytosis in blood donors candidates*

ABSTRACT

Context and Objective: Microcytic anaemia results from defective synthesis of haemoglobin in the erythroid precursors, causing a reduction in its mean corpuscular volume (MCV). The most common causes of microcytosis, without the increase in HbA₂ levels, are iron deficiency anaemia (IDA) and α-thalassemia. The aim of this study was to identify the causes of microcytic anaemia and evaluate the haematological parameters from blood donors deemed ineligible (due to the low haematocrit level) that would differentiate the IDA and α-thal, whether isolated or in association.

Methods: Genomic DNA was submitted to the polymerase chain reaction multiplex for the diagnosis of the most common allele deletions of α-thal and erythrogram and in order to verify haematological parameters. Iron deficiency (ID) was determined through the measurement of serum ferritin.

Results: Of the 204 samples, 82 (40.2%) were identified with ID, 24 (17.8%) with α-thal and 10 (4.9%) with ID associated with α-thal. In the α-thal with ID group haemoglobin (Hb), MCV, mean corpuscular Hb concentration (MCHC) and mean corpuscular Hb (MCH) values were significantly lower compared to the isolated α-thal. In the group with ID Hb, MCV, MCHC and MCH values were significantly lower compared to those with isolated α-thal. The α-thal with ID group, showed Hb, MCV, MCHC and MCH significantly reduced when compared to those with IDA.

Conclusions: This study showed that the values of haematological parameters, especially haematocrit, Hb, MCV, MCH, MCHC and red blood cell distribution width (RDW), are lower in patients with IDA, especially when associated with α-thal and therefore it may be useful to discriminate between the different types of microcytic anaemia.     

The differentiation of anaemia in rheumatoid arthritis: parameters of iron-deficiency in an Indian rheumatoid arthritis population

Iron deficiency anaemia (IDA) is common in Indian patients with rheumatoid arthritis (RA). We evaluated red blood cell indices, serum iron related and bone marrow iron stores measurements in diagnosing iron deficiency in patients with RA. Fifty consecutive anaemic patients with RA had their complete blood counts, red cell indices, serum iron, serum ferritin and serum total iron binding capacity (TIBC) measured and underwent posterior iliac crest bone marrow aspiration. Fixed smears were stained for iron with Perl’s Prussian blue and patients who had no (grade 0) or minimal stainable iron (grade I) were regarded as iron deficient and rest iron replete (grade II–IV) and hence as having anaemia of chronic disease (ACD). To determine diagnostic power of tests used for diagnosing iron deficiency in addition to positive likelihood ratio, sensitivity, specificity and negative predictive values; receiver operating characteristics (ROC) curves were plotted and areas under the receiver-operating curves were compared. Eighteen patients (36%) had IDA and 32 (64%) had ACD. Correlation between the bone marrow iron stores and serum ferritin was poor in the IDA group (r = −0.09, P = 0.57) and significant in the ACD group (r = 0.79, P < 0.0001). Areas under the ROC curves for mean corpuscular haemoglobin (MCV), serum iron, TIBC and mean corpuscular haemoglobin concentration (MCHC) were relatively low (0.52, 0.71, 0.75 and 0.77, respectively) and these tests had low positive likelihood ratios (1.08, 2.13, 4.62 and 1.5, respectively). Both area under ROC curve [0.98, 95% confidence interval (0.94, 0.99)] and negative predictive value (97%) were highest when cut off serum ferritin was <82 μg/l. In patients with RA serum iron, TIBC, MCV and MCHC have limited value in diagnosing iron deficiency. In this study compared to American and European studies a much higher cut off value of serum ferritin had most diagnostic power for detecting iron deficiency. Bone marrow iron stores measurements appears to be the most reliable method for diagnosing IDA however, it needs to be taken in conjunction with other laboratory findings and the clinical scenario.     

ANAEMIA OF CHRONIC DISEASE: DIAGNOSTIC SIGNIFICANCE OF ERYTHROCYTE AND SEROLOGICAL PARAMETERS IN IRON DEFICIENT RHUEMATIOD ARTHRITIS PATEINTS

Erythrocyte and serological parameters were assessed in 44 anaemicrheumatoid arthritis (RA) patients to detect irondeficiencyas assessed by stainable bone marrow iron. The anaemia was normochromic normocytic in 60% and hypochromicnormocytic in 30% of those with anaemia of chronic disease (ACD). Iron deficiency was present in 55%and the anaemia was hypochromicmicrocytic in 54% and hypochromic normocytic or normochromicnormocytic in 21%. Iron absorption was found to be higher iniron deficient patients. In ACD patients, iron absorption correlatedinversely with ESR and CRP. For the detection of iron deficiency among RA patients withACD, the MCV showed the highest specificity (90%) and predictivevalue (87%). Serum ferritin was the most sensitive (82%) andvalid (86%) test. Combination of MCV, ferritin and transferrinresulted in 100% validity. It was concluded that iron deficiency can be detected accuratelywithout bone marrow aspiration using combinations of blood parameter. KEY WORDS: Iron deficiency, Diagnosis, Serum ferritin, Erythrocyte ferritin, Iron absorption, MCV, Transferrin     

Iron deficiency anaemia in hospitalised patients: value of various laboratory parameters. Differentiation between IDA and ACD.

BACKGROUND: for the diagnostic evaluation of microcytic or normocytic anaemia in a heterogeneous group of patients, the value of newer parameters, such as zinc protoporphyrin (ZPP), plasma transferrin receptor (PtrfR) and PtrfR/ferritin ratio is not clear. We have performed a prospective study to determine the predictive value of these parameters and ferritin, for diagnosing iron deficiency anaemia (IDA). METHODS: sixty-two patients with Hb<8.2 (men) or <7.0 (women) and mean cell volume (MCV)<96 fl were included. Exclusion criteria were: known haematological disease, pregnancy, bone marrow suppression or iron therapy within the previous 7 days. Bone marrow examination was used as a golden standard to discriminate between IDA and non-IDA. RESULTS: twenty-four patients had depleted iron stores. We found that the reticulocyte response on iron supplementation correlated well with the iron-status of the bone marrow. Univariate analysis showed that ferritin, PtrfR/ferritin ratio, ZPP and PtrfR have significant predictive values for differentiating IDA from non-IDA. Interestingly, multivariate analysis revealed that ferritin was the only significant, independent predictor of IDA, with a cut-off point of 32 microg/l (sensitivity 79.2%, specificity 96.9%). CONCLUSIONS: the low sensitivity and specificity of ZPP, PtrfR and PtrfR/ferritin ratio render them insufficient to be used as a single 'best' test for the identification IDA in a non-selected group of anaemic patients and do not even add to the prediction if the value of ferritin is known.     

ORIGINAL ARTICLE: RET-Y and RBC-Y in the diagnosis of iron deficiency associated with anaemia of inflammation

We evaluated the usefulness of RET-Y and RBC-Y in distinguishing functional iron deficiency from iron-deficiency anaemia (IDA) in patients with anaemia of inflammation (AI). Sixty healthy blood donors constituted the control group. We studied RET-Y and RBC-Y in 115 patients with hypochromic/microcytic anaemia. Of these 42 patients had uncomplicated IDA and 73 had AI. The AI patients were further subdivided into AI with IDA and AI with functional IDA based on soluble transferrin receptor (sTfR) levels. The mean RBC-Y and RET-Y values in iron-deficient patients were 122.4 and 119.8, respectively, which were significantly lower than the control (P < 0.001). The mean level of RET-Y in patients with AI associated with IDA was 149.3 and this level in AI patients with functional iron deficiency was 147.4. RET-Y levels in both subgroups of AI patients were significantly lower than control but no significant difference was observed between the two subgroups. Similar findings were observed for RBC-Y. Receiver operating characteristic analysis also showed lower specificity for RBC-Y and RET-Y compared with that of sTfR and its log ferritin ratio (F-index). RET-Y and RBC-Y are useful in the diagnosis of simple IDA but have limited utility in the diagnosis of IDA with AI.     

Prepartum anaemia: prevention and treatment

This review focuses on the occurrence, prevention and treatment of anaemia during pregnancy in Western societies. Iron deficiency anaemia (IDA) is the most prevalent deficiency disorder and the most frequent form of anaemia in pregnant women. Minor causes of anaemia are folate and vitamin B₁₂ deficiency, haemoglobinopathy and haemolytic anaemia. Anaemia is defined as haemoglobin of <110 g/L in the first and third trimester and <105 g/L in the second trimester. The diagnosis relies on haemoglobin, a full blood count and plasma ferritin, which can be supported by plasma transferrin saturation and serum soluble transferrin receptor. Among fertile, non-pregnant women, ∼40% have ferritin of ≤30 μg/L, i.e. small or absent iron reserves and therefore an unfavourable iron status with respect to upcoming pregnancy. The prevalence of prepartum anaemia in the third trimester ranges 14–52% in women taking placebo and 0–25% in women taking iron supplements, dependent on the doses of iron. In studies incorporating serum ferritin, the frequency of IDA in placebo-treated women ranges 12–17% and in iron-supplemented women 0–3%. Requirements for absorbed iron increase during pregnancy from 0.8 mg/day in the first trimester to 7.5 mg/day in the third trimester, on the average ∼4.4 mg/day, and dietary measures are inadequate to reduce the frequency of prepartum IDA. However, IDA is efficiently prevented by oral iron supplements in doses of 30–40 mg ferrous iron taken between meals from early pregnancy to delivery. Treatment of IDA should aim at replenishing body iron deficits by oral and/or intravenous administration of iron. In women with slight to moderate IDA, i.e. haemoglobin of 90–105 g/L, treatment with oral ferrous iron of ∼100 mg/day between meals is the therapeutic option in the first and second trimester; haemoglobin should be checked after 2 weeks and provided an increase of ≥10 g/L, oral iron therapy has proved effective and should continue. Treatment with intravenous iron is superior to oral iron with respect to the haematological response. Intravenous iron is considered safe in the second and third trimester, while there is little experience in the first trimester. Intravenous iron of 600–1,200 mg should be considered: (1) as second option if oral iron fails to increase haemoglobin within 2 weeks; (2) as first option at profound IDA, i.e. haemoglobin of <90 g/L in any trimester beyond 14 weeks gestation; and (3) as first option for IDA in third trimester. Profound IDA has serious consequences for both woman and foetus and requires prompt intervention with intravenous iron. This is especially important for the safety of women who for various reasons oppose blood transfusions.     

Serum ferritin as indicator of iron responsive anaemia in patients with rheumatoid arthritis.

In order to test the hypothesis that serum ferritin below 60 micrograms/l is a good indicator of iron deficiency in patients with rheumatoid arthritis peroral iron was given to 67 patients with active rheumatoid arthritis over a three month period. A rise in haemoglobin concentration was taken as evidence of iron responsive anaemia. In anaemic patients serum ferritin below 60 micrograms/l was a good indicator of iron responsive anaemia, with a predictive value of 83%. Although high plasma transferrin and low mean cell volume showed similar predictive values, more patients with iron deficiency anaemia could be diagnosed by serum ferritin measurements than by other conventional blood tests. In contrast, the predictive value of serum ferritin above 60 micrograms/l was low (50%). The test was of no predictive value in non-anaemic patients. In patients with anaemia and active rheumatoid arthritis serum ferritin is the best blood test currently available for the prediction of iron responsive anaemia.     

Effects of psychological stress on serum iron and erythropoiesis

There are about one billion patients with iron deficiency anaemia all over the world. Recently, researchers have reported successively that stress can cause decrease of serum iron, in consistent with our studies showing that heat exposure and acceleration stress led to significant decrease of serum iron in rats. However, so far whether pure psychological stress can cause decrease of serum iron and consequently affect erythropoiesis has not been reported. To study the characteristic effects of psychological stress on serum iron and erythropoiesis, and to establish an useful experimental basis for further study involving how sufficient intake of dietary iron causes decrease of serum iron and the consequent effects on physiological function of the human body. Psycological stress was adminstered to 20 rats with Communication Box system. On the 7th and 14th day after administration, 10 rats were executed, respectively, and the rat blood and femoral bone marrow were collected for analysis of serum iron (SI), serum ferritin (SF), serum transferrin receptor (sTfR), haemoglobin (Hb), red blood cell count (RBC), RBC distribution width (RDW), mean corpuscular volume (MCV), serum erythropoietin (EPO) and bone marrow iron. Experimental data were statistically analysed with SPSS 11.0. For rats analysed on the 7th and 14th day in psychological stress group, (1) femoral bone marrow iron was significantly decreased; (2) serum iron was decreased by 28.6% (P < 0.01) and 27.5% (P < 0.01); (3) Hb was decreased by 10.0% (P < 0.01) and 12.8% (P < 0.01), RBC count was decreased by 5.1% (P < 0.05) and 9.8% (P < 0.01), MCV was decreased by 1.7% (P < 0.05) and 7.3% (P < 0.01), RDW was increased by 10.7 and 22.5%; (4) serum ferritin, transferrin receptor and EPO showed no significant changes in comparison with controls after 7-day administration, but serum ferritin and EPO were decreased by 23.8 and 12.3% while transferrin receptor increased by 31.5% after 14-day administration. For rats receiving different period of pure psychological stress: (1) serum iron and bone marrow iron showed significant decrease compared with the controls; (2) erythropoiesis was significantly inhibited; however, (3) how psychological stress affects serum iron and erythropoiesis need to be further investigated.     

Body iron and individual iron prophylaxis in pregnancy—should the iron dose be adjusted according to serum ferritin?

This study aims to evaluate iron prophylaxis in pregnant women from the individual aspect, i.e. according to serum ferritin levels at the beginning of pregnancy, and to assess which dose of iron would be adequate to prevent iron deficiency (ID) and iron deficiency anaemia (IDA) during pregnancy and postpartum. A randomised, double-blind study comprising 301 healthy Danish pregnant women allocated into four groups taking ferrous iron (as fumarate) in doses of 20 mg (n=74), 40 mg (n=76), 60 mg (n=77) and 80 mg (n=75) from 18 weeks gestation (inclusion) to 8 weeks postpartum. Iron status markers [serum ferritin, serum soluble transferrin receptor (sTfR), haemoglobin] were recorded at 18, 32 and 39 weeks gestation and 8 weeks postpartum. Body iron was calculated using the serum sTfR/serum ferritin ratio. ID was defined by serum ferritin <12 μg/l in pregnancy and <15 μg/l postpartum; IDA as serum ferritin <12 μg/l and haemoglobin <5th percentile in iron-replete pregnant women. Women in the iron supplement groups were stratified according to serum ferritin levels at inclusion; 50.7% had ferritin ≤30 μg/l, 37.7% ferritin 30–70 μg/l and 11.6% ferritin >70 μg/l. At 32 weeks, women with ferritin ≤30 μg/l had an ID frequency of: 20-mg group 54.1%, 40 mg 29.7%, 60 mg 24.4%, 80 mg 20.6% (p<0.001); women with ferritin >30 μg/l had an ID frequency of: 20-mg group 20.0%, 40 mg 13.9%, 60 mg 5.7%, 80 mg 5.1% (p<0.001). Women with ferritin >70 μg/l had no ID. Postpartum, ID was found in 4.7% in 20-mg group, 2.9% in group 40 mg and 0% in group 60 and 80 mg. IDA: At 32 weeks, women with ferritin ≤30 μg/l had an IDA frequency of: 20-mg group 2.7%, 40 mg 2.7%, 60 and 80 mg 0%; none of the women with ferritin >30 μg/l displayed IDA. Body iron at 18 weeks was 10.4 mg/kg, similar in the four iron groups. Later in pregnancy body iron declined significantly, being lower the 20 mg group, and similar in the 40, 60 and 80-mg groups. Postpartum body iron rose to inclusion levels being 9.3 mg/kg in the 20-mg group and 10.5 mg/kg in the 40-, 60- and 80-mg groups. This study gives an estimate of iron dosage in individual iron prophylaxis adjusted to serum ferritin levels in early pregnancy. In the prevention of ID, we suggest 80–100 mg ferrous iron/day to women having ferritin ≤30 μg/l and 40 mg ferrous iron/day to women having ferritin 31–70 μg/l. In the prevention of IDA, we suggest 40 mg ferrous iron/day to women having ferritin ≤70 μg/l. Women with ferritin >70 μg/l have no need for iron supplement.     

Haematological effects of the C282Y HFE mutation in homozygous and heterozygous states among subjects of northern and southern European ancestry

High frequencies of the C282Y and H63D mutations of the HFE gene occur in European populations, even though homozygous and compound heterozygous states are associated with hereditary haemochromatosis, which is a disease that decreases fitness. This suggests that heterozygotes may possess a selective advantage. HFE mutations increase iron absorption in patients with haemochromatosis, and the mean transferrin saturations and ferritin levels are mildly increased in heterozygotes, suggesting that HFE mutations may protect against iron depletion and iron deficiency anaemia. In this study of 23,681 Caucasian adults, mean transferrin saturation, serum ferritin and haemoglobin levels were significantly higher in subjects carrying HFE mutations compared with wild types. Analysed by ethnicity, mean haemoglobin and mean erythrocyte volume (MCV) were significantly lower in those with a southern versus northern European ancestry. C282Y mutation carriers had an increased mean haemoglobin level in both ethnic groups. Prevalence of non-anaemic iron deficiency was significantly lower among female carriers of the C282Y mutation compared with HFE wild types. However, prevalence of frank iron deficiency anaemia did not differ significantly among genotypes. Quantile:quantile plots showed a small but significant upward shift in the mid-range of the haemoglobin distribution among C282Y mutation carriers that was consistent with an increased mean haemoglobin level without significant changes in the anaemic range.     

Factor V Leiden mutation carriership and venous thromboembolism in polycythemia vera and essential thrombocythemia

The aim of the present study is to evaluate in an elderly hospitalized population the diagnostic value of the serum transferrin receptor (sTfR) in distinguishing IDA (iron deficiency anemia) from ACD (anemia of chronic disease) as compared to conventional laboratory tests of iron metabolism, especially serum ferritin. In a prospective study, 34 patients with IDA and 38 patients with ACD (a chronic disorder in 23 and an acute infection in 15) were evaluated using iron status tests including serum transferrin receptor assay. The iron stores were assessed by bone marrow examination. sTfR levels were elevated (>28.1 nmol/L) in 68% of the IDA patients but also in 43% of the patients with ACD-chronic inflammation and 33% with ACD-acute infection. Serum ferritin was the best test to differentiate IDA from ACD patients. We conclude that serum ferritin is a more sensitive and specific parameter than the sTfR assay to predict the bone marrow iron status in an elderly anemic population.     

IS SERUM TRANSFERRIN RECEPTOR USEFUL FOR DETECTING IRON-DEFICIENCY IN ANAEMIC PATIENTS WITH CHRONIC INFLAMMATORY DISEASES?

We investigated whether determination of serum transferrin receptor(TfR) is useful for detecting iron-deficiency in patients withchronic inflammatory diseases and for differentiating betweeniron-deficiency anaemia and anaemia of inflammation. Using animmunofluorometric assay, serum TfR was measured in 34 anaemicpatients Of these patients, 23 had a chronic rheumatic disease,13 with both inflammation and iron-deficiency and 10 with anaemiaof inflammation only; the other 11 patients had iron-deficiencyanaemia and no evidence of inflammation. Serum TfR concentrationswere lower in patients with anaemia of inflammation (2.6 ±0.2 mg/l, mean ± S.E.M.) than in patients with iron-deficiencyanaemia (6.7 ± 1.1 mg/l, P<0.01) or those with bothinflammation and iron deficiency (5.8 ± 1.0 mg/l, P<0.01).Among patients with inflammatory disease, correlations betweenTfR and ferritin concentrations (r = –0.62, Pc0.05) andTfR and erythropoietin concentrations (r = 0.69, P<0.001)were observed in iron-deficient subjects only. TfR, though notsuperior to serum ferritin, can help to distinguish betweenanaemia of inflammation and iron-deficiency anaemia and to identifyiron-deficiency in subjects with chronic inflammation. KEY WORDS: Transferrin receptor, Anaemia, Iron-deficiency, Rheumatoid arthritis     

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.     

Diagnosis and management of iron-deficiency anaemia

Anaemia is typically the first clue to iron deficiency, but an isolated haemoglobin measurement has both low specificity and low sensitivity. The latter can be improved by including measures of iron-deficient erythropoiesis such as the transferrin iron saturation, mean corpuscular haemoglobin concentration, erythrocyte zinc protoporphyrin, percentage of hypochromic erythrocytes or reticulocyte haemoglobin concentration. However, the changes in these measurements with iron deficiency are indistinguishable from those seen in patients with the anaemia of chronic disease. The optimal diagnostic approach is to measure the serum ferritin as an index of iron stores and the serum transferrin receptor as a index of tissue iron deficiency. The treatment of iron deficiency should always be initiated with oral iron. When this fails because of large blood losses, iron malabsorption, or intolerance to oral iron, parenteral iron can be given using iron dextran, iron gluconate or iron sucrose.     

Iron status in pregnant women: which measurements are valid?

Anaemia in pregnancy in developing countries continues to be a public health problem of significant proportion. At least 50% of the anaemia has been blamed on iron deficiency. In populations where chronic inflammation and iron deficiency anaemia coexist, the criteria to accurately define iron status are not always clear. Similarly, in pregnancy, with marked physiological changes, cut-off points for biochemical parameters need to be re-examined. In this study we examined the diagnostic accuracy of iron parameters including mean cellular volume (MCV), serum iron, transferrin, total iron binding capacity (TIBC) and its saturation, zinc protoporphyrin (ZPP), ferritin and serum transferrin receptor (TfR) for the assessment of iron status in a population of anaemic pregnant women in Malawi. Stained bone marrow aspirates were used as the standard for comparison.
Results show that for the purpose of screening, serum ferritin is the best single indicator of storage iron provided a cut-off point of 30 μg/l is used. A number of other commonly used parameters of iron status were shown to have limited diagnostic accuracy. Logistic regression was used to obtain mathematical models for the prediction of bone marrow iron status using a combination of available parameters.