Red blood cell microcytosis and hypochromia in the differential diagnosis of iron deficiency and beta-thalassaemia trait

Iron deficiency anaemia (IDA) and beta-thalassaemia are the most common causes of microcytic anaemia. Some indices have been defined to quickly discriminate this diseases based on red cell parameters obtained from automated blood cell analyzers, and can be effective for use as a preliminary screening tool to allow the reflex HbA(2) analysis, when a proper cut-off is chosen. Advia 2120 (Siemens Medical Solutions Diagnostics) directly measures volume and haemoglobin concentration of individual red cells, and quantifies the percentage of microcytic, normocytic, macrocytic, hypochromic, normochromic and hyperchromic red cells. Because of the inverse behaviour of the % microcytic and % hypochromic red cells in beta-thalassaemia trait and in IDA the ratio between these two values was computed and its discriminant efficiency assessed. The aim of the study was to assess the predictive value of the new index % microcytic/% hypochromic ratio in the differential diagnosis of beta-thalassaemia compared with Mentzer index, currently used in our Laboratory. Sensitivity, specificity and total efficiency of both indices were calculated for a set of 110 IDA patients and 150 beta-thalassaemia carriers. Discriminant efficiency was similar for both indices.     

Reticulocytosis, hypochromia, and microcytosis: an unusual presentation of the preleukemic syndrome

Two patients exhibiting a highly unusual preleukemic syndrome with marked reticulocytosis, hypochromia, and microcytosis are reported. This red cell phenotype has been investigated by means of HbF, HbA2, and i-antigen activity dosages, immunofluorescence labeling of F cells, reticulocyte survival, globin chain synthesis, and electron microscopy study. The marked reticulocytosis is explained by a delayed disappearance of the reticulum. Serum iron is normal, and a thalassemic syndrome is excluded because of a balanced alpha/non-alpha globin chain synthesis. Electron microscopy studies are consistent with a defect in iron uptake by erythroid cells. All the hematologic data and investigations are similar to those observed for the Belgrade laboratory rat. It is hypothesized that the low expression of HbF and i- Ag associated with microcytosis are related to a prolongation of erythroid maturation as reflected by abnormal reticulocyte survival.     

Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2)

Iron regulatory protein 2 (IRP2)-deficient mice have been reported to suffer from late-onset neurodegeneration by an unknown mechanism. We report that young adult Irp2-/- mice display signs of iron mismanagement within the central iron recycling pathway in the mammalian body, the liver-bone marrow-spleen axis, with altered body iron distribution and compromised hematopoiesis. In comparison with wild-type littermates, Irp2-/- mice are mildly microcytic with reduced serum hemoglobin levels and hematocrit. Serum iron and transferrin saturation are unchanged, and hence microcytosis is not due to an overt decrease in systemic iron availability. The liver and duodenum are iron loaded, while the spleen is iron deficient, associated with a reduced expression of the iron exporter ferroportin. A reduction in transferrin receptor 1 (TfR1) mRNA levels in the bone marrow of Irp2-/- mice can plausibly explain the microcytosis by an intrinsic defect in erythropoiesis due to a failure to adequately protect TfR1 mRNA against degradation. This study links a classic regulator of cellular iron metabolism to systemic iron homeostasis and erythropoietic TfR1 expression. Furthermore, this work uncovers aspects of mammalian iron metabolism that can or cannot be compensated for by the expression of IRP1.     

Prevalence of gastrointestinal malignancy in iron deficiency without anaemia: A systematic review and meta-analysis

BackgroundIron deficiency anaemia is associated with gastrointestinal (GI) malignancy and is an indication for GI investigations. However, the relevance of iron deficiency without anaemia (IDWA) and the underlying risks of GI malignancy are uncertain. Therefore, the aim of this study was to estimate the prevalence of GI malignancy in patients with IDWA overall and in clinically relevant subgroups.MethodsWe searched MEDLINE and EMBASE for studies that reported on the prevalence or risk of GI malignancy in patients with confirmed IDWA. We performed a random effects meta-analysis of proportions and assessed statistical heterogeneity using the I² statistic.ResultsA total of 1923 citations were screened and 5 studies (4 retrospective cohorts, 1 prospective cohort) comprising 3329 participants with IDWA were included in the meta-analysis. Overall pooled random-effects estimates for prevalence of GI malignancy in those with IDWA were low (0.38%, 95% CI 0.00%–1.84%, I2 = 87.7%). Older patients (2.58%, 95% CI 0.00%–8.77%); non-screening populations (2.45%, 95% CI 0.16%–6.39%) and men and post-menopausal women (0.90%, 95% CI 0.11%–3.23%) with IDWA were at increased risk of GI malignancy compared to younger patients (0.00%, 95% CI 0.00%–0.21%); screened populations (0.24%, 95% CI 0.00%–1.10%) and pre-menopausal women (0.00%, 95% CI 0.00%–1.05%).ConclusionOverall, IDWA is associated with a low risk of GI malignancy. Older patients and non-screening populations are at elevated risk and require GI investigations. Those not in these subgroups have a lower risk of GI malignancy and may wish to be monitored following discussion of the risk and potential benefits of GI investigations.     

Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

Objectives: Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron.

Materials and methods: A retrospective cohort study was designed involving children with inflammatory bowel disease followed in that unit between January 2001 and April 2016. Laboratory results were collected at the moment of diagnosis, after one-year follow-up and prior each IV iron administration performed during the study period. Anemia was defined according to World Health Organization criteria and the iron deficiency was defined using recent guidelines.

Results: Were studied 69 patients 71% had CD and 29% UC. 50.7% were female. Mean patient age at diagnosis was 13.3 years (range 1--17 years). Prevalence of ID and IDA at diagnosis was 76.8% and 43.5%, respectively. After one year follow-up, those values decreased to 68.1% (p?=?.182) and 21.7% (p?=?.002), respectively. Hemoglobin significantly increased (p?<?.001). Intravenous iron was administered to 92.8% of patients. No adverse reactions were reported.

Conclusions: Intravenous iron is the first line in the treatment of Iron deficiency anemia in Inflammatory Bowel disease and it is safe and effective. Persistent anemia and iron deficiency are common.     

Prevalence of iron deficiency in different subtypes of pulmonary hypertension

Objectives

Iron deficiency (ID) prevalence in Chinese patients suffering from pulmonary hypertension (PH) is unclear so far. This study aimed to investigate ID prevalence in different subtypes of PH and its relevant factors.

Prevalence of iron deficiency in a total joint surgery population

Background: Iron deficiency without anemia has been associated with decreases in functional work capacity and fatigue. The aim of this study was to determine the prevalence of iron deficiency without anemia in a preoperative cohort of orthopedic patients and to determine if iron deficiency is a condition which warrants inclusion into a prehabilitation program prior to surgery.

Methods: One hundred consecutive patients going through preoperative testing for total joint replacement were enrolled in the study. In addition to the standard preoperative complete blood count, a ferritin concentration was also measured before the patients had their surgeries performed. Iron deficiency was defined as a ferritin concentration <50. Patients were then followed for 30 days following their surgical procedure to determine if any complications ensued, or if red blood cell transfusions were required.

Results: The average age of the patients in this study was 65.2?±?11.8 years and there were 41/100 males. Overall, 16 patients had anemia of which 6 patients also had low ferritin levels. Twenty-two other patients had ferritin levels consistent with iron deficiency but were not anemic. There was no association between iron deficiency and length of stay, complications, and transfusion.

Discussion: No association was found between simple iron deficiency and any perioperative complications. Only a ferritin level was assessed so other measures of iron deficiency may have revealed a higher prevalence of iron deficiency. A study with a larger sample size is warranted in order to further understand iron deficiency in a preoperative setting.     

Prevalence and pathogenesis of iron deficiency in Japanese women (1981-1991)]

Iron deficiency anemia is the most prevalent among form of anemia in the world. In Japan, there is no overall report concerning prevalence and pathogenesis of iron deficiency. We estimated the prevalence of iron deficiency from the results of a survey of 3,015 Japanese women. The reference range for hemoglobin was derived from the average value of subjects with normal iron status (> or = 16% of transferrin saturation and > or = 12 ng/ml of serum ferritin). Using these reference standards, the prevalence of iron deficiency anemia, latent iron deficiency, storage iron deficiency, normal and others were 8.5%, 8.0%, 33.4%, 43.6% and 6.5%, respectively. The prevalence of iron deficiency anemia increased beginning in early lower teen girls, was highest in high teen-girls and, young women and decreased in elderly women. In elderly women, the cause of iron deficiency was often obvious associated with anemia of chronic disorders. The strategy for iron deficiency was discussed concerning iron fortification, mega-ingestion of vitamin C and low dose administration of iron tablets in the higher incidence group.     

A new α-thalassemia-2 deletion resulting in microcytosis and hypochromia and in vitro chain imbalance in the heterozygote

We have detected a novel α-thalassemia-2 with a large (18⁺ kb) deletion involving the α₁-and θ-globin genes and the 3′ hypervariable region sequence. Unexpectedly, the heterozygote had a mild anemia with a marked microcytosis and hypochromia, and an in vitro α/β chain synthesis ratio of 0.62-0.66. It is suggested that the deletion includes a sequence that is involved in the in cis regulation of the α₂-globin gene.     

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.     

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia.MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin < 100 μg/L and functional ID was defined as normal serum ferritin (100–300 μg/L) with low TSAT (<20%).ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89 ± 0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p = 0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb.ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.     

Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency.

Mucosal uptake, mucosal transfer, and retention of a physiological dose of ferrous iron were studied in women with active rheumatoid arthritis (RA): 19 with normal and 17 with depleted bone marrow iron stores. Control subjects were 26 normal women and 20 women with uncomplicated iron deficiency. Iron absorption was measured with 59Fe as a tracer and by whole body counting. Compared with controls, final iron retention was considerably decreased in both groups of patients with RA. Analysis of the two sequential steps of iron absorption showed that mucosal uptake was normal in iron replete patients with RA but was significantly lower in patients with RA with depleted iron stores compared with iron deficient controls. Mucosal transfer of iron was considerably decreased in patients with RA with normal iron stores. The impaired absorption of iron in patients with active RA may delay the correction of the haemoglobin concentration when anaemia of chronic disease is complicated by iron deficiency.