Iron Deficiency Syndrome Research Articles

Importance of ferritin research in clinical practice

Serum ferritin (SF) is typically present in serum at concentrations directly related to iron (Fe) storage and is therefore traditionally used as an indicator of Fe levels in body tissues. Reducing its level is the “gold standard” for diagnosing widespread iron deficiency conditions. No less significant is hyperferritinemia — a nonspecific syndrome that occurs when Fe reserves are overloaded, a number of immunoinflammatory, infectious, oncological diseases, liver diseases, etc. In many pathological conditions, the level of SF determines the severity and prognosis of the disease. Ferritin concentrations greater than 1000 ng/mL, regardless of cause, have been shown to be associated with higher mortality. The reason for the increase in the level of SF in liver pathologies (cancer, hepatitis, cirrhosis) is associated with the process of its release from hepatocytes during their destruction. On the other hand, excessive synthesis and/or cellular secretion of ferritin occurs under the influence of various stimuli (cytokines, oxidative stress, hypoxia, oncogenes and growth factors). The interpretation of elevated ferritin values goes far beyond the role of an indicator of replenishment of Fe stores in tissues. Only 10% of cases of hyperferritinemia are associated with iron overload; in most patients, it is defined as the result of the acute phase and a reactive increase in ferritin levels against the background of any disease. The variety of symptoms of iron deficiency syndromes and hyperferritinemia is due to the involvement of many organs and systems, which requires a thorough examination (study of complaints, anamnesis, family and concomitant diseases, as well as the necessary laboratory and instrumental studies) to search for possible causes. Systemic Fe homeostasis must be closely monitored on a regular basis. It is required to comply with the conditions for blood sampling for SF. Reference values for SF concentrations vary depending on the analytical methods used and the population studied. Age and gender play an important role. Given the range of reference values, it is important for a particular patient to focus on the initial level of his ferritin, determined against the background of health and well-being during clinical observation.

A Role of Sodium-Glucose Co-Transporter 2 in Cardiorenal Anemia Iron Deficiency Syndrome.

Heart failure, renal dysfunction, anemia, and iron deficiency affect each other and form a vicious cycle, a condition referred to as cardiorenal anemia iron deficiency syndrome. The presence of diabetes further accelerates this vicious cycle. Surprisingly, simply inhibiting sodium-glucose co-transporter 2 (SGLT2), which is expressed almost exclusively in the proximal tubular epithelial cells of the kidney, not only increases glucose excretion into the urine and effectively controls blood glucose levels in diabetes but can also correct the vicious cycle of cardiorenal anemia iron deficiency syndrome. This review describes how SGLT2 is involved in energy metabolism regulation, hemodynamics (i.e., circulating blood volume and sympathetic nervous system activity), erythropoiesis, iron bioavailability, and inflammatory set points in diabetes, heart failure, and renal dysfunction.

Iron absorption stimulation by administration of soy protein hydrolysates containing bioactive peptides in rats

The prevalence of iron deficiency anemia in Indonesia is high. Most of the anemia is caused by iron deficiency syndrome due to inadequate iron intake and low bioavailability of iron sources. Some studies indicated that bioactive peptides from certain protein hydrolysates could support iron absorption. Our previous study showed that soy protein hydrolysates containing bioactive peptides indicated an iron-binding activity and could increase its solubility in water. Aim of this study was to investigate the effect of soy protein hydrolysates administration on iron serum levels in anemic Sprague Dawley rats. Anemia induction was performed by applying NaNO2 (0.5 mg/ml per 200 g body weight (BW) of rats per day for 14 days) orally. The experiment was carried out in a completely randomized design, consisting of six groups. The first group was the control normal group (N), without induction and the others were treatment groups that were induced with NaNO2 and supplemented with iron (0.3 mg/200 g BW), consisted of control group (CMC), control iron (Fe) group, iron and soy protein hydrolysate-1 (270 mg/200 g BW) (FeSH-1) group, iron and soy protein hydrolysate-2 (270 mg/200 g BW) (Fe-SH2) group and positive control iron vitamin C (0.24 mg/200 g BW) (Fe Vit. C) group. The result showed that Fe-SH2 treatment group had a better iron-binding capacity rather than other groups. This result suggests that soy protein hydrolysates could enhance iron absorption, which might be applied in human as a functional food to reduce anemia prevalence.

Iron absorption stimulation by administration of soy protein hydrolysates containing bioactive peptides in rats

The prevalence of iron deficiency anemia in Indonesia is high. Most of the anemia is caused by iron deficiency syndrome due to inadequate iron intake and low bioavailability of iron sources. Some studies indicated that bioactive peptides from certain protein hydrolysates could support iron absorption. Our previous study showed that soy protein hydrolysates containing bioactive peptides indicated an iron-binding activity and could increase its solubility in water. Aim of this study was to investigate the effect of soy protein hydrolysates administration on iron serum levels in anemic Sprague Dawley rats. Anemia induction was performed by applying NaNO2 (0.5 mg/ml per 200 g body weight (BW) of rats per day for 14 days) orally. The experiment was carried out in a completely randomized design, consisting of six groups. The first group was the control normal group (N), without induction and the others were treatment groups that were induced with NaNO2 and supplemented with iron (0.3 mg/200 g BW), consisted of control group (CMC), control iron (Fe) group, iron and soy protein hydrolysate-1 (270 mg/200 g BW) (FeSH-1) group, iron and soy protein hydrolysate-2 (270 mg/200 g BW) (Fe-SH2) group and positive control iron vitamin C (0.24 mg/200 g BW) (Fe Vit. C) group. The result showed that Fe-SH2 treatment group had a better iron-binding capacity rather than other groups. This result suggests that soy protein hydrolysates could enhance iron absorption, which might be applied in human as a functional food to reduce anemia prevalence.

Iron deficiency syndromes in clinical oncology and their correction with nutritive action drugs

Treatment of iron deficiency conditions by nutritive support media is one of the debatable areas. In the analysis of nutritional status, nutritional risk and ferrumdeficiency parameters in patients with operated colorectal cancer in different stages, the possibility of correction of prelatent and latent iron deficiency with ferrum‑containing media of nutritional alimentation is shown. With the development of anemia, the use of с intravenous correction (preferably with drugs sorbed on a special matrix that allows the gland to be isolated in portions) is shown.

Cytoreductive Treatment in ‘Real Life’ - Interim-Analysis of 434 Polycythemia Vera Patients in Germany

Treatment recommendations for cytoreductive treatment of patients with polycythemia vera (PV) are well established. However, the clinical use and limitation of phlebotomies remain a matter of current debate (Barbui et al, Leukemia, 32; Heidel et al, Leukemia, 32). While multicenter trials investigating therapeutic strategies for PV have been conducted at specialized academic centers, the majority of patients is treated in an outpatient (ambulatory) setting. The aim of this study is to evaluate the 'real live' situation especially in regard to the use of phlebotomy and cytoreductive therapy in a cohort of 1500 patients from a survey conducted at private practices and primary care centers. Eligible centers treating patients with MPN in Germany were recruited to participate in a paper-pencil based ongoing survey conducted from December 2018 and planned until December 2019. Hematologists were asked to report from patient charts. Descriptive analyses were conducted to assess for therapeutic interventions and outcomes and examined by reported prognostic risk scores, symptom scores, and clinical response criteria. For this interim analysis (data cutoff on May 31, 2019) a total of 11 centers participated in a retrospective survey and provided data on 434 patients. Gender was balanced with 211 (48.6%) male and 223 (51.4%) female patients. Most patients were of older age (mean 71.4 years; 62.7 years at diagnosis and 63,4% over the age of 60), which is a main risk factor according to published criteria (Tefferi et al, Am J Hematol, 94). 154 patients (35.5%) had a disease history of more than 10 years, 95 pts (21.9%) 6 to 10 years and 42.6% less than 6 years. Thromboembolic complications were reported in 100 patients (23.0%) at time of diagnosis and for 61 (14.1%) during treatment. Additional cardiovascular (CV) risk-factors were reported for 320 patients (73.7%), whereas 107 (24.7%) had none (and no data available in 1,6% (n=7) of cases). Hypertension was the most prevalent CV risk factor with 86.9% (n=278) affected, followed by hypercholesteremia 18.8% (n=60), diabetes mellitus 16.2% (n=52) and smoking 15.9% (n=51). Phlebotomy was the primary therapy in 301 patients (69.4%). Of those, 83 (27.6%) received 1-3 phlebotomies/year, 113 (37.5%) 4-6/year, 71 (23.6%) 7-12 times/year and 8 pts (2,6%) >13 times/year. Main triggers to start pharmacologic cytoreduction included the presence of high-risk criteria (53.2%) and insufficient disease control (22.6%). Of note, asymptomatic iron deficiency (5.6%), symptomatic iron deficiency (9.3%) and intolerance to phlebotomy (5.3%) have been reported in a significant number of patients and contributed to the limitation of phlebotomy treatment. Choice of cytoreductive agents included hydroxycarbamide (n=320; 73.3%), JAK-inhibitors (n=80, 18.4%), Interferon alpha (n=15; 3,5%), IMIDEs (n=2; 0.5%) and other cytoreductive agents (n=6; 1.4%). While 11 patients (2.5%) required combination of cytoreductive agents, 137 (31.3%) patients had a persistent need for phlebotomy. In summary, the patient population investigated here was older than in published large multicenter trials. Age was the main factor accounting for the majority of patients being categorized as 'high risk'. Although the majority of patients (>60%) presented as 'high risk' according to international guidelines, 69.4% of patients received phlebotomy as primary therapeutic approach, in part at high frequency (>25% with more than 7 phlebotomies per year). The low number of primary cytoreductive treatment and occurrence of symptomatic iron deficiency in 9.3% and of intolerance in 5.3% of patients indicates the need to reconsider indication and limitations of phlebotomy. We conclude that phlebotomy as a prophylactic measure of risk reduction should result in mild iron-deficient erythropoiesis and hematocrit control without inducing a severe iron-deficiency syndrome as indicated by increased levels of soluble transferrin-receptor or Zn-protoporphyrin. Pharmacologic cytoreduction is necessary for high risk patients older than 60 years or with previous thromboembolic complications. For patients, who require permanent phlebotomies at high frequency for sufficient hematocrit control (<45%), pharmacologic intervention should be discussed even in the low-risk situation to balance the looming risk of iron-deficiency symptoms with potential side effects of pharmacologic compounds. Disclosures Wunschel: Novartis Inc.: Employment. Hochhaus:MSD: Research Funding; Incyte: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Novartis: Research Funding. Heidel:Novartis: Research Funding.

Новые возможности лечения железодефицитных синдромов при воспалительных заболеваниях кишечника

The article describes the most common iron deficiency syndromes (IDS) in inflammatory bowel disease (IBD) and presents the modern principles of differential diagnosis of gastrointestinal disease, the advantages and disadvantages of standard methods for the correction of Iron-Deficiency (ID) and anemia in this group of patients. The authors give a circumstantial outline of their own data of examination and treatment of 77 patients with IBD and anemia, and prove the necessity of compulsory ferritin serum (FS) testing as the most important differential marker of the IDs., Inadequate production of erythropoietin as the main cause of anemia has been proven in 15% of patients with high FS values. On the contrary, the necessity of mandatory use of iron preparations in management of anemia was determined in 85% of patients. The high efficiency and safety of sucrosomial iron are proven in patients with IBD and anemia. The effectiveness of this method shows the normalization of hemoglobin in 68% of patients within 3 months. In contrast, intravenous iron administered during the inpatient treatment period is not sufficiently effective in this category of patients, which requires the continuation of outpatient therapy with preparations of sucrosomial iron. Conclusions: Based on the obtained data and international experience, there was formulated and substantiated the algorithm of differentiated therapy of IDS in patients with a mild form of IBD.

IRON DEFICIENCY AND ANEMIA IN PATIENTS WITH CHRONIC HEART FAILURE

Problems of iron deficiency and anemia in chronic heart failure (CHF) are discussed in the article. A review of the literature on the epidemiology, etiology and pathogenesis of anemia in this category of patients is presented. Various published data on the effect of anemia on the prognosis of CHF are given. The role of iron deficiency in the development of anemia, the features of its diagnosis and influence on the course of CHF are discussed. The author explains the role of various iron deficiency syndromes in the development of anemia in CHF, suggests a significant predominance of mixed forms of iron deficiency, such as iron deficiency anemia in combination with anemia of chronic disease, which are associated not so much with absolute iron deficiency as with systemic inflammatory response. All the existing approaches to the treatment of iron deficiency and anemia in patients with CHF are presented. The positive and negative results of the use of classical oral iron preparations, intravenous forms, isolated and combined use of recombinant human erythropoietin are presented. The author discusses the reasons for the failure in the treatment of anemia and the absence of a pronounced effect on the clinical manifestations of CHF in the application of standard approaches in treatment. As a possibility of more effective correction of iron deficiency and anemia in patients with CHF, new preparations of liposomial (sucrosomial) iron for oral administration are offered. The last extremely encouraging clinical results of the use of a new iron formulation in the treatment of iron deficiency and anemia in this group of patients are given.

The role of hepcidin in the main iron-deficiency syndromes in pregnancy

Currently, there is evidence that hepcidin is the main regulator of iron metabolism in human and pathogenesis key factor for anemia of inflammation. However, the role of hepcidin in multifactorial pathogenesis of anemia in pregnancy is not clear. We presented the results of the laboratory examinations of 78 pregnant women sera in hepcidin, ferritin, erythropoietin during pregnancy, and 116 sera of pregnant women with iron deficiency anemia (IDA) and anemia of mixed origin. The obtained data indicate a statistically significant decrease in the mean hepcidin concentration in pregnants versus non pregnant women. Mean hepcidin level in pregnant women with IDA was decreased, compared with anemia of mixed origin pregnants (p<0.0001). Evaluation of hepcidin concentrations may be useful laboratory test for differential diagnostic of anemia during pregnancy and for determination of optimal therapeutic option between oral iron, parenteral iron or using erythropoiesis -stimulating agents (ESAs) in combination with iron products.

Iron deficiency syndromes associated with diseases of the gastrointestinal tract: state-of-the-art and new prospects for treatment

Organs of the gastrointestinal tract (GIT) are essential for iron metabolism and hematopoiesis regulation. Iron deficiency is accompanied by a large number of diseases of GIT. The article discusses the problem of diagnosis and treatment of anemia, It describes mechanisms of development of anemia associated with bleeding, malabsorption, and chronic inflammation. It provides current data on the use of oral and intravenous iron-containing drugs, discusses advantages of the new oral form of sucrosomial iron for the treatment of anemia associated with GIT diseases.

Conserving therapy for symptomatic uterine leiomyoma in patient of reproductive age

Uterine leiomyoma is the most common benign tumor. The clinical incidence of this disease varies from 30 to 50%, morphological rate is up to 80%. Often uterine leiomyoma occurs asymptomatic until a certain period and can be spontaneously detected during routine examination and often have only one symptom which women can ignore – heavy menstruation over the past months or years. It is often develop iron deficiency syndrome and anemia.Management of patients with uterine leiomyoma in the last decades has dramatically changed – expectant management replaced early response since its diagnosis. Prevention of further tumor growth, stabilization or decrease its size are objectives of treatment at the detection stage.A clinical case of organ-saving surgical treatment of symptomatic uterine submucosal leiomyoma accompanied by abnormal uterine bleeding with subsequent development of posthemorrhagic anemia of moderate severity in patients of reproductive age is described in the article. According to STEP-W classification the submucous node assigned to group II, which required preliminary reducing its size prior to surgery. Ulipristal acetate 5 mg as a preparation of selective progesterone receptor modulators was administrated. For the post-hemorrhagic treatment of iron deficiency anemia drug iron hydroxide (III) complex polymaltose (maltofer) was used. This combination of drugs is not only possible to quickly eliminate clinical symptoms, as well as to create conditions for the organ-surgical treatment of uterine fibroids, increase the safety and efficiency of operations, to avoid complications in the postoperative period.Evaluation of the endometrium 6 months after hysteroscopic resection of myoma node after administration these drugs showed conformity with the phase of the menstrual cycle, a good blood supply, the absence of inflammation markers and a slight decrease of estrogen and progesterone receptors expression.

Double bull's eye for post-operative intravenous iron in patient blood management: better outcome and cost-effective.

Double bull's eye for post-operative intravenous iron in patient blood management: better outcome and cost-effective.

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

Growing awareness that heart failure, renal impairment, and anaemia are frequent co-morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR-HF trial raises a new hypothesis: is it time for ‘CRAS’ to be supplemented with new acronyms such as CRIDS (cardiorenal–iron deficiency syndrome) or even CRAIDS (cardiorenal–anaemia–iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14–2.17, P = 0.005). In the FAIR-HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron-deficient patients with heart failure, even in non-anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.

Iron deficiency syndromes and iron‐restricted erythropoiesis (CME)

The relationships between erythropoietin (EPO), iron, and erythropoiesis and the presence of iron-restricted erythropoiesis have important implications in anemia management. Iron-restricted erythropoiesis occurs in the presence of one or more iron deficiency syndromes: absolute iron deficiency, functional iron deficiency, and/or iron sequestration. Absolute iron deficiency is a common nutritional deficiency in women's health, pediatrics, and the elderly and is therefore an important public health problem. Functional iron deficiency occurs in patients with significant EPO-mediated erythropoiesis or therapy with erythropoiesis-stimulating agents, even when storage iron is present. Iron sequestration mediated by hepcidin is an underappreciated but common cause of iron-restricted erythropoiesis in patients with chronic inflammatory disease. The challenge for treating and laboratory-based physicians is to understand the contributory role(s) of each of these syndromes, so that the potential value of emerging and innovative pharmacologic strategies can be considered as options in patient blood management.

Structure, expression and chromosomal localisation of the metallothionein-like gene family of tomato.

Metallothioneins are small cysteine-rich proteins with strong binding capacity for heavy metals. In animals and fungi they are involved in cellular detoxification processes. Although genes for similar proteins exist in plants, less is known about the putative functions of their protein products. Here, we describe the characterisation of cDNAs specific for four genes (LEMT1, LEMT2, LEMT3 and LEMT4) encoding metallothionein-like proteins from tomato. Based on the characteristic cysteine pattern, the LEMT1, LEMT3 and LEMT4 gene products represent type 2 proteins. In contrast, the LEMT2 protein might establish a new structural pattern of metallothionein-like proteins not described before. Mapping experiments demonstrate that all four genes are localised at different genetic loci within the tomato genome. The members of the small gene family show a differential organ specific expression pattern. Expression of these genes is also influenced by heavy metals and by treatment with the thiol-oxidising drug diamide. We further describe the expression of the LEMT genes under different iron supply conditions both in tomato wild type as well as in the mutant chloronerva, which is defective in metal uptake regulation and exhibits a characteristic 'apparent iron deficiency syndrome'.

Nitrite-induced iron deficiency in the neonatal rat

Neonatal rats from dams receiving 2 or 3 g NaNO 2/liter in the drinking water through-gestation and lactation suffered severe microcytic anemia as well as growth retardation and high mortality. Lipemia, fatty liver damage, decreased erythropoiesis of spleen and bone marrow, and reduced plasma and tissue iron levels were noted in affected pups. These effects were all consistent with and characteristic of iron deficiency. Experiments presented here were designed to show that the maternally mediated toxicity of nitrite is actually an iron deficiency syndrome in the pups caused by inadequate iron transfer from dam to pup. It was found that administration of exogenous iron supplement to pups of treated mothers reversed the anemia and other effects of nitrite toxicity noted both in previous studies and in unsupplemented littermates. Mothers of affected pups were themselves anemic. Finally, we fully documented severe iron deficiency in pups of nitrite-treated mothers and showed that these mothers produced milk of reduced iron content. It appears then that nitrite-consuming dams have a reduced capacity to transfer iron to their pups. The nitrite-associated toxicities in the pups are actually a result of an iron deficiency.

CHANGES IN GROWTH AND METABOLISM OF EXCISED PEA ROOTS ASSOCIATED WITH IRON DEFICIENCY II. CHANGES IN NUCLEIC ACIDS

SummaryThe effects of iron deficiency on growth and metabolism of isolated pea roots grown in sterile culture have been further studied. Investigations at time intervals during a culture passage and by serial sectioning of roots at a critical stage of deficiency, have shown the distribution, concentration and composition of nucleic acids in relation to iron depletion. The significance of the results is discussed in relation to the primary role of iron in metabolism. It is suggested that the primary lesion resides in systems responsible for RNA synthesis. Formation of a soluble RNA fraction is inhibited, which in turn may cause failure to produce those enzyme proteins necessary for cell division and resulting in secondary disturbances which are a feature of the iron deficiency syndrome.