Pathogenesis Of Iron Deficiency Anemia Research Articles

Hematological manifestations of Helicobacter Pylori (literature review)

It is known that Helicobacter pylori to be a key factor in the etiology of various gastrointestinal diseases, ranging from chronic gastritis without clinical symptoms to peptic ulcer, autoimmune gastritis, adenocarcinoma and gastric MALT lymphoma. However, current research suggests that Helicobacter pylori may be associated with numerous extra-gastric diseases that lead to chronic local or systemic inflammation and the initiation of autoimmune reactions, including hematological ones. The article describes the role of Helicobacter pylori CagA in the pathogenesis of iron deficiency anemia, immune thrombocytopenic purpura and MALT lymphoma. Studies of the iron-deficiency anemia pathogenesis in infected H. pylori patients have shown a connection between the CagA oncoprotein and iron homeostasis. It was established that transferrin endocytosis is mediated and iron absorption increases. In the development of immune thrombocytopenic purpura, CagA leads to a systemic host immune response through mechanisms of molecular mimicry. In pathogenesis of MALT lymphoma, it is considered significant that after the transfer of CagA to B-cell lymphocytes, through the type 4 secretory system (T4SS), a phosphorylated CagA-SHP2 complex is formed by affecting endoplasmic reticulum kinases 1 and 2 (ERK1, ERK2), p38MAPK, BCL2 and NF -κB, as well as through inhibition of p53 accumulation or inhibition of the JAK-STAT signaling pathway, ultimately promoting lymphogenesis and immortalization of B-cell lymphocytes. So, it was established that the presence of CagA protein in the Helicobacter pylori strain is key to the development of inflammation and tumor transformation. The disclosure of these mechanisms is necessary for a more accurate understanding of some pathological processes caused by this bacterium, both in the stomach and outside it. This will help improve diagnosis, guide treatment and predict clinical prognosis. Keywords: hypomagnesaemia, blood pressure, diabetes mellitus.

Dynamic Thiol-Disulfide Homeostasis in Children with Newly Diagnosed Iron Deficiency Anemia

Objective: Iron is an element, which is found in the structure of antioxidant enzymes and has an important role in the inactivation of reactive oxygen species. Disruption of oxidant-antioxidant balance may be playing a role in the pathogenesis of iron deficiency anemia (IDA). Dynamic thiol-disulfide homeostasis (DTDH) and serum ischemia-modified albumin (IMA) levels are important indicators of pro-oxidant/antioxidant status. In this study, we aimed to evaluate DTDH parameters and serum IMA levels in children with newly diagnosed IDA, who did not receive iron therapy. Material and Methods: Fifty patients diagnosed with IDA and 33 healthy age- and sex-matched control patients were included in the study. DTDH parameters and IMA levels of the patients and control groups were measured. The same parameters were also compared in patients with Hb<7 g/dl (profound IDA) (n:14/50, 28%) and Hb≥7 g/dl (mild-moderate IDA) (n: 36/50, 72%) in the IDA group. The relationship between DTDH parameters in these groups were investigated. Results: Native thiol, total thiol, native thiol/total thiol levels, constituting antioxidant capacity indicators, were found to be significantly lower in IDA patients; while oxidant disulfide, disulfide/native thiol, disulfide/total thiol, and IMA levels were found to be statistically higher compared to those in the control group (p<0.050). When DTDH parameters and IMA levels were examined; there was a positive correlation between antioxidant parameters and a negative correlation between oxidative parameters with hemoglobin and ferritin levels (p<0.050). Also, oxidative parameters were found to be much higher in profound IDA group than in the group with Hb>7 g/dl (p<0.050). Conclusion: In this study, increase in serum disulfide and IMA levels with the decrease in serum native thiol and total thiol levels indicated oxidative stress in IDA patients before treatment, compared to the control group. Evaluation of these indicators in children is important in predicting the toxicity due to IDA.

Helicobacter pylori-Associated Iron Deficiency Anemia in Childhood and Adolescence-Pathogenesis and Clinical Management Strategy.

Many epidemiological studies and meta-analyses show that persistent Helicobacter pylori infection in the gastric mucosa can lead to iron deficiency or iron deficiency anemia (IDA), particularly in certain populations of children and adolescents. Moreover, it has been demonstrated that H. pylori infection can lead to and be closely associated with recurrent and/or refractory iron deficiency and IDA. However, the pathogenesis and specific risk factors leading to this clinical outcome in H. pylori-infected children remain poorly understood. In general, most of pediatric patients with H. pylori-associated IDA do not show evidence of overt blood loss due to gastrointestinal hemorrhagic lesions. In adult populations, H. pylori atrophic gastritis is reported to cause impaired iron absorption due to impaired gastric acid secretion, which, subsequently, results in IDA. However, significant gastric atrophy, and the resultant substantial reduction in gastric acid secretion, has not been shown in H. pylori-infected children. Recently, it has been hypothesized that competition between H. pylori and humans for iron availability in the upper gastrointestinal tract could lead to IDA. Many genes, including those encoding major outer membrane proteins (OMPs), are known to be involved in iron-uptake mechanisms in H. pylori. Recent studies have been published that describe H. pylori virulence factors, including specific OMP genes that may be associated with the pathogenesis of IDA. Daily iron demand substantively increases in children as they begin pubertal development starting with the associated growth spurt, and this important physiological mechanism may play a synergistic role for the microorganisms as a host pathogenetic factor of IDA. Like in the most recent pediatric guidelines, a test-and-treat strategy in H. pylori infection should be considered, especially for children and adolescents in whom IDA is recurrent or refractory to iron supplementation and other definitive causes have not been identified. This review will focus on providing the evidence that supports a clear biological plausibility for H. pylori infection and iron deficiency, as well as IDA.

The Resolution of Severe Iron-Deficiency Anemia After Successful Eradication of Helicobacter pylori in Teenagers.

In this case series, 7 H. pylori-infected patients with recurrent and/or refractory IDA (12-16 y old) received successful eradication therapy and were then followed for a median of 20 months (range, 9-76 mo) after oral iron supplementation therapy (1-4 mo) was discontinued. Five patients of our study cohort participated in rigorous sports activities. No visual appearance of ulcerations or erosions was found by esophagogastroduodenoscopy. In all patients studied, the gastric biopsies showed histological evidence of chronic gastritis without significant atrophy and intestinal metaplasia. Compared with the baseline (median values: hemoglobin, 6.3 g/dL; serum iron, 9 μg/dL; serum ferritin, 1.5 ng/mL), values of hemoglobin (P < 0.001), serum iron (P < 0.005), and ferritin (P < 0.001) significantly increased, on average, 2-3 months after eradication therapy and these iron indices were maintained at the same or higher levels at the endpoint of follow-up (median values: 14.2 g/dL, 102 μg/dL, and 29.3 ng/mL, respectively). No patient had recurrence of IDA at the time of final follow-up. H. pylori infection can be closely associated with recurrent or refractory IDA in teenage children. It is speculated that increased iron demands as a result of growth spurt in adolescents may play a synergistic role in combination with H. pylori in the pathogenesis of IDA.

PECULIARITIES OF OXIDATIVE STRESS IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION WITH IRON DEFICIENCY ANEMIA

The article presents changes in hemogram and oxidative stress in patients with acute myocardial infarction (AMI) on the background of iron deficiency anemia (IDA). Iron deficiency anemia is an additional factor that contributes to the deepening of myocardial ischemia and deepens the processes of peroxidation and damage to cardiomyocytes, which is an important factor in the unfavorable course, both acute period and recovery processes in myocardial necrosis. In order to study the indicators of the general analysis of blood and functional state of the antioxidant system in patients with acute myocardial infarction with IDA, 36 patients with AMI with IDA were examined, including 39% men and 61% women. The first group consisted of 10 patients with AMI without IDA, the second 26 patients with AMI and IDA of varying severity, the control group consisted of 30 healthy individuals. Hemogram parameters, glutathione system function, oxyproline, arginase and magnesium levels in the blood were determined. It has been established that women with mild and moderate anemia predominate among patients with acute myocardial infarction with concomitant iron deficiency anemia. Among men, half of the patients have severe anemia. In addition to a decrease in Hb levels, patients with ACS with IDA have the following laboratory signs of anemia: a tendency to increase the average concentration of hemoglobin in one erythrocyte, low serum iron levels and an increase in serum transferrin levels. In the presence of IDA in patients with ACS there are changes in the antioxidant system. Anemic syndrome in such patients is accompanied by increased concentrations of glutathione transferase and peroxidase, as well as decreased concentrations of oxyproline.&#x0D; Anemia can trigger oxidative stress, and an increase in OS may be associated with changes in cardiac function. Possible cardiovascular effects in patients with comorbid conditions should also be considered.&#x0D; Iron deficiency is the most prevalent micronutrient disorder globally. When severe, iron deficiency leads to anemia, which can be deleterious to cardiac function. Given the central role of iron and oxygen in cardiac biology, multiple pathways are expected to be altered in iron-deficiency anemia, and identifying these requires an unbiased approach.&#x0D; Oxidative stress is an imbalance between free radicals and antioxidant molecules that can play an important role in the pathogenesis of iron-deficiency anemia (IDA).&#x0D; Maintenance of the iron homeostasis is essential for metabolic and physiological processes. Iron plays a critical role in erythropoiesis, is incorporated into erythroblasts and reticulocytes, and has a crucial role in oxygen transport and oxygen storage. Moreover, iron is essential for cardiac and skeletal muscle metabolism, the synthesis and degradation of proteins, lipids, ribonucleic acids, and mitochondrial function.&#x0D; Research has now focused on non-traditional cardiovascular risk factors and the roles of iron and iron deficiency (ID) in patients with cardiovascular disease.&#x0D; The Iron required for immune response, hormonal balance, and plays an important role in regulating oxidative stress and aerobic metabolism. The myocardial tissue has a mainly aerobic cellular metabolism, which depends of mitochondria's Krebs cycle enzymes that need iron as an essential cofactor. In this regard, there is some evidence that myocardial iron deficiency is highly prevalent in HF and may play a role in the progression of the disease.

Role of hepcidin, altered iron metabolism and systemic inflammation in the pathogenesis of iron deficiency anemia, anemia of chronic disease, and iron refractory anemia in cirrhosis and ACLF.

Background and Aim: Anemia of Chronic Disease (ACD), iron deficiency anemia (IDA), vitamin B12/folate deficiency and hemolysis are causes of anemia in cirrhosis and acute-on-chronic liver failure (ACLF). Standard tests of iron metabolism like transferrin and ferritin are affected by inflammation, making assessment of iron therapy unclear. Diagnostic accuracy can be improved by soluble transferrin receptor (sTfR) or hepcidin levels, as novel markers.

Role of TMPRSS6 rs855791 (T>C) polymorphism in reproductive age women with iron deficiency anemia from Lahore, Pakistan.

Iron deficiency anemia (IDA) is the highest nutritional deficiency worldwide. It is a multifactorial disease, with a higher morbidity rate. TMPRSS6 polymorphisms importantly rs855791 is found to play an essential role in iron homeostasis in the human body. The rs855791 (T>C) polymorphism is highly associated with iron levels, and multiple blood parameters, leading to IDA. The role of TMPRSS6 rs855791 polymorphism and the significance of complete blood count (CBC) parameters in the pathogenesis of IDA is not yet studied in the Pakistani population. We enrolled 113 cases and 136 controls to conduct a case control study. Complete blood count (CBC) and iron parameters were analyzed for association studies. PCR-RFLP based genotyping was performed. The TMPRSS6 rs855791 (T>C) polymorphism is significantly associated with IDA pathogenesis as observed in the codominant model and recessive models (P<0.05, OR: 1.5 and 95% CI: 0.9, 2.6, P<0.05, OR: 0.5 and 95% CI: 0.2, 0.9 respectively). Elderly women among cases (30-49years) were found to be more susceptible to IDA (P<0.05, AOR: 2.1 and 95% CI: 1.0, 4.2). The most significant parameters associated with IDA were red blood cell count (RBC) and hematocrit (Hct%) (P<0.05, AOR: 16.5, 95% CI: 7.6, 35.9 and P<0.05, AOR: 10.1, 95% CI: 2.5, 41.6, respectively). TMPRSS6 polymorphism at rs855791 (T>C) is significantly associated with IDA susceptibility in reproductive age women in Pakistan. Age, RBC count and Hct% are found to play an important role in IDA pathogenesis in our study population.

The role of lipid peroxidation products in the development of iron deficiency anemia in cytomegalovirus infection in pregnant women of the first trimester

Aim. To establish the role of lipid peroxidation (LPO) products in the development of iron deficiency anemia in pregnant women of the first trimester during exacerbation of cytomegalovirus infection. Materials and methods . A prospective case-control study included 60 women in the first trimester of pregnancy (8-12 weeks), of which 35 were cytomegalovirus-positive with mild iron deficiency anemia (main group) and 25 - cytomegalovirus-seronegative (control group). Antibodies of IgM and IgG to CMV, low avid IgG (avidity index), and serum ferritin concentration were determined by enzyme-linked immunosorbent assay. In order to assess the intensity of LPO processes in blood serum spectrophoto-metric method was used to measure the levels of molecular products of oxidation: diene conjugates and active products of thiobarbituric acid. The concentration of arachidonic acid in blood serum was analyzed by means of the method of capillary gas-liquid chromatography. The concentration of total hemoglobin in red blood cells was measured by photometry. The study of iron metabolism included: evaluation of serum iron by spectrophotometric method, the total iron binding capacity of serum using commercial kits of the company “Lachema” (Czech Republic), transferrin saturation coefficient by means of calculation method. Results . Activation of LPO processes was noted in women of the main group, as evidenced by an increase in the concentration of diene conjugates by 1.54 times (p<0.001), active products of thiobarbituric acid by 2.4 times (p<0.001) and arachidonic acid by 1.3 times (p<0.001) compared with similar indicators of the control group. It has been found that hemoglobin levels were reduced by 1.2 times (p<0.001), serum iron and ferritin, respectively, by 1.4 (p<0.001) and 2 times (p<0.001), in the setting of an increase in the total iron binding capacity of serum while reducing the coefficient of iron saturation with transferrin. Conclusion . The data obtained indicate the important role of LPO products in the pathogenesis of iron deficiency anemia during exacerbation of cytomegalovirus infection in the first trimester of gestation.

Role of Oxidant/Antioxidant Status in the Pathogenesis of Iron-Deficiency Anemia: Case Study on Children of Qalyubiyya and Minoufiya Governorates, Egypt

Iron- deficiency anemia (IDA) is anemia due to insufficient iron. It is one of the major causes of morbidity and mortality worldwide affecting people of all ages in both developed and developing countries. The present study aims to investigate the role of oxidative/antioxidant status in the pathogenesis of IDA through a case study on children of Qalyubiyya and Minoufiya Governorates, Egypt. 119 with IDA and 150 healthy control, boys and girls, infants and young children, aged zero months to 6 years, were selected for the study from Rural Health Units and Maternity and Child Care Centers, Qalyubiyya and Minoufiya Governorates, Egypt. Based on hematological and biochemical analysis, the mean hemoglobin (Hb) level, mean corpuscular volume (MCV), reticulocyte hemoglobin content, serum iron and serum ferritin were significantly lower in infants and young children with IDA than healthy control. The opposite direction was observed for the red blood cell distribution width (RDW). The antioxidant defense system parameters including [enzymes (glutathione peroxidase, GSH-Px; glutathione reductase, GSH-Rd; superoxide dismutase, SOD and catalase, CAT) activities and none-enzymatic levels (glutathione, GSH and vitamins A, C and E)] of infants and young children with IDA were significantly (P≤0.05) lower. While the oxidative stress parameters thiobarbituric acid reactive substances, TBARS and nitric oxide, NO2 were significantly higher than the control group. In conclusion, oxidant/antioxidant status may play a role in the Pathogenesis of Iron-Deficiency Anemia.

The role of TMPRSS6 and HFE variants in iron deficiency anemia in celiac disease.

We investigated the role of HFE C282Y, H63D, and TMPRSS6 A736V variants in the pathogenesis of iron deficiency anemia (IDA) in celiac disease (CD) patients, at diagnosis and after 1year of gluten-free diet (GFD). Demographic and clinical features were prospectively recorded for all CD patients between 2013 and 2017. C282Y, H63D, and A736V variants were evaluated for CD patients and controls. Finally, 505 consecutive CD patients and 539 age-matched control subjects were enrolled. At diagnosis, 229 CD subjects had IDA (45.3%), with a subgroup of anemic patients (45.4%) presented persistent IDA at follow-up. C282Y allele frequency was significantly increased in CD compared with controls (1.1% vs 0.2%, P = .001), whereas H63D and A736V allele frequencies were similar among patients and controls (P = .92 and .84, respectively). At diagnosis, C282Y variant in anemic CD patients was significantly increased compared to nonanemic group (2% and 0.5%, P = .04). At follow-up, A736V was significantly increased in IDA persistent than in IDA not persistent (57.7% vs 35.2%, P < .0001). CD patients with H63D mutation showed higher Hb, MCV, serum iron, and ferritin levels than subjects without HFE mutations. Decreased hepcidin values were observed in anemic compared to nonanemic subjects at follow-up (1.22 ± 1.14 vs 2.08 ± 2.15, P < .001). This study suggests a protective role of HFE in IDA CD patients and confirms the role of TMPRSS6 in predicting oral iron response modulating hepcidin action on iron absorption. Iron supplementation therapeutic management in CD could depend on TMPRSS6 genotype that could predict persistent IDA despite iron supplementation and GFD.

Modern Treatment Strategy of Iron Deficient Anemia

Modern views of epidemiology, etiology and pathogenesis of iron deficiency anemia (IDA) are considered. This review deals with up-to-date methods of the laboratory diagnostics of IDA. Some ideas of iron methabolism in an organism and pathogenetic mechanisms of clinical and laboratory symptomps are briefly presented. The diagnostic value of laboratory methods for diagnosing IDA is interpreted. A conclusion is drawn about the integrated approach to the diagnostics of IDA diagnostics. Causes of low treatment efficiency are discussed and the ways to address this problem are proposed based on the published results of clinical research. Present article devoted to the steps for implementation unified clinical protocol of the primary, secondary (specialized) medical care “Iron deficiency” to the practical activities.

Prevalence of Factor V Leiden-G1691A and MTHFR-C677T Thrombosis Gene Modifier in Iron Deficiency Anemia: A Pathophysiological Effect in Indian Isolates.

Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR-RFLP method. Among the patients, 9 were heterozygous (G>A) and 2 were homozygous (A>A) carrier of FV Leiden; while 20 were heterozygous (C>T) and 3 were homozygous (T>T) for MTHFR polymorphism. None of the patient was identified with PT mutation. Patients with thrombosis gene marker had lower hemoglobin, mean corpuscular volume, mean corpuscular haemoglobin levels, and mean corpuscular hemoglobin concentration than patients without thrombosis gene marker. Serum ferritin was elevated in subject with the absence of thrombosis gene markers. Our data suggest a high impact of inherited hypercoagulability risk factors in the pathogenesis of IDA and its complications.

Helicobacter Pylori and Iron Deficiency Anemia in Children: Case Series and Review of Literature

Helicobacter pylori (H. pylori) infection has been described as a possible cause of refractory iron deficiency anemia (IDA) in children. Nevertheless, the relationship between H. pylori infection and IDA in children remains an area of controversy due to the contrasting data in literature. We report a case series of two children who presented with IDA refractory to iron treatment, which reversed only after eradication of H. pylori infection, supporting the causal role of this bacterium in pathogenesis of IDA. In both cases H. pylori presented a high antimicrobial resistance, raising the issue on the importance of considering geographical susceptibility of H. pylori strains when starting empirical treatment and the importance of performing antimicrobial susceptibility testings, in particular if standard empirical therapy fails. The present review gives a complete overview of the literature regarding the relationship between H. pylori and IDA in children, explains the possible pathogenetic mechanisms involved in H. pylori-related IDA and addresses the issue of the high antimicrobial resistance often encountered in H. pylori infection in children.

Positive Relationship Between a Polymorphism in Helicobacter pylori Neutrophil‐Activating Protein A Gene and Iron‐Deficiency Anemia

Numerous studies have suggested a link between iron-deficiency anemia (IDA) and Helicobacter pylori infection. Previously, we found that strains isolated from IDA patients showed higher levels of Fe ion uptake and Fe-ion-dependent rapid proliferation than those of strains derived from patients without IDA. Twenty-four H. pylori strains from IDA patients (IDA strains) and 25 strains from patients who had H. pylori gastritis without anemia (non-IDA strains) were examined. Their nucleotide sequences of napA, fur, and feoB, which contribute to Fe ion uptake, were determined. Numerous polymorphisms of the three genes were found in both strains. Frequency of neutrophil-activating protein A (NapA), which encoded by napA, with threonine at amino acid residue No. 70 (Thr70-type NapA) was significantly higher in IDA strains than in non-IDA strains. Strains with Thr70-type NapA showed significantly higher levels of Fe(3+) and Fe(2+) uptake than did strains with other types, Ser70-type of NapA, which is found in standard strains. Other significantly different occurrences of polymorphisms between IDA and non-IDA groups were not observed in these genes. The results suggest that H. pylori strains with Thr70-type NapA have enhanced Fe ion uptake ability and are associated with the pathogenesis of IDA.

Iron deficiency anemia and total antioxidant capacity.

I read the recent publication on evaluation of iron deficiency anemia via total antioxidant capacity with great interest [1]. It concluded that, “increased oxidative stress may play a role in the pathogenesis of iron deficiency anemia” and that ,“the automated assay is a reliable and easily applied method for measurement of serum total antioxidant capacity in iron deficiency anemia” [1]. There are some issues I want to address. First, based on the limited and imbalanced number of cases and controls in that study, the statistical acceptance is questionable. Second, there was no exclusion of important confounding conditions, especially hemoglobin disorders and thalassemias. Indeed, those conditions are associated with oxidative stress [2]. Finally, there wasn’t a complete assessment of the analytical (detection limit, interference, precision, accuracy, etc.) or diagnostic (sensitivity, specificity, predictive value, etc.) properties of the automated assay. Hence, it might not be appropriate to report that the assay is reliable.

Decreased erythrocyte catalase level in iron deficiency

Arslan et al.’s recent study provides an opportunity to discuss our earlier results from a 1964 study on early diagnosis only iron deficiency anemia and sideropenia [1,2]. Catalase is present in almost all cells, including red cells, and is known to be the most active enzyme involved in the destruction of hydrogen peroxide, which causes oxidative stress. In iron deficiency red cell catalase synthesis decreases before the hemoglobin level does. When its synthesis decreases in iron deficiency anemia and sideropenia, the level of oxidative stress-associated substances increases as a result. As such, the authors’ statement, “increased oxidative stress may play a role in the pathogenesis of iron deficiency anemia” should be amended with, “as increased oxidative stress occurs as a result of iron deficiency”.

Evaluation of oxidative status in iron deficiency anemia through total antioxidant capacity measured using an automated method.

Oxidative stress, an increase in oxidants and/or a decrease in antioxidant capacity, is one of the potential biochemical mechanisms involved in the pathogenesis of iron deficiency anemia. The objective of this study was to evaluate the oxidative status and to determine whether there is any relationship between oxidative status and the severity of anemia in patients with iron deficiency anemia using an automated method. Twenty-six subjects with iron deficiency anemia and 20 healthy controls were enrolled in the present study. Serum total antioxidant capacity, serum total peroxide level and oxidative stress index were determined in all study subjects. Serum total antioxidant capacity was significantly lower in patients with iron deficiency anemia than controls (p<0.05), while serum total peroxide level and oxidative stress index were significantly higher (both p<0.05). There was a significant correlation between hemoglobin level and serum total peroxide level, oxidative stress index and total antioxidant capacity (r=-0.504, p<0.05; r=-0.503, p<0.05; r=0.417, p<0.05, respectively). Increased oxidative stress may play a role in the pathogenesis of iron deficiency anemia. Supplementation of antioxidant vitamins in conjunction with iron replacement therapy may offer better responses and provide early resolution of symptoms related to iron deficiency anemia. The automated assay is a reliable and easily applied method for measurement of serum total antioxidant capacity in iron deficiency anemia.

Oxidative status in iron‐deficiency anemia

Oxidative stress is an imbalance between free radicals and antioxidant molecules that can play an important role in the pathogenesis of iron-deficiency anemia (IDA). The aim of this study was to investigate oxidative status in patients with IDA and alteration of oxidative status after iron treatment. Thirty-three female patients with IDA and 25 healthy controls were included in this study. Oxidant and total antioxidant capacity were determined using free oxygen radicals test and free oxygen radicals defence (Form CR 3000, Callegari, Parma, Italy). Catalase activity was measured by spectrophotometer using a commercially available kit (Bioxytech Catalase-520, OxisResearch, Portland, OR). Oxidant activity in patients with IDA was significantly higher than controls (P<0.05), while total antioxidant and catalase activity were significantly lower (P<0.05). After treatment, oxidant, antioxidant, and catalase activity reached the levels of the control group, and no significant differences were observed among groups (P>0.05). In conclusion, our data indicate that blood reactive oxygen species was lower and total antioxidant and catalase activity were higher after rather than before treatment in patients with IDA. The results of our study support the higher oxidative stress hypothesis in IDA; however, due to the limited number of cases included, more studies may be required to confirm the results.

A new nutrient polypeptide-Fe and its antioxidant ability

Polypeptide-Fe is the hemoglobin that is purified highly from animal blood. It is an active material obtained by connecting heme with a different-length peptide section after physical and chemical processing. Polypeptide-Fe is non-toxic to the human body, does not have the side effects, and namely has iron enhancement function. Nitroblue tetrazolium staining showed that it retained the superoxide radical scavenging activity of hemoglobin. Polypeptide-Fe achieves the elimination of free radical by degradations of the polypeptide connected to iron. Oxidative stress has been considered to play an important role in the pathogenesis of iron-deficiency anemia. The primary free radicals in most of biological system are the superoxide anion, hydrogen peroxide, and the hydroxyl free radical. We performed experiments to detect the clearance ability on these three free radicals and maleic dialdehyde by polypeptide-Fe. Results of the present study showed that polypeptide-Fe had strong antioxidant ability and it may provide some useful information relevant to an additional contribution to the treatment of iron-deficiency anemia in future.

Resolving the Riddle of Obscure Iron Deficiency Anemia.

Conventional endoscopic and radiographic methods fail to identify a source of gastrointestinal blood loss in about one third of males and post-menopausal females and in most women of reproductive age with iron deficiency anemia (IDA). Such patients are often referred for hematologic evaluation. In recent years there is increasing awareness of non-bleeding conditions with abnormal iron absorption as possible causes of unexplained IDA. Both H pylori gastritis and autoimmune atrophic gastritis are associated with impaired gastric acidity interfering with iron absorption. In a prospective study performed in a community hematology clinic, 300 consecutive IDA patients were screened for non-bleeding GI conditions including celiac disease (antiendomysial antibodies), autoimmune atrophic gastritis (hypergastrinemia with strongly positive antiparietal cell antibodies) and H pylori gastritis (IgG antibodies confirmed by urease breath test). Their mean age was 39±18 y, and 251 of 300 (84%) were women. A likely cause of IDA was identified in 93% of patients. As expected in a population of females of reproductive age, only 10% had a source of gastrointestinal bleeding identified. There were 13 new cases of adult celiac disease (4%). A history suggestive of menorrhagia was present in 32%. Autoimmune atrophic gastritis was documented in 77 IDA patients (26%) of whom 39 had coexistent H pylori infection. H pylori infection was the only positive finding in 57 patients (19%). To exclude the compounding effect of menstrual blood loss in evaluating the role of H pylori in the pathogenesis of IDA, we have focused on the 29 male IDA patients with negative gastrointestinal workup, poor initial response to oral iron treatment, and a high prevalence of H pylori infection (25 of 29). Following H pylori eradication, all patients achieved normal hemoglobin levels with follow-up periods ranging from 4 to 69 months (38±15 months mean± 1SD). This was accompanied by a significant decrease in H pylori IgG antibodies and serum gastrin. Sixteen patients discontinued iron treatment, maintaining normal hemoglobin and ferritin and may be considered cured. Remarkably, 4 of the 16 achieved normal hemoglobin without ever having received oral iron after H pylori eradication. To define the relation between IDA-associated autoimmune gastritis, and pernicious anemia, we studied 160 patients with autoimmune gastritis including 83 subjects presenting with IDA, 48 presenting with normocytic indices, and 29 with macrocytic anemia. Stratification by age cohorts of autoimmune gastritis from <20 to >60 y showed coexistent H pylori infection in 87.5% at age <20 y, 47% at 20–40 y, 37.5% at 41–60 y, but only 12.5% at age > 60y. With increasing age cohorts, there was a regular and progressive increase in MCV from 68±9 to 95±16 fl, serum gastrin from 349±247 to 800±627 u/mL, and a decrease in cobalamin from 392±179 to 108±65 pg/mL. Conclusions: The favorable long-term clinical results of H pylori eradication offer strong evidence for a cause-and-effect relation between H pylori and IDA. A proportion of H pylori patients will develop autoimmune gastritis. Our findings in autoimmune gastritis imply a disease presenting as IDA many years before the establishment of clinical cobalamin deficiency. It is likely caused by an autoimmune process triggered by antigenic mimicry between H pylori epitopes and major autoantigens of the gastric mucosa. Recognition of H pylori and autoimmune gastritis as common causes of obscure iron deficiency anemia should have a strong impact on the efficacy of diagnostic workup and management of unexplained, or refractory iron deficiency anemia.