A comprehensive strategy for the subtyping of patients with Fanconi anaemia: conclusions from the Spanish Fanconi Anemia Research Network

PubMed Central

Casado, José Antonio; Callén, Elsa; Jacome, Ariana; Río, Paula; Castella, Maria; Lobitz, Stephan; Ferro, Teresa; Muñoz, Arturo; Sevilla, Julián; Cantalejo, Ángeles; Cela, Elena; Cervera, José; Sánchez‐Calero, Jesús; Badell, Isabel; Estella, Jesús; Dasí, Ángeles; Olivé, Teresa; Ortega, Juan José; Rodriguez‐Villa, Antonia; Tapia, María; Molinés, Antonio; Madero, Luis; Segovia, José C; Neveling, Kornelia; Kalb, Reinhard; Schindler, Detlev; Hanenberg, Helmut; Surrallés, Jordi; Bueren, Juan A

2007-01-01

Background Fanconi anaemia is a heterogeneous genetic disease, where 12 complementation groups have been already described. Identifying the complementation group in patients with Fanconi anaemia constitutes a direct procedure to confirm the diagnosis of the disease and is required for the recruitment of these patients in gene therapy trials. Objective To determine the subtype of Fanconi anaemia patients in Spain, a Mediterranean country with a relatively high population (23%) of Fanconi anaemia patients belonging to the gypsy race. Methods Most patients could be subtyped by retroviral complementation approaches in peripheral blood T cells, although some mosaic patients were subtyped in cultured skin fibroblasts. Other approaches, mainly based on western blot analysis and generation of nuclear RAD51 and FANCJ foci, were required for the subtyping of a minor number of patients. Results and conclusions From a total of 125 patients included in the Registry of Fanconi Anaemia, samples from 102 patients were available for subtyping analyses. In 89 cases the subtype could be determined and in 8 cases exclusions of common complementation groups were made. Compared with other international studies, a skewed distribution of complementation groups was observed in Spain, where 80% of the families belonged to the Fanconi anaemia group A (FA‐A) complementation group. The high proportion of gypsy patients, all of them FA‐A, and the absence of patients with FA‐C account for this characteristic distribution of complementation groups. PMID:17105750

Fanconi anemia links reactive oxygen species to insulin resistance and obesity.

PubMed

Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A; Rose, Susan R; Davies, Stella M; Pang, Qishen

2012-10-15

Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR.

Fanconi Anemia Links Reactive Oxygen Species to Insulin Resistance and Obesity

PubMed Central

Li, Jie; Sipple, Jared; Maynard, Suzette; Mehta, Parinda A.; Rose, Susan R.; Davies, Stella M.

2012-01-01

Abstract Aims: Insulin resistance is a hallmark of obesity and type 2 diabetes. Reactive oxygen species (ROS) have been proposed to play a causal role in insulin resistance. However, evidence linking ROS to insulin resistance in disease settings has been scant. Since both oxidative stress and diabetes have been observed in patients with the Fanconi anemia (FA), we sought to investigate the link between ROS and insulin resistance in this unique disease model. Results: Mice deficient for the Fanconi anemia complementation group A (Fanca) or Fanconi anemia complementation group C (Fancc) gene seem to be diabetes-prone, as manifested by significant hyperglycemia and hyperinsulinemia, and rapid weight gain when fed with a high-fat diet. These phenotypic features of insulin resistance are characterized by two critical events in insulin signaling: a reduction in tyrosine phosphorylation of the insulin receptor (IR) and an increase in inhibitory serine phosphorylation of the IR substrate-1 in the liver, muscle, and fat tissues from the insulin-challenged FA mice. High levels of ROS, spontaneously accumulated or generated by tumor necrosis factor alpha in these insulin-sensitive tissues of FA mice, were shown to underlie the FA insulin resistance. Treatment of FA mice with the natural anti-oxidant Quercetin restores IR signaling and ameliorates the diabetes- and obesity-prone phenotypes. Finally, pairwise screen identifies protein-tyrosine phosphatase (PTP)-α and stress kinase double-stranded RNA-dependent protein kinase (PKR) that mediate the ROS effect on FA insulin resistance. Innovation: These findings establish a pathogenic and mechanistic link between ROS and insulin resistance in a unique human disease setting. Conclusion: ROS accumulation contributes to the insulin resistance in FA deficiency by targeting both PTP-α and PKR. Antioxid. Redox Signal. 00, 000–000. PMID:22482891

Fanconi anemia in Tunisia: high prevalence of group A and identification of new FANCA mutations.

PubMed

Bouchlaka, Chiraz; Abdelhak, Sonia; Amouri, Ahlem; Ben Abid, Hela; Hadiji, Sondes; Frikha, Mounir; Ben Othman, Tarek; Amri, Fethi; Ayadi, Hammadi; Hachicha, Mongia; Rebaï, Ahmed; Saad, Ali; Dellagi, Koussay

2003-01-01

Fanconi anemia (FA) is a rare autosomal recessive disease characterized by progressive pancytopenia, congenital malformations, and predisposition to acute myeloid leukemia. Fanconi anemia is genetically heterogeneous, with at least eight distinct complementation groups of FA (A, B, C, D1, D2, E, F, and G) having been defined by somatic cell fusion studies. Six genes (FANCA, FANCC, FANCD2, FANCE, FANCG, and FANCF) have been cloned. Mutations of the seventh Fanconi anemia gene, BRCA2, have been shown to lead to FAD1 and probably FAB groups. In order to characterize the molecular defects underlying FA in Tunisia, 39 families were genotyped with microsatellite markers linked to known FA gene. Haplotype analysis and homozygosity mapping assigned 43 patients belonging to 34 families to the FAA group, whereas one family was probably not linked to the FANCA gene or to any known FA genes. For patients belonging to the FAA group, screening for mutations revealed four novel mutations: two small homozygous deletions 1693delT and 1751-1754del, which occurred in exon 17 and exon 19, respectively, and two transitions, viz., 513G-->A in exon 5 and A-->G at position 166 (IVS24+166A-->G) of intron 24. Two new polymorphisms were also identified in intron 24 (IVS24-5G/A and IVS24-6C/G).

FANCJ Helicase Operates in the Fanconi Anemia DNA Repair Pathway and the Response to Replicational Stress

PubMed Central

Wu, Yuliang; Brosh, Robert M.

2009-01-01

Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to have direct roles in DNA metabolism. One of the more recently identified FA proteins, shown to be responsible for complementation of the FA complementation group J, is the BRCA1 Associated C-terminal Helicase (BACH1, designated FANCJ), originally identified as a protein associated with breast cancer. FANCJ has been proposed to function downstream of FANCD2 monoubiquitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination (HR) pathway of double strand break (DSB) repair. In this review, we will summarize the current knowledge in terms of FANCJ functions through its enzymatic activities and protein interactions. The molecular roles of FANCJ in DNA repair and the response to replicational stress will be discussed. PMID:19519404

Update of the human and mouse Fanconi anemia genes.

PubMed

Dong, Hongbin; Nebert, Daniel W; Bruford, Elspeth A; Thompson, David C; Joenje, Hans; Vasiliou, Vasilis

2015-11-24

Fanconi anemia (FA) is a recessively inherited disease manifesting developmental abnormalities, bone marrow failure, and increased risk of malignancies. Whereas FA has been studied for nearly 90 years, only in the last 20 years have increasing numbers of genes been implicated in the pathogenesis associated with this genetic disease. To date, 19 genes have been identified that encode Fanconi anemia complementation group proteins, all of which are named or aliased, using the root symbol "FANC." Fanconi anemia subtype (FANC) proteins function in a common DNA repair pathway called "the FA pathway," which is essential for maintaining genomic integrity. The various FANC mutant proteins contribute to distinct steps associated with FA pathogenesis. Herein, we provide a review update of the 19 human FANC and their mouse orthologs, an evolutionary perspective on the FANC genes, and the functional significance of the FA DNA repair pathway in association with clinical disorders. This is an example of a set of genes--known to exist in vertebrates, invertebrates, plants, and yeast--that are grouped together on the basis of shared biochemical and physiological functions, rather than evolutionary phylogeny, and have been named on this basis by the HUGO Gene Nomenclature Committee (HGNC).

p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes

PubMed Central

Anur, Praveen; Yates, Jane; Garbati, Michael R.; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E.; Tyner, Jeffrey W.; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo

2012-01-01

Fanconi anemia, complementation group C (FANCC)–deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist–stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)–deficient macrophages containing an NF-κB/AP-1–responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK–dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation. PMID:22234699

p38 MAPK inhibition suppresses the TLR-hypersensitive phenotype in FANCC- and FANCA-deficient mononuclear phagocytes.

PubMed

Anur, Praveen; Yates, Jane; Garbati, Michael R; Vanderwerf, Scott; Keeble, Winifred; Rathbun, Keaney; Hays, Laura E; Tyner, Jeffrey W; Svahn, Johanna; Cappelli, Enrico; Dufour, Carlo; Bagby, Grover C

2012-03-01

Fanconi anemia, complementation group C (FANCC)-deficient hematopoietic stem and progenitor cells are hypersensitive to a variety of inhibitory cytokines, one of which, TNFα, can induce BM failure and clonal evolution in Fancc-deficient mice. FANCC-deficient macrophages are also hypersensitive to TLR activation and produce TNFα in an unrestrained fashion. Reasoning that suppression of inhibitory cytokine production might enhance hematopoiesis, we screened small molecules using TLR agonist-stimulated FANCC- and Fanconi anemia, complementation group A (FANCA)-deficient macrophages containing an NF-κB/AP-1-responsive reporter gene (SEAP). Of the 75 small molecules screened, the p38 MAPK inhibitor BIRB 796 and dasatinib potently suppressed TLR8-dependent expression of the reporter gene. Fanconi anemia (FA) macrophages were hypersensitive to the TLR7/8 activator R848, overproducing SEAP and TNFα in response to all doses of the agonist. Low doses (50nM) of both agents inhibited p38 MAPK-dependent activation of MAPKAPK2 (MK2) and suppressed MK2-dependent TNFα production without substantially influencing TNFα gene transcription. Overproduction of TNFα by primary FA cells was likewise suppressed by these agents and involved inhibition of MK2 activation. Because MK2 is also known to influence production and/or sensitivity to 2 other suppressive factors (MIP-1α and IFNγ) to which FA hematopoietic progenitor cells are uniquely vulnerable, targeting of p38 MAPK in FA hematopoietic cells is a rational objective for preclinical evaluation.

Fanconi anemia with biallelic FANCD1/BRCA2 mutations - Case report of a family with three affected children.

PubMed

Svojgr, Karel; Sumerauer, David; Puchmajerova, Alena; Vicha, Ales; Hrusak, Ondrej; Michalova, Kyra; Malis, Josef; Smisek, Petr; Kyncl, Martin; Novotna, Drahuse; Machackova, Eva; Jencik, Jan; Pycha, Karel; Vaculik, Miroslav; Kodet, Roman; Stary, Jan

2016-03-01

Fanconi anemia, complementation group D1 with bi-allelic FANCD1 (BRCA2) mutations, is a very rare genetic disorder characterized by early onset of childhood malignancies, including acute leukemia, brain cancer and nephroblastoma. Here, we present a case report of a family with 3 affected children in terms of treatment outcome, toxicity and characterization of the malignancies using comprehensive cytogenetic analysis. The first child was diagnosed with T-cell acute lymphoblastic leukemia when he was 11 months old. During chemotherapy, he suffered from repeated pancytopenia, sepsis and severe vincristine polyneuropathy, and 18 months after primary diagnosis, he succumbed to secondary acute monocytic leukemia. The second child was diagnosed with stage 2 triphasic nephroblastoma (Wilms tumor), when he was 3 years and 11 months old. During chemotherapy, he suffered from vincristine polyneuropathy. Currently, he is in complete remission, 29 months following the initial diagnosis. The third child was diagnosed with medulloblastoma with classical histology, when she was 4 years and 5 months old. After the first cycle of chemotherapy, she suffered from prolonged pancytopenia, sepsis and severe skin and mucosal toxicity. Six weeks after primary diagnosis, a first relapse in the posterior fossa was diagnosed, and at 7 and half months after primary diagnosis, a second relapse was diagnosed that led to the patient's death. Our case report underscores tumor heterogeneity, treatment toxicity and poor outcome in Fanconi anemia patients of complementation group D1. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Damage-dependent regulation of MUS81-EME1 by Fanconi anemia complementation group A protein

PubMed Central

Benitez, Anaid; Yuan, Fenghua; Nakajima, Satoshi; Wei, Leizhen; Qian, Liangyue; Myers, Richard; Hu, Jennifer J.; Lan, Li; Zhang, Yanbin

2014-01-01

MUS81-EME1 is a DNA endonuclease involved in replication-coupled repair of DNA interstrand cross-links (ICLs). A prevalent hypothetical role of MUS81-EME1 in ICL repair is to unhook the damage by incising the leading strand at the 3′ side of an ICL lesion. In this study, we report that purified MUS81-EME1 incises DNA at the 5′ side of a psoralen ICL residing in fork structures. Intriguingly, ICL repair protein, Fanconi anemia complementation group A protein (FANCA), greatly enhances MUS81-EME1-mediated ICL incision. On the contrary, FANCA exhibits a two-phase incision regulation when DNA is undamaged or the damage affects only one DNA strand. Studies using truncated FANCA proteins indicate that both the N- and C-moieties of the protein are required for the incision regulation. Using laser-induced psoralen ICL formation in cells, we find that FANCA interacts with and recruits MUS81 to ICL lesions. This report clarifies the incision specificity of MUS81-EME1 on ICL damage and establishes that FANCA regulates the incision activity of MUS81-EME1 in a damage-dependent manner. PMID:24170812

Small Molecule Protection of Bone Marrow Hematopoietic Stem Cells

DTIC Science & Technology

2017-12-01

using isogenic (mutant/complemented) human cell line pairs from patients with Fanconi anemia (FA), a heritable human bone marrow failure (BMF) syndrome ...small molecules could be therapeutically useful in reducing the risk of BMF in diseases such as Fanconi anemia, and perhaps after radiation exposure...damage-repair, DNA damage response, Fanconi anemia and associated bone marrow failure syndromes and environmental and molecular toxicology will all be

The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG.

PubMed

de Winter, J P; van der Weel, L; de Groot, J; Stone, S; Waisfisz, Q; Arwert, F; Scheper, R J; Kruyt, F A; Hoatlin, M E; Joenje, H

2000-11-01

Fanconi anemia (FA) is a chromosomal instability syndrome associated with a strong predisposition to cancer, particularly acute myeloid leukemia and squamous cell carcinoma. At the cellular level, FA is characterized by spontaneous chromosomal breakage and a unique hypersensitivity to DNA cross-linking agents. Complementation analysis has indicated that at least seven distinct genes are involved in the pathogenesis of FA. Despite the identification of four of these genes (FANCA, FANCC, FANCF and FANCG), the nature of the 'FA pathway' has remained enigmatic, as the FA proteins lack sequence homologies or motifs that could point to a molecular function. To further define this pathway, we studied the subcellular localizations and mutual interactions of the FA proteins, including the recently identified FANCF protein, in human lymphoblasts. FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. These interactions were detected in wild-type and FA-D lymphoblasts, but not in lymphoblasts of other FA complementation groups. This implies that each of the FA proteins, except FANCD, is required for these complexes to form. Similarly, we show that the interaction between FANCA and FANCC is restricted to wild-type and FA-D cells. Furthermore, we document the subcellular localization of FANCA and the FANCA/FANCG complex in all FA complementation groups. Our results, along with published data, culminate in a model in which a multi-protein FA complex serves a nuclear function to maintain genomic integrity.

Spectrum of sequence variations in the FANCA gene: an International Fanconi Anemia Registry (IFAR) study.

PubMed

Levran, Orna; Diotti, Raffaella; Pujara, Kanan; Batish, Sat D; Hanenberg, Helmut; Auerbach, Arleen D

2005-02-01

Fanconi anemia (FA) is an autosomal recessive disorder that is defined by cellular hypersensitivity to DNA cross-linking agents, and is characterized clinically by developmental abnormalities, progressive bone-marrow failure, and predisposition to leukemia and solid tumors. There is extensive genetic heterogeneity, with at least 11 different FA complementation groups. FA-A is the most common group, accounting for approximately 65% of all affected individuals. The mutation spectrum of the FANCA gene, located on chromosome 16q24.3, is highly heterogeneous. Here we summarize all sequence variations (mutations and polymorphisms) in FANCA described in the literature and listed in the Fanconi Anemia Mutation Database as of March 2004, and report 61 novel FANCA mutations identified in FA patients registered in the International Fanconi Anemia Registry (IFAR). Thirty-eight novel SNPs, previously unreported in the literature or in dbSNP, were also identified. We studied the segregation of common FANCA SNPs in FA families to generate haplotypes. We found that FANCA SNP data are highly useful for carrier testing, prenatal diagnosis, and preimplantation genetic diagnosis, particularly when the disease-causing mutations are unknown. Twenty-two large genomic deletions were identified by detection of apparent homozygosity for rare SNPs. In addition, a conserved SNP haplotype block spanning at least 60 kb of the FANCA gene was identified in individuals from various ethnic groups. (c) 2005 Wiley-Liss, Inc.

Fanconi anemia complementation group A (FANCA) localizes to centrosomes and functions in the maintenance of centrosome integrity.

PubMed

Kim, Sunshin; Hwang, Soo Kyung; Lee, Mihee; Kwak, Heejin; Son, Kook; Yang, Jiha; Kim, Sung Hak; Lee, Chang-Hun

2013-09-01

Fanconi anemia (FA) proteins are known to play roles in the cellular response to DNA interstrand cross-linking lesions; however, several reports have suggested that FA proteins play additional roles. To elucidate novel functions of FA proteins, we used yeast two-hybrid screening to identify binding partners of the Fanconi anemia complementation group A (FANCA) protein. The candidate proteins included never-in-mitosis-gene A (NIMA)-related kinase 2 (Nek2), which functions in the maintenance of centrosome integrity. The interaction of FANCA and Nek2 was confirmed in human embryonic kidney (HEK) 293T cells. Furthermore, FANCA interacted with γ-tubulin and localized to centrosomes, most notably during the mitotic phase, confirming that FANCA is a centrosomal protein. Knockdown of FANCA increased the frequency of centrosomal abnormalities and enhanced the sensitivity of U2OS osteosarcoma cells to nocodazole, a microtubule-interfering agent. In vitro kinase assays indicated that Nek2 can phosphorylate FANCA at threonine-351 (T351), and analysis with a phospho-specific antibody confirmed that this phosphorylation occurred in response to nocodazole treatment. Furthermore, U2OS cells overexpressing the phosphorylation-defective T351A FANCA mutant showed numerical centrosomal abnormalities, aberrant mitotic arrest, and enhanced nocodazole sensitivity, implying that the Nek2-mediated T351 phosphorylation of FANCA is important for the maintenance of centrosomal integrity. Taken together, this study revealed that FANCA localizes to centrosomes and is required for the maintenance of centrosome integrity, possibly through its phosphorylation at T351 by Nek2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Diagnosis of Fanconi anemia in patients with bone marrow failure

PubMed Central

Pinto, Fernando O.; Leblanc, Thierry; Chamousset, Delphine; Le Roux, Gwenaelle; Brethon, Benoit; Cassinat, Bruno; Larghero, Jérôme; de Villartay, Jean-Pierre; Stoppa-Lyonnet, Dominique; Baruchel, André; Socié, Gérard; Gluckman, Eliane; Soulier, Jean

2009-01-01

Background Patients with bone marrow failure and undiagnosed underlying Fanconi anemia may experience major toxicity if given standard-dose conditioning regimens for hematopoietic stem cell transplant. Due to clinical variability and/or potential emergence of genetic reversion with hematopoietic somatic mosaicism, a straightforward Fanconi anemia diagnosis can be difficult to make, and diagnostic strategies combining different assays in addition to classical breakage tests in blood may be needed. Design and Methods We evaluated Fanconi anemia diagnosis on blood lymphocytes and skin fibroblasts from a cohort of 87 bone marrow failure patients (55 children and 32 adults) with no obvious full clinical picture of Fanconi anemia, by performing a combination of chromosomal breakage tests, FANCD2-monoubiquitination assays, a new flow cytometry-based mitomycin C sensitivity test in fibroblasts, and, when Fanconi anemia was diagnosed, complementation group and mutation analyses. The mitomycin C sensitivity test in fibroblasts was validated on control Fanconi anemia and non-Fanconi anemia samples, including other chromosomal instability disorders. Results When this diagnosis strategy was applied to the cohort of bone marrow failure patients, 7 Fanconi anemia patients were found (3 children and 4 adults). Classical chromosomal breakage tests in blood detected 4, but analyses on fibroblasts were necessary to diagnose 3 more patients with hematopoietic somatic mosaicism. Importantly, Fanconi anemia was excluded in all the other patients who were fully evaluated. Conclusions In this large cohort of patients with bone marrow failure our results confirmed that when any clinical/biological suspicion of Fanconi anemia remains after chromosome breakage tests in blood, based on physical examination, history or inconclusive results, then further evaluation including fibroblast analysis should be made. For that purpose, the flow-based mitomycin C sensitivity test here described proved to be a reliable alternative method to evaluate Fanconi anemia phenotype in fibroblasts. This global strategy allowed early and accurate confirmation or rejection of Fanconi anemia diagnosis with immediate clinical impact for those who underwent hematopoietic stem cell transplant. PMID:19278965

Immune Thrombocytopenia in Two Unrelated Fanconi Anemia Patients – A Mere Coincidence?

PubMed Central

Karastaneva, Anna; Lanz, Sofia; Wawer, Angela; Behrends, Uta; Schindler, Detlev; Dietrich, Ralf; Burdach, Stefan; Urban, Christian; Benesch, Martin; Seidel, Markus G.

2015-01-01

Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA), are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP) represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here, we describe the clinical course of two independent FA patients with atypical – namely immune – thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG) and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2) had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure/tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed. PMID:26106590

DNA Damage Induced by Alkylating Agents and Repair Pathways

PubMed Central

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

Alpha-fetoprotein and Fanconi Anemia: Relevance to DNA Repair and Breast Cancer Susceptibility.

PubMed

Lakhi, Nisha A; Mizejewski, Gerald J

2017-02-01

Elevations of serum alpha-fetoprotein (sAFP) have been reported in fetal and infant states of anemia. Fanconi anemia (FA) belongs to a family of genetic instability disorders which lack the capability to repair DNA breaks. The lesion occurs at a checkpoint regulatory step of the G2 to mitotic transition, allowing FA cells to override cell-cycle arrest. FA DNA repair pathways contain complementation groups known as FANC proteins. FANC proteins form multi-protein complexes with BRCA proteins and are involved in homologous DNA repair. An impaired cascade in these events imparts an increased breast cancer susceptibility to female FA patients. Elevations of sAFP have availed this fetal protein to serve as a biomarker for FA disease. However, the origin of the synthesis of sAFA has not been determined in FA patients. We hypothesize that hematopoietic multipotent progenitor stem cells in the bone marrow are the source of sAFP production in FA patients.

In vivo therapeutic responses contingent on Fanconi anemia/BRCA2 status of the tumor.

PubMed

van der Heijden, Michiel S; Brody, Jonathan R; Dezentje, David A; Gallmeier, Eike; Cunningham, Steven C; Swartz, Michael J; DeMarzo, Angelo M; Offerhaus, G Johan A; Isacoff, William H; Hruban, Ralph H; Kern, Scott E

2005-10-15

BRCA2, FANCC, and FANCG gene mutations are present in a subset of pancreatic cancer. Defects in these genes could lead to hypersensitivity to interstrand cross-linkers in vivo and a more optimal treatment of pancreatic cancer patients based on the genetic profile of the tumor. Two retrovirally complemented pancreatic cancer cell lines having defects in the Fanconi anemia pathway, PL11 (FANCC-mutated) and Hs766T (FANCG-mutated), as well as several parental pancreatic cancer cell lines with or without mutations in the Fanconi anemia/BRCA2 pathway, were assayed for in vitro and in vivo sensitivities to various chemotherapeutic agents. A distinct dichotomy of drug responses was observed. Fanconi anemia-defective cancer cells were hypersensitive to the cross-linking agents mitomycin C (MMC), cisplatin, chlorambucil, and melphalan but not to 5-fluorouracil, gemcitabine, doxorubicin, etoposide, vinblastine, or paclitaxel. Hypersensitivity to cross-linking agents was confirmed in vivo; FANCC-deficient xenografts of PL11 and BRCA2-deficient xenografts of CAPAN1 regressed on treatment with two different regimens of MMC whereas Fanconi anemia-proficient xenografts did not. The MMC response comprised cell cycle arrest, apoptosis, and necrosis. Xenografts of PL11 also regressed after a single dose of cyclophosphamide whereas xenografts of genetically complemented PL11(FANCC) did not. MMC or other cross-linking agents as a clinical therapy for pancreatic cancer patients with tumors harboring defects in the Fanconi anemia/BRCA2 pathway should be specifically investigated.

A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA.

PubMed

Yagasaki, H; Adachi, D; Oda, T; Garcia-Higuera, I; Tetteh, N; D'Andrea, A D; Futaki, M; Asano, S; Yamashita, T

2001-12-15

Fanconi anemia (FA) is an autosomal recessive disease with congenital anomalies, bone marrow failure, and susceptibility to leukemia. Patient cells show chromosome instability and hypersensitivity to DNA cross-linking agents. At least 8 complementation groups (A-G) have been identified and 6 FA genes (for subtypes A, C, D2, E, F, and G) have been cloned. Increasing evidence indicates that a protein complex assembly of multiple FA proteins, including FANCA and FANCG, plays a crucial role in the FA pathway. Previously, it was reported that FANCA was phosphorylated in lymphoblasts from normal controls, whereas the phosphorylation was defective in those derived from patients with FA of multiple complementation groups. The present study examined phosphorylation of FANCA ectopically expressed in FANCA(-) cells. Several patient-derived mutations abrogated in vivo phosphorylation of FANCA in this system, suggesting that FANCA phosphorylation is associated with its function. In vitro phosphorylation studies indicated that a physiologic protein kinase for FANCA (FANCA-PK) forms a complex with the substrate. Furthermore, at least a part of FANCA-PK as well as phosphorylated FANCA were included in the FANCA/FANCG complex. Thus, FANCA-PK appears to be another component of the FA protein complex and may regulate function of FANCA. FANCA-PK was characterized as a cytoplasmic serine kinase sensitive to wortmannin. Identification of the protein kinase is expected to elucidate regulatory mechanisms that control the FA pathway.

Finnish Fanconi anemia mutations and hereditary predisposition to breast and prostate cancer.

PubMed

Mantere, T; Haanpää, M; Hanenberg, H; Schleutker, J; Kallioniemi, A; Kähkönen, M; Parto, K; Avela, K; Aittomäki, K; von Koskull, H; Hartikainen, J M; Kosma, V-M; Laasanen, S-L; Mannermaa, A; Pylkäs, K; Winqvist, R

2015-07-01

Mutations in downstream Fanconi anemia (FA) pathway genes, BRCA2, PALB2, BRIP1 and RAD51C, explain part of the hereditary breast cancer susceptibility, but the contribution of other FA genes has remained questionable. Due to FA's rarity, the finding of recurrent deleterious FA mutations among breast cancer families is challenging. The use of founder populations, such as the Finns, could provide some advantage in this. Here, we have resolved complementation groups and causative mutations of five FA patients, representing the first mutation confirmed FA cases in Finland. These patients belonged to complementation groups FA-A (n = 3), FA-G (n = 1) and FA-I (n = 1). The prevalence of the six FA causing mutations was then studied in breast (n = 1840) and prostate (n = 565) cancer cohorts, and in matched controls (n = 1176 females, n = 469 males). All mutations were recurrent, but no significant association with cancer susceptibility was observed for any: the prevalence of FANCI c.2957_2969del and c.3041G>A mutations was even highest in healthy males (1.7%). This strengthens the exclusive role of downstream genes in cancer predisposition. From a clinical point of view, current results provide fundamental information of the mutations to be tested first in all suspected FA cases in Finland. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Novel homozygous FANCL mutation and somatic heterozygous SETBP1 mutation in a Chinese girl with Fanconi Anemia.

PubMed

Wu, Weiqing; Liu, Yang; Zhou, Qinghua; Wang, Qin; Luo, Fuwei; Xu, Zhiyong; Geng, Qian; Li, Peining; Zhang, Hui Z; Xie, Jiansheng

2017-07-01

Fanconi Anemia (FA) is a rare genetically heterogeneous disorder with 17 known complement groups caused by mutations in different genes. FA complementation group L (FA-L, OMIM #608111) occurred in 0.2% of all FA and only eight mutant variants in the FANCL gene were documented. Phenotype and genotype correlation in FANCL associated FA is still obscure. Here we describe a Chinese girl with FA-L caused by a novel homozygous mutation c.822_823insCTTTCAGG (p.Asp275LeufsX13) in the FANCL gene. The patient's clinical course was typical for FA with progression to bone marrow failure, and death from acute myelomonocytic leukemia (AML-M4) at 9 years of age. Mutation analysis also detected a likely somatic c.2608G > A (p.Gly870Ser) in the SETBP1 gene. Consistent copy number losses of 7q and 18p and gains of 3q and 21q and accumulated non-clonal single cell chromosomal abnormalities were detected in blood leukocytes as her FA progressed. This is the first Chinese FA-L case caused by a novel FANCL mutation. The somatic gene mutation and copy number aberrations could be used to monitor disease progression and the clinical findings provide further information for genotype-phenotype correlation for FA-L. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Fanconi Anemia complementation group C protein in metabolic disorders.

PubMed

Nepal, Manoj; Ma, Chi; Xie, Guoxiang; Jia, Wei; Fei, Peiwen

2018-06-21

Given importance of 22-Fanconi Anemia (FA) proteins together to act in a signaling pathway in preventing deleterious clinical symptoms, e.g. severe bone marrow failure, congenital defects, an early onset of aging and cancer, studies on each FA protein become increasingly attractive. However, an unbiased and systematic investigation of cellular effects resulting from each FA protein is missing. Here, we report roles of FA complementation C group protein (FANCC) in the protection from metabolic disorders. This study was prompted by the diabetes-prone feature displayed in FANCC knockout mice, which is not typically shown in patients with FA. We found that in cells expressing FANCC at different levels, there are representative alterations in metabolites associated with aging (glycine, citrulline, ornithine, L-asparagine, L-tyrosine, L-arginine, L-glutamine, L-leucine, L-isoleucine, L-valine, L-proline and L-alanine), Diabetes Mellitus (DM) (carbon monoxide, collagens, fatty acids, D-glucose, fumaric acid, 2-oxoglutaric acid, C3), inflammation (inosine, L-arginine, L-isoleucine, L-leucine, L-lysine, L-phenylalanine, hypoxanthine, L-methionine), and cancer ( L-methionine, sphingomyelin, acetyl-L-carnitine, L-aspartic acid, L-glutamic acid, niacinamide, phospho-rylethanolamine). We also found that FANCC can act in an FA-pathway-independent manner in tumor suppression. Collectively, featured-metabolic alterations are readouts of functional mechanisms underlying reduced tumorigenicity driven by FANCC, demonstrating close links among cancer, aging, inflammation and DM.

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

PubMed Central

Näf, Dieter; Kupfer, Gary M.; Suliman, Ahmed; Lambert, Kathleen; D’Andrea, Alan D.

1998-01-01

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability. PMID:9742112

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernstein, S.E.; Russell, E.S.; Barker, J.E.

Hereditary anemias of mice have been investigated including four macrocytic anemias, three hemolytic anemias, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, an ..cap alpha..-thalassemia, and a new target-cell anemia. Each of these blood dyscrasias is caused by the action of a unique mutant gene, which determines the structure of different intracellular molecules controlling a different metabolic process. Thus the wide range of different hereditary anemias has considerable potential for uncovering many different aspects of hemopoietic homeostatic mechanisms in the mouse and by extension to man from an understanding of mammalian mechanisms utilized in the control of erythropoiesis. Eachmore » of the different anemias is studied through: (a) biochemical and biophysical characterization of peripheral blood cells; (b) determinations of cellular and organismic radiosensitivity under a variety of conditions; (c) measurements of iron metabolism and heme biosynthesis; (d) morphological and biochemical study of blood-forming tissue; (e) functional tests of the stem cell component; (f) examination of responses to erythroid stimuli and inhibitors; and (g) physiological complementation analysis via transplantation of tissue between individuals of differently affected genotypes.« less

Complementation of a Fanconi anemia group A cell line by UbA{sup 52}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moses, R.E.; Heina, J.A.; Jakobs, P.M.

1994-09-01

Cells from patients with Fanconi anemia (FA) display chromosomal instability and increased sensitivity to mitomycin C (MMC) and diepoxybutane (DEB) relative to normal cells. Several genes act in this pathway of DNA damage processing based upon four known complementation groups in FA. We have made a cDNA expression library in a vector with a G418 selectable marker to identify FA genes other than the FA-C group. Approximately 1 x 10{sup 6} independent cDNA clones were isolated with an average cDNA size of 1.5 kb. Five cell lines resistant to MMC and DEB were isolated from 6 x 10{sup 6} G418-resistantmore » transfectants from 65 individual transfections of the FA-A fibroblast line GM6914. The isolated cell lines also showed normal chromosome stability. The same cDNA (600 bp) was recovered from three independent cell lines by PCR using flanking sequence primers. The gene has sequence identity with a known gene, the ubiquitin fusion gene, UbA{sub 52}. Interestingly, each of the cDNAs were inserted in antisense orientation relative to the cytomegalovirus (CMV) promoter as determined by sequencing and PCR using UbA{sub 52}-specific internal primers. Southern blot analysis indicated the cell lines had distinct chromosomal insertion sites. Mutation analysis by chemical cleavage showed no reading frame mutations, indicating that UbA{sub 52} is not the FA-A gene. Re-transfection with the UbA{sub 52} gene in antisense gave complementation for MMC, DEB and chromosome stability to varying degrees. Re-transfection of the antisense construct with the CMV promotor removed or with a sense construct did not alter the MMC sensitivity. We conclude that the antisense UbA{sub 52} gene has a non-specific effect, perhaps acting by altering the cell cycle or susceptibility to apoptosis.« less

Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology

PubMed Central

De Rocco, Daniela; Bottega, Roberta; Cappelli, Enrico; Cavani, Simona; Criscuolo, Maria; Nicchia, Elena; Corsolini, Fabio; Greco, Chiara; Borriello, Adriana; Svahn, Johanna; Pillon, Marta; Mecucci, Cristina; Casazza, Gabriella; Verzegnassi, Federico; Cugno, Chiara; Locasciulli, Anna; Farruggia, Piero; Longoni, Daniela; Ramenghi, Ugo; Barberi, Walter; Tucci, Fabio; Perrotta, Silverio; Grammatico, Paola; Hanenberg, Helmut; Della Ragione, Fulvio; Dufour, Carlo; Savoia, Anna

2014-01-01

Fanconi anemia is an inherited disease characterized by congenital malformations, pancytopenia, cancer predisposition, and sensitivity to cross-linking agents. The molecular diagnosis of Fanconi anemia is relatively complex for several aspects including genetic heterogeneity with mutations in at least 16 different genes. In this paper, we report the mutations identified in 100 unrelated probands enrolled into the National Network of the Italian Association of Pediatric Hematoly and Oncology. In approximately half of these cases, mutational screening was carried out after retroviral complementation analyses or protein analysis. In the other half, the analysis was performed on the most frequently mutated genes or using a next generation sequencing approach. We identified 108 distinct variants of the FANCA, FANCG, FANCC, FANCD2, and FANCB genes in 85, 9, 3, 2, and 1 families, respectively. Despite the relatively high number of private mutations, 45 of which are novel Fanconi anemia alleles, 26% of the FANCA alleles are due to 5 distinct mutations. Most of the mutations are large genomic deletions and nonsense or frameshift mutations, although we identified a series of missense mutations, whose pathogenetic role was not always certain. The molecular diagnosis of Fanconi anemia is still a tiered procedure that requires identifying candidate genes to avoid useless sequencing. Introduction of next generation sequencing strategies will greatly improve the diagnostic process, allowing a rapid analysis of all the genes. PMID:24584348

Targeted disruption of the murine Facc gene: Towards the establishment of a mouse model for Fanconi anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, M.; Auerbach, W.; Buchwald, M.

1994-09-01

Fanconi anemia (FA) is an autosomal recessive disease characterized by bone marrow failure, congenital malformations and predisposition to malignancies. The gene responsible for the defect in FA group C has been cloned and designated the Fanconi Anemia Complementation Group C gene (FACC). A murine cDNA for this gene (Facc) was also cloned. Here we report our progress in the establishment of a mouse model for FA. The mouse Facc cDNA was used as probe to screen a genomic library of mouse strain 129. More than twenty positive clones were isolated. Three of them were mapped and found to be overlappingmore » clones, encompassing the genomic region from exon 8 to the end of the 3{prime} UTR of the mouse cDNA. A targeting vector was constructed using the most 5{prime} mouse genomic sequence available. The end result of the homologous recombination is that exon 8 is deleted and the neo gene is inserted. The last exon, exon 14, is essential for the complementing function of the FACC gene product; the disruption in the middle of the murine Facc gene should render this locus biologically inactive. This targeting vector was linearized and electroporated into R1 embryonic stem (ES) cells which were derived from the 129 mouse. Of 102 clones screened, 19 positive cell lines were identified. Four targeted cell lines have been used to produce chimeric mice. 129-derived ES cells were aggregated ex vivo into the morulas derived from CD1 mice and then implanted into foster mothers. 22 chimeras have been obtained. Moderately and strongly chimeric mice have been bred to test for germline transmission. Progeny with the expected coat color derived from 2 chimeras are currently being examined to confirm transmission of the targeted allele.« less

Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair.

PubMed

Leung, Justin Wai Chung; Wang, Yucai; Fong, Ka Wing; Huen, Michael Shing Yan; Li, Lei; Chen, Junjie

2012-03-20

The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.

Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair

PubMed Central

Leung, Justin Wai Chung; Wang, Yucai; Fong, Ka Wing; Huen, Michael Shing Yan; Li, Lei; Chen, Junjie

2012-01-01

The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway. PMID:22396592

Acquisition of Relative Interstrand Crosslinker Resistance and PARP Inhibitor Sensitivity in Fanconi Anemia Head and Neck Cancers.

PubMed

Lombardi, Anne J; Hoskins, Elizabeth E; Foglesong, Grant D; Wikenheiser-Brokamp, Kathryn A; Wiesmüller, Lisa; Hanenberg, Helmut; Andreassen, Paul R; Jacobs, Allison J; Olson, Susan B; Keeble, Winifred W; Hays, Laura E; Wells, Susanne I

2015-04-15

Fanconi anemia is an inherited disorder associated with a constitutional defect in the Fanconi anemia DNA repair machinery that is essential for resolution of DNA interstrand crosslinks. Individuals with Fanconi anemia are predisposed to formation of head and neck squamous cell carcinomas (HNSCC) at a young age. Prognosis is poor, partly due to patient intolerance of chemotherapy and radiation requiring dose reduction, which may lead to early recurrence of disease. Using HNSCC cell lines derived from the tumors of patients with Fanconi anemia, and murine HNSCC cell lines derived from the tumors of wild-type and Fancc(-/-) mice, we sought to define Fanconi anemia-dependent chemosensitivity and DNA repair characteristics. We utilized DNA repair reporter assays to explore the preference of Fanconi anemia HNSCC cells for non-homologous end joining (NHEJ). Surprisingly, interstrand crosslinker (ICL) sensitivity was not necessarily Fanconi anemia-dependent in human or murine cell systems. Our results suggest that the increased Ku-dependent NHEJ that is expected in Fanconi anemia cells did not mediate relative ICL resistance. ICL exposure resulted in increased DNA damage sensing and repair by PARP in Fanconi anemia-deficient cells. Moreover, human and murine Fanconi anemia HNSCC cells were sensitive to PARP inhibition, and sensitivity of human cells was attenuated by Fanconi anemia gene complementation. The observed reliance upon PARP-mediated mechanisms reveals a means by which Fanconi anemia HNSCCs can acquire relative resistance to the ICL-based chemotherapy that is a foundation of HNSCC treatment, as well as a potential target for overcoming chemoresistance in the chemosensitive individual. ©2015 American Association for Cancer Research.

Some aspects of the anemia of chronic disorders modeled and analyzed by petri net based approach.

PubMed

Formanowicz, Dorota; Sackmann, Andrea; Kozak, Adam; Błażewicz, Jacek; Formanowicz, Piotr

2011-06-01

Anemia of chronic disorders is a very important phenomenon and iron is a crucial factor of this complex process. To better understand this process and its influence on some other factors we have built a mathematical model of the human body iron homeostasis, which possibly most exactly would reflect the metabolism of iron in the case of anemia and inflammation. The model has been formulated in the language of Petri net theory, which allows for its simulation and precise analysis. The obtained results of the analysis of the model's behavior, concerning the influence of anemia and inflammation on the transferrin receptors, and hepcidin concentration changes are the valuable complements to the knowledge following from clinical research. This analysis is one of the first attempts to investigate properties and behavior of a not fully understood biological system on a basis of its Petri net based model.

Continuous in vivo infusion of interferon-gamma (IFN-γ) enhances engraftment of syngeneic wild-type cells in Fanca–/– and Fancg–/– mice

PubMed Central

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J.; Critser, John; Arwert, Fre; Haneline, Laura S.; Clapp, D. Wade

2006-01-01

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc–/– cells to interferon-gamma (IFN-γ), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc–/– mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca–/– and Fancg–/– mice are hypersensitive to IFN-γ and that in vivo infusion of IFN-γ at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-γ conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients. PMID:16946306

Continuous in vivo infusion of interferon-gamma (IFN-gamma) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice.

PubMed

Si, Yue; Ciccone, Samantha; Yang, Feng-Chun; Yuan, Jin; Zeng, Daisy; Chen, Shi; van de Vrugt, Henri J; Critser, John; Arwert, Fre; Haneline, Laura S; Clapp, D Wade

2006-12-15

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow (BM) failure and cancer susceptibility. Identification of the cDNAs of FA complementation types allows the potential of using gene transfer technology to introduce functional cDNAs as transgenes into autologous stem cells and provide a cure for the BM failure in FA patients. However, strategies to enhance the mobilization, transduction, and engraftment of exogenous stem cells are required to optimize efficacy prior to widespread clinical use. Hypersensitivity of Fancc-/- cells to interferon-gamma (IFN-gamma), a nongenotoxic immune-regulatory cytokine, enhances engraftment of syngeneic wild-type (WT) cells in Fancc-/- mice. However, whether this phenotype is of broad relevance in other FA complementation groups is unresolved. Here we show that primitive and mature myeloid progenitors in Fanca-/- and Fancg-/- mice are hypersensitive to IFN-gamma and that in vivo infusion of IFN-gamma at clinically relevant concentrations was sufficient to allow consistent long-term engraftment of isogenic WT repopulating stem cells. Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% of all FA patients, these data provide evidence that IFN-gamma conditioning may be a useful nongenotoxic strategy for myelopreparation in FA patients.

Fanconi anemia protein, FANCG, is a phosphoprotein and is upregulated with FANCA after TNF-alpha treatment.

PubMed

Futaki, M; Watanabe, S; Kajigaya, S; Liu, J M

2001-02-23

Fanconi anemia (FA) is a genetic syndrome characterized by bone marrow failure, birth defects, and a predisposition to malignancy. At this time, six FA genes have been identified, and several gene products have been found to interact in a protein complex. FA cells appear to overexpress the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha). We therefore examined the effects of TNF-alpha on the regulation of FA complementation group proteins, FANCG and FANCA. We found that treatment with TNF-alpha induced FANCG protein expression. FANCA was induced concurrently with FANCG, and the FANCA/FANCG complex was increased in the nucleus following TNF-alpha treatment. Inactivation of inhibitory kappa B kinase-2 modulated the expression of FANCG. We also found that both nuclear and cytoplasmic FANCG fractions were phosphorylated. These results show that FANCG is a phosphoprotein and suggest that the cellular accumulation of FA proteins is subject to regulation by TNF-alpha signaling.

FANCA Gene Mutations with 8 Novel Molecular Changes in Indian Fanconi Anemia Patients.

PubMed

Solanki, Avani; Mohanty, Purvi; Shukla, Pallavi; Rao, Anita; Ghosh, Kanjaksha; Vundinti, Babu Rao

2016-01-01

Fanconi anemia (FA), a rare heterogeneous genetic disorder, is known to be associated with 19 genes and a spectrum of clinical features. We studied FANCA molecular changes in 34 unrelated and 2 siblings of Indian patients with FA and have identified 26 different molecular changes of FANCA gene, of which 8 were novel mutations (a small deletion c.2500delC, 4 non-sense mutations c.2182C>T, c.2630C>G, c.3677C>G, c.3189G>A; and 3 missense mutations; c.1273G>C, c.3679 G>C, and c.3992 T>C). Among these only 16 patients could be assigned FA-A complementation group, because we could not confirm single exon deletions detected by MLPA or cDNA amplification by secondary confirmation method and due to presence of heterozygous non-pathogenic variations or heterozygous pathogenic mutations. An effective molecular screening strategy should be developed for confirmation of these mutations and determining the breakpoints for single exon deletions.

Investigation of FANCA mutations in Greek patients.

PubMed

Selenti, Nikoletta; Sofocleous, Christalena; Kattamis, Antonis; Kolialexi, Aggeliki; Kitsiou, Sophia; Fryssira, Elena; Polychronopoulou, Sophia; Kanavakis, Emmanouel; Mavrou, Ariadni

2013-08-01

Fanconi anemia (FA) is a rare genetic disease characterized by considerable heterogeneity. Fifteen subtypes are currently recognised and deletions of the Fanconi anemia complementation group A (FANCA) gene account for more than 65% of FA cases. We report on the results from a cohort of 166 patients referred to the Department of Medical Genetics of Athens University for genetic investigation after the clinical suspicion of FA. For clastogen-induced chromosome damage, cultures were set up with the addition of mitomycin C (MMC) and diepoxybutane (DEB), respectively. Following a positive cytogenetic result, molecular analysis was performed to allow identification of causative mutations in the FANCA gene. A total of 13/166 patients were diagnosed with FA and 8/13 belonged to the FA-A subtype. A novel point mutation was identified in exon 26 of FANCA gene. In our study 62% of FA patients were classified in the FA-A subtype and a point mutation in exon 26 was noted for the first time.

FANCA Gene Mutations with 8 Novel Molecular Changes in Indian Fanconi Anemia Patients

PubMed Central

Solanki, Avani; Mohanty, Purvi; Shukla, Pallavi; Rao, Anita; Ghosh, Kanjaksha; Vundinti, Babu Rao

2016-01-01

Fanconi anemia (FA), a rare heterogeneous genetic disorder, is known to be associated with 19 genes and a spectrum of clinical features. We studied FANCA molecular changes in 34 unrelated and 2 siblings of Indian patients with FA and have identified 26 different molecular changes of FANCA gene, of which 8 were novel mutations (a small deletion c.2500delC, 4 non-sense mutations c.2182C>T, c.2630C>G, c.3677C>G, c.3189G>A; and 3 missense mutations; c.1273G>C, c.3679 G>C, and c.3992 T>C). Among these only 16 patients could be assigned FA-A complementation group, because we could not confirm single exon deletions detected by MLPA or cDNA amplification by secondary confirmation method and due to presence of heterozygous non-pathogenic variations or heterozygous pathogenic mutations. An effective molecular screening strategy should be developed for confirmation of these mutations and determining the breakpoints for single exon deletions. PMID:26799702

Mitochondrial respiratory chain Complex I defects in Fanconi anemia complementation group A.

PubMed

Ravera, Silvia; Vaccaro, Daniele; Cuccarolo, Paola; Columbaro, Marta; Capanni, Cristina; Bartolucci, Martina; Panfoli, Isabella; Morelli, Alessandro; Dufour, Carlo; Cappelli, Enrico; Degan, Paolo

2013-10-01

Fanconi anemia (FA) is a rare and complex inherited blood disorder of the child. At least 15 genes are associated with the disease. The highest frequency of mutations belongs to groups A, C and G. Genetic instability and cytokine hypersensitivity support the selection of leukemic over non-leukemic stem cells. FA cellular phenotype is characterized by alterations in red-ox state, mitochondrial functionality and energy metabolism as reported in the past however a clear picture of the altered biochemical phenotype in FA is still elusive and the final biochemical defect(s) still unknown. Here we report an analysis of the respiratory fluxes in FANCA primary fibroblasts, lymphocytes and lymphoblasts. FANCA mutants show defective respiration through Complex I, diminished ATP production and metabolic sufferance with an increased AMP/ATP ratio. Respiration in FANCC mutants is normal. Treatment with N-acetyl-cysteine (NAC) restores oxygen consumption to normal level. Defective respiration in FANCA mutants appear correlated with the FA pro-oxidative phenotype which is consistent with the altered morphology of FANCA mitochondria. Electron microscopy measures indeed show profound alterations in mitochondrial ultrastructure and shape. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Lay health workers perceptions of an anemia control intervention in Karnataka, India: a qualitative study.

PubMed

Shet, Arun S; Rao, Abha; Jebaraj, Paul; Mascarenhas, Maya; Zwarenstein, Merrick; Galanti, Maria Rosaria; Atkins, Salla

2017-09-18

Lay health workers (LHWs) are increasingly used to complement health services internationally. Their perceptions of the interventions they implement and their experiences in delivering community based interventions in India have been infrequently studied. We developed a novel LHW led intervention to improve anemia cure rates in rural community dwelling children attending village day care centers in South India. Since the intervention is delivered by the village day care center LHW, we sought to understand participating LHWs' acceptance of and perspectives regarding the intervention, particularly in relation to factors affecting daily implementation. We conducted a qualitative study alongside a cluster randomized controlled trial evaluating a complex community intervention for childhood anemia control in Karnataka, South India. Focus group discussions (FGDs) were conducted with trained LHWs assigned to deliver the educational intervention. These were complemented by non-participant observations of LHWs delivering the intervention. Transcripts of the FGDs were translated and analyzed using the framework analysis method. Several factors made the intervention acceptable to the LHWs and facilitated its implementation including pre-implementation training modules, intervention simplicity, and ability to incorporate the intervention into the routine work schedule. LHWs felt that the intervention impacted negatively on their preexisting workload. Fluctuating relationships with mothers weakened the LHWs position as providers of the intervention and hampered efficient implementation, despite the LHWs' highly valued position in the community. Modifiable barriers to the successful implementation of this intervention were seen at two levels. At a broader contextual level, hindering factors included the LHW being overburdened, inadequately reimbursed, and receiving insufficient employer support. At the health system level, lack of streamlining of LHW duties, inability of LHWs to diagnose anemia and temporary shortfalls in the availability of iron supplements constituted potentially modifiable barriers. This qualitative study identified some of the practical challenges as experienced by LHWs while delivering a community health intervention in India. Methodologically, it highlights the value of qualitative research in understanding implementation of complex community interventions. On the contextual level, the results indicate that efficient delivery of community interventions will require streamlining of LHW workloads and improved health system infrastructure support. This trial was registered with ISRCTN.com (identifier: ISRCTN68413407 ) on 23 September 2013.

Fanconi anemia founder mutation in Macedonian patients.

PubMed

Madjunkova, Svetlana; Kocheva, Svetlana A; Plaseska-Karanfilska, Dijana

2014-01-01

Fanconi anemia (FA) is a rare autosomal recessive disorder clinically characterized by developmental abnormalities, progressive bone marrow failure (BMF) and profound cancer predisposition. Approximately 65% of all affected individuals have mutation in the FANCA (Fanconi anemia complementation group A) gene. The mutation spectrum of the FANCA gene is highly heterogeneous. FA-A is usually associated with private FANCA mutations in individual families. We describe 3 unrelated patients with FA with a similar clinical presentation: BMF, renal anomalies and café-au-lait pigmentation without major skeletal abnormality. The molecular analysis of the FANCA gene using the FA MLPA kit P031-A2/P032 FANCA, showed homozygous deletion of exon 3 in all 3 patients. Molecular analysis of the flanking regions of exon 3 precisely defined unique deletion of 2,040 bp and duplication of C (1788_3828dupC). These are the first 3 patients homozygous for deletion of FANCA exon 3 described to date. Although not related, the patients originated from the same Gypsy-like ethnic population. We conclude that c.190-256_283 + 1680del2040 dupC mutation in the FANCA gene is a founder mutation in Macedonian FA patients of Gypsy-like ethnic origin. Our finding has very strong implications for these patients in formulating diagnostic and carrier-screening strategy for BMF and FA and to enable comprehensive genetic counseling. © 2013 S. Karger AG, Basel.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks.

PubMed

Chun, Min Jeong; Kim, Sunshin; Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-08-16

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway.

Resistance of hypoxic cells to ionizing radiation is influenced by homologous recombination status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sprong, Debbie; Janssen, Hilde L.; Vens, Conchita

2006-02-01

Purpose: To determine the role of DNA repair in hypoxic radioresistance. Methods and Materials: Chinese hamster cell lines with mutations in homologous recombination (XRCC2, XRCC3, BRAC2, RAD51C) or nonhomologous end-joining (DNA-PKcs) genes were irradiated under normoxic (20% oxygen) and hypoxic (<0.1% oxygen) conditions, and the oxygen enhancement ratio (OER) was calculated. In addition, Fanconi anemia fibroblasts (complementation groups C and G) were compared with fibroblasts from nonsyndrome patients. RAD51 foci were studied using immunofluorescence. Results: All hamster cell lines deficient in homologous recombination showed a decrease in OER (1.5-2.0 vs. 2.6-3.0 for wild-types). In contrast, the OER for the DNA-PKcs-deficientmore » line was comparable to wild-type controls. The two Fanconi anemia cell strains also showed a significant reduction in OER. The OER for RAD51 foci formation at late times after irradiation was considerably lower than that for survival in wild-type cells. Conclusion: Homologous recombination plays an important role in determining hypoxic cell radiosensitivity. Lower OERs have also been reported in cells deficient in XPF and ERCC1, which, similar to homologous recombination genes, are known to play a role in cross-link repair. Because Fanconi anemia cells are also sensitive to cross-linking agents, this strengthens the notion that the capacity to repair cross-links determines hypoxic radiosensitivity.« less

Architecture and DNA Recognition Elements of the Fanconi Anemia FANCM-FAAP24 Complex

PubMed Central

Coulthard, Rachel; Deans, Andrew J.; Swuec, Paolo; Bowles, Maureen; Costa, Alessandro; West, Stephen C.; McDonald, Neil Q.

2013-01-01

Summary Fanconi anemia (FA) is a disorder associated with a failure in DNA repair. FANCM (defective in FA complementation group M) and its partner FAAP24 target other FA proteins to sites of DNA damage. FANCM-FAAP24 is related to XPF/MUS81 endonucleases but lacks endonucleolytic activity. We report a structure of an FANCM C-terminal fragment (FANCMCTD) bound to FAAP24 and DNA. This S-shaped structure reveals the FANCM (HhH)2 domain is buried, whereas the FAAP24 (HhH)2 domain engages DNA. We identify a second DNA contact and a metal center within the FANCM pseudo-nuclease domain and demonstrate that mutations in either region impair double-stranded DNA binding in vitro and FANCM-FAAP24 function in vivo. We show the FANCM translocase domain lies in proximity to FANCMCTD by electron microscopy and that binding fork DNA structures stimulate its ATPase activity. This suggests a tracking model for FANCM-FAAP24 until an encounter with a stalled replication fork triggers ATPase-mediated fork remodeling. PMID:23932590

[The significance of sickle cell anemia within the context of the Brazilian government's 'racial policies' (1995-2004)].

PubMed

Fry, Peter H

2005-01-01

This essay reflects on the social significance of growing interest in sickle cell anemia and other illnesses associated with the black body in Brazil. I explore the discursive network that has taken shape around the disease within the social context of its production. I first summarize anthropologist Melbourne Tapper's analysis of the United States program to fight sickle cell anemia in the 1970s, shortly after blacks attained victories in the civil rights movement. Tapper (1999) argues that one of the consequences of this policy was the creation of a responsible black citizenry. In the late 1990s, the Brazilian government developed a program (Programa de Anemia Falciforme) that counted on the heavy participation of black activists and that also contributed to the formation of a "responsible black community". My argument is that sickle cell anemia becomes much more than an illness to be eradicated. The discourse surrounding it is a powerful element in the process of naturalization of the "black race" (and, by logical and political complement, the "white race") in a country that until recently imagined itself a biologically and culturally hybrid nation.

Identification and characterization of novel mutations of the major Fanconi anemia gene FANCA in the Japanese population.

PubMed

Yagasaki, Hiroshi; Hamanoue, Satoshi; Oda, Tsukasa; Nakahata, Tatsutoshi; Asano, Shigetaka; Yamashita, Takayuki

2004-12-01

Fanconi anemia (FA) is a rare autosomal recessive disorder of hematopoiesis, with at least 11 complementation groups. FANCA, a gene for group A, accounts for the majority of FA patients. Previous studies of FANCA mutations revealed high allelic heterogeneity, frequent occurrence of large deletions, and interpopulation differences. However, systematic mutational analysis, including gene dosage assay to detect large deletions, has not been documented for Asian populations. A newly developed TaqMan quantitative PCR-based gene dosage assay, combined with sequencing of exons and cDNA fragments, allowed for detection of 48 mutant alleles of FANCA in 27 (77%) of 35 unrelated Japanese FA families with no detectable mutations in FANCC or FANCG. We identified 29 different mutations (21 nucleotide substitutions or small deletions/insertions and eight large deletions), at least 20 of which were novel. The FANCA mutational spectrum of the Japanese was different from that of other ethnic groups so far studied. This is the largest scale of mutation analysis of FANCA in the Japanese population. Characterization of these mutations provided new information regarding the mutagenesis mechanisms and structure-function relationship of FANCA. Specifically, our data suggest that diverse mechanisms including nonhomologous recombination as well as Alu-mediated homologous recombination are involved in the generation of large deletions in FANCA. Copyright 2004 Wiley-Liss, Inc.

Quiescent complement in nonhuman primates during E coli Shiga toxin-induced hemolytic uremic syndrome and thrombotic microangiopathy.

PubMed

Lee, Benjamin C; Mayer, Chad L; Leibowitz, Caitlin S; Stearns-Kurosawa, D J; Kurosawa, Shinichiro

2013-08-01

Enterohemorrhagic Escherichia coli (EHEC) produce ribosome-inactivating Shiga toxins (Stx1, Stx2) responsible for development of hemolytic uremic syndrome (HUS) and acute kidney injury (AKI). Some patients show complement activation during EHEC infection, raising the possibility of therapeutic targeting of complement for relief. Our juvenile nonhuman primate (Papio baboons) models of endotoxin-free Stx challenge exhibit full spectrum HUS, including thrombocytopenia, hemolytic anemia, and AKI with glomerular thrombotic microangiopathy. There were no significant increases in soluble terminal complement complex (C5b-9) levels after challenge with lethal Stx1 (n = 6) or Stx2 (n = 5) in plasma samples from T0 to euthanasia at 49.5 to 128 hours post-challenge. d-dimer and cell injury markers (HMGB1, histones) confirmed coagulopathy and cell injury. Thus, complement activation is not required for the development of thrombotic microangiopathy and HUS induced by EHEC Shiga toxins in these preclinical models, and benefits or risks of complement inhibition should be studied further for this infection.

[Anemic syndrome frequency in complicated obstetrical patients].

PubMed

Martínez, Maria Guadalupe Veloz; Erasto, Luis Cruz; Maxines, Claudia García; Rodríguez, María Antonia Basavilvazo; Valencia, Marcelino Hernández

2008-09-01

The prevalence of anemia varies from country to country and there is not a trustworthy record. To determine the frequency of anemia in obstetric patients and the association among healthy pregnancy and aggregate complications. Was carried out as transversal, observational and comparative study. Obstetrical patients entered and responded in the period of a year, were formed a group with normal pregnancy and another with complicated pregnancy, with a total sample of 194 patients. In the statistical analysis was employed Student t test for independent groups, with value if p < 0.05. When was included all patients from both groups of study a general frequency of anemia was found in 22.4%. Hematological stage from group with normal pregnancy was mild anemia in 16.9% and anemia moderated in 4.1% of the cases. The anemia degrees in the group with associated illness and pregnancy were mild anemia in 19.2% and moderated anemia in 4.2%. Not any case was found with severe anemia. The statistical analysis showed difference significant among both groups p < 0.05. The most frequently causes of the obstetrical morbidity were preeclampsia severe (22.6%), type 2 diabetes (13.9%), gestational diabetes (12.2%) and the remainder with other complications that include to the hypertiroidism, rheumatoid arthritis, lupus, asthma and vein deep thrombosis. Frequency of anemia in this study was greater upon informing in the international literature. The obstetrical complication more frequently relates to diverse anemia degrees were the hypertensive stage during pregnancy. The anemia is presented with greater frequency in pregnancy patients with others associated illness.

Cloning and characterization of murine fanconi anemia group A gene: Fanca protein is expressed in lymphoid tissues, testis, and ovary.

PubMed

van de Vrugt, H J; Cheng, N C; de Vries, Y; Rooimans, M A; de Groot, J; Scheper, R J; Zhi, Y; Hoatlin, M E; Joenje, H; Arwert, F

2000-04-01

Fanconi anemia (FA) is an autosomal recessive disorder in humans characterized by bone marrow failure, cancer predisposition, and cellular hypersensitivity to cross-linking agents such as mitomycin C and diepoxybutane. FA genes display a caretaker function essential for maintenance of genomic integrity. We have cloned the murine homolog of FANCA, the gene mutated in the major FA complementation group (FA-A). The full-length mouse Fanca cDNA consists of 4503 bp and encodes a protein with a predicted molecular weight of 161 kDa. The deduced Fanca mouse protein shares 81% amino acid sequence similarity and 66% identity with the human protein. The nuclear localization signal and partial leucine zipper consensus motifs found in the human FANCA protein were also present in the murine homolog. In spite of the species difference, the murine Fanca cDNA was capable of correcting the cross-linker sensitive phenotype of human FA-A cells, suggesting functional conservation. Based on Northern as well as Western blots, Fanca was mainly expressed in lymphoid tissues, testis, and ovary. This expression pattern correlates with some of the clinical symptoms observed in FA patients. The availability of the murine Fanca cDNA now allows the gene to be studied in experimental mouse models.

Characteristics of anemia in subclinical and overt hypothyroid patients.

PubMed

Erdogan, Mehmet; Mehmet, Erdogan; Kösenli, Aybike; Aybike, Kosenli; Ganidagli, Sencer; Kulaksizoglu, Mustafa; Mustafa, Kulaksizoglu

2012-01-01

Thyroid hormones stimulate directly or indirectly growth of erythroid colonies through erythropoietin. Anemia is often the first sign of hypothyroidism. Hypothyroidism can cause a wide variety of anemic disorders. Numerous mechanisms are involved in the pathogenesis of these anemias that can be microcytic, macrocytic and normocytic. We designed this study to investigate the anemia frequency and if present, etiology of anemia in hypothyroid patients. 100 patients with overt hypothyroid, 100 patients with subclinical hypothyroid, and 200 healthy controls were enrolled in this study. Overt hypothyroidism diagnosis is done when elevated TSH and low levels of free T4 and/or free T3 have been observed. Subclinical hypothyroidism is defined as elevated serum TSH with normal free T(4) and free T(3) levels. Peripheral smears of the anemic patients were examined. Anemia prevalence was 43% in the overt hypothyroid group, 39% in the subclinical hypothyroid group, and 26% in the control group (p=0.0003 and p=0.021 respectively related to controls). Thus, the frequency of anemia in subclinical hypothyroidism is as high as that in overt hypothyroidism. There was no difference between the hypothyroid groups in terms of anemia. Vitamin B12, Fe, and folic acid were similar between these groups. According to our findings, anemia of chronic disease is the most common type of anemia in hypothyroid patients. Suspicion of hypothyroidism should be considered in anemias with uncertain etiology.

Structural insights into the functions of the FANCM-FAAP24 complex in DNA repair

PubMed Central

Yang, Hui; Zhang, Tianlong; Tao, Ye; Wang, Fang; Tong, Liang; Ding, Jianping

2013-01-01

Fanconi anemia (FA) is a genetically heterogeneous disorder associated with deficiencies in the FA complementation group network. FA complementation group M (FANCM) and FA-associated protein 24 kDa (FAAP24) form a stable complex to anchor the FA core complex to chromatin in repairing DNA interstrand crosslinks. Here, we report the first crystal structure of the C-terminal segment of FANCM in complex with FAAP24. The C-terminal segment of FANCM and FAAP24 both consist of a nuclease domain at the N-terminus and a tandem helix-hairpin-helix (HhH)2 domain at the C-terminus. The FANCM-FAAP24 complex exhibits a similar architecture as that of ApXPF. However, the variations of several key residues and the electrostatic property at the active-site region render a catalytically inactive nuclease domain of FANCM, accounting for the lack of nuclease activity. We also show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. These results reveal the mechanistic insights into the functions of FANCM-FAAP24 in DNA repair. PMID:24003026

Predictors of anemia in preschool children: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

PubMed Central

Aaron, Grant J; Huang, Jin; Varadhan, Ravi; Temple, Victor; Rayco-Solon, Pura; Macdonald, Barbara

2017-01-01

Background: A lack of information on the etiology of anemia has hampered the design and monitoring of anemia-control efforts. Objective: We aimed to evaluate predictors of anemia in preschool children (PSC) (age range: 6–59 mo) by country and infection-burden category. Design: Cross-sectional data from 16 surveys (n = 29,293) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed separately and pooled by category of infection burden. We assessed relations between anemia (hemoglobin concentration <110 g/L) and severe anemia (hemoglobin concentration <70 g/L) and individual-level (age, anthropometric measures, micronutrient deficiencies, malaria, and inflammation) and household-level predictors; we also examined the proportion of anemia with concomitant iron deficiency (defined as an inflammation-adjusted ferritin concentration <12 μg/L). Countries were grouped into 4 categories on the basis of risk and burden of infectious disease, and a pooled multivariable logistic regression analysis was conducted for each group. Results: Iron deficiency, malaria, breastfeeding, stunting, underweight, inflammation, low socioeconomic status, and poor sanitation were each associated with anemia in >50% of surveys. Associations between breastfeeding and anemia were attenuated by controlling for child age, which was negatively associated with anemia. The most consistent predictors of severe anemia were malaria, poor sanitation, and underweight. In multivariable pooled models, child age, iron deficiency, and stunting independently predicted anemia and severe anemia. Inflammation was generally associated with anemia in the high- and very high–infection groups but not in the low- and medium-infection groups. In PSC with anemia, 50%, 30%, 55%, and 58% of children had concomitant iron deficiency in low-, medium-, high-, and very high–infection categories, respectively. Conclusions: Although causal inference is limited by cross-sectional survey data, results suggest anemia-control programs should address both iron deficiency and infections. The relative importance of factors that are associated with anemia varies by setting, and thus, country-specific data are needed to guide programs. PMID:28615260

[Molecular basis of Fanconi's anemia].

PubMed

Digweed, M

1999-01-01

Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterised clinically by progressive bone marrow failure, skeletal deformities and a predisposition to neoplasia. Patient cells manifest an extreme chromosomal instability and hypersensitivity to polyfunctional alkylating agents. It is assumed that the basic defect is related to the repair of DNA damage, in particular that of so-called DNA crosslinks. Currently there are eight complementation groups in FA (FA-A-FA-H) which indicates that at least eight independent genes can lead to FA. Three of these genes have been identified: FANCA, FANCC and FANCG. In this review, the molecular biology and genetics of FA are presented and possible functions of the FANC proteins are discussed.

The association of pagophagia with Helicobacter pylori infection in patients with iron-deficiency anemia.

PubMed

Asma, Suheyl; Boga, Can; Ozdogu, Hakan; Serin, Ender

2009-07-01

This study aimed to determine the relationship between pagophagia (compulsive ice eating) and H. pylori infection in patients with iron-deficiency anemia. We identified H. pylori infection using the (13)C-urea breath test in 45 patients with iron-deficiency anemia (group 1) and 55 patients with iron-deficiency anemia and pagophagia (group 2). Subgroups for testing oral intestinal iron absorption were randomly assigned from both groups. These subgroups consisted of (a) 10 patients with iron-deficiency anemia, (b) 10 patients with iron-deficiency anemia and pagophagia, (c) 10 patients with iron-deficiency anemia, pagophagia, and H. pylori infection before the eradication of H. pylori and (d) subgroup c after eradication therapy. There was no difference in the rate of H. pylori infection in the iron-deficiency anemia groups, with or without pagophagia. Furthermore, oral intestinal iron absorption was not influenced by pagophagia and/or H. pylori infection. Pagophagia did not increase the risk of H. pylori infection in patients with iron-deficiency anemia. Pagophagia and H. pylori infection do not synergistically affect the development of intestinal iron absorption abnormalities.

AMP-activated protein kinase is involved in the activation of the Fanconi anemia/BRCA pathway in response to DNA interstrand crosslinks

PubMed Central

Hwang, Soo Kyung; Kim, Bong Sub; Kim, Hyoun Geun; Choi, Hae In; Kim, Jong Heon; Goh, Sung Ho; Lee, Chang-Hun

2016-01-01

Fanconi anemia complementation group (FANC) proteins constitute the Fanconi Anemia (FA)/BRCA pathway that is activated in response to DNA interstrand crosslinks (ICLs). We previously performed yeast two-hybrid screening to identify novel FANC-interacting proteins and discovered that the alpha subunit of AMP-activated protein kinase (AMPKα1) was a candidate binding partner of the FANCG protein, which is a component of the FA nuclear core complex. We confirmed the interaction between AMPKα and both FANCG using co-immunoprecipitation experiments. Additionally, we showed that AMPKα interacted with FANCA, another component of the FA nuclear core complex. AMPKα knockdown in U2OS cells decreased FANCD2 monoubiquitination and nuclear foci formation upon mitomycin C-induced ICLs. Furthermore, AMPKα knockdown enhanced cellular sensitivity to MMC. MMC treatment resulted in an increase in AMPKα phosphorylation/activation, indicating AMPK is involved in the cellular response to ICLs. FANCA was phosphorylated by AMPK at S347 and phosphorylation increased with MMC treatment. MMC-induced FANCD2 monoubiquitination and nuclear foci formation were compromised in a U2OS cell line that stably overexpressed the S347A mutant form of FANCA compared to wild-type FANCA-overexpressing cells, indicating a requirement for FANCA phosphorylation at S347 for proper activation of the FA/BRCA pathway. Our data suggest AMPK is involved in the activation of the FA/BRCA pathway. PMID:27449087

Exploiting Pre-rRNA Processing in Diamond Blackfan Anemia Gene Discovery and Diagnosis

PubMed Central

Farrar, Jason E.; Quarello, Paola; Fisher, Ross; O’Brien, Kelly A.; Aspesi, Anna; Parrella, Sara; Henson, Adrianna L.; Seidel, Nancy E.; Atsidaftos, Eva; Prakash, Supraja; Bari, Shahla; Garelli, Emanuela; Arceci, Robert J.; Dianzani, Irma; Ramenghi, Ugo; Vlachos, Adrianna; Lipton, Jeffrey M.; Bodine, David M.; Ellis, Steven R.

2014-01-01

Diamond Blackfan anemia (DBA), a syndrome primarily characterized by anemia and physical abnormalities, is one among a group of related inherited bone marrow failure syndromes (IBMFS) which share overlapping clinical features. Heterozygous mutations or single-copy deletions have been identified in 12 ribosomal protein genes in approximately 60% of DBA cases, with the genetic etiology unexplained in most remaining patients. Unlike many IBMFS, for which functional screening assays complement clinical and genetic findings, suspected DBA in the absence of typical alterations of the known genes must frequently be diagnosed after exclusion of other IBMFS. We report here a novel deletion in a child that presented such a diagnostic challenge and prompted development of a novel functional assay that can assist in the diagnosis of a significant fraction of patients with DBA. The ribosomal proteins affected in DBA are required for pre-rRNA processing, a process which can be interrogated to monitor steps in the maturation of 40S and 60S ribosomal subunits. In contrast to prior methods used to assess pre-rRNA processing, the assay reported here, based on capillary electrophoresis measurement of the maturation of rRNA in pre-60S ribosomal subunits, would be readily amenable to use in diagnostic laboratories. In addition to utility as a diagnostic tool, we applied this technique to gene discovery in DBA, resulting in the identification of RPL31 as a novel DBA gene. PMID:25042156

The Fanconi anemia ortholog FANCM ensures ordered homologous recombination in both somatic and meiotic cells in Arabidopsis.

PubMed

Knoll, Alexander; Higgins, James D; Seeliger, Katharina; Reha, Sarah J; Dangel, Natalie J; Bauknecht, Markus; Schröpfer, Susan; Franklin, F Christopher H; Puchta, Holger

2012-04-01

The human hereditary disease Fanconi anemia leads to severe symptoms, including developmental defects and breakdown of the hematopoietic system. It is caused by single mutations in the FANC genes, one of which encodes the DNA translocase FANCM (for Fanconi anemia complementation group M), which is required for the repair of DNA interstrand cross-links to ensure replication progression. We identified a homolog of FANCM in Arabidopsis thaliana that is not directly involved in the repair of DNA lesions but suppresses spontaneous somatic homologous recombination via a RecQ helicase (At-RECQ4A)-independent pathway. In addition, it is required for double-strand break-induced homologous recombination. The fertility of At-fancm mutant plants is compromised. Evidence suggests that during meiosis At-FANCM acts as antirecombinase to suppress ectopic recombination-dependent chromosome interactions, but this activity is antagonized by the ZMM pathway to enable the formation of interference-sensitive crossovers and chromosome synapsis. Surprisingly, mutation of At-FANCM overcomes the sterility phenotype of an At-MutS homolog4 mutant by apparently rescuing a proportion of crossover-designated recombination intermediates via a route that is likely At-MMS and UV sensitive81 dependent. However, this is insufficient to ensure the formation of an obligate crossover. Thus, At-FANCM is not only a safeguard for genome stability in somatic cells but is an important factor in the control of meiotic crossover formation.

Homozygosity mapping of Fanconi anemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gschwend, M.; Botstein, D.; Kruglyak, L.

1994-09-01

Fanconi anemia (FA) is a rare, recessive, genetically heterogeneous disease characterized by progressive insufficiency of the bone marrow and increased cellular sensitivity to DNA crosslinking agents. Complementation tests among different FA cells have indicated the presence of at least 4 FA-causing genes. One of the genes, FACC, was identified by functional complementation but appears unlikely to account for many phenotypically indistinguishable FA caes. We have begun a linkage study of FA using {open_quotes}homozygosity mapping{close_quotes}, a method that involves genotyping with DNA markers on affected individuals whose parents are related. Because FA is a rare recessive disease, it is most likelymore » that probands are homozygous by descent at the disease locus and, therefore, at nearby DNA markers. Although the probability that any given marker will be homozygous in an inbred individual is high, given markers with moderate heterozygosities, the chance that two unrelated inbred individuals will be homozygous at the same marker is considerably lower. By locating overlapping regions of homozygosity between different families we hope to identify genes that cause FA. Sixteen consanguineous non-FACC FA families from the International Fanconi Anemia Registry at Rockefeller University are under study. An efficient algorithm for data analysis was developed and incorporated into software that can quickly compute exact multipoint lod scores using all markers on an entire chromosome. At the time of this writing, 171 of 229 microsatellite markers spaced at 20 cM intervals across the genome have been analyzed.« less

Malfunction of Nuclease ERCC1-XPF Results in Diverse Clinical Manifestations and Causes Cockayne Syndrome, Xeroderma Pigmentosum, and Fanconi Anemia

PubMed Central

Kashiyama, Kazuya; Nakazawa, Yuka; Pilz, Daniela T.; Guo, Chaowan; Shimada, Mayuko; Sasaki, Kensaku; Fawcett, Heather; Wing, Jonathan F.; Lewin, Susan O.; Carr, Lucinda; Li, Tao-Sheng; Yoshiura, Koh-ichiro; Utani, Atsushi; Hirano, Akiyoshi; Yamashita, Shunichi; Greenblatt, Danielle; Nardo, Tiziana; Stefanini, Miria; McGibbon, David; Sarkany, Robert; Fassihi, Hiva; Takahashi, Yoshito; Nagayama, Yuji; Mitsutake, Norisato; Lehmann, Alan R.; Ogi, Tomoo

2013-01-01

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders—CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF. PMID:23623389

Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes Cockayne syndrome, xeroderma pigmentosum, and Fanconi anemia.

PubMed

Kashiyama, Kazuya; Nakazawa, Yuka; Pilz, Daniela T; Guo, Chaowan; Shimada, Mayuko; Sasaki, Kensaku; Fawcett, Heather; Wing, Jonathan F; Lewin, Susan O; Carr, Lucinda; Li, Tao-Sheng; Yoshiura, Koh-ichiro; Utani, Atsushi; Hirano, Akiyoshi; Yamashita, Shunichi; Greenblatt, Danielle; Nardo, Tiziana; Stefanini, Miria; McGibbon, David; Sarkany, Robert; Fassihi, Hiva; Takahashi, Yoshito; Nagayama, Yuji; Mitsutake, Norisato; Lehmann, Alan R; Ogi, Tomoo

2013-05-02

Cockayne syndrome (CS) is a genetic disorder characterized by developmental abnormalities and photodermatosis resulting from the lack of transcription-coupled nucleotide excision repair, which is responsible for the removal of photodamage from actively transcribed genes. To date, all identified causative mutations for CS have been in the two known CS-associated genes, ERCC8 (CSA) and ERCC6 (CSB). For the rare combined xeroderma pigmentosum (XP) and CS phenotype, all identified mutations are in three of the XP-associated genes, ERCC3 (XPB), ERCC2 (XPD), and ERCC5 (XPG). In a previous report, we identified several CS cases who did not have mutations in any of these genes. In this paper, we describe three CS individuals deficient in ERCC1 or ERCC4 (XPF). Remarkably, one of these individuals with XP complementation group F (XP-F) had clinical features of three different DNA-repair disorders--CS, XP, and Fanconi anemia (FA). Our results, together with those from Bogliolo et al., who describe XPF alterations resulting in FA alone, indicate a multifunctional role for XPF. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

The Prevalence of Anemia and Moderate-Severe Anemia in the US Population (NHANES 2003-2012)

PubMed Central

2016-01-01

Since anemia is associated with poor health outcomes, the prevalence of anemia is a significant public health indicator. Even though anemia is primarily caused by iron deficiency, low oxygen-carrying capacity may result from other conditions such as chronic diseases, which remain a relevant health concern in the United States. However, studies examining current rates of anemia in the total US population and in more specific subgroups are limited. Data from five National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2012 were analyzed to assess two outcomes: anemia and moderate-severe anemia, which were based upon serum hemoglobin levels (Hb) as per World Health Organization (WHO) definitions. Statistical analysis using SAS examined temporal trends and the prevalence of anemia among sexes, age groups, and races/ethnicities. The study estimated that an average of 5.6% of the U.S. population met the criteria for anemia and 1.5% for moderate-severe anemia during this 10-year period. High-risk groups such as pregnant women, elderly persons, women of reproductive age, non-Hispanic blacks, and Hispanics were identified, and relationships between multiple risk factors were examined. Rates of anemia in men increased monotonically with age, while that of women increased bimodally with peaks in age group 40–49 years and 80–85 years. The effect of risk factors was observed to compound. For instance, the prevalence of anemia in black women aged 80–85 years was 35.6%, 6.4 times higher than the population average. Moreover, anemia is a growing problem because of the increased prevalence of anemia (4.0% to 7.1%) and moderate-severe anemia (1.0% to 1.9%), which nearly doubled from 2003–2004 to 2011–2012. Thus, these results augment the current knowledge on anemia prevalence, severity, and distribution among subgroups in the US and raised anemia as an issue that requires urgent public health intervention. PMID:27846276

The Prevalence of Anemia and Moderate-Severe Anemia in the US Population (NHANES 2003-2012).

PubMed

Le, Chi Huu Hong

2016-01-01

Since anemia is associated with poor health outcomes, the prevalence of anemia is a significant public health indicator. Even though anemia is primarily caused by iron deficiency, low oxygen-carrying capacity may result from other conditions such as chronic diseases, which remain a relevant health concern in the United States. However, studies examining current rates of anemia in the total US population and in more specific subgroups are limited. Data from five National Health and Nutrition Examination Surveys (NHANES) from 2003 to 2012 were analyzed to assess two outcomes: anemia and moderate-severe anemia, which were based upon serum hemoglobin levels (Hb) as per World Health Organization (WHO) definitions. Statistical analysis using SAS examined temporal trends and the prevalence of anemia among sexes, age groups, and races/ethnicities. The study estimated that an average of 5.6% of the U.S. population met the criteria for anemia and 1.5% for moderate-severe anemia during this 10-year period. High-risk groups such as pregnant women, elderly persons, women of reproductive age, non-Hispanic blacks, and Hispanics were identified, and relationships between multiple risk factors were examined. Rates of anemia in men increased monotonically with age, while that of women increased bimodally with peaks in age group 40-49 years and 80-85 years. The effect of risk factors was observed to compound. For instance, the prevalence of anemia in black women aged 80-85 years was 35.6%, 6.4 times higher than the population average. Moreover, anemia is a growing problem because of the increased prevalence of anemia (4.0% to 7.1%) and moderate-severe anemia (1.0% to 1.9%), which nearly doubled from 2003-2004 to 2011-2012. Thus, these results augment the current knowledge on anemia prevalence, severity, and distribution among subgroups in the US and raised anemia as an issue that requires urgent public health intervention.

Early severe anemia as the first sign of cystic fibrosis.

PubMed

Sismanlar, Tugba; Aslan, Ayşe Tana; Köse, Mehmet; Pekcan, Sevgi; Ezgü, Fatih Süheyl; Budakoğlu, Işıl İrem; Yenicesu, İdil

2016-09-01

Severe anemia is reported to occur rarely in patients with cystic fibrosis (CF). This study aimed to determine the factors associated with early severe anemia in infants with CF. This study included 231 infants with CF from 3 pediatric CF centers ten year period that were retrospectively reviewed in terms of severe anemia as the first sign of CF. Factors that could affect anemia, such as age, pancreatic insufficiency, mutations, vitamin A and E, and albumin level were evaluated. Clinical and laboratory findings in CF patients that presented with severe anemia and no respiratory symptoms were compared to those in CF patients that did not present with severe anemia. Severe anemia as the first sign of CF was noted in 17 of 231 patients. Patient age, prolonged PT/INR and the albumin level differed significantly between the 2 groups of patients (P < 0.001). Feeding pattern, pancreatic insufficiency, vitamin E and A levels, and the types of genetic mutations did not differ between the 2 groups. The mean hemoglobin level was 5.59 ± 0.21 g/dL and respiratory symptoms began a mean 6.3 months after diagnosis of CF in the anemia group. In early infancy severe anemia in the absence of respiratory symptoms can be the first sign of CF. CF should be considered in the differential diagnosis of severe anemia in infants. Anemia can occur several months before respiratory symptoms in patients with CF and may be caused due to several reasons. • Severe anemia as a first sign is reported to occur rarely in patients with cystic fibrosis. • Although anemia is well known in cystic fibrosis, factors that cause severe anemia are not known clearly. What is New: • This study shows the importance of severe anemia as the first sign of cystic fibrosis. • Anemia can occur several months before respiratory symptoms in patients with CF.

Iron-deficiency anemia as a subclinical celiac disease presentation in an Argentinian population.

PubMed

Lasa, J S; Olivera, P; Soifer, L; Moore, R

There is a wide heterogeneity in the reports of celiac disease prevalence in iron-deficiency anemia patients. To determine the prevalence of celiac disease in patients with iron-deficiency anemia. Adult patients with a diagnosis of iron-deficiency anemia were enrolled for upper endoscopy with duodenal biopsies. Healthy volunteers that underwent upper endoscopy were enrolled as controls. A total of 135 patients with iron-deficiency anemia and 133 controls were enrolled. Celiac disease prevalence was higher in the iron-deficiency anemia group [11.11 vs. 1.51%, OR: 8.18 (1.83-36.55), P=.001). Of the celiac disease patients in the iron-deficiency anemia group, 73.3% had at least one endoscopic sign suggesting villous atrophy, whereas 100% of the celiac disease patients in the control group presented with at least one endoscopic sign. Patients with iron-deficiency anemia have an increased risk for celiac disease. Up to 25% of these patients may not present any endoscopic sign suggesting villous atrophy. Copyright © 2017 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors.

PubMed

Taniguchi, Toshiyasu; Tischkowitz, Marc; Ameziane, Najim; Hodgson, Shirley V; Mathew, Christopher G; Joenje, Hans; Mok, Samuel C; D'Andrea, Alan D

2003-05-01

Ovarian tumor cells are often genomically unstable and hypersensitive to cisplatin. To understand the molecular basis for this phenotype, we examined the integrity of the Fanconi anemia-BRCA (FANC-BRCA) pathway in those cells. This pathway regulates cisplatin sensitivity and is governed by the coordinate activity of six genes associated with Fanconi anemia (FANCA, FANCC, FANCD2, FANCE, FANCF and FANCG) as well as BRCA1 and BRCA2 (FANCD1). Here we show that the FANC-BRCA pathway is disrupted in a subset of ovarian tumor lines. Mono-ubiquitination of FANCD2, a measure of the function of this pathway, and cisplatin resistance were restored by functional complementation with FANCF, a gene that is upstream in this pathway. FANCF inactivation in ovarian tumors resulted from methylation of its CpG island, and acquired cisplatin resistance correlated with demethylation of FANCF. We propose a model for ovarian tumor progression in which the initial methylation of FANCF is followed by FANCF demethylation and ultimately results in cisplatin resistance.

Combined prognostic value of pretreatment anemia and cervical node necrosis in patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: A large-scale retrospective study.

PubMed

Zhang, Lu-Lu; Zhou, Guan-Qun; Li, Yi-Yang; Tang, Ling-Long; Mao, Yan-Ping; Lin, Ai-Hua; Ma, Jun; Qi, Zhen-Yu; Sun, Ying

2017-12-01

This study investigated the combined prognostic value of pretreatment anemia and cervical node necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC). Retrospective review of 1302 patients with newly diagnosed nonmetastatic NPC treated with intensity-modulated radiotherapy (IMRT) ± chemotherapy. Patients were classified into four groups according to anemia and CNN status. Survival was compared using the log-rank test. Independent prognostic factors were identified using the Cox proportional hazards model. The primary end-point was overall survival (OS); secondary end-points were disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS). Pretreatment anemia was an independent, adverse prognostic factor for DMFS; pretreatment CNN was an independent adverse prognostic factor for all end-points. Five-year survival for non-anemia and non-CNN, anemia, CNN, and anemia and CNN groups were: OS (93.1%, 87.2%, 82.9%, 76.3%, P < 0.001), DFS (87.0%, 84.0%, 73.9%, 64.6%, P < 0.001), DMFS (94.1%, 92.1%, 82.4%, 72.5%, P < 0.001), and LRRFS (92.8%, 92.4%, 88.7%, 84.0%, P = 0.012). The non-anemia and non-CNN group had best survival outcomes; anemia and CNN group, the poorest. Multivariate analysis demonstrated combined anemia and CNN was an independent prognostic factor for OS, DFS, DMFS, and LRRFS (P < 0.05). The combination of anemia and CNN is an independent adverse prognostic factor in patients with NPC treated using IMRT ± chemotherapy. Assessment of pretreatment anemia and CNN improved risk stratification, especially for patients with anemia and CNN who have poorest prognosis. This study may aid the design of individualized treatment plans to improve treatment outcomes. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Prevalence of anemia and consumption of iron-rich food groups in Mexican children and adolescents: Ensanut MC 2016.

PubMed

De la Cruz-Góngora, Vanessa; Villalpando, Salvador; Shamah-Levy, Teresa

2018-01-01

To describe the prevalence of anemia and con-sumption of iron rich groups among Mexican children and adolescents who participated in the Halfway National Health and Nutrition Survey, 2016. Our study sample included children and adolescents who provided full capillary hemoglobin data. Anemia was defined accord-ing to WHO criteria. Logistic regression models were used to explore the association among consumption of iron-rich food groups, sociodemographic characteristics and anemia. In 2016, the prevalence of anemia was 26.9% in children aged 1 to 4 years old, 12.5% in those aged 5 to 11, and 9.6% in adolescents aged 12 to 19 years. Rates were the highest among females who lived in the southern and central parts of Mexico, belonged to an indigenous ethnic group and fell within the first tercile of the Household Wealth Index. Consumption of beef by preschoolers and viscera by ado-lescents was associated with lower risk for anemia; higher risk was associated with consumption of Liconsa milk and non-heme iron by preschoolers. Anemia is highly prevalent in Mexican children and adolescents, affect-ing mainly the poorest and youngest populations. Sources of heme iron are the principal dietary factor associated with low risk for anemia.

[Effect of anemia on child development: long-term consequences].

PubMed

Zavaleta, Nelly; Astete-Robilliard, Laura

2017-01-01

Anemia in children younger than 3 years is a public health problem in Peru and worldwide. It is believed that one of the primary causes of anemia is iron deficiency. Numerous studies and reviews have reported that iron deficiency limited psychomotor development in children and that, despite the correction of anemia, children with iron deficiency experienced poorer long-term performance in cognitive, social, and emotional functioning. These outcomes were reported in observational studies, follow-up studies, and experimental studies with a control group. Anemia can decrease school performance, productivity in adult life, quality of life, and the general income of affected individuals. Here we describe possible mechanisms underlying the effect of iron deficiency, with or without anemia, on childhood development. The high rate of anemia in this age group is a cause for concern. Moreover, anemia should be prevented in the first year of life to avoid long-term negative effects on individual development.

Polymorphisms within the FANCA gene associate with premature ovarian failure in Korean women.

PubMed

Pyun, Jung-A; Kim, Sunshin; Cha, Dong Hyun; Kwack, KyuBum

2014-05-01

This study investigated whether polymorphisms within the Fanconi anemia complementation group A (FANCA) gene contribute to the increased risk of premature ovarian failure (POF) in Korean women. Ninety-eight women with POF and 218 controls participated in this study. Genomic DNA from peripheral blood was isolated, and GoldenGate genotyping assay was used to identify single nucleotide polymorphisms (SNPs) within the FANCA gene. Two significant SNPs (rs1006547 and rs2239359; P < 0.05) were identified by logistic regression analysis, but results were insignificant after Bonferroni correction. Six SNPs formed a linkage disequilibrium block, and three main haplotypes were found. Two of three haplotypes (AAAGAA and GGGAGG) distributed highly in the POF group, whereas the remaining haplotype (GGAAGG) distributed highly in the control group by logistic regression analysis (highest odds ratio, 2.515; 95% CI, 1.515-4.175; P = 0.00036). Our observations suggest that genetic variations in the FANCA gene may increase the risk for POF in Korean women.

Frequency of and reasons for paroxysmal nocturnal haemoglobinuria screening in patients with unexplained anaemia.

PubMed

England, James T; Dalal, Bakul; Leitch, Heather A

2018-04-01

Referral to hematology for anemia is common. In paroxysmal nocturnal hemoglobinuria (PNH), cells deficient in the glycosylphosphatidyl inositol (GPI) anchor are lysed by complement. Eculizumab improves overall survival and quality of life while reducing hemolysis, transfusion requirements, and thrombosis. We evaluated the frequency of screening for PNH in patients with unexplained anemia. Key clinical features, laboratory data, and investigations were recorded for patients referred for anemia since 2010, without a specific cause found. PNH testing was done by flow cytometry. 540 patients had: anemia not yet diagnosed (NYD, n=318 (including unexplained iron deficiency, n=92; DAT-negative hemolysis, n=9)); anemia of chronic disease, n=173; and pancytopenia NYD, n=49. 82.4% had LDH testing done; 85.0% total bilirubin; 78.7% reticulocyte counts; and 40.6% haptoglobin level; 131 (24.2%) had possible hemolysis. PNH testing was done in 56 (10.4%). Those screened for PNH were more likely to have: younger age (P=0.04); a history of thrombosis (P<0.001); undergone a BMBx (P<0.001); received RBC transfusions (P=0.0018); or evidence of DAT-negative hemolysis (P<0.001). In summary, PNH was tested for in a minority of patients with unexplained anemia (10.4%) despite potential indicators of hemolysis in 24.2%. Increased screening could identify patients who would benefit from treatment and should be considered. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex.

PubMed

Garcia-Higuera, I; Kuang, Y; Denham, J; D'Andrea, A D

2000-11-01

Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FA-A cell line, with a reciprocal increase in the half-life of FANCG. Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm. The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA.

[Laboratory diagnosis of auto-immune hemolytic anemia: characteristics of the manual direct test of Polybrene].

PubMed

Braga, G W; Bordin, J O; Moreira Júnior, G; Kuroda, A

1998-01-01

The direct manual Polybrene test (DPT) and the direct antiglobulin tests (DAT) were employed to detect antibody sensitizing red blood cell (RCB) in patients with clinical and laboratorial findings of autoimmune hemolytic anemia (AIHA). To compare the sensitivity and specificity of DPT and DAT in the diagnosis of AIHA. Eighteen consecutive patients with diagnosis of AIHA were evaluated. The control group consisted of 20 normal volunteers blood donors and 20 patients with sickle cell anemia. All patients and controls were submitted to DPT and DAT. All DAT positive samples were further tested using monospecific reagents (anti-IgG heavy chain and anti-C3d). Positive samples for either DPT or DAT were evaluated by eluate technique using. The dichloromethane (DCM). The DAT was positive in 14 patients and negative in 4 subjects, while the DPT was positive in 17 patients and negative in 1 individual who had a positive DAT owing to complement (C3d). All positive eluates performed with DCM showed RBC autoantibodies with presumed "anti-Rh" specificity. The sensitivity rate of the DPT (94%) was significantly (p < 0.05) higher than the sensitivity rate of DAT (78%) to determine whether IgG was bound in vivo, but no difference was found regarding the specificity of the two tests. 1) The DPT is more sensitive than the DAT in detecting IgG autoantibody on the RBCs of patients with AIHA; 2) because of its simplicity and rapidity, the DPT is a useful additional screening test for the investigation of Coombs-negative AIHA.

Anemia as a complication of parvovirus b19 infection in renal transplant recipients.

PubMed

Čapenko, Svetlana; Kozireva, Svetlana; Folkmane, Inese; Bernarde, Kristīna; Rozentāls, Rafails; Murovska, Modra

2012-01-01

The frequency of B19 infection in renal transplant donors and recipients was studied to determine the significance of active viral infection in the development of anemia. Serum, plasma, and peripheral blood leukocyte samples of 47 renal transplant donors, 38 recipients with anemia (Group 1), and 25 without anemia (Group 2) after renal transplantation were evaluated for the presence of anti-B19 specific antibodies (ELISA) and B19 DNA (nPCR). Active persistent B19 infection after renal transplantation was detected in 12 of the 38 in the Group 1 (10 had reactivation and 2 primary infection), and none of the recipients in the Group 2 had it. Of the 12 recipients in the Group 1, 10 were seropositive and 2 seronegative before renal transplantation; 10 received the transplants from the seropositive and 2 from seronegative donors. rHuEPO therapy-resistant severe anemia was detected only in the recipients with active B19 infection after renal transplantation in the Group 1 (7/12). The logistic regression analysis revealed a significant relationship between active B19 infection and severe anemia (OR, 0.039; 95% CI, 0.006-0.257; P=0.001). Active B19 infection was documented only in the anemic recipients and could be associated with the development of severe anemia after renal transplantation. This allows us to recommend concurrent screening for viral DNA in plasma and detection of anti-B19 IgM class antibodies. To find the association between B19 infection and the development of anemia, further investigations are necessary.

Can soluble transferrin receptor be used in diagnosing iron deficiency anemia and assessing iron response in infants with moderate acute malnutrition?

PubMed

Büyükkaragöz, Bahar; Akgun, Necat A; Bulus, Ayse D; Durmus Aydogdu, Sultan; Bal, Cengiz

2017-04-01

To evaluate the efficacy of soluble transferrin receptor (sTfR) in diagnosing iron deficiency anemia (IDA) and evaluating iron response in infants with moderate acute malnutrition (MAM). Infants with hemoglobin (Hb) levels lower than threshold values for anemia for their ages and hypochromic/ microcytic anemia on peripheral smear were recruited. MAM was defined as weight/height z score < -2 to -3. Complete blood count (CBC), iron parameters and sTfR were compared among 41 infants with MAM and anemia (MA group), 32 infants with anemia without MAM (group A), and healthy controls (n= 30). Following anemia and malnutrition treatment, tests were repeated. Besides hematological indices compatible with IDA, serum iron (Fe) and transferrin saturation (TS) were significantly lower, while transferrin was significantly higher in MA and A groups compared to controls (p <0.001). Ferritin and C-reactive protein (CRP) were significantly higher in MA group (p <0.05 ferritin, p 0.01 for CRP). Mean sTfR was similar in both MA and A groups (p >0.05) and significantly higher than controls (p <0.001). Following iron treatment, sTfR decreased in both MA and A groups (p <0.001) to similar values as controls. sTfR was negatively correlated to Hb throughout the study (for MA group, r= -0.350, p <0.05; for A group, r= -0.683, p <0.01). As sTfR values in both MA and A groups decreased following iron treatment, we believe that this parameter was not influenced by MAM or inflammation; and it alone can be used to detect IDA and monitor treatment response in infants with MAM.

[Temporal evolution of anemia prevalence in pregnant adolescents of a public maternity of Rio de Janeiro].

PubMed

Pessoa, Lidiane da Silva; Saunders, Cláudia; Belfort, Gabriella Pinto; da Silva, Letícia Barbosa Gabriel; Veras, Lívia Soares; Esteves, Ana Paula Vieira dos Santos

2015-05-01

To describe the evolution of the prevalence of anemia in pregnant adolescents attended at a public maternity in the city of Rio de Janeiro from 2004 to 2013. A retrospective cross-sectional study with 628 pregnant/postpartum women divided into 3 groups: Group A (2004-2006), Group B (2007-2010) and Group C (2013). Information about anthropometric, clinical, sociodemographic data and obstetric and prenatal care of adolescents was obtained from medical records of the pregnant women. A hemoglobin concentration n<11 g/dL was considered to be anemia. Data were analyzed statistically by the chi-square test, Student's t-test and ANOVA, and the post hoc Tukey test. The prevalence of gestational anemia over the years was 43% (GA=138), 36% (GB=80) and 47.1% (GC=40) and the overall prevalence for the 2004-2013 period was 41.1% (n=258). The occurrence of anemic pregnant women increased with the progression of pregnancy; however, in the 3rd quarter there was a decrease in the prevalence of anemia in GB (29.3%) compared to GA (38.7%; p=0.04). Factors associated with anemia were number of prenatal visits and prenatal nutritional assistance, place of residence, pre-pregnancy BMI, and gestational weight gain. The results showed that the prevalence of anemia among pregnant adolescents seen at a public maternity is high. There was no reduction of anemia during the study period and other factors in addition to iron deficiency were involved in the genesis of anemia in this population.

Novel Variations of FANCA Gene Provokes Fanconi Anemia: Molecular Diagnosis in a Special Chinese Family.

PubMed

Li, Niu; Song, Aiyun; Ding, Lixia; Zhu, Hua; Li, Guoqiang; Miao, Yan; Wang, Jian; Li, Benshang; Chen, Jing

2018-07-01

Fanconi anemia (FA) is a rare autosomal recessive or X-linked disorder with highly variable clinical manifestations and an incidence of ∼1 to 5 in 1 million births. To date, 15 bona fide FA genes have been reported to be responsible for the known FA complementation groups and the FANCA gene accounts for almost 60%. In the present study, we report a special Chinese family, which has 2 children with classic FA characteristics. Via 2-step analysis of the whole-exome sequencing data and verification using multiplex ligation-dependent probe amplification test, one child was found to have a novel compound heterozygous mutation of a splicing variant (c.1471-1G>A) and a large intragenic deletion (exons 23-30 del) of the FANCA gene. The other child had the same splicing variant and another novel large deletion (exons 1-18 del) in the FANCA gene. Clone sequencing showed the c.1471-1G>A variant generate an altered transcript with 1 cryptic splice site in intron 15, resulting in a premature termination codon (p.Val490HisfsX6). This study not only shows the complexity of FA molecular diagnosis via comprehensively studying the FA pathogenic genes and the mutational spectrum, but also has significant reference value for the future molecular diagnosis of FA.

The genomic organization of the Fanconi anemia group A (FAA) gene

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ianzano, L.; Centra, M.; Savino, M.

1997-05-01

Fanconi anemia (FA) is a genetically heterogeneous disease involving at least five genes on the basis of complementation analysis (FAA to FAE). The FAA gene has been recently isolated by two independent approaches, positional and functional cloning. In the present study we describe the genomic structure of the FAA gene. The gene contains 43 exons spanning approximately 80 kb as determined by the alignment of four cosmids and the fine localization of the first and the last exons in restriction fragments of these clones. Exons range from 34 to 188 bp. All but three of the splice sites were consistentmore » with the ag-gt rule. We also describe three alternative splicing events in cDNA clones that result in the loss of exon 37, a 23-bp deletion at the 5{prime} end of exon 41. Sequence analysis of the 5{prime} region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes. Knowledge of the structure of the FAA gene will provide an invaluable resource for the discovery of mutations in the gene that accounts for about 60-66% of FA patients. 24 refs., 3 figs., 1 tab.« less

Factors Influencing the Use of Biomedical Health Care by Rural Bolivian Anemic Women: Structural Barriers, Reproductive Status, Gender Roles, and Concepts of Anemia.

PubMed

Bedwell, Rebecca M; Spielvogel, Hilde; Bellido, Diva; Vitzthum, Virginia J

2017-01-01

Non-pregnant women from a rural town and its surrounding region were tested for anemia. During phase 1 (n = 181), anemic women received a written recommendation for low-cost purchase of iron pills at the nearest health center. They were subsequently interviewed on their actions and experiences. Estimated anemia prevalence among these non-pregnant women was 50% higher than the national average. Despite holding conceptualizations of anemia generally aligned with biomedical concepts, only 40% of anemic women attempted to obtain iron supplements from the health center. Town residents were about twice as likely to attempt to purchase pills as outside-town residents. Town women who were concurrently breastfeeding and menstruating, considered anemia most serious for women, and considered family health the shared responsibility of spouses were most likely to decide to purchase iron pills. Age, education, or native language did not negatively influence this health care behavior. Securing iron supplements involves individual trade-offs in the allocation of time, cost and effort. Nonetheless, suitably tailored programs can potentially harness local perceptions in the service of reducing anemia. Because of their comparatively high motivation to obtain iron supplements, targeting concurrently breastfeeding and menstruating women could have a positive cascade effect such that these women continue attending to their iron needs once they stop breastfeeding and if they become pregnant again. Because a sense of shared responsibility for family health appears to encourage women to attend to their own health, programs for women could involve their spouses. Complementing centralized availability, biomedical and traditional healers could distribute iron supplements on rotating visits to outlying areas and/or at highly attended weekly markets.

Suicidal death of erythrocytes in cancer and its chemotherapy: A potential target in the treatment of tumor-associated anemia.

PubMed

Lang, Elisabeth; Bissinger, Rosi; Qadri, Syed M; Lang, Florian

2017-10-15

In analogy to apoptosis of nucleated cells, erythrocytes may enter eryptosis characterized by cell shrinkage and cell membrane scrambling. Eryptotic erythrocytes are rapidly cleared from circulating blood and may adhere to the vascular wall. Stimulation of eryptosis thus impairs microcirculation and leads to anemia as soon as the loss of erythrocytes cannot be fully compensated by enhanced erythropoiesis. Signaling stimulating eryptosis includes increase of cytosolic Ca 2+ -activity, ceramide, caspases, calpain, p38-kinase, protein-kinase C, Janus-activated kinase 3, casein-kinase 1α, and cyclin-dependent kinase 4. Eryptosis is inhibited by AMP-activated kinase, p21-activated kinase 2, cGMP-dependent protein-kinase, mitogen- and stress-activated kinase, and sorafenib- and sunitinib-sensitive tyrosine-kinases. Eryptosis is triggered by complement, hyperosmotic shock, energy-depletion, oxidative stress, multiple xenobiotics including diverse cytostatic drugs, diabetes, hepatic failure, iron-deficiency, chronic kidney disease, hemolytic-uremic-syndrome, fever, systemic lupus erythematosus, infections, sepsis, sickle cell anemia, thalassemia, glucose-6-phosphate-dehydrogenase deficiency, and Wilson´s disease. Compelling evidence points to a decisive role of eryptosis in anemia of malignancy. As shown for lung cancer, eryptosis inducing plasma components accumulate in cancer patients and trigger oxidative stress and ceramide. The tumor-induced eryptosis leads to anemia despite increased erythropoiesis. The stimulation of eryptosis in malignancy is compounded by cytostatic treatment, as a large number of cytostatic agents trigger eryptosis. Inhibiting eryptosis may be a useful strategy in reducing tumor-induced anemia and impaired microcirculation. Inhibitors of eryptosis may, however, be harmful, if they similarly interfere with death of tumor cells. Clearly, additional experimental effort is required to achieve killing of tumor cells with simultaneous avoidance of stimulated eryptosis. © 2017 UICC.

Elevated levels of STAT1 in Fanconi anemia group A lymphoblasts correlate with the cells’ sensitivity to DNA interstrand crosslinking drugs

PubMed Central

Prieto-Remón, Inés; Sánchez-Carrera, Dámaso; López-Duarte, Mónica; Richard, Carlos; Pipaón, Carlos

2013-01-01

Progressive bone marrow failure starting in the first decade of life is one of the main characteristics of Fanconi anemia. Along with the bone marrow failure, this pathology is characterized by congenital malformations, endocrine dysfunction and an extraordinary predisposition to develop cancer. The fact that hematopoietic progenitor cells from subjects with Fanconi anemia are sensitive to both DNA-interstrand crosslinking agents and inflammatory cytokines, which are aberrantly overproduced in these patients, has led to different explanations for the causes of the bone marrow failure. We analyzed STAT1 expression in lymphoblastoid cell lines derived from patients with Fanconi anemia group A and correlated this with aspects of the Fanconi anemia phenotype such as sensitivity to genotoxic agents or to inhibitory cytokines. We provide evidence of overexpression of STAT1 in FANCA-deficient cells which has both transcriptional and post-translational components, and is related to the constitutive activation of ERK in Fanconi anemia group A cells, since it can be reverted by treatment with U0126. STAT1 phosphorylation was not defective in the lymphoblasts, so these cells accumulated higher levels of active STAT1 in response to interferon gamma, probably in relation to their greater sensitivity to this cytokine. On the other hand, inhibition of STAT1 by genetic or chemical means reverted the hypersensitivity of Fanconi anemia group A lymphoblasts to DNA interstrand crosslinking agents. Our data provide an explanation for the mixed sensitivity of Fanconi anemia group A cells to both genotoxic stress and inflammatory cytokines and indicate new targets for the treatment of bone marrow failure in these patients. PMID:23585528

Factors Influencing the Use of Biomedical Health Care by Rural Bolivian Anemic Women: Structural Barriers, Reproductive Status, Gender Roles, and Concepts of Anemia

PubMed Central

Bedwell, Rebecca M.; Spielvogel, Hilde; Bellido, Diva

2017-01-01

The persistently high prevalence of anemia in rural highland Bolivia argues for targeted iron supplementation. We evaluated the cultural, structural and behavioral factors that may facilitate or impede an anemic woman's decision to secure this biomedical treatment from a rural Bolivian health center. Methods Non-pregnant women from a rural town and its surrounding region were tested for anemia. During phase 1 (n = 181), anemic women received a written recommendation for low-cost purchase of iron pills at the nearest health center. They were subsequently interviewed on their actions and experiences. Results Estimated anemia prevalence among these non-pregnant women was 50% higher than the national average. Despite holding conceptualizations of anemia generally aligned with biomedical concepts, only 40% of anemic women attempted to obtain iron supplements from the health center. Town residents were about twice as likely to attempt to purchase pills as outside-town residents. Town women who were concurrently breastfeeding and menstruating, considered anemia most serious for women, and considered family health the shared responsibility of spouses were most likely to decide to purchase iron pills. Age, education, or native language did not negatively influence this health care behavior. Conclusions Securing iron supplements involves individual trade-offs in the allocation of time, cost and effort. Nonetheless, suitably tailored programs can potentially harness local perceptions in the service of reducing anemia. Because of their comparatively high motivation to obtain iron supplements, targeting concurrently breastfeeding and menstruating women could have a positive cascade effect such that these women continue attending to their iron needs once they stop breastfeeding and if they become pregnant again. Because a sense of shared responsibility for family health appears to encourage women to attend to their own health, programs for women could involve their spouses. Complementing centralized availability, biomedical and traditional healers could distribute iron supplements on rotating visits to outlying areas and/or at highly attended weekly markets. PMID:28125636

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

PubMed

Strauss, J; Pardo, V; Koss, M N; Griswold, W; McIntosh, R M

1975-03-01

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

Mutation analysis of the Fanconi Anemia Gene FACC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verlander, P.C.; Lin, J.D.; Udono, M.U.

1994-04-01

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder characterized by a unique hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C (FACC) has recently been cloned. The authors have amplified FACC exons with their flanking intron sequences from genomic DNA from 174 racially and ethnically diverse families in the International Fanconi Anemia Registry and have screened for mutations by using SSCP analysis. They have identified eight different variants in 32 families; three were detected in exon 1, one in exon 4, one in intron 4, two in exon 6, and one in exon 14.more » Two of the eight variants, in seven families, did not segregate with the disease allele in multiplex families, suggesting that these variants represented benign polymorphisms. Disease-associated mutations in FACC were detected in a total of 25 (14.4%) of 174 families screened. The most frequent mutations were IVS4 + 4 A [yields] T (intron 4; 12 families) and 322delG (exon 1; 9 families). Other, less common mutations include Q13X in exon 1, R185X and D195V in exon 6, and L554P in exon 14. The polymorphisms were S26F in exon 1 and G139E in exon 4. All patients in the study with 322delG, Q13X, R185X, and D195V are of northern or eastern European or southern Italian ancestry, and 18 of 19 have a mild form of the disease, while the 2 patients with L554P, both from the same family, have a severe phenotype. All 19 patients with IVS4 + 4 A [yields] T have Jewish ancestry and have a severe phenotype. 19 refs., 1 fig., 3 tabs.« less

The Fanconi anemia pathway sensitizes to DNA alkylating agents by inducing JNK-p53-dependent mitochondrial apoptosis in breast cancer cells.

PubMed

Zhao, Lin; Li, Yanlin; He, Miao; Song, Zhiguo; Lin, Shu; Yu, Zhaojin; Bai, Xuefeng; Wang, Enhua; Wei, Minjie

2014-07-01

The Fanconi anemia/BRCA (FA/BRCA) DNA damage repair pathway plays a pivotal role in the cellular response to DNA alkylating agents and greatly influences drug response in cancer treatment. However, the molecular mechanisms underlying the FA/BRCA pathway reversed resistance have received limited attention. In the present study, we investigated the effect of Fanconi anemia complementation group F protein (FANCF), a critical factor of the FA/BRCA pathway, on cancer cell apoptosis induced by DNA alkylating agents such as mitomycin c (MMC). We found that FANCF shRNA potentiated MMC-induced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 breast cancer cells. At a mechanistic level, FANCF shRNA downregulated the anti-apoptotic protein Bcl-2 and upregulated the pro-apoptotic protein Bax, accompanied by release of cyt-c and smac into the cytosol in MMC-treated cells. Furthermore, activation of caspase-3 and -9, other than caspase-8, cleavage of poly(ADP ribose) polymerase (PARP), and a decrease of mitochondrial membrane potential (MMP) indicated that involvement of the mitochondrial apoptotic pathway in FANCF silencing of MMC-treated breast cancer cells. A decrease in IAP family proteins XIAP and survivin were also observed following FANCF silencing in MMC-treated breast cancer cells. Notably, FANCF shRNA was able to increase p53 levels through activation of the JNK pathway in MMC-treated breast cancer cells. Furthermore, p53 inhibition using pifithrin-α abolished the induction of caspase-3 and PARP by FANCF shRNA and MMC, indicating that MMC-induced apoptosis is substantially enhanced by FANCF shRNA via p53-dependent mechanisms. To our knowledge, we provide new evidence for the potential application of FANCF as a chemosensitizer in breast cancer therapy.

Multiparameter FLAER-based flow cytometry for screening of paroxysmal nocturnal hemoglobinuria enhances detection rates in patients with aplastic anemia.

PubMed

Sachdeva, Man Updesh Singh; Varma, Neelam; Chandra, Dinesh; Bose, Parveen; Malhotra, Pankaj; Varma, Subhash

2015-05-01

Flow cytometry is the gold standard methodology for screening of paroxysmal nocturnal hemoglobinuria. In the last few years, proaerolysin conjugated with fluorescein (FLAER) has become an important component of antibody panel used for the detection of paroxysmal nocturnal hemoglobinuria (PNH) clone. This study aimed to compare PNH clone detection by flow cytometry in the pre-FLAER era versus the FLAER era. This was a retrospective analysis of 4 years and included 1004 individuals screened for PNH clone, either presenting as hemolytic anemia or as aplastic anemia. In the pre-FLAER time period, the RBCs and neutrophils were screened with antibodies against CD55 and CD59. With the introduction of FLAER, neutrophils were screened with FLAER/CD24/CD15 and monocytes with FLAER/CD14/CD33 combination. A comparative analysis was done for detection of PNH clone in aplastic anemia patients versus non-aplastic anemia patients, as well as between pre-FLAER and FLAER era. Out of a total of 1004 individuals, 59 (5.8%) were detected to have PNH clone positivity. The frequency of PNH clone detected in aplastic anemia and non-aplastic anemia groups was 12.02 and 3.36%, respectively. The detection rate of PNH clone increased from 4.5% (32/711) in the pre-FLAER era to 9.2% (27/293) with the introduction of FLAER. However, this increase could be attributed to increased detection of PNH clone in the aplastic anemia group, which showed a significant increase from 8.3 to 18.2% after use of FLAER. In the non-aplastic group, PNH clone was detected with similar frequencies before and after use of FLAER (3.2 versus 3.8%, respectively). Mean PNH clone size was lower in the aplastic anemia group when compared with the non-aplastic group. RBCs always showed a lower clone size than neutrophils. PNH clone on neutrophils and monocytes was however similar. Inclusion of FLAER increases the sensitivity of the test which is especially useful in picking up small PNH clones in patients of aplastic anemia.

Chlorella pyrenoidosa supplementation reduces the risk of anemia, proteinuria and edema in pregnant women.

PubMed

Nakano, Shiro; Takekoshi, Hideo; Nakano, Masuo

2010-03-01

Pregnancy anemia and pregnancy-induced hypertension (PIH) are common and potentially dangerous disorder in human pregnancy, and nutritional status of pregnant women is one of the leading causes. Chlorella contains large quantities of folate, vitamin B-12 and iron, and can help improve anemia and hypertensive disorder. Our objective was to investigate the preventive effects of Chlorella supplement on pregnancy anemia and PIH in Japanese pregnant women. A total of 70 pregnant women were placed into the control group (n = 38) or the Chlorella group (n = 32). The subjects in the Chlorella group were supplemented daily from 12th-18th wk of gestation until delivery with 6 g of Chlorella supplement. The proportion of anemic (hemoglobin level < 11 g/dL) subjects in the Chlorella group were significantly lower compared with the control group at the second and third trimesters. Additionally, in the Chlorella group, the incidences of proteinuria and edema, signs of PIH, were significantly lower during the third trimester. These results suggest that Chlorella supplementation significantly reduces the risk of pregnancy associated anemia, proteinuria and edema. Chlorella supplement may be useful as a resource of natural folate, vitamin B-12 and iron for pregnant women.

Relationship between anemia and depressive mood in the last trimester of pregnancy.

PubMed

Yılmaz, Elif; Yılmaz, Zehra; Çakmak, Bülent; Gültekin, İsmail Burak; Çekmez, Yasemin; Mahmutoğlu, Selma; Küçüközkan, Tuncay

2017-04-01

To compare the relationship between the severity of anemia and depressive mood in the last trimester of pregnancy. A cross-sectional study, enrolled a total of 450 pregnant women who attended the antenatal clinics in their third trimester for their routine antenatal follow-up. Depressive symptoms were assessed by the Edinburgh Postnatal Depression Scale. The study group was divided into two groups according to presence of anemia; anemic group (Hb < 11 gr/L; n = 150) and non-anemic group (Hb ≥ 11 gr/L; n = 300) and depression scores were compared. One hundred and fourteen (25.3%) women scored ≥13 points which were considered the cutoff value for depression on the EPDS. Anemia frequency was found as 33.3%. The total EPDS score was significantly higher in the anemic group (EPDS score 11 [min-max 0-29]) compared with the non-anemic group (EPDS score 7 [min-max 0-21]) (p = 0.000). Multiple regression analysis also revealed that serum Hb level was an independent factor for antenatal depressive mood. As anemia is associated with higher depressive symptom levels, it should be carefully considered during pregnancy. Prospective studies are needed to confirm our results.

Myelodysplastic syndrome patients present more severe respiratory muscle impairment and reduced forced vital capacity: Is disordered inflammatory signaling the culprit?

PubMed

Okubo, Bruno Memória; Matos, Anacélia Gomes de; Ribeiro Junior, Howard Lopes; Borges, Daniela de Paula; Oliveira, Roberta Taiane Germano de; de Castro, Marilena Facundo; Martins, Manoel Ricardo Alves; Gonçalves, Romélia Pinheiro; Bruin, Pedro Felipe Carvalhedo; Pinheiro, Ronald Feitosa; Magalhães, Silvia Maria Meira

2017-01-01

The ageing process is associated with gradual decline in respiratory system performance. Anemia is highly prevalent among older adults and usually associated with adverse outcomes. Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies with increasing incidence with age and characterized by anemia and other cytopenias. The main objectives of this study were to evaluate respiratory muscle strength and lung function in elderly patients with anemia, compare data between myelodysplastic syndromes and non-clonal anemias and evaluate the influence of serum IL-8 level and NF-kB activity on deteriorate pulmonary function in this specific population. Individuals aged 60 and older with anemia secondary to MDS, non-clonal anemia and healthy elderly individuals. Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV1/ FVC ratio were measured by spirometry. Respiratory muscle strength was evaluated by maximal static respiratory pressures measurement. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. Mean Hb concentration was comparable between patients with anemia. Significant differences were detected between all patients with anemia and controls for maximum-effort inspiratory mouth pressure (PImax) and also for maximum-effort expiratory mouth pressure (PEmax). The MDS group recorded a significantly lower PImax and PEmax percent predicted when compared to non-clonal anemia group. For FVC and FEV1, a significant difference was found in anemic patients, with even significantly lower values for FVC and FEV1 in MDS group. No significant differences were detected for PImax and PEmax and spirometry parameters when anemic patients were stratified according to the degree of anemia. A significant negative impact in FVC (% pred), PImax (% pred) and PEmax (% pred) was observed in patients with MDS and higher levels of IL-8 or increased activity of NF-kB. A negative impact of anemia, independent of its degree, was demonstrated in respiratory muscle strength and lung function particularly in MDS. The well known elevated proinflammatory cytokines in MDS patients were proposed to play a role as was demonstrated by detrimental effect of higher IL-8 and NF-kB in pulmonary function tests in this population.

[Treatment of anemia in chronic kidney disease--position statement of the Croatian Society for Nephrology, Dialysis and Transplantation and review of the KDIGO and ERPB guidelines].

PubMed

Rački, Sanjin; Bašić-Jukić, Nikolina; Kes, Petar; Ljutić, Dragan; Lovčić, Vesna; Prkačin, Ingrid; Radić, Josipa; Vujičić, Božidar; Bubić, Ivan; Jakić, Marko; Belavić, Žarko; Sefer, Siniša; Pehai, Mario; Klarić, Dragan; Gulin, Marijana

2014-04-01

Renal anemia is the result of chronic kidney disease (CKD) and deteriorates with disease progression. Anemia may be the first sign of kidney disease. In all patients with anemia and CKD, diagnostic evaluation is required. Prior to diagnosing renal anemia, it is necessary to eliminate the other possible causes. Direct correlation between the concentration of hemoglobin and the stage of renal failure is well known. Early development of anemia is common in diabetic patients. Correction of anemia may slow the progression of CKD. Anemia is an independent risk factor for developing cardiovascular disease in patients with CKD. Treatment of anemia in patients with CKD is based on current guidelines. Recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group has produced comprehensive clinical practice guidelines for the management of anemia in CKD patients and ERBP (European Renal Best Practice) group its position statement and comments on the KDIGO guidelines. The Croatian Society of Nephrology, Dialysis and Transplantation (HDNDT) has already published its own guidelines based on the recommendations and positive experience of European and international professional societies, as well as on own experience. The latest version of Croatian guidelines was published in 2008. Since then, on the basis of research and clinical practice, there have been numerous changes in the modern understanding of the treatment of anemia in CKD. Consequently, HDNDT hereby publishes a review of the recent recommendations of international professional societies, expressing the attitude about treating anemia in CKD as a basis for new guidelines tailored to the present time.

Treatment of anemia with darbepoetin alfa in systolic heart failure.

PubMed

Swedberg, Karl; Young, James B; Anand, Inder S; Cheng, Sunfa; Desai, Akshay S; Diaz, Rafael; Maggioni, Aldo P; McMurray, John J V; O'Connor, Christopher; Pfeffer, Marc A; Solomon, Scott D; Sun, Yan; Tendera, Michal; van Veldhuisen, Dirk J

2013-03-28

Patients with systolic heart failure and anemia have worse symptoms, functional capacity, and outcomes than those without anemia. We evaluated the effects of darbepoetin alfa on clinical outcomes in patients with systolic heart failure and anemia. In this randomized, double-blind trial, we assigned 2278 patients with systolic heart failure and mild-to-moderate anemia (hemoglobin level, 9.0 to 12.0 g per deciliter) to receive either darbepoetin alfa (to achieve a hemoglobin target of 13 g per deciliter) or placebo. The primary outcome was a composite of death from any cause or hospitalization for worsening heart failure. The primary outcome occurred in 576 of 1136 patients (50.7%) in the darbepoetin alfa group and 565 of 1142 patients (49.5%) in the placebo group (hazard ratio in the darbepoetin alfa group, 1.01; 95% confidence interval, 0.90 to 1.13; P=0.87). There was no significant between-group difference in any of the secondary outcomes. The neutral effect of darbepoetin alfa was consistent across all prespecified subgroups. Fatal or nonfatal stroke occurred in 42 patients (3.7%) in the darbepoetin alfa group and 31 patients (2.7%) in the placebo group (P=0.23). Thromboembolic adverse events were reported in 153 patients (13.5%) in the darbepoetin alfa group and 114 patients (10.0%) in the placebo group (P=0.01). Cancer-related adverse events were similar in the two study groups. Treatment with darbepoetin alfa did not improve clinical outcomes in patients with systolic heart failure and mild-to-moderate anemia. Our findings do not support the use of darbepoetin alfa in these patients. (Funded by Amgen; RED-HF ClinicalTrials.gov number, NCT00358215.).

Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project.

PubMed

Wirth, James P; Woodruff, Bradley A; Engle-Stone, Reina; Namaste, Sorrel Ml; Temple, Victor J; Petry, Nicolai; Macdonald, Barbara; Suchdev, Parminder S; Rohner, Fabian; Aaron, Grant J

2017-07-01

Background: Anemia in women of reproductive age (WRA) (age range: 15-49 y) remains a public health problem globally, and reducing anemia in women by 50% by 2025 is a goal of the World Health Assembly. Objective: We assessed the associations between anemia and multiple proximal risk factors (e.g., iron and vitamin A deficiencies, inflammation, malaria, and body mass index) and distal risk factors (e.g., education status, household sanitation and hygiene, and urban or rural residence) in nonpregnant WRA. Design: Cross-sectional, nationally representative data from 10 surveys ( n = 27,018) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and pooled by the infection burden and risk in the country. We examined the severity of anemia and measured the bivariate associations between anemia and factors at the country level and by infection burden, which we classified with the use of the national prevalences of malaria, HIV, schistosomiasis, sanitation, and water-quality indicators. Pooled multivariate logistic regression models were constructed for each infection-burden category to identify independent determinants of anemia (hemoglobin concertation <120 g/L). Results: Anemia prevalence was ∼40% in countries with a high infection burden and 12% and 7% in countries with moderate and low infection burdens, respectively. Iron deficiency was consistently associated with anemia in multivariate models, but the proportion of anemic women who were iron deficient was considerably lower in the high-infection group (35%) than in the moderate- and low-infection groups (65% and 71%, respectively). In the multivariate analysis, inflammation, vitamin A insufficiency, socioeconomic status, and age were also significantly associated with anemia, but malaria and vitamin B-12 and folate deficiencies were not. Conclusions: The contribution of iron deficiency to anemia varies according to a country's infection burden. Anemia-reduction programs for WRA can be improved by considering the underlying infection burden of the population and by assessing the overlap of micronutrient deficiencies and anemia.

Evaluation of the effect of LED radiation in the repair of skin wounds on the dorsum of rats with iron deficiency anemia

NASA Astrophysics Data System (ADS)

de Oliveira, Susana Carla Pires Sampaio; de Carvalho Monteiro, Juliana Santos; dos Santos Aciole, Gilberth Tadeu; DeCastro, Isabele Cardoso V.; Menezes, Diego Silva; de Fátima Lima Ferreira, Maria; dos Santos, Jean Nunes; Zanin, Fátima; Barbosa Pinheiro, Antônio Luiz

2010-05-01

Iron deficiency anemia causes reduction on the level of hemoglobin and of the number of RBC and affects around 35% of the human population. Laser and LED therapies have been successfully used on wound healing studies. The aim of the present study was to assess histologically the effect of LED Phototherapy on the healing of cutaneous wounds on anemic rats. Fifty one 21 days old male wistar rats weighting around 50 g were kept under iron free die (Sem ferro-AIN93-G) during 15 days in order to induce anemia. Non treated animals acted as controls. A standartized cutaneous wound was created on the dorsum of each animal whom were distributed into four groups: Group I—Anemia+LED, Group II—Non anemic+LED, Group III—Anemia+no treatment, Group IV—No anemic+no-treatment. Irradiation started immediately after surgery and repeated at 48 h intervals during 21 days. Animal death occurred after 7, 14 and 21 days after wounding. The results of the histologic analysis showed that LED Phototherapy stimulated fibroblastic proliferation. It is concluded that LED irradiation improves wound healing on iron deficient anemic animals.

Resistance to mitomycin C requires direct interaction between the Fanconi anemia proteins FANCA and FANCG in the nucleus through an arginine-rich domain.

PubMed

Kruyt, F A; Abou-Zahr, F; Mok, H; Youssoufian, H

1999-11-26

Fanconi anemia (FA) is a genetically heterogeneous disorder characterized by bone marrow failure, birth defects, and chromosomal instability. Because FA cells are sensitive to mitomycin C (MMC), FA gene products could be involved in cellular defense mechanisms. The FANCA and FANCG proteins deficient in FA groups A and G interact directly with each other. We have localized the mutual interaction domains of these proteins to amino acids 18-29 of FANCA and to two noncontiguous carboxyl-terminal domains of FANCG encompassing amino acids 400-475 and 585-622. Site-directed mutagenesis of FANCA residues 18-29 revealed a novel arginine-rich interaction domain (RRRAWAELLAG). By alanine mutagenesis, Arg(1), Arg(2), and Leu(8) but not Arg(3), Trp(5), and Glu(7) appeared to be critical for binding to FANCG. Similar immunolocalization for FANCA and FANCG suggested that these proteins interact in vivo. Moreover, targeting of FANCA to the nucleus or the cytoplasm with nuclear localization and nuclear export signals, respectively, showed concordance between the localization patterns of FANCA and FANCG. The complementation function of FANCA was abolished by mutations in its FANCG-binding domain. Conversely, stable expression of FANCA mutants encoding intact FANCG interaction domains induced hypersensitivity to MMC in HeLa cells. These results demonstrate that FANCA-FANCG complexes are required for cellular resistance to MMC. Because the FANCC protein deficient in FA group C works within the cytoplasm, we suggest that FANCC and the FANCA-FANCG complexes suppress MMC cytotoxicity within distinct cellular compartments.

Somatic, hematologic phenotype, long-term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology-Oncology).

PubMed

Svahn, Johanna; Bagnasco, Francesca; Cappelli, Enrico; Onofrillo, Daniela; Caruso, Silvia; Corsolini, Fabio; De Rocco, Daniela; Savoia, Anna; Longoni, Daniela; Pillon, Marta; Marra, Nicoletta; Ramenghi, Ugo; Farruggia, Piero; Locasciulli, Anna; Addari, Carmen; Cerri, Carla; Mastrodicasa, Elena; Casazza, Gabriella; Verzegnassi, Federico; Riccardi, Francesca; Haupt, Riccardo; Barone, Angelica; Cesaro, Simone; Cugno, Chiara; Dufour, Carlo

2016-07-01

We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy-two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow-up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow-up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666-671, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Preservation of renal function in atypical hemolytic uremic syndrome by eculizumab: a case report.

PubMed

Giordano, Mario; Castellano, Giuseppe; Messina, Giovanni; Divella, Claretta; Bellantuono, Rosa; Puteo, Flora; Colella, Vincenzo; Depalo, Tommaso; Gesualdo, Loreto

2012-11-01

Genetic mutations in complement components are associated with the development of atypical hemolytic uremic syndrome (aHUS), a rare disease with high morbidity rate triggered by infections or unidentified factors. The uncontrolled activation of the alternative pathway of complement results in systemic endothelial damage leading to progressive development of renal failure. A previously healthy 8-month-old boy was referred to our hospital because of onset of fever, vomiting, and a single episode of nonbloody diarrhea. Acute kidney injury with preserved diuresis, hemolytic anemia, and thrombocytopenia were detected, and common protocols for management of HUS were followed without considerable improvement. The persistent low levels of complement component C3 led us to hypothesize the occurrence of aHUS. In fact, the child carried a specific mutation in complement factor H (Cfh; nonsense mutation in 3514G>T, serum levels of Cfh 138 mg/L, normal range 350-750). Given the lack of response to therapy and the occurrence of kidney failure requiring dialysis, we used eculizumab as rescue therapy, a monoclonal humanized antibody against the complement component C5. One week from the first administration, we observed a significant improvement of all clinical and laboratory parameters with complete recovery from hemodialysis, even in the presence of systemic infections. Our case report shows that complement inhibiting treatment allows the preservation of renal function and avoids disease relapses during systemic infections.

Anemia and iron deficiency before and after bariatric surgery.

PubMed

Salgado, Wilson; Modotti, Caue; Nonino, Carla Barbosa; Ceneviva, Reginaldo

2014-01-01

Iron deficiency and anemia are changes often associated with obesity. Bariatric surgery is responsible for increasing the iron loss and reducing its absorption. The objective of this study was to evaluate anemia and iron deficiency before and after bariatric surgery and to relate them to possible predisposing factors. A retrospective study was conducted on obese patients submitted to open Roux-en-Y gastric bypass, in which clinical and laboratory data were obtained up to 48 months postoperatively. Patients were divided into groups according to the presence or absence of anemia and to the presence or absence of iron deficiency (even without anemia), and all data were compared between these groups. Preoperatively, 21.5% of patients had anemia and 20% had iron deficiency. The number of patients with anemia did not vary through the 4 years of the study, but ferritin levels significantly decreased with time (P<.01). Younger patients and patients with greater weight loss had a higher incidence of anemia. Female gender was a variable associated with a greater incidence of iron deficiency. Anemia and iron deficiency are frequent in obese patients and must be treated before surgery. Medical and nutritional surveillance is important in the postoperative period of bariatric surgery. Management of each condition must be directed at correcting the 2 major sources of iron deficiency and anemia: food intolerance (mostly meat intolerance) and losses (frequently due to menstruation). These are the factors more related to iron deficient anemia. Copyright © 2014 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Microarray mRNA expression analysis of Fanconi anemia fibroblasts.

PubMed

Galetzka, D; Weis, E; Rittner, G; Schindler, D; Haaf, T

2008-01-01

Fanconi anemia (FA) cells are generally hypersensitive to DNA cross-linking agents, implying that mutations in the different FANC genes cause a similar DNA repair defect(s). By using a customized cDNA microarray chip for DNA repair- and cell cycle-associated genes, we identified three genes, cathepsin B (CTSB), glutaredoxin (GLRX), and polo-like kinase 2 (PLK2), that were misregulated in untreated primary fibroblasts from three unrelated FA-D2 patients, compared to six controls. Quantitative real-time RT PCR was used to validate these results and to study possible molecular links between FA-D2 and other FA subtypes. GLRX was misregulated to opposite directions in a variety of different FA subtypes. Increased CTSB and decreased PLK2 expression was found in all or almost all of the analyzed complementation groups and, therefore, may be related to the defective FA pathway. Transcriptional upregulation of the CTSB proteinase appears to be a secondary phenomenon due to proliferation differences between FA and normal fibroblast cultures. In contrast, PLK2 is known to play a pivotal role in processes that are linked to FA defects and may contribute in multiple ways to the FA phenotype: PLK2 is a target gene for TP53, is likely to function as a tumor suppressor gene in hematologic neoplasia, and Plk2(-/-) mice are small because of defective embryonal development. (c) 2008 S. Karger AG, Basel.

Influence of laser and LED irradiation on mast cells of cutaneous wounds of rats with iron deficiency anemia

NASA Astrophysics Data System (ADS)

Becher Rosa, Cristiane; Oliveira Sampaio, Susana C. P.; Monteiro, Juliana S. C.; Ferreira, Maria F. L.; Zanini, Fátima A. A.; Santos, Jean N.; Cangussú, Maria Cristina T.; Pinheiro, Antonio L. B.

2011-03-01

This work aimed to study histologically the effect of Laser or LED phototherapy on mast cells on cutaneous wounds of rats with iron deficiency. 18 rats were used and fed with special peleted iron-free diet. An excisional wound was created on the dorsum of each animal which were divided into: Group I - Control with anemia + no treatment; Group II - Anemia + Laser; Group III - Anemia + LED; Group IV - Healthy + no treatment; Group V - Healthy + Laser; Group VI - Healthy + LED. Irradiation was performed using a diode Laser (λ660nm, 40mW, CW, total dose of 10J/cm2, 4X2.5J/cm2) or a RED-LED ( λ700nm, 15mW, CW, total dose of 10J/cm2). Histological specimens were routinely processed, cut and stained with toluidine blue and mast cell counts performed. No significant statistic difference was found between groups as to the number of degranulated, non-degradulated or total mast cells. Greater mean values were found for degranulated mast cells in the Anemia + LED. LED irradiation on healthy specimens resulted in a smaller number of degranulated mast cells. Our results leads to conclude that there are no significant differences in the number of mast cells seven days after irradiation following Laser or LED phototherapy.

Association of renal tubular damage with cardio-renal anemia syndrome in patients with heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Narumi, Taro; Kadowaki, Shinpei; Honda, Yuki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2014-05-01

Cardio-renal anemia syndrome (CRAS) has begun to gather attention as a vicious circle since chronic heart failure (CHF), chronic kidney disease (CKD), and anemia are all able to be caused and exacerbated by each other. However, it remains unclear whether renal tubular damage (RTD), another type of kidney dysfunction, is associated with this vicious circle. The aim of the present study was to assess the association of RTD with CRAS in patients with CHF. We included 300 consecutive patients with CHF. RTD was defined as a urinary β2-microglobulin to creatinine ratio ≥ 300 μg/g. Patients with RTD had lower serum iron and higher levels of high sensitivity C-reactive protein than those without it. Multivariate logistic analysis showed that RTD was closely associated with anemia in patients with CHF, after adjustment for confounding factors. During a median period of 1,098 days, there were 86 cardiac events, including 14 cardiac deaths and 72 re-hospitalizations for worsening heart failure. Net reclassification improvement was significantly improved by addition of RTD to the model including age, New York Heart Association functional class, brain natriuretic peptide, anemia, and CKD. All patients were divided into 3 groups: CRAS+RTD group, CRAS group, and control group. Kaplan-Meier analysis demonstrated that CRAS+RTD had the greatest risk in patients with CHF. RTD was associated with normocytic anemia, accompanying iron deficiency and inflammation. RTD added prognostic information to conventional CRAS, suggesting the importance of RTD in cardio-renal anemia interaction. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Anemia and malnutrition in indigenous children and adolescents of the Peruvian Amazon in a context of lead exposure: a cross-sectional study.

PubMed

Anticona, Cynthia; San Sebastian, Miguel

2014-01-01

Indigenous children and adolescents of the Peruvian Amazon live in precarious conditions that could increase the risk of malnutrition. A particular problem in the Corrientes river communities is the high exposure to lead among children and adolescents. This study aimed to determine the nutritional status of children and adolescents in indigenous communities in the Corrientes river basin and examine risk factors for anemia, stunting, underweight, and wasting. This was a cross-sectional assessment in children and adolescents aged 0-17 years from six communities (n=330). Data collection included measurement of hemoglobin levels, anthropometrics, blood lead levels (BLLs); a parental questionnaire including demographic and dwelling information; parents' occupation; and the child's duration of breastfeeding and food consumption. Analysis included univariate, bivariate, and logistic regression. Overall, anemia prevalence was 51.0%, stunting (proxy for chronic malnutrition) 50.0%, and underweight 20.0%. Bivariate analysis showed that anemia and underweight prevalence was higher in the 0-4 years group (p<0.05). No association was found between anemia, stunting, or underweight with gender, community exposure to oil activity, or consumption of river water. Stunting prevalence was higher in the group whose BLLs were >5 µg/dL (p<0.05). In the logistic regression analysis, no variable was associated with anemia or underweight. The group 5-11 years and >12 years had 1.9 and 3.1 times higher risk of stunting than the group under five years, respectively. Children and adolescents with BLLs >5 µg/dL had twice the risk of stunting compared to those with lower BLLs. Half of the study population was found with anemia and stunting. Anemia was more prevalent in the 0- to 5-year age group and stunting in the 12- to 17-year group. The association between stunting and BLLs might be attributed to a direct effect of lead on human growth. Also, poor nutrition and other socioeconomic-related factors may contribute to the simultaneous existence of stunting and elevated BLLs.

Anemia and malnutrition in indigenous children and adolescents of the Peruvian Amazon in a context of lead exposure: a cross-sectional study

PubMed Central

Anticona, Cynthia; San Sebastian, Miguel

2014-01-01

Background Indigenous children and adolescents of the Peruvian Amazon live in precarious conditions that could increase the risk of malnutrition. A particular problem in the Corrientes river communities is the high exposure to lead among children and adolescents. Objective This study aimed to determine the nutritional status of children and adolescents in indigenous communities in the Corrientes river basin and examine risk factors for anemia, stunting, underweight, and wasting. Design This was a cross-sectional assessment in children and adolescents aged 0–17 years from six communities (n=330). Data collection included measurement of hemoglobin levels, anthropometrics, blood lead levels (BLLs); a parental questionnaire including demographic and dwelling information; parents’ occupation; and the child's duration of breastfeeding and food consumption. Analysis included univariate, bivariate, and logistic regression. Results Overall, anemia prevalence was 51.0%, stunting (proxy for chronic malnutrition) 50.0%, and underweight 20.0%. Bivariate analysis showed that anemia and underweight prevalence was higher in the 0–4 years group (p<0.05). No association was found between anemia, stunting, or underweight with gender, community exposure to oil activity, or consumption of river water. Stunting prevalence was higher in the group whose BLLs were >5 µg/dL (p<0.05). In the logistic regression analysis, no variable was associated with anemia or underweight. The group 5–11 years and >12 years had 1.9 and 3.1 times higher risk of stunting than the group under five years, respectively. Children and adolescents with BLLs >5 µg/dL had twice the risk of stunting compared to those with lower BLLs. Conclusions Half of the study population was found with anemia and stunting. Anemia was more prevalent in the 0- to 5-year age group and stunting in the 12- to 17-year group. The association between stunting and BLLs might be attributed to a direct effect of lead on human growth. Also, poor nutrition and other socioeconomic-related factors may contribute to the simultaneous existence of stunting and elevated BLLs. PMID:24560254

Maternal anemia effects during pregnancy on male and female fetuses: are there any differences?

PubMed

Orlandini, Cinzia; Torricelli, Michela; Spirito, Nicoletta; Alaimo, Lucia; Di Tommaso, Mariarosaria; Severi, Filiberto Maria; Ragusa, Antonio; Petraglia, Felice

2017-07-01

Sideropenic anemia is a common pregnancy disorder. The relationship between anemia and adverse pregnancy outcome are contradictory, and it is related to the severity of the hemoglobin deficit. The aim of the study was to evaluate the relationship between maternal mild anemia at third trimester of pregnancy, fetal birth weight and fetal gender. A retrospective study including 1131 single physiological term pregnancies was conducted. According to maternal Hb levels during the third trimester, pregnant women enrolled were divided in two groups: Group A (n = 156) with Hb ≤ 11 g/dl and Group B (n = 975) with Hb ≥ 11,1 g/dl. Maternal characteristics, gestational age at delivery, Apgar score and post-partum hemorrhage were similar between groups. However, when neonatal sex was considerate, female newborns of anemic women had a higher birth weight (p = 0.01). Moreover, anemic women showed a significantly higher rate of emergency cesarean section (p = 0.006), in particular when the newborn was a male (p= 0.03). Maternal mild anemia in third trimester of pregnancy correlates with fetal birth weight, influencing fetal growth and delivery outcome on the basis of fetal gender. Even though the reason of this phenomenon is still unknown, these new data may represent a novel parameter to add significant prognostic information in relation to maternal mild anemia and neonatal outcome.

Annual Defense Department Report FY 1973

DTIC Science & Technology

1972-02-22

program of combatting Sickle- Cell Anemia. Finally, as we approach an all-volunteer force we will continually assess our recruiting and retention programs...GNP devoted to Defense continues to decline -- from 7.0% in FY 1972 to 6.4% in FY 1973. This is a 22 year low. 59 We also are requesting a suplemental ...complement Total Force Planning. Some of these initiatives will fall in areas where the U.S. bears the primary responsibility, while others stem from

Patterns and risk factors of helminthiasis and anemia in a rural and a peri-urban community in Zanzibar, in the context of helminth control programs.

PubMed

Knopp, Stefanie; Mohammed, Khalfan A; Stothard, J Russell; Khamis, I Simba; Rollinson, David; Marti, Hanspeter; Utzinger, Jürg

2010-05-11

The control of helminth infections and prevention of anemia in developing countries are of considerable public health importance. The purpose of this study was to determine patterns and risk factors of helminth infections and anemia in a rural and a peri-urban community of Zanzibar, Tanzania, in the context of national helminth control programs. We carried out a community-based cross-sectional study in 454 individuals by examining at least two stool samples with different methods for soil-transmitted helminths (Ascaris lumbricoides, hookworm, Strongyloides stercoralis, and Trichuris trichiura) and one urine sample for Schistosoma haematobium. Finger-prick blood was taken to estimate anemia levels and to detect antibody reactions against ascariasis, strongyloidiasis and schistosomiasis, using an enzyme-linked immunosorbent assay (ELISA) approach. Parasitological methods determined a helminth prevalence of 73.7% in the rural, and 48.9% in the peri-urban setting. Most helminth infections were of light intensity with school-aged children showing the highest intensities. Multiple helminth species infections were pervasive in rural dwellers regardless of age. More than half of the participants were anemic, with a particularly high prevalence in the peri-urban setting (64.7%). Risk factors for helminth infections were age, sex, consumption of raw vegetables or salad, recent travel history, and socio-economic status. After several years of chemotherapy-based morbidity control efforts in Zanzibar, helminth prevalences are still high and anemia is common, but helminth infection intensities are low. Hence, chemotherapy should be continued, and complemented with improved access to clean water, adequate sanitation, and health education, along with poverty alleviation measures for a more enduring impact.

Hemolytic uremic syndrome complicating Mycoplasma pneumoniae infection.

PubMed

Godron, Astrid; Pereyre, Sabine; Monet, Catherine; Llanas, Brigitte; Harambat, Jérôme

2013-10-01

Mycoplasma pneumoniae can cause various extrapulmonary manifestations but, to our knowledge, no case of Mycoplasma pneumoniae associated with hemolytic uremic syndrome (HUS) has been reported. We describe a 1-year-old boy with M. pneumoniae respiratory tract infection and associated microangiopathic hemolytic anemia, slightly decreased platelet count and mild renal impairment, suggesting a diagnosis of HUS. Assuming M. pneumoniae infection was the cause of HUS in this case, the different possible mechanisms, including an atypical HUS due to preexisting complement dysregulation, an alternative complement pathway activation induced by M. pneumoniae infection at the acute phase, an autoimmune disorder, and a direct role of the bacteria in inducing endothelial injury, are discussed. The signs of HUS resolved with treatment of the M. pneumoniae infection. Hemolytic uremic syndrome may be an unusual complication of M. pneumoniae infection.

Efficacy of multiple micronutrient supplementation for improving anemia, micronutrient status, growth, and morbidity of Peruvian infants.

PubMed

López de Romaña, Guillermo; Cusirramos, Sandra; López de Romaña, Daniel; Gross, Rainer

2005-03-01

Anemia, micronutrient deficiencies, and growth faltering are still common in Peru. The study objective was to determine the efficacy of different micronutrient supplements in preventing growth failure, anemia, and micronutrient deficiencies in Peruvian infants. Three hundred and thirteen infants aged 6 to 12 mo participated in a double-blind, masked, controlled trial in which they were randomly assigned to receive either a daily dose of iron (DI), a daily dose of multiple micronutrients (DMM), a weekly dose of multiple micronutrients, or a placebo (P) for 6 mo. None of the supplements tested prevented growth faltering or the morbidities common during infancy. Anemia and plasma homocysteine concentrations fell significantly in all groups during the study, but the mean change of plasma homocysteine during the trial period was significantly smaller in the DI group than in other groups, and the increase in hemoglobin concentrations was smaller in the P group than the micronutrient treatment groups. Plasma ferritin concentrations decreased least in the groups taking daily micronutrient supplements containing iron (DI and DMM). There were no significant differences among groups in mean final values or changes in plasma zinc, retinol, tocopherol, or riboflavin. Although the DMM intervention was the most efficacious for preventing anemia, iron, and zinc deficiencies, 15%, 20%, and 50% of this group still remained anemic, zinc deficient, and iron deficient, respectively, at the end of the study. Further research thus should investigate whether higher doses of iron and zinc, together with infection control measures, are more efficacious.

Predictors of anemia in women of reproductive age: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

PubMed Central

Woodruff, Bradley A; Petry, Nicolai; Macdonald, Barbara; Aaron, Grant J

2017-01-01

Background: Anemia in women of reproductive age (WRA) (age range: 15–49 y) remains a public health problem globally, and reducing anemia in women by 50% by 2025 is a goal of the World Health Assembly. Objective: We assessed the associations between anemia and multiple proximal risk factors (e.g., iron and vitamin A deficiencies, inflammation, malaria, and body mass index) and distal risk factors (e.g., education status, household sanitation and hygiene, and urban or rural residence) in nonpregnant WRA. Design: Cross-sectional, nationally representative data from 10 surveys (n = 27,018) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and pooled by the infection burden and risk in the country. We examined the severity of anemia and measured the bivariate associations between anemia and factors at the country level and by infection burden, which we classified with the use of the national prevalences of malaria, HIV, schistosomiasis, sanitation, and water-quality indicators. Pooled multivariate logistic regression models were constructed for each infection-burden category to identify independent determinants of anemia (hemoglobin concertation <120 g/L). Results: Anemia prevalence was ∼40% in countries with a high infection burden and 12% and 7% in countries with moderate and low infection burdens, respectively. Iron deficiency was consistently associated with anemia in multivariate models, but the proportion of anemic women who were iron deficient was considerably lower in the high-infection group (35%) than in the moderate- and low-infection groups (65% and 71%, respectively). In the multivariate analysis, inflammation, vitamin A insufficiency, socioeconomic status, and age were also significantly associated with anemia, but malaria and vitamin B-12 and folate deficiencies were not. Conclusions: The contribution of iron deficiency to anemia varies according to a country’s infection burden. Anemia-reduction programs for WRA can be improved by considering the underlying infection burden of the population and by assessing the overlap of micronutrient deficiencies and anemia. PMID:28615262

[Iron supplementation in Chilean Mapuche infants of the Cautin Province, Chile].

PubMed

Franco, E; Hertrampf, E; Hazbún, J; Segú, S; Illanes, J C; Palacios, L; Figueroa, G; Orellana, J

1996-06-01

A 1.8 ml iron supplementation of ferrous sulfate is administered for 90 days to 76 Mapuche infants, 12 months of age, male and female, from the rural area of the Cautin province of Chile. The iron nutrition is evaluated before and after the supplementation, through: hemoglobin, haematocrit, transferrin saturation and seric ferritin. Stools test are taken at the infant's home, to confirm the supplement intake and to measure the iron excreted. To study the contained of dietary Fe a Recordatory 24 hour Inquest (RI) is applied moreover a Proximal Chemical Analysis (PCHA) to meal test proceeding from the infant's homes. At 12 months before starting the supplementation, the anemia prevalence was of 28.3%, but it disappear as a result of the intervention. Also 65.3% of the infants showed and increase of 1 g or more on their hemoglobin, which indicates that they were anemic at the beginning of the iron supplementation. By means of this therapeutic test it was find 31% more of anemic infants, indicating more sensibility of this method. The high levels of anemia prevalence are due to the low iron intake, characteristic of the non lactious foods, which according results of the RI reaches an average of 2.8 +/- 1.2 mg of Fe/day, versus 4.8 +/- 4.0 mg of Fe/day according to PCHA. The observed difference between both test showed that there is a process of food environmental contamination, by the use of iron utensils and great soil contact. The high environmental contamination could also be proved by the high iron excretion stools (140 mg of Fe/100 g of stools). This method used to measure the Fe excretion of the supplement, would not be valid in rural population groups with similar characteristics to those of the studied group, because it does not discriminate between the intake and the extremely high environmental contamination. To prevent anemia due to iron absence in infants, it is absolutely necessary to have some iron fortified food starting at 6 months of age, as a complement for breast milk.

Altered expression of intestinal duodenal cytochrome b and divalent metal transporter 1 might be associated with cardio-renal anemia syndrome.

PubMed

Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Okuno, Keisuke; Yasumura, Seiki; Okuhara, Yoshitaka; Eguchi, Akiyo; Nishimura, Koichi; Soyama, Yuko; Asakura, Masanori; Ishihara, Masaharu; Tsujino, Takeshi; Masuyama, Tohru

2017-11-01

The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome. CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. Sham-operated rats served as a control. After 24-week surgery, CKD rats exhibited normocytic normochromic anemia and normal serum erythropoietin levels despite of anemia. Serum iron levels were decreased in CKD rats compared with the controls. Of interest, intestinal expression of critical iron importers, such as duodenal cytochrome b (Dcyt-b) and divalent metal transporter 1 (DMT-1), was decreased in CKD rats compared with the controls. On the other hand, intestinal expression of ferroportin, an intestinal iron exporter, was not different in the control and CKD groups. Moreover, hepatic expression of hepcidin, a regulator of iron homeostasis, did not differ between the control and CKD groups. These results suggest that impaired intestinal expression of Dcyt-b and DMT-1 might be associated with the reduction of an iron uptake in CKD. Taken together, impaired these intestinal iron transporters may become a novel therapeutic target for cardio-renal anemia syndrome.

A systematic analysis of global anemia burden from 1990 to 2010

PubMed Central

Jasrasaria, Rashmi; Naghavi, Mohsen; Wulf, Sarah K.; Johns, Nicole; Lozano, Rafael; Regan, Mathilda; Weatherall, David; Chou, David P.; Eisele, Thomas P.; Flaxman, Seth R.; Pullan, Rachel L.; Brooker, Simon J.; Murray, Christopher J. L.

2014-01-01

Previous studies of anemia epidemiology have been geographically limited with little detail about severity or etiology. Using publicly available data, we estimated mild, moderate, and severe anemia from 1990 to 2010 for 187 countries, both sexes, and 20 age groups. We then performed cause-specific attribution to 17 conditions using data from the Global Burden of Diseases, Injuries and Risk Factors (GBD) 2010 Study. Global anemia prevalence in 2010 was 32.9%, causing 68.36 (95% uncertainty interval [UI], 40.98 to 107.54) million years lived with disability (8.8% of total for all conditions [95% UI, 6.3% to 11.7%]). Prevalence dropped for both sexes from 1990 to 2010, although more for males. Prevalence in females was higher in most regions and age groups. South Asia and Central, West, and East sub-Saharan Africa had the highest burden, while East, Southeast, and South Asia saw the greatest reductions. Iron-deficiency anemia was the top cause globally, although 10 different conditions were among the top 3 in regional rankings. Malaria, schistosomiasis, and chronic kidney disease–related anemia were the only conditions to increase in prevalence. Hemoglobinopathies made significant contributions in most populations. Burden was highest in children under age 5, the only age groups with negative trends from 1990 to 2010. PMID:24297872

[Current insights into anemia in old age : Summary of the symposium "Anemia in old age" on the occasion of the annual congress of the German Society for Geriatrics (DGG) 2016 in Stuttgart].

PubMed

Röhrig, Gabriele; Gütgemann, Ines; von Gersdorff, Gero; Polidori, Maria Cristina; Lupescu, Adrian; Lang, Florian; Kolb, Gerald

2018-04-01

Anemia in advanced age is often a multifactorial condition requiring an interdisciplinary approach. The contributions to the opening interdisciplinary symposium on anemia in older subjects focused on physiological and histopathological as well as on nephrological and neurogeriatric aspects and on the therapeutic implications of this underdiagnosed, yet highly frequent disease. The symposium was the kick-off event for the founding of the German Geriatric Society special interest group on anemia in advanced age.

Meta-analysis of Huangqi injection for the adjunctive therapy of aplastic anemia

PubMed Central

Zhu, Changtai; Gao, Yulu; Jiang, Ting; Hao, Cao; Gao, Zongshuai; Sun, Yongning

2015-01-01

Aplastic anemia therapy remains difficult, due to lack of effective treatment regimens. In recent years, Huangqi injection for the adjunctive therapy of aplastic anemia has been reported in many clinical trials. Considering that Huangqi injection may be a novel approach to aplastic anemia treatment, we conducted a meta-analysis of clinical controlled trials to assess the clinical value of Huangqi injection in the treatment of aplastic anemia. We searched the Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Full-text Database (VIP), Wanfang Database, PubMed and EMBASE database to collect the data about the trials of Huangqi injection combined with androgens for treating aplastic anemia. A total of ten studies involving 720 patients with aplastic anemia were included in this study. The meta-analysis showed significant increases in the pool effectiveness rate, white blood cells (WBC), haematoglobin (Hb), platelets (PLT), and reticulocytes (Ret) between the experimental group versus the control group. No severe side effects were found in this study. However, the lower Jadad scores and asymmetric funnel plot degrades the validity of the meta-analysis as the clinical evidence. Therefore, Huangqi injection may significantly enhance the efficacy of androgens for aplastic anemia, suggesting that the novel approach of Chinese traditional medicine combined with Western medicine is promising. The exact outcome required confirmation with rigorously well-designed multi-center trials. PMID:26379817

[Pernicious anemia: diagnosis and course in Burkina Faso].

PubMed

Koulidiati, J; Sawadogo, S; Sagna, Y; Somda, K S; Tieno, H; Kafando, E; Drabo, Y J

2015-01-01

Pernicious anemia (also known as Biermer disease or anemia, Addison or Addisonian anemia, and Addison-Biermer anemia) is an autoimmune atrophic gastritis responsible for vitamin B12 malabsorption due to a deficiency of intrinsic factor. We report eight cases of pernicious anemia in Burkina Faso, collected over a 44-month period. The three criteria for diagnosis of pernicious anemia were: vitamin B12 deficiency, gastric disease (gastric histology) with presence of anti-intrinsic factor, and/or anti-gastric parietal cell antibodies in serum. All patients had anemia, with a mean hemoglobin level of 8.75 g/100 mL. The average mean corpuscular volume (MCV) was 122.1 fL the average mean corpuscular hemoglobin (MCH) 39.3 pg, the mean reticulocyte count 12.069 10(9)/L reticulocytes, and the mean rate of megaloblast marrow cells 17.2%. The serum vitamin B12 level ranged from 35 to 71 pmol/L. Antibodies against intrinsic factor were found in all eight patients. All ABO blood groups were present with a predominance (4 cases) of group O. Endoscopy found a normal fundic mucosa in three patients. Histology showed gastric atrophy and intestinal metaplasia for six patients (85.7%). Under B12 vitamin therapy, the course was favorable in all patients; seven patients also had 10 days of iron therapy. We recommend a gastric biopsy even in the absence of macroscopic gastric lesions on the upper gastrointestinal endoscopy.

De Novo Chromosome Copy Number Variation in Fanconi Anemia-Associated Hematopoietic Defects

DTIC Science & Technology

2013-04-01

We have confirmed re-expression of FANCA , FANCD2, and FANCG in the FA-A + FANCA , FA-D2 + FANCD2, and FA-G + FANCG cells, respectively. We have also...confirmed restoration of FANCD2 and FANCI monoubiquitination and functional complementation of the FA-A + FANCA and FA-D2 + FANCD2 cells. In... gene products BRCA1 and BRCA2 function cooperatively in the FA-BRCA pathway to repair damaged DNA. Recent studies have demonstrated that the FA-BRCA

Red Blood Cell Immune Complex Binding Capacity in Children with Sickle Cell Trait (HbAS) Living in P. falciparum Malaria Holoendemic Region of Western Kenya

DTIC Science & Technology

2012-12-08

the erythrocytes in normal individuals and also in certain disease states such as systemic lupus erythematosus, HIV and some hemolytic anemia. In these...chronic conditions including malaria, HIV infection and others are known to interfere with the parameters under investigation such as complement...Craig M, Deichmann U, Marsh K. Estimating mortality, morbidity and disability due to malaria among Africa’s non- pregnant population. Bull World Health

Effect of a nutrition education program and diet modification in Beninese adolescent girls suffering from mild iron deficiency anemia.

PubMed

Alaofé, Halimatou; Zee, John; Dossa, Romain; O'Brien, Huguette Turgeon

2009-01-01

A 26-week nutrition intervention, including 4 weeks of nutrition education, combined with an increase in the content and bioavailability of dietary iron for 22 weeks was carried out in 34 intervention and 34 control adolescent girls suffering from mild iron deficiency anemia (IDA). In post-intervention, hemoglobin and serum ferritin were significantly higher in the intervention group, whereas the incidence of IDA was significantly lower in the intervention group compared to the control group. Nutrition knowledge scores were significantly higher in intervention girls compared to control girls. Dietary changes to improve available dietary iron can reduce iron deficiency anemia.

Blood typing

MedlinePlus

... matching; Rh typing; ABO blood typing; Blood group; Anemia - immune hemolytic blood type; ABO blood type; A ... during pregnancy. Careful testing can prevent a severe anemia in the newborn and jaundice .

Clinical efficacy of Punarnava Mandura and Dhatri Lauha in the management of Garbhini Pandu (anemia in pregnancy).

PubMed

Khandelwal, Deepika A; Donga, Shilpa B; Dei, Laxmipriya

2015-01-01

India is one of the countries with high prevalence of anemia during pregnancy. Anemia in pregnancy is multifactorial. Iron deficiency anemia is the most common conditions in a pregnant woman. As per ayurvedic classics, this condition occurs due to improper Rasa Dhatu in mother and continuously increasing fetal demands and is considered as Rasa Pradoshajavikara . A large number of Lauha preparations have been used widely for centuries to cure Anemia. To evaluate efficacy of Punarnava Mandura and Dhatri Lauha on Garbhini Pandu . A total 24 pregnant women with symptoms of Garbhini Pandu were randomly divided into two groups (A and B). In Group A ( n = 15) Punarnava Mandura , two tablets (each of 500 mg) thrice a day with one cup (100 ml) of buttermilk and in Group B ( n = 9) Dhatri Lauha , two tablets (each of 500 mg) thrice a day with luke warm water were administered for 90 days. The assessment was done with subjective parameters such as pallor, general weakness, dyspnea, etc., and objective parameters such as hematological parameters. Results were statistically analyzed using Student's t -test. The results revealed that overall clinical improvement was better in Group A when compared to Group B. Hemoglobin was increased in patients of Group A, which was statistically significant. No adverse drug reaction was observed during the treatment period. Punarnava Mandura is more effective on Garbhini Pandu in comparison to Dhatri Lauha .

Assessment of Gaps in Care and the Development of a Care Pathway for Anemia in Patients with Inflammatory Bowel Diseases.

PubMed

Hou, Jason K; Gasche, Christoph; Drazin, Noam Z; Weaver, Sarah Alandra; Ehrlich, Orna G; Oberai, Ridhima; Zapala, Sophie; Siegel, Corey A; Melmed, Gil

2017-01-01

Anemia is a common complication among patients with inflammatory bowel diseases (IBD) and is associated with high rates of IBD-related complications, resource utilization, and impaired quality of life. Despite practice guidelines for anemia in patients with IBD, gaps remain in the perceptions of anemia among health care providers. The aims of this study were to identify gaps in care and to develop a care pathway for anemia in patients with IBD. The Crohn's & Colitis Foundation of America anemia care pathway was developed by a committee using principles of cognitive task analysis. Focus groups of providers of patients with IBD were performed to identify domains of perceptions and management decisions for anemia and IBD. Knowledge elicitation from subject experts in anemia was conducted using case-based scenarios of patients with IBD and anemia to determine decision-making branch points. The care pathway was modified in an iterative fashion to encompass clinical presentations of anemia in IBD and potential barriers to the recognition, management, and follow-up of anemia. Variations were observed in how providers define iron deficiency, thresholds for treatment of anemia, and route of iron therapy. A care pathway for anemia incorporating the World Health Organization definition of anemia, universal hemoglobin and ferritin screening, evaluation of iron stores using ferritin and transferrin saturation, management of anemia based on adequacy of iron stores, and follow-up was developed. The authors identified domains of how providers perceive and manage patients with IBD and anemia, and developed a care pathway to align clinical practices with guideline recommendations.

A Group Counseling Approach for Persons Who Work With Sickle Cell Anemia Clients.

ERIC Educational Resources Information Center

Calvin, Richmond

Although many workshops on sickle cell anemia have been held, it is still difficult to implement a comprehensive training program for sickle cell anemia clients in many communities. Research data on the topic are somewhat nebulous and insufficient political and social pressure have been exerted to change attitudes and take action towards the…

Prevalence and Associated Risk Factors of Anemia in Children and Adolescents with Intellectual Disabilities

ERIC Educational Resources Information Center

Lin, Jin-Ding; Lin, Pei-Ying; Lin, Lan-Ping; Hsu, Shang-Wei; Loh, Ching-Hui; Yen, Chia-Feng; Fang, Wen-Hui; Chien, Wu-Chien; Tang, Chi-Chieh; Wu, Chia-Ling

2010-01-01

Anemia is known to be a significant public health problem in many countries. Most of the available information is incomplete or limited to special groups such as people with intellectual disability. The present study aims to provide the information of anemia prevalence and associated risk factors of children and adolescents with intellectual…

Protective Effect of Morocco Carob Honey Against Lead-Induced Anemia and Hepato-Renal Toxicity.

PubMed

Fihri, Aicha Fassi; Al-Waili, Noori S; El-Haskoury, Redouan; Bakour, Meryem; Amarti, Afaf; Ansari, Mohammad J; Lyoussi, Badiaa

2016-01-01

Natural honey has many biological activities including protective effect against toxic materials. The aim of this study was to evaluate the protective effect of carob honey against lead-induced hepato-renal toxicity and lead-induced anemia in rabbits. Twenty four male rabbits were allocated into four groups six rabbits each; group 1: control group, received distilled water (0.1 ml / kg.b.wt /daily); group 2: received oral lead acetate (2 g/kg.b.wt/daily); group 3: treated with oral honey (1g /kg.b.wt/daily) and oral lead (2 g/kg.b.wt/daily), and group 4: received oral honey (1 g/kg.b.wt/daily). Honey and lead were given daily during 24 days of experimentation. Laboratory tests and histopathological evaluations of kidneys were done. Oral administration of lead induced hepatic and kidney injury and caused anemia during three weeks of the exposure. Treatment with honey prevented hepato-renal lead toxicity and ameliorated lead-induced anemia when honey was given to animals during lead exposure. It might be concluded that honey has a protective effect against lead-induced blood, hepatic and renal toxic effects. © 2016 The Author(s) Published by S. Karger AG, Basel.

Hemoglobin level as a risk factor for lower respiratory tract infections in Lebanese children.

PubMed

Mourad, Sawsan; Rajab, Mariam; Alameddine, Aouni; Fares, Mohammad; Ziade, Fouad; Merhi, Bassem Abou

2010-10-01

Pneumonia is the biggest single cause of childhood death under the age of 5 years, and anemia affects approximately 30% of infants and children all over the world. Determination of the relationship between anemia and lower respiratory tract infection as a risk factor in Lebanese children. A total number of two hundred infants and children aged nine months to twelve years were included; One hundred cases were hospitalized for lower respiratory tract infection in Department of Pediatrics, Makassed General Hospital, and one hundred healthy, age and sex matched controls, were selected from outpatient department. Complete blood count, iron level, ferritin level, and total iron binding capacity were taken if hemoglobin level less than eleven gram per deci-liter. In addition peripheral blood smear, chest radiograph and C-reactive protein were done to hospitalized cases. Definition of iron deficiency anemia and normal laboratory values were predetermined. Anemia was found in 32% of hospitalized cases and 16% of healthy controls. Mean hemoglobin level was 9.99 ± 0.62 gram per deci-liter and 11.99 ± 0.92 gram per deci-liter in anemic and non-anemic group respectively with a significant P-value of 0.001. C-reactive protein levels and number hospitalization days were similar among the anemic and non-anemic group. History of recurrent chest infections was significantly higher in both anemic group and hospitalized cases compared to non-anemic group and healthy controls. Low hemoglobin level was a risk factor for lower respiratory tract infection with a P-value of 0.008. Anemic children were two times more susceptible to lower respiratory tract infection compared to the control group, and iron deficiency anemia was predominating. Accurate diagnosis and prevention of anemia, whatever its etiology, is essential.

Potential effects of omega-3 fatty acids on anemia and inflammatory markers in maintenance hemodialysis patients.

PubMed

Gharekhani, Afshin; Khatami, Mohammad-Reza; Dashti-Khavidaki, Simin; Razeghi, Effat; Abdollahi, Alireza; Hashemi-Nazari, Seyed-Saeed; Mansournia, Mohammad-Ali

2014-01-07

Anemia is a common complication among hemodialysis (HD) patients. Although intravenous iron and erythropoiesis-stimulating agents revolutionized anemia treatment, about 10% of HD patients show suboptimal response to these agents. Systemic inflammation and increased serum hepcidin level may contribute to this hyporesponsiveness. Considering the anti-inflammatory properties of omega-3 fatty acids, this study aimed to evaluate potential role of these fatty acids in improving anemia and inflammation of chronic HD patients. In this randomized, placebo-controlled trial, 54 adult patients with HD duration of at least 3 months were randomized to ingest 1800 mg of either omega-3 fatty acids or matching placebo per day for 4 months. Anemia parameters including blood hemoglobin, serum iron, transferrin saturation (TSAT), erythropoietin resistance index, and required dose of intravenous iron and erythropoietin, and serum concentrations of inflammatory/anti-inflammatory markers including interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-10, C-reactive protein (CRP), hepcidin, ferritin, intact parathyroid hormone (iPTH), and ratios of IL-10 to IL-6 and IL-10 to TNF-α were measured at baseline and after 4 months of the intervention. 45 subjects (25 in the omega-3 and 20 in the placebo group) completed the study. No significant changes were observed in blood hemoglobin, serum iron, TSAT, and required dose of intravenous iron in either within or between group comparisons. Additionally, erythropoietin resistance index as well as required dose of intravenous erythropoietin showed no significant change in the omega-3 group compared to the placebo group. Although a relative alleviation in inflammatory state appeared in the omega-3 group, the mean differences of inflammatory and anti-inflammatory markers between the two groups did not reach statistically significant level except for IL-10-to-IL-6 ratio and serum ferritin level which showed significant changes in favor of omega-3 treatment (P <0.001 and P = 0.003, respectively). Omega-3 fatty acids relatively improved systemic inflammation of chronic HD patients without any prominent benefits on anemia. However, future well-designed studies on larger number of patients may determine utility of omega-3 fatty acids in HD patients with respect to inflammation and anemia.

Dietary diversity during pregnancy is associated with reduced risk of maternal anemia, preterm delivery, and low birth weight in a prospective cohort study in rural Ethiopia.

PubMed

Zerfu, Taddese A; Umeta, Melaku; Baye, Kaleab

2016-06-01

Anemia during pregnancy is a leading nutritional disorder with serious short- and long-term consequences for both the mother and the fetus. The objective was to investigate the association between dietary diversity during pregnancy and maternal anemia, low birth weight (LBW), preterm birth (PTB), and stillbirth in rural Ethiopia. We conducted a prospective cohort study and enrolled 432 pregnant women in their first antenatal care visit (24-28 gestational weeks); 374 women completed the follow-up. By using the FAO Women's Dietary Diversity Scores (WDDSs), subjects were categorized into "inadequate" (WDDS <4) and "adequate" (WDDS ≥4) groups and were followed until delivery. Primary outcomes were maternal anemia, birth weight, term delivery, and stillbirth. The attrition rate was 13.7% and was balanced across the 2 groups. The proportion of women consuming dairy, animal-source foods, fruits, and vegetables including vitamin A-rich ones was higher in the adequate than in the inadequate WDDS group (P < 0.05). The overall incidence of maternal anemia increased from 28.6% to 32.4% during the follow-up period. The overall proportion of LBW, PTB, and stillbirth were 9.1%, 13.6%, and 4.5%, respectively. After control for baseline differences, women in the inadequate group had a higher risk of anemia [adjusted RR (ARR: 2.29; 95% CI: 1.62, 3.24], LBW (ARR: 2.06; 95% CI: 1.03, 4.11), and PTB (ARR: 4.61; 95% CI: 2.31, 9.19) but not of stillbirth (ARR: 2.71; 95% CI: 0.88, 8.36) than women in the adequate group (P < 0.05). A WDDS of ≥4 food groups during pregnancy was shown to be associated with lower risk of maternal anemia, LBW, and PTB. Population-based controlled trials of various options to improve dietary diversity are needed before conclusive recommendations can be made. This trial was registered at clinicaltrials.gov as NCT02620943. © 2016 American Society for Nutrition.

Persistent pulmonary hypertension of the newborn associated with severe congenital anemia of various etiologies.

PubMed

Landau, Danielle; Kapelushnik, Josef; Harush, Miri B; Marks, Kyla; Shalev, Hanna

2015-01-01

Among the many associated features of persistent pulmonary hypertension of the neonate (PPHN), severe congenital anemia has been described only occasionally and is not included in the list of conditions that may cause PPHN in the neonate. We describe the clinical course of a group of 12 full-term neonates with PPHN and congenital anemia due to congenital dyserythropoietic anemia (7/12), α thalasemia (1/12), Diamond-Blackfan (1/12), and epsilon gamma delta beta thalassemia (3/12). The association of congenital anemia and PPHN is more common than previously thought; it can exist with various etiologies and severity of anemia. Congenital anemia has not been described until now as a cause or risk factor for PPHN; it should be considered as such alone or in combination with other known causes to be recognized early and treated appropriately to improve outcome. In families with known cases of congenital anemia due to the above-mentioned diagnosis, closer prenatal follow-up should be offered to anticipate possible fetal distress and/or fetal anemia and PPHN after birth.

[Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors].

PubMed

Peces, R; Díaz Corte, C; Navascués, R A

2001-01-01

Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.

Characterization of Human and Yeast Mitochondrial Glycine Carriers with Implications for Heme Biosynthesis and Anemia*

PubMed Central

Lunetti, Paola; Damiano, Fabrizio; De Benedetto, Giuseppe; Siculella, Luisa; Pennetta, Antonio; Muto, Luigina; Paradies, Eleonora; Marobbio, Carlo Marya Thomas; Dolce, Vincenza

2016-01-01

Heme is an essential molecule in many biological processes, such as transport and storage of oxygen and electron transfer as well as a structural component of hemoproteins. Defects of heme biosynthesis in developing erythroblasts have profound medical implications, as represented by sideroblastic anemia. The synthesis of heme requires the uptake of glycine into the mitochondrial matrix where glycine is condensed with succinyl coenzyme A to yield δ-aminolevulinic acid. Herein we describe the biochemical and molecular characterization of yeast Hem25p and human SLC25A38, providing evidence that they are mitochondrial carriers for glycine. In particular, the hem25Δ mutant manifests a defect in the biosynthesis of δ-aminolevulinic acid and displays reduced levels of downstream heme and mitochondrial cytochromes. The observed defects are rescued by complementation with yeast HEM25 or human SLC25A38 genes. Our results identify new proteins in the heme biosynthetic pathway and demonstrate that Hem25p and its human orthologue SLC25A38 are the main mitochondrial glycine transporters required for heme synthesis, providing definitive evidence of their previously proposed glycine transport function. Furthermore, our work may suggest new therapeutic approaches for the treatment of congenital sideroblastic anemia. PMID:27476175

Fanconi Anemia and Laron Syndrome.

PubMed

Castilla-Cortazar, Inma; de Ita, Julieta Rodriguez; Aguirre, Gabriel Amador; Castorena-Torres, Fabiola; Ortiz-Urbina, Jesús; García-Magariño, Mariano; de la Garza, Rocío García; Diaz Olachea, Carlos; Elizondo Leal, Martha Irma

2017-05-01

Fanconi anemia (FA) is a condition characterized by genetic instability and short stature, which is due to growth hormone (GH) deficiency in most cases. However, no apparent relationships have been identified between FA complementation group genes and GH. In this study, we thereby considered an association between FA and Laron syndrome (LS) (insulin-like growth factor 1 [IGF-1] deficiency). A 21-year-old female Mexican patient with a genetic diagnosis of FA was referred to our research department for an evaluation of her short stature. Upon admission to our facility, her phenotype led to a suspicion of LS; accordingly, serum levels of IGF-1 and IGF binding protein 3 were analyzed and a GH stimulation test was performed. In addition, we used a next-generation sequencing approach for a molecular evaluation of FA disease-causing mutations and genes involved in the GH-IGF signaling pathway. Tests revealed low levels of IGF-1 and IGF binding protein 3 that remained within normal ranges, as well as a lack of response to GH stimulation. Sequencing confirmed a defect in the GH receptor signaling pathway. To the best of our knowledge, this study is the first to suggest an association between FA and LS. We propose that IGF-1 administration might improve some FA complications and functions based upon IGF-1 beneficial actions observed in animal, cell and indirect clinical models: erythropoiesis modulation, immune function improvement and metabolic regulation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Quantitative PCR analysis reveals a high incidence of large intragenic deletions in the FANCA gene in Spanish Fanconi anemia patients.

PubMed

Callén, E; Tischkowitz, M D; Creus, A; Marcos, R; Bueren, J A; Casado, J A; Mathew, C G; Surrallés, J

2004-01-01

Fanconi anaemia is an autosomal recessive disease characterized by chromosome fragility, multiple congenital abnormalities, progressive bone marrow failure and a high predisposition to develop malignancies. Most of the Fanconi anaemia patients belong to complementation group FA-A due to mutations in the FANCA gene. This gene contains 43 exons along a 4.3-kb coding sequence with a very heterogeneous mutational spectrum that makes the mutation screening of FANCA a difficult task. In addition, as the FANCA gene is rich in Alu sequences, it was reported that Alu-mediated recombination led to large intragenic deletions that cannot be detected in heterozygous state by conventional PCR, SSCP analysis, or DNA sequencing. To overcome this problem, a method based on quantitative fluorescent multiplex PCR was proposed to detect intragenic deletions in FANCA involving the most frequently deleted exons (exons 5, 11, 17, 21 and 31). Here we apply the proposed method to detect intragenic deletions in 25 Spanish FA-A patients previously assigned to complementation group FA-A by FANCA cDNA retroviral transduction. A total of eight heterozygous deletions involving from one to more than 26 exons were detected. Thus, one third of the patients carried a large intragenic deletion that would have not been detected by conventional methods. These results are in agreement with previously published data and indicate that large intragenic deletions are one of the most frequent mutations leading to Fanconi anaemia. Consequently, this technology should be applied in future studies on FANCA to improve the mutation detection rate. Copyright 2003 S. Karger AG, Basel

DNA excision repair in cell extracts from human cell lines exhibiting hypersensitivity to DNA-damaging agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hansson, J.; Keyse, S.M.; Lindahl, T.

Whole cell extracts from human lymphoid cell lines can perform in vitro DNA repair synthesis in plasmids damaged by agents including UV or cis-diamminedichloroplatinum(II) (cis-DDP). Extracts from xeroderma pigmentosum (XP) cells are defective in repair synthesis. We have now studied in vitro DNA repair synthesis using extracts from lymphoblastoid cell lines representing four human hereditary syndromes with increased sensitivity to DNA-damaging agents. Extracts of cell lines from individuals with the sunlight-sensitive disorders dysplastic nevus syndrome or Cockayne's syndrome (complementation groups A and B) showed normal DNA repair synthesis in plasmids with UV photoproducts. This is consistent with in vivo measurementsmore » of the overall DNA repair capacity in such cell lines. A number of extracts were prepared from two cell lines representing the variant form of XP (XP-V). Half of the extracts prepared showed normal levels of in vitro DNA repair synthesis in plasmids containing UV lesions, but the remainder of the extracts from the same cell lines showed deficient repair synthesis, suggesting the possibility of an unusually labile excision repair protein in XP-V. Fanconi's anemia (FA) cells show cellular hypersensitivity to cross-linking agents including cis-DDP. Extracts from cell lines belonging to two different complementation groups of FA showed normal DNA repair synthesis in plasmids containing cis-DDP or UV adducts. Thus, there does not appear to be an overall excision repair defect in FA, but the data do not exclude a defect in the repair of interstrand DNA cross-links.« less

[Blunted erythropoietic response in the anemia of anorexia nervosa].

PubMed

Juncà, Jordi; Sorigué, Marc; Rodríguez-Hernández, Inés; Aldea, Marta; Granada, María Luisa; Sánchez-Planell, Lluis

2015-11-20

The cause of the anemia in anorexia nervosa (AN) has not been fully ascertained. Ferritin, folate and cobalamin values are usually within normal ranges. Anemia does not have a relationship with bone marrow changes and erythropoietin (EPO) levels have not been investigated. The objective of this study was to evaluate the EPO response in a small group of AN patients. EPO levels were measured in serum samples of 41 female AN patients (11 with anemia, and 30 with normal blood cell count). The adequacy of EPO response was assessed by comparing the increase observed in a group of normal weight patients with anemia. EPO concentrations in anemic AN patients were higher than in non-anemic: 20.63mU/mL (4.04-28.46) vs 8.7mU/mL (3.9-20.93), P=.0088, but the increase in EPO was lower than expected (27.85mU/mL [17.7-118.9]), P=.014. BMI and the difference between actual and expected EPO were inversely correlated. Inadequate EPO response may partly explain anemia in AN, but further studies are necessary. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Combatting anemia in adolescent girls: a report from India.

PubMed

Kanani, S

1994-01-01

In a study on anemia in adolescent girls living in slum areas, 105 girls, aged 10 to 18, participated in qualitative (focus group discussions; open ended, in depth interviews) and quantitative (structured survey and hemoglobin estimation) research activities before and after intervention. Perceptions of mothers were also surveyed. The qualitative methods were used on selected subsamples in order to represent all age and ethnic groups and geographic areas of the slum. Quantitative methods were used on all 105 girls. The prevalence of anemia was 98%. The patterns of responses were similar for the focus groups, interviews, and surveys. Mothers and their daughters believed the girls were healthy (" one who ate well, worked without tiring easily and did not fall sick often"). There was no major connection made between menstruation and health, or between present and future health. Most of the girls were unaware of the Gujarati term for anemia, pandurog, which is used in awareness campaigns. The girls described symptoms (weakness = kamshakti) associated with anemia and knew these could be remedied with green leafy vegetables, fruit, milk, meat, tonics from the doctor, and iron tablets (shakti ni goli). Based on these results, a puppet show, using local terms and events, was developed that covered the causes, symptoms, treatment, and prevention of anemia. The term, pandurog, was introduced and reinforced. The girls were encouraged to have their blood tested and to take iron tablets. The hemoglobin levels of the girls were taken after the show and after an iron supplement program lasting three months. Compliance with the supplementation program was monitored biweekly. Group discussions with flash cards reinforced the information in the puppet show. Results from the last hemoglobin level showed a significant increase; however, the prevalence of anemia was 87%. About half of the girls consumed at least 60% of the tablets; one-fifth consumed 80%. Forgetfulness and fasting during Ramzaan were cited as reasons for noncompliance. There was a significant increase in awareness of the term, pandurog; the symptoms of anemia; the importance of diet in preventing pandurog; and the role of menstruation in increasing iron needs and contributing to pandurog.

Reduction of vitamin A deficiency and anemia in pregnancy after implementing proposed prenatal nutritional assistance.

PubMed

Barbosa Chagas, C; Ramalho, A; de Carvalho Padilha, P; Delia Libera, B; Saunders, C

2011-01-01

Micronutrient deficiency is an unquestionable public health problem, specially anemia and vitamin A deficiency (VAD). This is due to the collective dimension of these carencies, which reflects on morbimortality rates in the maternal and infant group. to evaluate the impact of a proposal for prenatal nutritional assistance, comparing the prevalence of anemia and VAD, in pre-intervention (GI) and intervention (GII) groups. this is a prospective intervention study in a cohort of pregnant women. The GI group was made up of 225 the GII group of 208 pregnant adults and their respective newborns, attended a Public Maternity Ward in Rio de Janeiro, Brazil. Concentration of hemoglobin was used to diagnose anemia and a standardized interview to diagnose night blindness (XN). after adjusting for confounding variables, through logistic regression, the protective effect of intervention at the onset of anemia (OR = 0.420; IC 95% = 0.251-0.702), with a significant reduction in prevalence, of 28.4% in the GI to 16.8% in the GII, also observed at the onset of XN (OR = 0.377; IC95% = 0.187- 0.759), with a reduction in prevalence of 18.7 % in the GI to 6.2% in the GII. Nutritional intervention has a beneficial effect on maternal health, reducing nutritional deficiencies most prevalent during pregnancy and the impact of these on the obstetric ailment.

[Comparison of two types of antithymocyte globulin in the treatment of children with aplastic anemia].

PubMed

Xie, X T; He, W; Shi, W; Zhou, X X; Qiao, X H

2016-04-01

This study was designed to compare the effects of the anti-human T lymphocyte globulin (Fresenius, ATG-F)and rabbit anti-human thymocyte immunoglobulin (Genzyme, R-ATG)in the treatment of childhood aplastic anemia (AA) and their effects. A total of 59 children with aplastic anemia were analyzed in the present study, including 34 cases of severe aplastic anemia (SAA), 12 cases of very severe aplastic anemia (VSAA) and 13 cases of transfusion-dependent non-severe aplastic anemia (NSAA). While receiving immunosuppressive therapy (IST), 30 and 29 patients, with long-term oral supplement with cyclosporin A (CSA), androgen and Chinese traditional medicines, were treated with ATG-F and R-ATG, respectively. When it was necessary, some supportive cares such as component transfusion and infection control were also employed. Absolute counts of peripheral blood lymphocyte (ALC) at various time points were dynamically detected after ATG therapy. According to the International Aplastic Anemia Treatment and Effect standards. There were no statistically significant differences in the overall response rate (67%(20/30)vs. 69%(20/29), χ(2)=0.036, P=0.676) and the survival rate (87%(26/30)vs. 83%(24/29), χ(2)=0.173, P=0.676) between the ATG-F and R-ATG groups. There were significant and long-term ALC decrease after ATG therapy, the rate of ALC decrease in ATG-F and R-ATG group, the ALC only recovered to 47.8% (ATG-F group) and 47.4% (R-ATG group) of the pre-treatment level respectively. ATG-F 5 mg/(kg·d) and R-ATG 3.75 mg/(kg·d)could achieve similar effects in the treatment of childhood AA, through similar significant clearance of T cells. Therefore, all of these suggest that ATG-F and R-ATG might serve as the drugs of front-line choice for IST in childhood AA patients who do not have an available human leukocyte antigen identical related donor.

Beta-erythropoietin effects on ventricular remodeling, left and right systolic function, pulmonary pressure, and hospitalizations in patients affected with heart failure and anemia.

PubMed

Palazzuoli, Alberto; Silverberg, Donald S; Calabrò, Anna; Spinelli, Tommaso; Quatrini, Ilaria; Campagna, Maria S; Franci, Beatrice; Nuti, Ranuccio

2009-06-01

Anemia in heart failure is related to advanced New York Heart Association classes, severe systolic dysfunction, and reduced exercise tolerance. Although anemia is frequently found in congestive heart failure (CHF), little is known about the effect of its' correction with erythropoietin (EPO) on cardiac structure and function. The present study examines, in patients with advanced CHF and anemia, the effects of beta-EPO on left ventricular volumes, left ventricular ejection fraction (LVEF), left and right longitudinal function mitral anular plane systolic excursion (MAPSE), tricuspid anular plane excursion (TAPSE), and pulmonary artery pressures in 58 patients during 1-year follow-up in a double-blind controlled study of correction of anemia with subcutaneous beta-EPO. Echocardiographic evaluation, B-Type natriuretic peptide (BNP) levels, and hematological parameters are reported at 4 and 12 months. The patients in group A after 4 months of follow-up period demonstrated an increase in LVEF and MAPSE (P < 0.05 and P < 0.01, respectively) with left ventricular systolic volume reduction (P < 0.02) with respect to baseline and controls. After 12 months, results regarding left ventricular systolic volume LVEF and MAPSE persisted (P < 0.001). In addition, TAPSE increased and pulmonary artery pressures fell significantly in group A (P < 0.01). All these changes occurred together with a significant BNP reduction and significant hemoglobin increase in the treated group. Therefore, we revealed a reduced hospitalization rate in treated patients with respect to the controls (25% in treated vs. 54% in controls). In patients with anemia and CHF, correction of anemia with beta-EPO and oral iron over 1 year leads to an improvement in left and right ventricular systolic function by reducing cardiac remodeling, BNP levels, and hospitalization rate.

[Nutritional evaluation, micronutrient deficiencies and anemia among female adolescents in an urban and a rural zone from Zulia state, Venezuela].

PubMed

Ortega, Pablo; Leal, Jorymar; Amaya, Daysi; Chávez, Carlos

2010-03-01

Female adolescents in reproductive age are a susceptible group to anemia and micronutrient deficiencies. The objective of this study was to know the nutritional, anthropometric and dietetic status, the prevalence of anemia, depletion of iron deposits (FeD) and Vitamin A deficiency (VAD) in female adolescents. Seventy-eight not pregnant female adolescents (15.9 +/- 1.1 years old), from an urban and a periurban zone of Maracaibo, and a rural zone near this city, without infectious and inflammatory processes, were analyzed. Anemia in adolescents was considered when Hb < 120 g/L; FeD: ferritin < 12 microg/L; VAD serum retinol <20 microg/dL; risk of VAD (RVAD) 20-30 microg/dL. The data were analyzed with the SAS program and expressed as Means +/- Standard Deviations, statistical significance was considered when p < 0.05. The percentage of caloric and protean adjustment in all groups was below the daily requirements. Adolescents from the rural zone showed significant lower values of weight (p = 0.0024), height (p = 0.0027), body mass index BMI (p = 0.0487), fatty area (p = 0.0183), MCV (p = 0.0241), MCH (p = 0.0488), MHCC (p = 0.0228), and the highest prevalence of anemia (66.67%), anemia+FeD (33.33%), and anemia+FeD+RVAD (5.56%), with respect to adolescents from the urban zone. Although, anemic adolescents from the rural zone showed a non significant decrease of the iron percentage adjustment. Iron requirements are increased during adolescence, reaching a maximum at the peak of growth and remaining almost as high in girls after menarche, to replace menstrual losses. The low iron status among adolescents from the rural zone determine that this is a high risk group to anemia and FeD and they require prevention, control and suplementation strategies.

Daily use of Sprinkles micronutrient powder for 2 months reduces anemia among children 6 to 36 months of age in the Kyrgyz Republic: a cluster-randomized trial.

PubMed

Lundeen, Elizabeth; Schueth, Tobias; Toktobaev, Nurjan; Zlotkin, Stanley; Hyder, S M Ziauddin; Houser, Robert

2010-09-01

Iron-deficiency anemia is widespread among young children in the Kyrgyz Republic, and there is an urgent need to identify an effective intervention to address this significant public health problem. To test the effectiveness of a 2-month intervention with daily home fortification of complementary food using micronutrient powder (Sprinkles) in reducing anemia among children 6 to 36 months of age in the Kyrgyz Republic. In this cluster-randomized, community-based effectiveness trial conducted in three regions of the Kyrgyz Republic, 24 clusters of children aged 6 to 36 months were randomly assigned to two groups. The intervention group (12 clusters, n = 1,103) received 60 sachets of micronutrient powder (12.5 mg elemental iron), which were taken as one sachet daily for 2 months. The control group (12 clusters, n = 1,090) did not receive micronutrient powder until after the study period. Blood hemoglobin concentration was assessed at the start and end of the intervention. From baseline to follow-up, the mean hemoglobin concentration in the intervention group increased by 7 g/L, whereas it decreased by 2 g/L in the control group (p < .001). The prevalence of anemia (hemoglobin < 110 g/L) in the intervention group decreased from 72% at baseline to 52% at follow-up, whereas it increased from 72% to 75% in the control group (p < .001). Compliance with the intervention was high, with children consuming on average 45 of the 60 sachets given. A course of 60 Sprinkles micronutrient powder sachets taken daily for 2 months is effective in improving hemoglobin levels and reducing the prevalence of anemia among young children in the Kyrgyz Republic.

Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants.

PubMed

Lozoff, Betsy; De Andraca, Isidora; Castillo, Marcela; Smith, Julia B; Walter, Tomas; Pino, Paulina

2003-10-01

To determine the behavioral and developmental effects of preventing iron-deficiency anemia in infancy. Healthy full-term Chilean infants who were free of iron-deficiency anemia at 6 months were assigned to high- or low-iron groups or to high- or no-added-iron groups. Behavioral/developmental outcomes at 12 months of age included overall mental and motor test scores and specific measures of motor functioning, cognitive processing, and behavior. There were no differences between high- and low-iron groups in the prevalence of iron-deficiency anemia or behavioral/developmental outcome, and they were combined to form an iron-supplemented group (n = 1123) for comparison with the no-added-iron group (n = 534). At 12 months, iron-deficiency anemia was present in 3.1% and 22.6% of the supplemented and unsupplemented groups, respectively. The groups differed in specific behavioral/developmental outcomes but not on global test scores. Infants who did not receive supplemental iron processed information slower. They were less likely to show positive affect, interact socially, or check their caregivers' reactions. A smaller proportion of them resisted giving up toys and test materials, and more could not be soothed by words or objects when upset. They crawled somewhat later and were more likely to be tremulous. The results suggest that unsupplemented infants responded less positively to the physical and social environment. The observed differences seem to be congruent with current understanding of the effects of iron deficiency on the developing brain. The study shows that healthy full-term infants may receive developmental and behavioral benefits from iron supplementation in the first year of life.

Modeling Fanconi Anemia pathogenesis and therapeutics using integration-free patient-derived iPSCs

PubMed Central

Montserrat, Nuria; Tarantino, Carolina; Gu, Ying; Yi, Fei; Xu, Xiuling; Zhang, Weiqi; Ruiz, Sergio; Plongthongkum, Nongluk; Zhang, Kun; Masuda, Shigeo; Nivet, Emmanuel; Tsunekawa, Yuji; Soligalla, Rupa Devi; Goebl, April; Aizawa, Emi; Kim, Na Young; Kim, Jessica; Dubova, Ilir; Li, Ying; Ren, Ruotong; Benner, Chris; del Sol, Antonio; Bueren, Juan; Trujillo, Juan Pablo; Surralles, Jordi; Cappelli, Enrico; Dufour, Carlo; Esteban, Concepcion Rodriguez; Belmonte, Juan Carlos Izpisua

2014-01-01

Fanconi Anemia (FA) is a recessive disorder characterized by genomic instability, congenital abnormalities, cancer predisposition and bone marrow failure. However, the pathogenesis of FA is not fully understood partly due to the limitations of current disease models. Here, we derive integration-free induced pluripotent stem cells (iPSCs) from an FA patient without genetic complementation and report in situ gene correction in FA-iPSCs as well as the generation of isogenic FANCA deficient human embryonic stem cell (ESC) lines. FA cellular phenotypes are recapitulated in iPSCs/ESCs and their adult stem/progenitor cell derivatives. By using isogenic pathogenic mutation-free controls as well as cellular and genomic tools, our model serves to facilitate the discovery of novel disease features. We validate our model as a drug-screening platform by identifying several compounds that improve hematopoietic differentiation of FA-iPSCs. These compounds are also able to rescue the hematopoietic phenotype of FA-patient bone marrow cells. PMID:24999918

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

PubMed

Tulpule, Asmin; Lensch, M William; Miller, Justine D; Austin, Karyn; D'Andrea, Alan; Schlaeger, Thorsten M; Shimamura, Akiko; Daley, George Q

2010-04-29

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Drug discovery for Diamond-Blackfan anemia using reprogrammed hematopoietic progenitors

PubMed Central

Doulatov, Sergei; Vo, Linda T.; Macari, Elizabeth R.; Wahlster, Lara; Kinney, Melissa A.; Taylor, Alison M.; Barragan, Jessica; Gupta, Manav; McGrath, Katherine; Lee, Hsiang-Ying; Humphries, Jessica M.; DeVine, Alex; Narla, Anupama; Alter, Blanche P.; Beggs, Alan H.; Agarwal, Suneet; Ebert, Benjamin L.; Gazda, Hanna T.; Lodish, Harvey F.; Sieff, Colin A.; Schlaeger, Thorsten M.; Zon, Leonard I.; Daley, George Q.

2017-01-01

Diamond-Blackfan anemia (DBA) is a congenital disorder characterized by the failure of erythroid progenitor differentiation, severely curtailing red blood cell production. Because many DBA patients fail to respond to corticosteroid therapy, there is considerable need for therapeutics for this disorder. Identifying therapeutics for DBA requires circumventing the paucity of primary patient blood stem and progenitor cells. To this end, we adopted a reprogramming strategy to generate expandable hematopoietic progenitor cells from induced pluripotent stem cells (iPSCs) from DBA patients. Reprogrammed DBA progenitors recapitulate defects in erythroid differentiation, which were rescued by gene complementation. Unbiased chemical screens identified SMER28, a small-molecule inducer of autophagy, which enhanced erythropoiesis in a range of in vitro and in vivo models of DBA. SMER28 acted through autophagy factor ATG5 to stimulate erythropoiesis and up-regulate expression of globin genes. These findings present an unbiased drug screen for hematological disease using iPSCs and identify autophagy as a therapeutic pathway in DBA. PMID:28179501

Temporal trend of anemia among reproductive-aged women in India.

PubMed

Bharati, Susmita; Pal, Manoranjan; Som, Suparna; Bharati, Premananda

2015-03-01

Anemia is one of the major leading nutritional deficiencies in India, and the most vulnerable groups are preschool and adolescent children and pregnant and lactating women. The main objective of the study is to determine the temporal trend of anemia among reproductive-aged women of age 15-49 years. The study uses data from second and third rounds of the National Family Health Surveys (NFHS-2, 1998-1999, and NFHS-3, 2005-2006), conducted by the International Institute for Population Sciences. The dependent variable was the status of anemia of women. The determining variables were type of residence, age group, religion and castes, educational status, marital status, and household standard of living index. Anemia was most prevalent in the east zone for both the periods. The changes at the all India level were not much, but the north-east zone improved very well, whereas the south zone deteriorated drastically. The occurrence of severely anemic women in India varied between 1% and 2%. The highest prevalence rates were observed among women who were 15 to 24 years of age, illiterate, from non-Christian scheduled tribes (STs), unmarried, and whose standard of living was low. Rates of anemia have increased over time except in the case of Buddhists, Parsees, Jains, and the STs. From the viewpoint of our study, illiteracy and low standard of living may be the main causes of anemia among women in India. It is also necessary to take appropriate steps to curb anemia in women in their early adulthood. © 2012 APJPH.

Prevalence of Anemia and Hemoglobin Disorders Among School Children in Myanmar.

PubMed

Wah, Saw Thu; Yi, Yoon Shwe; Khin, Aye Aye; Plabplueng, Chotiros; Nuchnoi, Pornlada

2017-01-01

The prevalence of anemia is high in the population of Myanmar and hypochromic microcytic anemia (HMA) is predominant. The objective of our study was to determine the prevalence of anemia and causes of HMA among school children. A cross-sectional study was conducted on 239 children from Thanlyin and Insein Townships, Yangon Region, Myanmar. Complete blood count (CBC) and blood film morphology was examined on venous blood samples. Hypochromic microcytic anemia cases were subsequently analyzed for serum ferritin and cellulose acetate hemoglobin (Hb) electrophoresis. The prevalence of anemia was 46.4%; 27.6% had mild, while 18.8% had moderate anemia, and no case of severe anemia was detected. The mean Hb concentration was 11.7 ± 0.9 g/dL. The younger age group (8-11 years) had a significantly higher prevalence of anemia than the older age group (12-15 years) (p = 0.029). Blood film morphology revealed a 50.6% red blood cell (RBC) disorder; HMA was the most common type (70.2%). Out of 85 children with HMA, three children (3.5%) had iron deficiency and all had comorbidity with Hb AE (β A /β E ) (Hb E trait). Hemoglobin electrophoresis illustrated that Hb AA (β A /β A ) (31, 36.5%) and Hb AE (β A /β E ) trait (31, 36.5%) were the most common types followed by β-thalassemia (β-thal) trait (19, 22.3%) and Hb EE (β E /β E ) (homozygous Hb E; HBB: c.79G>A) (three, 3.5%). Hematocrit [or packed cell volume (PCV)], mean corpuscular volume (MCV), mean corpuscular Hb (MCH) and mean corpuscular Hb concentration (MCHC), showed a significant difference between Hb AE, Hb EE and β-thal trait (p = 0.029, 0.023, 0.015 and 0.01, respectively). Our findings will provide valuable information for the management of anemia in the Myanmar school-age population.

Prevalence of Anemia and Its Risk Factors Among Lactating Mothers in Myanmar

PubMed Central

Zhao, Ai; Zhang, Yumei; Li, Bo; Wang, Peiyu; Li, Jiayin; Xue, Yong; Gao, Hongchong

2014-01-01

In Myanmar, 60% of the population consists of mothers and children, and they are the groups most vulnerable to anemia. The objectives of this study are to determine (1) the anemia prevalence among lactating women and (2) the risk factors associated with anemia. Convenience sampling was used to select three villages in two different regions (Kachin and Shan) in Myanmar. Hemoglobin and anthropometric indicators were measured for 733 lactating women. Logistic regression analyses were used to determine factors associated with anemia. The anemia prevalence rate was 60.3% in lactating women, with 20.3% of lactating women having severe anemia. Factors of malnutrition (P = 0.026), self-reported symptoms of night blindness or poor dark adaptation (P < 0.001), lack of primary education experience (P < 0.001), low family annual capita income (< 800 MMK; P < 0.001), drinking spring or river water (P < 0.001), and drinking unboiled water (P = 0.016) were associated with anemia. To promote health in lactating women, a comprehensive intervention is needed in these regions. PMID:24639302

Impact of minimized extracorporeal circulation on outcome in patients with preoperative anemia undergoing coronary artery bypass surgery.

PubMed

Haneya, Assad; Philipp, Alois; Von Suesskind-Schwendi, Marietta; Diez, Claudius; Hirt, Stephan W; Kolat, Philipp; Attmann, Tim; Schoettler, Jan; Zausig, York; Ried, Michael; Schmid, Christof

2013-01-01

Preoperative anemia and low hematocrit during cardiopulmonary bypass have been associated with worse outcome in patients undergoing cardiac surgery. The minimized extracorporeal circulation (MECC) allows a reduction of the negative effects associated with conventional extracorporeal circulation (CECC). In this study, the impact of the MECC on outcome of anemic patients after coronary artery bypass grafting (CABG) was assessed. Between January 2004 and December 2011, 1,945 consecutive patients with preoperative anemia underwent isolated CABG using CECC (44.8%) or MECC (55.2%). The cutoff point for anemia was 13 g/dl for men and 12 g/dl for women. The postoperative creatine kinase and lactate levels were significantly lower in the MECC group (p < 0.001). There was no difference in postoperative blood loss between the groups. However, the intraoperative and postoperative transfusion requirements were significantly lower in the MECC group (p < 0.05). Furthermore, MECC patients had lower incidences of postoperative acute renal failure, and low cardiac output syndrome, shorter intensive care unit lengths of stay and reduced 30-day mortality (p < 0.05). In conclusion, a reduced postoperative mortality, lower transfusion requirements, and less renal and myocardial damage encourage the use of MECC for CABG, especially in the specific high-risk subgroup of patients with anemia.

Recommendations regarding splenectomy in hereditary hemolytic anemias

PubMed Central

Iolascon, Achille; Andolfo, Immacolata; Barcellini, Wilma; Corcione, Francesco; Garçon, Loïc; De Franceschi, Lucia; Pignata, Claudio; Graziadei, Giovanna; Pospisilova, Dagmar; Rees, David C.; de Montalembert, Mariane; Rivella, Stefano; Gambale, Antonella; Russo, Roberta; Ribeiro, Leticia; Vives-Corrons, Jules; Martinez, Patricia Aguilar; Kattamis, Antonis; Gulbis, Beatrice; Cappellini, Maria Domenica; Roberts, Irene; Tamary, Hannah

2017-01-01

Hereditary hemolytic anemias are a group of disorders with a variety of causes, including red cell membrane defects, red blood cell enzyme disorders, congenital dyserythropoietic anemias, thalassemia syndromes and hemoglobinopathies. As damaged red blood cells passing through the red pulp of the spleen are removed by splenic macrophages, splenectomy is one possible therapeutic approach to the management of severely affected patients. However, except for hereditary spherocytosis for which the effectiveness of splenectomy has been well documented, the efficacy of splenectomy in other anemias within this group has yet to be determined and there are concerns regarding short- and long-term infectious and thrombotic complications. In light of the priorities identified by the European Hematology Association Roadmap we generated specific recommendations for each disorder, except thalassemia syndromes for which there are other, recent guidelines. Our recommendations are intended to enable clinicians to achieve better informed decisions on disease management by splenectomy, on the type of splenectomy and the possible consequences. As no randomized clinical trials, case control or cohort studies regarding splenectomy in these disorders were found in the literature, recommendations for each disease were based on expert opinion and were subsequently critically revised and modified by the Splenectomy in Rare Anemias Study Group, which includes hematologists caring for both adults and children. PMID:28550188

Anemia and iron deficiency in Mexican elderly population: Results from the Ensanut 2012.

PubMed

Contreras-Manzano, Alejandra; Cruz, Vanessa de la; Villalpando, Salvador; Rebollar, Rosario; Shamah-Levy, Teresa

2015-01-01

To describe de prevalence of iron deficiency (ID) and anemia in a sample of Mexican elderly population from the National Health and Nutrition Survey (Ensanut) 2012. 1 920 subjects ≥60 years of age were included. Hemoglobin, serum concentrations of ferritin and CRP were measured. The risk for ID and anemia adjusted for potential confounders was assessed in logistic regression models. The overall prevalence of anemia was 13.9%, 15.2% in males and 12.8% females. For ID, overall it was 4.2%, males 4.0% and females 4.3%. The greatest prevalence of ID was found in males and females over 80 years old (6.9 and 7.0%, respectively). ID was present in 1.5 of 10 Mexican elders with anemia. The prevalence of anemia was high in the elderly, however the prevalence of ID was low; there is a need to further investigate the causes of anemia in this age group.

Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

PubMed

Go, Ronald S; Winters, Jeffrey L; Leung, Nelson; Murray, David L; Willrich, Maria A; Abraham, Roshini S; Amer, Hatem; Hogan, William J; Marshall, Ariela L; Sethi, Sanjeev; Tran, Cheryl L; Chen, Dong; Pruthi, Rajiv K; Ashrani, Aneel A; Fervenza, Fernando C; Cramer, Carl H; Rodriguez, Vilmarie; Wolanskyj, Alexandra P; Thomé, Stephan D; Hook, C Christopher

2016-09-01

Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Endoscopic investigation in non-iron deficiency anemia: a cost to the health system without patient benefit

PubMed Central

Mogilevski, Tamara; Smith, Rebecca; Johnson, Douglas; Charles, Patrick G. P.; Churilov, Leonid; Vaughan, Rhys; Ma, Ronald; Testro, Adam

2016-01-01

Background and aims: The indication for endoscopy to investigate anemia of causes other than iron deficiency is not clear. Increasing numbers of endoscopic procedures for anemia raises concerns about costs to the health system, waiting times, and patient safety. The primary aim of this study was to determine the diagnostic yield of endoscopy in patients referred to undergo investigation for anemia. Secondary aims were to identify additional factors enabling the risk stratification of those likely to benefit from endoscopic investigation, and to undertake a cost analysis of performing endoscopy in this group of patients. Methods: We performed a retrospective review of endoscopy referrals for the investigation of anemia over a 12-month period at a single center. The patients were divided into three groups: those who had true iron deficiency anemia (IDA), tissue iron deficiency without anemia (TIDWA), or anemia of other cause (AOC). Outcome measures included finding a lesion responsible for the anemia and a significant change of management as a result of endoscopy. A costing analysis was performed with an activity-based costing method. Results: We identified 283 patients who underwent endoscopy to investigate anemia. A likely cause of anemia was found in 31 of 150 patients with IDA (21 %) and 0 patients in the other categories (P < 0.001). A change of management was observed in 35 patients with IDA (23 %), 1 of 14 patients with TIDWA (7.14 %), and 8 of 119 patients with AOC (6.7 %) (P < 0.001). The cost of a single colonoscopy or gastroscopy was approximated to be $ 2209. Conclusions: Endoscopic investigation for non-IDA comes at a significant cost to our institution, equating to a minimum of $ 293 797 per annum in extra costs, and does not result in a change of management in the majority of patients. No additional factors could be established to identify patients who might be more likely to benefit from endoscopic investigation. The endoscopic investigation of non-IDA should be minimized. PMID:26878049

Endoscopic investigation in non-iron deficiency anemia: a cost to the health system without patient benefit.

PubMed

Mogilevski, Tamara; Smith, Rebecca; Johnson, Douglas; Charles, Patrick G P; Churilov, Leonid; Vaughan, Rhys; Ma, Ronald; Testro, Adam

2016-02-01

The indication for endoscopy to investigate anemia of causes other than iron deficiency is not clear. Increasing numbers of endoscopic procedures for anemia raises concerns about costs to the health system, waiting times, and patient safety. The primary aim of this study was to determine the diagnostic yield of endoscopy in patients referred to undergo investigation for anemia. Secondary aims were to identify additional factors enabling the risk stratification of those likely to benefit from endoscopic investigation, and to undertake a cost analysis of performing endoscopy in this group of patients. We performed a retrospective review of endoscopy referrals for the investigation of anemia over a 12-month period at a single center. The patients were divided into three groups: those who had true iron deficiency anemia (IDA), tissue iron deficiency without anemia (TIDWA), or anemia of other cause (AOC). Outcome measures included finding a lesion responsible for the anemia and a significant change of management as a result of endoscopy. A costing analysis was performed with an activity-based costing method. We identified 283 patients who underwent endoscopy to investigate anemia. A likely cause of anemia was found in 31 of 150 patients with IDA (21 %) and 0 patients in the other categories (P < 0.001). A change of management was observed in 35 patients with IDA (23 %), 1 of 14 patients with TIDWA (7.14 %), and 8 of 119 patients with AOC (6.7 %) (P < 0.001). The cost of a single colonoscopy or gastroscopy was approximated to be $ 2209. Endoscopic investigation for non-IDA comes at a significant cost to our institution, equating to a minimum of $ 293 797 per annum in extra costs, and does not result in a change of management in the majority of patients. No additional factors could be established to identify patients who might be more likely to benefit from endoscopic investigation. The endoscopic investigation of non-IDA should be minimized.

Markers of nutritional status and mortality in older adults: The role of anemia and hypoalbuminemia.

PubMed

Corona, Ligiana Pires; de Oliveira Duarte, Yeda Aparecida; Lebrão, Maria Lúcia

2018-01-01

The aim of the present study was to analyze the impact of anemia and hypoalbuminemia on mortality in a 5-year period. This was longitudinal population-based observational survey part of the Saúde, Bem-Estar e Envelhecimento study (Health, Well-being and Aging), carried out with 1256 older adults from the third wave of the cohort, followed for 5 years, when they were contacted for the fourth wave, in Sao Paulo, Brazil. Anemia was defined when hemoglobin was <12 g/dL for women and <13 g/dL for men, and hypoalbuminemia when serum albumin was <3.5 g/dL. Survival functions were estimated according to nutritional status in four groups: (i) without nutritional alteration; (ii) anemia only; (iii) hypoalbuminemia only; and (iv) anemia and hypoalbuminemia. Hazard ratios were calculated, following the Cox proportional hazards model, controlling for baseline covariates. All analyses considered sample weights, and were carried out using the Stata 12. After the 5-year period, 12.3% of the participants died, and 8.2% were lost to follow up. Those who died had lower hemoglobin and albumin concentrations (13.4 g/dL and 3.7 g/dL) compared with survivors (14.3d/dL and 3.9 g/dL; P < 0.001). The crude death rate was 27.6/1000 person-years for participants in group i, 124.3 in group ii, 116.0 in group iii and 222.8 in group iv (P < 0.001). In the final Cox models, group 2 and 3 had a similar effect (hazard ratio 2.23, P = 0.020; 2.53, P = 0.005; respectively) and group 4 had a higher risk (hazard ratio 3.36; P = 0.004). Anemia and hypoalbuminemia are important markers for death in older adults, and have an additive effect on mortality. Because they are common and cost-effective biomarkers, their use should be encouraged in geriatric evaluation for all health professionals and in population settings, such as primary care. Geriatr Gerontol Int 2018; 18: 177-182. © 2017 Japan Geriatrics Society.

Improving dietary intake to prevent anemia in adolescent girls through community kitchens in a periurban population of Lima, Peru.

PubMed

Creed-Kanashiro, H M; Uribe, T G; Bartolini, R M; Fukumoto, M N; López, T T; Zavaleta, N M; Bentley, M E

2000-02-01

Peru has high rates of iron deficiency anemia. The prevalence is 35% in nonpregnant women of fertile age and 24.7% in adolescent girls in slums of periurban Lima. The major cause of anemia is low intake of dietary iron. A community-based, randomized behavioral and dietary intervention trial was conducted to improve dietary iron intake and iron bioavailability of adolescent girls living in periurban areas of Lima, Peru. Results show that there was a change in knowledge about anemia and improved dietary iron intake in the 71 girls who completed the study compared with the 66 girls in the control group. Although the 9-mo. intervention was not sufficient to improve hemoglobin levels significantly, there appeared to be a protective effect in maintaining the iron status of girls in comparison with the control group.

Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure.

PubMed

Fan, Ling; Chen, Li-Feng; Fan, Jing

2017-12-01

To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Guinea pigs model of iron deficiency anemia complicated with chronic heart failure in 10 guinea pigs of the experimental group was made by feeding a low iron diet, pure water and subcutaneous injection of isoproterenol. The control group consisting of 11 guinea pigs was given normal food, normal water and injected with normal saline. The left ventricular outflow tract model specimen was also prepared. The standard microelectrode technique was used to observe electrophysiological changes of autonomic cells in the outflow tract of left ventricular heart failure complicated with iron deficiency anemia in guinea pig model. The indicators of observation were maximal diastolic potential, action potential amplitude, 0 phase maximal depolarization velocity, 4 phase automatic depolarization velocity, repolarization 50% and 90%, and spontaneous discharge frequency. Compared with the control group, 4 phase automatic depolarization velocity, spontaneous discharge frequency and 0 phase maximal depolarization velocity decreased significantly (P < 0.01) and action potential amplitude reduced (P < 0.01) in model group. Moreover, repolarization 50% and 90% increased (P < 0.01). There are electrophysiological abnormalities of the left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with heart failure. Copyright © 2017 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Reducing iron deficiency anemia in Bolivian school children: calcium and iron combined versus iron supplementation alone.

PubMed

Miranda, Melissa; Olivares, Manuel; Brito, Alex; Pizarro, Fernando

2014-01-01

The aim of this study was to determine the effect of combined calcium and iron versus single iron supplementation on iron status in Bolivian schoolchildren. Children ages 6 to 10 y old (N = 195), were randomly assigned to receive either 700 mg Ca (as calcium carbonate) plus 30 mg Fe (as ferrous sulfate) (Ca + Fe group) or 30 mg Fe (as ferrous sulfate) (Fe group). The doses were administered daily, from Monday to Friday, between meals at school over 3 mo. Iron status was assessed at baseline and after intervention. Additionally, overall nutritional status was assessed by anthropometry and an estimation of dietary intake. At baseline, the prevalence of anemia in the Ca + Fe group and the Fe group were 15% and 21.5%, respectively. After 3 mo follow-up, the prevalence of iron deficiency anemia dropped significantly (P < 0.001) to 3% in both groups (χ(2) = NS). Iron dietary intake was within recommended levels, but calcium intake only covered 39% of the Recommended Daily Intake. Combined calcium and iron supplementation is equally as effective as single iron supplementation in reducing the prevalence of iron deficiency anemia in Bolivian school children. Copyright © 2014 Elsevier Inc. All rights reserved.

[Risk factors for iron deficiency anemia in infants aged 6 to 12 months and its effects on neuropsychological development].

PubMed

Xu, Kang; Zhang, Cui-Mei; Huang, Lian-Hong; Fu, Si-Mao; Liu, Yu-Ling; Chen, Ang; Ou, Jun-Bin

2015-08-01

To study the risk factors for moderate and severe iron deficiency anemia (IDA) in infants aged 6-12 months, and to preliminarily investigate the effects of IDA on the neuromotor development and temperament characteristics of infants. A total of 326 infants aged 6-12 months with IDA were classified into three groups: mild IDA (n=176), moderate IDA (n=111), and severe IDA (n=39) according to the severity of anemia. The risk factors for moderate or severe IDA were investigated by multivariate logistic regression analysis. Three hundred and forty-six infants without IDA who showed matched age, sex, and other backgrounds were selected as the control group. The Gesell Development Diagnosis Scale was used to evaluate children's mental development. The Temperament Scale for infants was used for evaluating children's temperament. The univariate analysis showed that the severity of IDA was associated with sex, birth weight, gestational age, multiple birth, maternal anemia during pregnancy, and mother's lack of knowledge about IDA (P<0.05). Setting the mild IDA group as control, the multivariate logistic regression analysis showed that multiple birth, premature birth, low birth weight (<2500 g), maternal anemia during pregnancy, breast feeding, and mother's lack of knowledge about IDA were the risk factors for severe IDA (OR>1; P<0.05); premature birth, breast feeding, and mixed feeding were the risk factors for moderate IDA (OR>1; P<0.05). The IDA group had significantly lower scores in Gesell general development quotient, gross motor, adaptive behavior, and fine motor than the control group (P<0.05). The IDA group had higher percentages of children with difficulty and intermediate difficulty temperaments than the control group (P<0.05). The IDA group had significantly higher scores in activity level, rhythmicity, adaptability, and perseverance than the control group (P<0.05). The severity of IDA is associated with premature birth, multiple birth, low birth weight, feeding pattern, maternal anemia during pregnancy and mother's lack of knowledge about IDA in infants aged 6-12 months. Infants with IDA have delayed neuromotor development and most of them have negative temperaments. More attention should be paid to mental and behavior problems for the infants. It is necessary to provide guidance for their parents in feeding and education.

Erythropoietin Levels in Elderly Patients with Anemia of Unknown Etiology

PubMed Central

Sriram, Swetha; Martin, Alison; Xenocostas, Anargyros; Lazo-Langner, Alejandro

2016-01-01

Background In many elderly patients with anemia, a specific cause cannot be identified. This study investigates whether erythropoietin levels are inappropriately low in these cases of “anemia of unknown etiology” and whether this trend persists after accounting for confounders. Methods This study includes all anemic patients over 60 years old who had erythropoietin measured between 2005 and 2013 at a single center. Three independent reviewers used defined criteria to assign each patient’s anemia to one of ten etiologies: chronic kidney disease, iron deficiency, chronic disease, confirmed myelodysplastic syndrome (MDS), suspected MDS, vitamin B12 deficiency, folate deficiency, anemia of unknown etiology, other etiology, or multifactorial etiology. Iron deficiency anemia served as the comparison group in all analyses. We used linear regression to model the relationship between erythropoietin and the presence of each etiology, sequentially adding terms to the model to account for the hemoglobin concentration, estimated glomerular filtration rate (eGFR) and Charlson Comorbidity Index. Results A total of 570 patients met the inclusion criteria. Linear regression analysis showed that erythropoietin levels in chronic kidney disease, anemia of chronic disease and anemia of unknown etiology were lower by 48%, 46% and 27%, respectively, compared to iron deficiency anemia even after adjusting for hemoglobin, eGFR and comorbidities. Conclusions We have shown that erythropoietin levels are inappropriately low in anemia of unknown etiology, even after adjusting for confounders. This suggests that decreased erythropoietin production may play a key role in the pathogenesis of anemia of unknown etiology. PMID:27310832

Anemia among Children Exposed to Polyparasitism in Coastal Kenya

PubMed Central

Cojulun, Alicia Chang; Bustinduy, Amaya L.; Sutherland, Laura J.; Mungai, Peter L.; Mutuku, Francis; Muchiri, Eric; Kitron, Uriel; King, Charles H.

2015-01-01

Anemia represents a substantial problem for children living in areas with limited resources and significant parasite burden. We performed a cross-sectional study of 254 Kenyan preschool- and early school-age children in a setting endemic for multiple chronic parasitic infections to explore mechanisms of their anemia. Complete venous blood cell counts revealed a high prevalence of local childhood anemia (79%). Evaluating the potential links between low hemoglobin and socioeconomic factors, nutritional status, hemoglobinopathy, and/or parasite infection, we identified age < 9 years (odds ratio [OR]: 12.0, 95% confidence interval [CI]: 4.4, 33) and the presence of asymptomatic malaria infection (OR: 6.8, 95% CI: 2.1, 22) as the strongest independent correlates of having anemia. A total of 130/155 (84%) of anemic children with iron studies had evidence of iron-deficiency anemia (IDA), 16% had non-IDA; 50/52 of additionally tested anemic children met soluble transferrin-receptor (sTfR) criteria for combined anemia of inflammation (AI) with IDA. Children in the youngest age group had the greatest odds of iron deficiency (OR: 10.0, 95% CI: 3.9, 26). Although older children aged 9–11 years had less anemia, they had more detectable malaria, Schistosoma infection, hookworm, and proportionately more non-IDA. Anemia in this setting appears multifactorial such that chronic inflammation and iron deficiency need to be addressed together as part of integrated management of childhood anemia. PMID:26324733

MCPIP1 Deficiency in Mice Results in Severe Anemia Related to Autoimmune Mechanisms

PubMed Central

Zhou, Zhou; Miao, Ruidong; Huang, Shengping; Elder, Brandon; Quinn, Tim; Papasian, Christopher J.; Zhang, Jifeng; Fan, Daping; Chen, Y. Eugene; Fu, Mingui

2013-01-01

Autoimmune gastritis is an organ-specific autoimmune disease of the stomach associated with pernicious anemia. The previous work from us and other groups identified MCPIP1 as an essential factor controlling inflammation and immune homeostasis. MCPIP1-/- developed severe anemia. However, the mechanisms underlying this phenotype remain unclear. In the present study, we found that MCPIP1 deficiency in mice resulted in severe anemia related to autoimmune mechanisms. Although MCPIP1 deficiency did not affect erythropoiesis per se, the erythropoiesis in MCPIP1-/- bone marrow erythroblasts was significantly attenuated due to iron and vitamin B12 (VB12) deficiency, which was mainly resulted from autoimmunity-associated gastritis and parietal cell loss. Consistently, exogenous supplement of iron and VB12 greatly improved the anemia phenotype of MCPIP1-/- mice. Finally, we have evidence suggesting that autoimmune hemolysis may also contribute to anemia phenotype of MCPIP1-/- mice. Taken together, our study suggests that MCPIP1 deficiency in mice leads to the development of autoimmune gastritis and pernicious anemia. Thus, MCPIP1-/- mice may be a good mouse model for investigating the pathogenesis of pernicious anemia and testing the efficacy of some potential drugs for treatment of this disease. PMID:24324805

Anemia and Iron Status Among Different Body Size Phenotypes in Chinese Adult Population: a Nation-Wide, Health and Nutrition Survey.

PubMed

Li, Jiang; Xiao, Cheng; Yang, Hui; Zhou, Yun; Wang, Rui; Cao, Yongtong

2017-12-09

Previous studies have shown that there is a controversial relationship between iron homeostasis and obesity. This study aims to explore the relationship of anemia and iron status with different body size phenotypes in adult Chinese population. Using information on iron status-related parameters and lifestyle data from 8462 participants of the 2009 wave of China Health and Nutrition Survey (2009 CHNS), we performed multivariable logistic regression analyses to estimate the odds ratios (ORs) for the risk of anemia and iron parameters according to different body size phenotypes. Participants with higher body mass index (BMI) had a lower anemia prevalence with significant trends in both metabolic status groups (P < 0.001). Serum ferritin, transferrin, and soluble transferrin receptor (sTfR)/log ferritin index were significant in different metabolic status groups and in different body size phenotypes, respectively. The ORs for higher ferritin and transferrin increased across different body size phenotypes in both genders, and for sTfR/log ferritin index decreased (P < 0.01 for trend). This association was still statistically significant after adjustment for multiple confounders. We found an inverse association of BMI levels with the prevalence of anemia and strong association of serum ferritin and transferrin with higher risk of obesity or overweight in both metabolic status groups.

Analysis of oxidative status and biochemical parameters in adult patients with sickle cell anemia treated with hydroxyurea, Ceará, Brazil

PubMed Central

Teixeira Neto, Paulo Florentino; Gonçalves, Romélia Pinheiro; Elias, Darcielle Bruna Dias; de Araújo, Cleiton Pinheiro; Magalhães, Hemerson Iury Ferreira

2011-01-01

Background Sickle cell anemia is a hemoglobinopathy caused by a mutation that results in the production of an abnormal hemoglobin molecule, hemoglobin S (Hb S). This is responsible for profound physiological changes, such as the sickling of red blood cells. Several studies have shown that hydroxyurea protects against vaso-occlusive crises. Objective The aim of this study was to evaluate the oxidative stress associated with biochemical parameters in patients with sickle cell anemia treated with hydroxyurea. Methods The study was conducted with 20 male and 25 female patients at the Hospital Universitário Walter Cantídio. The patients were divided into two groups: a study group (n = 12), patients with sickle cell anemia who were receiving hydroxyurea and a control group (n = 33) of sickle cell anemia patients not submitted to hydroxyurea treatment. The biochemical parameters analyzed were ferritin, transferrin, and serum iron. Glutathione was measured in its reduced form to analyze the oxidative state. Results The results showed insignificant increases in the levels of serum iron, transferrin and ferritin in patients treated with hydroxyurea when compared with those who did not take the medication. However, the glutathione levels were significantly higher in patients taking hydroxyurea than in controls. Conclusions These results indicate that hydroxyurea possibly acts as an antioxidant by increasing glutathione levels. PMID:23049297

Effect of anemia on tumor radiosensitivity under normo and hyperbaric conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rojas, A.; Stewart, F.A.; Smith, K.A.

1987-11-01

The effect of chronic anemia on tumor radiosensitivity in a murine tumor has been investigated. Anemia was induced by bilateral kidney irradiation given several months before tumor implantation. Anemic, anemic transfused, and normal non-anemic age-matched tumor bearing animals were irradiated with X rays (2 F/24 hr) either in air, air plus misonidazole, or under hyperbaric oxygen. The most resistant response was that of tumors grown in normal mice treated in air. Anemia produced an increase in radiosensitivity which was further enhanced by red blood cell replacement. The most sensitive overall response was seen in the anemic-transfused group treated with HBO.

Local concepts of anemia-related illnesses and public health implications in the Taabo health demographic surveillance system, Côte d'Ivoire.

PubMed

Kouadio, M'Bra Kd; Righetti, Aurélie A; Abé, Noël N; Wegmüller, Rita; Weiss, Mitchell G; N'Goran, Eliézer K; Utzinger, Jürg

2013-05-06

A 14-month prospective longitudinal study conducted in the Taabo health demographic surveillance system (HDSS), south-central Côte d'Ivoire, revealed high prevalence of anemia in different population groups in three types of settings (i.e., small town, village, and hamlet). Demographic parameters and several variables related to parasitic infections, micronutrient status, and inflammation were significantly associated with higher odds of anemia. However, cultural concepts and knowledge of various anemia-related illnesses and their relation with people's behaviors have not been investigated. Sixteen focus group discussions and six key informant interviews were performed with village authorities, health workers, and traditional healers. Questionnaires were administrated to 200 school-aged children and 115 young women. Of these individuals, 206 participated in the preceding longitudinal study, whereas the remaining 109 people were not exposed to prior research, but had similar age and sex profiles. Mean prominence of participants' responses was compared between groups of participants and across study settings. Local concepts of anemia-related illnesses referred to its perceived causes based on two logical frameworks - biomedical and sociocultural - although a clear distinction was often blurred. We found few differences in knowledge, beliefs, and behaviors across study settings and between participants who were exposed to prior research and newly recruited ones. Malaria und nutritional issues as understood and managed by the population differed from definitions and recommendations provided by the health system. Malaria was not acknowledged as an exclusive mosquito-transmitted disease and participants referred to the quantity, rather than the quality, of food when talking about nutritional issues. Local concepts and ideas about anemia have public health implications, inasmuch as they are related to people's attitudes, risk-related and help-seeking behaviors, which in turn might affect their health status. Local terminology and beliefs about anemia and malaria should be carefully considered when developing health intervention and education programs. The similarity in knowledge about anemia-related illnesses and associated behaviors, regardless of study setting and prior exposure to research, suggests that a uniform communication strategy may be used to develop education programs and awareness campaigns aimed at the prevention and control of anemia in south-central Côte d'Ivoire.

Local concepts of anemia-related illnesses and public health implications in the Taabo health demographic surveillance system, Côte d’Ivoire

PubMed Central

2013-01-01

Background A 14-month prospective longitudinal study conducted in the Taabo health demographic surveillance system (HDSS), south-central Côte d’Ivoire, revealed high prevalence of anemia in different population groups in three types of settings (i.e., small town, village, and hamlet). Demographic parameters and several variables related to parasitic infections, micronutrient status, and inflammation were significantly associated with higher odds of anemia. However, cultural concepts and knowledge of various anemia-related illnesses and their relation with people’s behaviors have not been investigated. Methods Sixteen focus group discussions and six key informant interviews were performed with village authorities, health workers, and traditional healers. Questionnaires were administrated to 200 school-aged children and 115 young women. Of these individuals, 206 participated in the preceding longitudinal study, whereas the remaining 109 people were not exposed to prior research, but had similar age and sex profiles. Mean prominence of participants’ responses was compared between groups of participants and across study settings. Results Local concepts of anemia-related illnesses referred to its perceived causes based on two logical frameworks – biomedical and sociocultural – although a clear distinction was often blurred. We found few differences in knowledge, beliefs, and behaviors across study settings and between participants who were exposed to prior research and newly recruited ones. Malaria und nutritional issues as understood and managed by the population differed from definitions and recommendations provided by the health system. Malaria was not acknowledged as an exclusive mosquito-transmitted disease and participants referred to the quantity, rather than the quality, of food when talking about nutritional issues. Conclusions Local concepts and ideas about anemia have public health implications, inasmuch as they are related to people’s attitudes, risk-related and help-seeking behaviors, which in turn might affect their health status. Local terminology and beliefs about anemia and malaria should be carefully considered when developing health intervention and education programs. The similarity in knowledge about anemia-related illnesses and associated behaviors, regardless of study setting and prior exposure to research, suggests that a uniform communication strategy may be used to develop education programs and awareness campaigns aimed at the prevention and control of anemia in south-central Côte d’Ivoire. PMID:24499516

Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

PubMed

Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

2017-02-01

Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population

PubMed Central

Abbasi, Sakineh; Rasouli, Mina

2017-01-01

Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957–8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996–5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer. PMID:28440412

A rare FANCA gene variation as a breast cancer susceptibility allele in an Iranian population.

PubMed

Abbasi, Sakineh; Rasouli, Mina

2017-06-01

Fanconi Anemia (FA) is an autosomal recessive syndrome characterized by congenital abnormalities, progressive bone marrow failure and Fanconi anemia complementation group A (FANCA) is also a potential breast and ovarian cancer susceptibility gene. A novel allele with tandem duplication of 13 base pair sequence in promoter region was identified. To investigate whether the 13 base pair sequence of tandem duplication in promoter region of the FANCA gene is of high penetrance in patients with breast cancer and to determine if the presence of the duplicated allele was associated with an altered risk of breast cancer, the present study screened DNA in blood samples from 304 breast cancer patients and 295 normal individuals as controls. The duplication allele had a frequency of 35.4 and 21.2% in patients with breast cancer and normal controls, respectively. There was a significant increase in the frequency of the duplication allele in patients with familial breast cancer compared with controls (45.1%, P=0.001). Furthermore, the estimated risk of breast cancer in individuals with a homozygote [odds ratio (OR), 4.093; 95% confidence intervals (CI), 1.957‑8.561] or heterozygote duplicated genotype (OR, 3.315; 95% CI, 1.996‑5.506) was higher compared with the corresponding normal homozygote genotype. In conclusion, the present study indicated that the higher the frequency of the duplicated allele, the higher the risk of breast cancer. To the best of our knowledge, the present study is the first to report FANCA gene duplication in patients with breast cancer.

Maternal anemia during pregnancy and subsequent risk for cardiovascular disease.

PubMed

Azulay, Carmit Erez; Pariente, Gali; Shoham-Vardi, Ilana; Kessous, Roy; Sergienko, Ruslan; Sheiner, Eyal

2015-01-01

To investigate the association between anemia during pregnancy and subsequent future maternal cardiovascular morbidity and mortality. A retrospective cohort study was conducted, comparing women with and without anemia during pregnancy. Deliveries occurred during 1988-1998 and had followed for more than a decade. Incidence of long-term cardiovascular morbidity was compared between the two groups. During the study period, 47 657 deliveries met the inclusion criteria; of these 12 362 (25.9%) occurred in women with anemia at least once during their pregnancies. Anemia of pregnancy was noted as a risk factor for long-term complex cardiovascular events (OR = 1.6, 95% CI 1-2.8, p = 0.04). Using a Cox multivariable regression model, controlling for ethnicity and maternal age, anemia was found to be an independent risk factor for long-term maternal cardiovascular hospitalization (OR for total hospitalizations = 1.2, 95% CI 1.1-1.4, p < 0.001). Anemia of pregnancy is an independent risk factor for long-term cardiovascular morbidity in a follow-up period of more than a decade.

Clinical roundtable monograph: Paroxysmal nocturnal hemoglobinuria: a case-based discussion.

PubMed

Szer, Jeff; Hill, Anita; Weitz, Ilene Ceil

2012-11-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disorder characterized by chronic intravascular hemolysis as the primary clinical manifestation and morbidities that include anemia, thrombosis, renal impairment, pulmonary hypertension, and bone marrow failure. The prevalence of the PNH clone (from <1-100% PNH granulocytes) is approximately 16 per million, and careful monitoring is required. The average age of onset of the clinical disease is the early 30s, although it can present at all ages. PNH is caused by the acquisition of a somatic mutation of the gene phosphatidylinositol glycan anchor (PIG-A) in a multipotent hematopoietic stem cell (HSC), with clonal expansion of the mutated HSC. The mutation causes a deficiency in the synthesis of glycosylphosphatidylinositol (GPI). In cells derived from normal HSCs, the complement regulatory proteins CD55 and CD59 are anchored to the hematopoietic cell membrane surface via GPI, protecting the cells from complement-mediated lysis. However, in patients with PNH, these 2 proteins, along with numerous other GPI-linked proteins, are absent from the cell surface of red cells, granulocytes, monocytes, and platelets, resulting in complement-mediated intravascular hemolysis and other complications. Lysis of red blood cells is the most obvious manifestation, but as other cell lineages are also affected, this complement-mediated attack contributes to additional complications, such as thrombosis. Eculizumab, a humanized monoclonal antibody against the C5 complement protein, is the only effective drug therapy for PNH patients. The antibody prevents cleavage of the C5 protein by C5 convertase, in turn preventing generation of C5b-9 and release of C5a, thereby protecting from hemolysis of cells lacking the CD59 surface protein and other complications associated with complement activation. Drs. Ilene C. Weitz, Anita Hill, and Jeff Szer discuss 3 recent cases of patients with PNH.

Eculizumab in paroxysmal nocturnal hemoglobinuria with Budd-Chiari syndrome progressing despite anticoagulation

PubMed Central

2012-01-01

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, life-threatening disorder characterized by chronic intravascular hemolysis caused by uncontrolled complement activation. Hepatic vein thrombosis (Budd-Chiari syndrome) is common in PNH patients. This case report describes the response to eculizumab (a humanized monoclonal antibody that inhibits terminal complement activation) in a 25-year-old male with progressive liver function deterioration despite standard anticoagulation therapy and transjugular intrahepatic porto-systemic shunt. The patient presented with anemia, severe thrombocytopenia, headache, abdominal pain, and distention. He was diagnosed with PNH, cerebral vein thrombosis, and Budd-Chiari syndrome. Despite adequate anticoagulation, diuretic administration, and placement of a transjugular shunt, additional thrombotic events and progressive liver damage were observed. Eculizumab therapy was initiated, resulting in rapid blockade of intravascular hemolysis, increased platelet counts, ascites resolution, and liver function recovery, all of which are presently sustained. Since starting eculizumab the patient has had no further thrombotic events and his quality of life has dramatically improved. This is the first report to confirm the role of complement-mediated injury in the progression of Budd-Chiari syndrome in a patient with PNH. This case shows that terminal complement blockade with eculizumab can reverse progressive thromboses and hepatic failure that is unresponsive to anticoagulation therapy and suggests that early initiation of eculizumab should be included in the therapeutic regimen of patients with PNH-related Budd-Chiari syndrome. PMID:23210433

Glucose-6-Phosphate Dehydrogenase Deficiency Mimicking Atypical Hemolytic Uremic Syndrome.

PubMed

Walsh, Patrick R; Johnson, Sally; Brocklebank, Vicky; Salvatore, Jacobo; Christian, Martin; Kavanagh, David

2018-02-01

A 4-year-old boy presented with nonimmune hemolysis, thrombocytopenia, and acute kidney injury. Investigations for an underlying cause failed to identify a definitive cause and a putative diagnosis of complement-mediated atypical hemolytic uremic syndrome (aHUS) was made. The patient was started initially on plasma exchange and subsequently eculizumab therapy, after which his kidney function rapidly improved. While on eculizumab therapy, despite adequate complement blockade, he presented 2 more times with hemolytic anemia and thrombocytopenia, but without renal involvement. Genetic analysis did not uncover a mutation in any known aHUS gene (CFH, CFI, CFB, C3, CD46, THBD, INF2, and DGKE) and anti-factor H antibodies were undetectable. Whole-exome sequencing was undertaken to identify a cause for the eculizumab resistance. This revealed a pathogenic variant in G6PD (glucose-6-phosphate dehydrogenase), which was confirmed by functional analysis demonstrating decreased erythrocyte G6PD activity. Eculizumab therapy was withdrawn. Complement-mediated aHUS is a diagnosis of exclusion and this case highlights the diagnostic difficulty that remains without an immediately available biomarker for confirmation. This case of G6PD deficiency presented with a phenotype clinically indistinguishable from complement-mediated aHUS. We recommend that G6PD deficiency be included in the differential diagnosis of patients presenting with aHUS and suggest measuring erythrocyte G6PD concentrations in these patients. Copyright © 2017. Published by Elsevier Inc.

Red blood cell vesiculation in hereditary hemolytic anemia

PubMed Central

Alaarg, Amr; Schiffelers, Raymond M.; van Solinge, Wouter W.; van Wijk, Richard

2013-01-01

Hereditary hemolytic anemia encompasses a heterogeneous group of anemias characterized by decreased red blood cell survival because of inherited membrane, enzyme, or hemoglobin disorders. Affected red blood cells are more fragile, less deformable, and more susceptible to shear stress and oxidative damage, and show increased vesiculation. Red blood cells, as essentially all cells, constitutively release phospholipid extracellular vesicles in vivo and in vitro in a process known as vesiculation. These extracellular vesicles comprise a heterogeneous group of vesicles of different sizes and intracellular origins. They are described in literature as exosomes if they originate from multi-vesicular bodies, or as microvesicles when formed by a one-step budding process directly from the plasma membrane. Extracellular vesicles contain a multitude of bioactive molecules that are implicated in intercellular communication and in different biological and pathophysiological processes. Mature red blood cells release in principle only microvesicles. In hereditary hemolytic anemias, the underlying molecular defect affects and determines red blood cell vesiculation, resulting in shedding microvesicles of different compositions and concentrations. Despite extensive research into red blood cell biochemistry and physiology, little is known about red cell deformability and vesiculation in hereditary hemolytic anemias, and the associated pathophysiological role is incompletely assessed. In this review, we discuss recent progress in understanding extracellular vesicles biology, with focus on red blood cell vesiculation. Also, we review recent scientific findings on the molecular defects of hereditary hemolytic anemias, and their correlation with red blood cell deformability and vesiculation. Integrating bio-analytical findings on abnormalities of red blood cells and their microvesicles will be critical for a better understanding of the pathophysiology of hereditary hemolytic anemias. PMID:24379786

Socio-economic and demographic determinants of childhood anemia.

PubMed

Goswmai, Sankar; Das, Kishore K

2015-01-01

To evaluate socio-economic and demographic determinants of anemia among Indian children aged 6-59 months. Statistical analysis was performed on the cross-sectional weighted sample of 40,885 children from 2005 to 2006 National Family Health Survey by using multinomial logistic regression to assess the significance of some risk factors in different degrees of child anemia. Anemia was diagnosed by World Health Organization (WHO) cut-off points on hemoglobin level. Pearson's chi-squared test was applied to justify the associations of anemia with different categories of the study population. The prevalence of anemia was 69.5%; 26.2% mild, 40.4% moderate, and 2.9% severe anemia. Overall prevalence rate, along with mild and moderate cases, showed an increasing trend up to 2 years of age and then decreased. Rural children had a higher prevalence rate. Of 28 Indian states in the study, 10 states showed very high prevalence, the highest being Bihar (77.9%). Higher birth order, high index of poverty, low level of maternal education, mother's anemia, non-intake of iron supplements during pregnancy, and vegetarian mother increased the risks of all types of anemia among children (p<0.05). Christian population was at lower risk; and Scheduled Caste, Scheduled Tribe, and Other Backward Class categories were at higher risk of anemia. The results suggest a need for proper planning and implementation of preventive measures to combat child anemia. Economically under-privileged groups, maternal nutrition and education, and birth control measures should be priorities in the programs. Copyright © 2015 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

[Association between hematopoietic nutrient intake and the origin of nutritional anemia in women of childbearing age in Colombia].

PubMed

Manjarrés, Luz Mariela; Díaz, Abel; Carriquiry, Alicia

2012-01-01

Compare the nutritional origin of anemia by sociodemographic variables and analyze its association with deficient hematopoietic nutrient intake. The database of Colombia's 2005 National Survey of Nutritional Status was used. The data were obtained through complex representative sampling of the population and processed using SPSS v.15. Anemic women of childbearing age were selected and divided into two groups according to serum ferritin levels. Their customary hematopoietic nutrient intake and risk of deficiency were determined. The proportions of anemia types were compared by sociodemographic variables using the F-distribution, the Rao-Scott second order correction (P < 0.05). The association between the origin of the anemia and classification of the nutrient was analyzed using the odds ratio (OR). 595 women. Non-hypoferric anemia (67.2%) predominated, with no statistical difference by sociodemographic variable, except in the Pacific region (hypoferric anemia, 52.1%). The prevalence of deficiency in the customary intake of hematopoietic nutrients was high. There was no significant association between the deficit in consumption and the origin of the anemia. Non-hypoferric anemia was most common, with no difference by sociodemographic indicators except in the Pacific region. All the women were at high risk of deficiency in their customary hematopoietic nutrient intake, but a statistically significant association between the deficiency and the origin of the nutritional anemia was not observed. Programs to improve nutrient intake and a continued search for causes of nutritional anemia other than iron deficiency are justified.

The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal.

PubMed

Chandyo, R K; Henjum, S; Ulak, M; Thorne-Lyman, A L; Ulvik, R J; Shrestha, P S; Locks, L; Fawzi, W; Strand, T A

2016-04-01

Iron deficiency anemia is a widespread public health problem, particularly in low- and middle-income countries. Maternal iron status around and during pregnancy may influence infant iron status. We examined multiple biomarkers to determine the prevalence of iron deficiency and anemia among breastfed infants and explored its relationship with maternal and infant characteristics in Bhaktapur, Nepal. In a cross-sectional survey, we randomly selected 500 mother-infant pairs from Bhaktapur municipality. Blood was analyzed for hemoglobin, ferritin, total iron-binding capacity, transferrin receptors and C-reactive protein. The altitude-adjusted prevalence of anemia was 49% among infants 2-6-month-old (hemaglobin (Hb) <10.8 g/dl) and 72% among infants 7-12-month-old (Hb <11.3 g/dl). Iron deficiency anemia, defined as anemia and serum ferritin <20 or <12 μg/l, affected 9 and 26% of infants of these same age groups. Twenty percent of mothers had anemia (Hb <12.3 g/dl), but only one-fifth was explained by depletion of iron stores. Significant predictors of infant iron status and anemia were infant age, sex and duration of exclusive breastfeeding and maternal ferritin concentrations. Our findings suggest that iron supplementation in pregnancy is likely to have resulted in a low prevalence of postpartum anemia. The higher prevalence of anemia and iron deficiency among breastfed infants compared with their mothers suggests calls for intervention targeting newborns and infants.

Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine.

PubMed

Hama, Asahito; Takahashi, Yoshiyuki; Muramatsu, Hideki; Ito, Masafumi; Narita, Atsushi; Kosaka, Yoshiyuki; Tsuchida, Masahiro; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-11-01

The 2008 World Health Organization classification proposed a new entity in childhood myelodysplastic syndrome, refractory cytopenia of childhood. However, it is unclear whether this morphological classification reflects clinical outcomes. We retrospectively reviewed bone marrow morphology in 186 children (median age 8 years; range 1-16 years) who were enrolled in the prospective study and received horse antithymocyte globulin and cyclosporine between July 1999 and November 2008. The median follow-up period was 87 months (range 1-146 months). Out of 186 patients, 62 (33%) were classified with aplastic anemia, 94 (49%) with refractory cytopenia of childhood, and 34 (18%) with refractory cytopenia with multilineage dysplasia. Aplastic anemia patients received granulocyte colony-stimulating factor more frequently and for longer durations than other patients (P<0.01). After six months, response rates to immunosuppressive therapy were not significantly different among the 3 groups. Acquisition of chromosomal abnormalities was observed in 5 patients with aplastic anemia, 4 patients with refractory cytopenia of childhood, and 3 patients with refractory cytopenia with multilineage dysplasia. Although the cumulative incidence of total clonal evolution at ten years was not significantly different among the 3 groups, the cumulative incidence of monosomy 7 development was significantly higher in aplastic anemia than in the other groups (P=0.02). Multivariate analysis revealed that only granulocyte colony-stimulating factor administration duration of 40 days or more was a significant risk factor for monosomy 7 development (P=0.02). These findings suggest that even the introduction of a strict morphological distinction from hypoplastic myelodysplastic syndrome cannot eradicate clonal evolution in children with aplastic anemia. Copyright© Ferrata Storti Foundation.

Life and Death of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficient Erythrocytes - Role of Redox Stress and Band 3 Modifications.

PubMed

Arese, Paolo; Gallo, Valentina; Pantaleo, Antonella; Turrini, Franco

2012-10-01

G6PD catalyzes the first, pace-making reaction of pentosephosphate cycle (PPC) which produces NADPH. NADPH maintains glutathione and thiol groups of proteins and enzymes in the reduced state which is essential for protection against oxidative stress. Individuals affected by G6PD deficiency are unable to regenerate reduced glutathione (GSH) and are undefended against oxidative stress. G6PD deficiency accelerates normal senescence and enhances the precocious removal of chronologically young, yet biologically old cells. The term hemolytic anemia is misleading because RBCs do not lyse but are removed by phagocytosis. Acute hemolysis by fava bean ingestion in G6PD deficient individuals (favism) is described being the best-studied natural model of oxidant damage. It bears strong analogies to hemolysis by oxidant drugs or chemicals. Membrane alterations observed in vivo during favism are superimposable to changes in senescent RBCs. In summary, RBC membranes isolated from favic patients contained elevated amounts of complexes between IgG and the complement fragment C3b/C3c and were prone to vesiculation. Anti-band 3 IgG reacted to aggregated band 3-complement complexes. In favism extensive clustering of band 3 and membrane deposition of hemichromes were also observed. Severely damaged RBCs isolated from early crises had extensive membrane cross-bonding and very low GSH levels and were phagocytosed 10-fold more intensely compared to normal RBCs.

Prevalence and Determinants of Anemia and Iron Deficiency in Kuwait

PubMed Central

Al Zenki, Sameer; Alomirah, Husam; Al Hooti, Suad; Al Hamad, Nawal; Jackson, Robert T.; Rao, Aravinda; Al Jahmah, Nasser; Al Obaid, Ina’am; Al Ghanim, Jameela; Al Somaie, Mona; Zaghloul, Sahar; Al Othman, Amani

2015-01-01

The objective of this study was to assess the prevalence of anemia and iron deficiency (ID) of a nationally representative sample of the Kuwait population. We also determined if anemia differed by socioeconomic status or by RBC folate and vitamins A and B12 levels. The subjects who were made up of 1830 males and females between the ages of 2 months to 86 years, were divided into the following age groups (0–5, 5–11, 12–14, 15–19, 20–49, ≥50 years). Results showed that the prevalence of anemia was 3% in adult males and 17% in females. The prevalence of ID varied according to age between 4% (≥50 years) and 21% (5–11 years) and 9% (12–14 years) and 23% (15–19 years), respectively, in males and females. The prevalence of anemia and ID was higher in females compared to males. Adults with normal ferritin level, but with low RBC folate and vitamins A and B12 levels had higher prevalence of anemia than those with normal RBC folate and vitamins A and B12 levels. This first nationally representative nutrition and health survey in Kuwait indicated that anemia and ID are prevalent and ID contributes significantly to anemia prevalence. PMID:26264015

From Bad to Worse: Anemia on Admission and Hospital-Acquired Anemia.

PubMed

Koch, Colleen G; Li, Liang; Sun, Zhiyuan; Hixson, Eric D; Tang, Anne S; Phillips, Shannon C; Blackstone, Eugene H; Henderson, J Michael

2017-12-01

Anemia at hospitalization is often treated as an accompaniment to an underlying illness, without active investigation, despite its association with morbidity. Development of hospital-acquired anemia (HAA) has also been associated with increased risk for poor outcomes. Together, they may further heighten morbidity risk from bad to worse. The aims of this study were to (1) examine mortality, length of stay, and total charges in patients with present-on-admission (POA) anemia and (2) determine whether these are exacerbated by development of HAA. In this cohort investigation, from January 1, 2009, to August 31, 2011, a total of 44,483 patients with POA anemia were admitted to a single health system compared with a reference group of 48,640 without POA anemia or HAA. Data sources included the University HealthSystem Consortium database and electronic medical records. Risk-adjustment methods included logistic and linear regression models for mortality, length of stay, and total charges. Present-on-admission anemia was defined by administrative coding. Hospital-acquired anemia was determined by changes in hemoglobin values from the electronic medical record. Approximately one-half of the patients experienced worsening of anemia with development of HAA. Risk for death and resource use increased with increasing severity of HAA. Those who developed severe HAA had 2-fold greater odds for death; that is, mild POA anemia with development of severe HAA resulted in greater mortality (odds ratio, 2.57; 95% confidence interval, 2.08-3.18; P < 0.001), increased length of stay (2.23; 2.16-2.31; P < 0.001), and higher charges (2.09; 2.03-2.15; P < 0.001). Present-on-admission anemia is associated with increased mortality and resource use. This risk is further increased from bad to worse when patients develop HAA. Efforts to address POA anemia and HAA deserve attention.

Incidence and risk factors of aplastic anemia in Latin American countries: the LATIN case-control study

PubMed Central

Maluf, Eliane; Hamerschlak, Nelson; Cavalcanti, Alexandre Biasi; Júnior, Álvaro Avezum; Eluf-Neto, José; Falcão, Roberto Passetto; Lorand-Metze, Irene G.; Goldenberg, Daniel; Santana, Cézar Leite; de Oliveira Werneck Rodrigues, Daniela; da Motta Passos, Leny Nascimento; Rosenfeld, Luis Gastão Mange; Pitta, Marimilia; Loggetto, Sandra; Feitosa Ribeiro, Andreza A.; Velloso, Elvira Deolinda; Kondo, Andrea Tiemi; de Miranda Coelho, Erika Oliveira; Pintão, Maria Carolina Tostes; de Souza, Hélio Moraes; Borbolla, José Rafael; Pasquini, Ricardo

2009-01-01

Background Associations between aplastic anemia and numerous drugs, pesticides and chemicals have been reported. However, at least 50% of the etiology of aplastic anemia remains unexplained. Design and Methods This was a case-control, multicenter, multinational study, designed to identify risk factors for agranulocytosis and aplastic anemia. The cases were patients with diagnosis of aplastic anemia confirmed through biopsy or bone marrow aspiration, selected through an active search of clinical laboratories, hematology clinics and medical records. The controls did not have either aplastic anemia or chronic diseases. A total of 224 patients with aplastic anemia were included in the study, each case was paired with four controls, according to sex, age group, and hospital where the case was first seen. Information was collected on demographic data, medical history, laboratory tests, medications, and other potential risk factors prior to diagnosis. Results The incidence of aplastic anemia was 1.6 cases per million per year. Higher rates of benzene exposure (≥30 exposures per year) were associated with a greater risk of aplastic anemia (odds ratio, OR: 4.2; 95% confidence interval, CI: 1.82–9.82). Individuals exposed to chloramphenicol in the previous year had an adjusted OR for aplastic anemia of 8.7 (CI: 0.87–87.93) and those exposed to azithromycin had an adjusted OR of 11.02 (CI 1.14–108.02). Conclusions The incidence of aplastic anemia in Latin America countries is low. Although the research study centers had a high coverage of health services, the underreporting of cases of aplastic anemia in selected regions can be discussed. Frequent exposure to benzene-based products increases the risk for aplastic anemia. Few associations with specific drugs were found, and it is likely that some of these were due to chance alone. PMID:19734415

Assessment of maternal anemia in rural Western China between 2001 and 2005: a two-level logistic regression approach

PubMed Central

2013-01-01

Background There are multiple adverse effects of anemia on human function, particularly on women. However, few researches are conducted on women anemia in rural Western China. This study mainly aims to investigate the levels and associated factors of maternal anemia between 2001 and 2005 in this region. Methods 6172 and 5372 mothers with children under three years old were selected from 8 provinces in 2001 and from 9 provinces in 2005 respectively in Western China by means of a multi-stage probability proportion to size sampling method (PPS). The blood samples were tested and related socio-demographic information was obtained through questionnaires. A two-level logistic regression model was employed to identify the determinants and provincial variations of women anemia in 2001 and 2005. Results The results indicated that the crude prevalence of women anemia in 2005 was higher than the rate in 2001(45.7% vs 33.6%). Based on the nationwide census data in 2000, the age-standardized prevalence of women anemia in the study were obtained as 38.0% in 2001 and 50.0% in 2005 respectively. Two-level logistic model analysis showed that compared to the average, women were more likely to be anemic in Guangxi and Qinghai in 2001 as well as in Chongqing and Qinghai in 2005; that women from Minority groups had higher odds of anemia in contrast with Han; that women with higher parity, longer breastfeeding duration and higher socioeconomic level had a lower rate of anemia, while age of women was positively associated with anemia. The positive correlation between women anemia and altitude was also observed. Conclusions The study demonstrated that the burden of maternal anemia in rural Western China increased considerably between 2001 and 2005. The Chinese government should conduct integrated interventions on anemia of mothers in this region. PMID:23597320

Determinants of anemia among 6-59 months aged children in Bangladesh: evidence from nationally representative data.

PubMed

Khan, Jahidur Rahman; Awan, Nabil; Misu, Farjana

2016-01-11

Anemia is a global public health problem but the burden of anemia is disproportionately borne among children in developing countries. Anemia in early stages of life has serious consequences on the growth and development of the children. We examine the prevalence of anemia, possible association between anemia and different socio-economic, demographic, health and other factors among children with ages from 6 to 59 months from the nationally representative 2011 Bangladesh Demographic and Health Survey (BDHS). Data on hemoglobin (Hb) concentration among the children aged 6-59 months from the most recent BDHS (2011) were used. This nationally representative survey allowed a multistage stratified cluster sampling design and provided data on a wide range of indicators such as fertility, mortality, women and child health, nutrition and other background characteristics. Anemia status was determined using hemoglobin level (<11.0 g/dl), and weighted prevalence of childhood anemia along with 95 % confidence intervals were provided. We also examined the distribution of weighted anemia prevalence across different groups and performed logistic regression to assess the association of anemia with different factors. A total of 2171 children aged 6-59 months were identified for this analysis, with weighted prevalence of anemia being 51.9 % overall- 47.4 % in urban and 53.1 % in rural regions. Results of a multivariable logistic regression analysis showed that, children below 24 months of age (odds ratio, [OR] 3.01; 95 % confidence interval [CI] 2.38-3.81), and those from an anemic mother (OR 1.80; 95 % CI 1.49-2.18) were at higher risk of anemia. Childhood anemia was significantly associated with chronic malnutrition of child, source of drinking water, household wealth and geographical location (defined by division). A high prevalence of anemia among 6-59 months aged children was observed in Bangladesh. Given the negative impact of anemia on the development of children in future, there is an urgent need for effective and efficient remedial public health interventions.

Nutrient Intake and Anemia Risk in the WHI Observational Study

PubMed Central

Stanaway, Jeffrey; Neuhouser, Marian L.; Snetselaar, Linda G.; Stefanick, Marcia L.; Arendell, Leslie; Chen, Zhao

2011-01-01

Background Nutritional anemia among post-menopausal women is preventable; recent data on prevalence are limited. Objective To investigate the association between nutrient intakes and anemia prevalence, in relation to both incidence and persistence, in a longitudinal sample of post-menopausal women. We hypothesized that anemia prevalence, incidence and persistence would be greater among women reporting lower intake of B12, folate and iron. Design Prospective cohort analysis. Participants/setting Observational Cohort of the Women’s Health Initiative(WHI-OS) including 93,676 postmenopausal women, age 50 to 79 years, were recruited across the United States at 40 clinical study sites. Women were enrolled between 1993 and 1998; data collection for these analyses continued through 2000. Main outcome measures Anemia was defined as a blood hemoglobin concentration of <12.0 mg/dL. Persistent anemia was defined as anemia present at each measurement time point. Diet was assessed by food frequency questionnaire for iron, folate, B12, red meat and cold breakfast cereal; inadequacies were based on dietary reference intakes for women over age 50 years. Statistical analysis Descriptive statistics (mean and standard deviation) were used to characterize the population demographics, anemia rates and diet. Unconditional logistic regression was used to investigate associations between diet and incident and persistent anemia. Associations are presented as odds ratio (OR) and 95% confidence intervals (CI). Results Anemia was identified in 3,979 women or 5.5% of the cohort. Inadequate intakes of multiple anemia-associated nutrients were less frequent in non-Hispanic whites (7.4%) than other race/ethnic groups (inadequacies demonstrated in 14.6 to 16.3% of sample). Age, body mass index and smoking were associated with anemia. Women with anemia reported lower intakes of energy, protein, folate, B12, iron, vitamin C and red meat. Multiple (more than a single nutrient) dietary deficiencies were associated with a 21% greater risk of persistent anemia (OR-1.21, 95% CI: 1.05–1.41) and three deficiencies resulted in a 44% increase in risk for persistent anemia (OR-1.44, 95% CI: 1.20–1.73). Conclusion Inadequate nutrient intake, a modifiable condition, is associated with greater risk for anemia in post-menopausal women participating in the WHI-OS. Efforts to identify and update incidence estimates for anemia-associated nutrient deficiencies in aging women should be undertaken. PMID:21443985

Fanconi anemia protein, FANCA, associates with BRG1, a component of the human SWI/SNF complex.

PubMed

Otsuki, T; Furukawa, Y; Ikeda, K; Endo, H; Yamashita, T; Shinohara, A; Iwamatsu, A; Ozawa, K; Liu, J M

2001-11-01

Fanconi anemia (FA) is a genetic disorder that predisposes to hematopoietic failure, birth defects and cancer. We identified an interaction between the FA protein, FANCA and brm-related gene 1 (BRG1) product. BRG1 is a subunit of the SWI/SNF complex, which remodels chromatin structure through a DNA-dependent ATPase activity. FANCA was demonstrated to associate with the endogenous SWI/SNF complex. We also found a significant increase in the molecular chaperone, glucose-regulated protein 94 (GRP94) among BRG1-associated factors isolated from a FANCA-mutant cell line, which was not seen in either a normal control cell line or the mutant line complemented by wild-type FANCA. Despite this specific difference, FANCA did not appear to be absolutely required for in vitro chromatin remodeling. Finally, we demonstrated co-localization in the nucleus between transfected FANCA and BRG1. The physiological action of FANCA on the SWI/SNF complex remains to be clarified, but our work suggests that FANCA may recruit the SWI/SNF complex to target genes, thereby enabling coupled nuclear functions such as transcription and DNA repair.

Atypical presentation of paroxysmal nocturnal hemoglobinuria treated by eculizumab

PubMed Central

Quinquenel, Anne; Maestraggi, Quentin; Lecoq-Lafon, Carinne; Régis, Peffault de Latour; Delmer, Alain; Servettaz, Amélie

2017-01-01

Abstract Rationale: Paroxysmal nocturnal hemoglobinuria (PNH) is a nonmalignant acquired hematopoietic stem cell disease, which can be revealed by hemolytic anemia, thromboembolism, or bonemarrow failure. Thrombosis can occur at any site, but coronary thrombosis is extremely rare. Controlled trials have demonstrated that eculizimab, an inhibitor of the terminal complement cascade, was able to reduce both hemolysis and thrombosis, but its efficacy in cases of PNH with coronary thrombosis is unknown. Patient concerns and diagnoses: We report herein the unusual case of a 73-year-old patient presenting with recurrent coronary syndromes without associated stenosis, fever, marked inflammatory syndrome, and anemia, leading to a delayed diagnosis of PNH. Intervention and outcomes: Eculizumab allowed the resolution of fever and inflammation, and prevented further thromboembolism. Lessons: This case emphasizes the importance of performing aflow cytometry test for PNH in front of unusual or unexplained recurrent thromboses. Thromboses, as observed in our case, may be associated with fever and marked inflammation. This case also provides useful information on eculizumab ability to prevent further thromboembolism in PNH patients with a medical history of arterial thrombosis. PMID:28328837

[Social Representations Related to Anemia in Children Under Three years in Awajún and Wampis Communities of Peru].

PubMed

Mayca-Pérez, Julio; Medina-Ibañez, Armando; Velásquez-Hurtado, José E; Llanos-Zavalaga, Luis F

2017-01-01

To understand the social representations of the Awajún and Wampis communities related to the symptoms and treatment of anemia in children younger than 3 years, as well as the relationship of these representations with the symbolism, constructs, and type of diet of these populations. This qualitative study was conducted from June to August 2015 in the districts of Río Santiago, Cenepa, and Nieva (Amazon region, Peru), and included in-depth interviews (IDIs) of health personnel, community authorities, parents, and focus groups (FGs) for mothers. A total of 38 IDIs and 13 FGs were conducted. The evaluated populations had limited awareness about anemia and health personnel, but anemia with symptoms were correlated with social representations and cultural manifestations. This behavior was reflected in the parents' choice of treatments that were not necessarily the same as those indicated by the health personnel, and these social groups preferred the consumption of certain foods that were considered to cure the "putsumat". Visiting a health care center or using micronutrients was not their first treatment option. Social representations and traditional practices still exist, and include interpretative systems in health, disease, and disease management. The logic, meaning, and coherence of these practices depend on the cultural group considered. The "putsumat" or "putsuju" is an interpretive model for anemia, and the symptoms in children include pallor, thinness, and fatigue; this model is based on the cultural system of the Awajún and Wampis populations.

Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam

PubMed Central

Nguyen, Phuong H.; Young, Melissa; Gonzalez-Casanova, Ines; Pham, Hoa Q.; Nguyen, Hieu; Truong, Truong V.; Nguyen, Son V.; Harding, Kimberly B.; Reinhart, Gregory A.; Martorell, Reynaldo; Ramakrishnan, Usha

2016-01-01

Objective Preconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum. Methods We conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 μg FA (control group), IFA (60 mg Fe and 2800 μg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 μg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception). Results At baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 μg/L) and 3% had iron deficiency (ferritin <12 μg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (μg/L) [95% CI]: 93.6 [89.3–98.2]) and IFA (91.9 [87.6–96.3]) compared to control (85.3 [81.5–89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3–127.8]), IFA 117.8 [108.7–127.7] vs control 101.5 [94.0–109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1–192.9]), IFA 189.9 [181.6–198.3] vs control 175.1 [167.9–182.6]). Conclusion Preconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia. Trial Registration ClinicalTrials.Gov NCT01665378 PMID:27918586

Impact of Preconception Micronutrient Supplementation on Anemia and Iron Status during Pregnancy and Postpartum: A Randomized Controlled Trial in Rural Vietnam.

PubMed

Nguyen, Phuong H; Young, Melissa; Gonzalez-Casanova, Ines; Pham, Hoa Q; Nguyen, Hieu; Truong, Truong V; Nguyen, Son V; Harding, Kimberly B; Reinhart, Gregory A; Martorell, Reynaldo; Ramakrishnan, Usha

2016-01-01

Preconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum. We conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 μg FA (control group), IFA (60 mg Fe and 2800 μg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 μg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception). At baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 μg/L) and 3% had iron deficiency (ferritin <12 μg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (μg/L) [95% CI]: 93.6 [89.3-98.2]) and IFA (91.9 [87.6-96.3]) compared to control (85.3 [81.5-89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3-127.8]), IFA 117.8 [108.7-127.7] vs control 101.5 [94.0-109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1-192.9]), IFA 189.9 [181.6-198.3] vs control 175.1 [167.9-182.6]). Preconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia. ClinicalTrials.Gov NCT01665378.

Evidence for a founder effect for the IVS4 +4 A{r_arrow}T mutation in the Fanconi anemia gene FACC in a Jewish population

DOE Office of Scientific and Technical Information (OSTI.GOV)

Verlander, P.C.; Kaporis, A.G.; Qian, L.

1994-09-01

Fanconi anemia (FA) is a genetically heterogeneous autosomal recessive disorder defined by hypersensitivity of cells to DNA cross-linking agents; a gene for complementation group C(FACC) has been cloned. Two common mutations, IVS4 +4 A{r_arrow}T and 322delG, and several rare mutations have recently been reported in affected individuals. We now report the development of amplification refractory mutation system (ARMS) assays for rapid, non-radioactive detection of these known mutations in FACC. Primer pairs specific for variant sequences were designed, with the 3{prime} terminal base of one primer matching the variant base. PCR products are separated by electrophoresis on 2.5% agarose gels; mutationsmore » are indicated by the presence of a band of a specific size. These ARMS assays can be multiplexed to allow screening for all known mutations in two PCR reactions. We have used these assays for detection of FACC mutations in affected individuals in the International Fanconi Anemia Registry (IFAR), and for carrier detection FACC families. IVS4 +4 A{r_arrow}T is the only FACC mutation found in Jewish FA patients and their families, of both Ashkenazi and Sephardic ancestry. This mutation was not found in any affected individual of non-Jewish origin. In addition, DNA samples from 1596 healthy Jewish individuals primarily of Ashkenazi ancestry were supplied to us by Dor Yeshorim. These samples, ascertained for carrier screening for Tay Sachs, cystic fibrosis, and other genetic diseases with a high frequency in the religious Jewish community served by this organization, were tested for both IVS4 +4 A{r_arrow}T and 322delG mutations; seventeen IVS4 +4 A{r_arrow}T are of Sephardic Jewish ancestry. We hypothesize that IVS4 +4 A{r_arrow}T is a very old mutation, predating the divergence of the Ashkenazi and Sephardic populations. Haplotype analysis with microsatellite markers is in progress.« less

Increased Risk of Severe Infant Anemia Following Exposure to Maternal HAART, Botswana

PubMed Central

Dryden-Peterson, Scott; Shapiro, Roger L.; Hughes, Michael D.; Powis, Kathleen; Ogwu, Anthony; Moffat, Claire; Moyo, Sikhulile; Makhema, Joseph; Essex, Max; Lockman, Shahin

2011-01-01

Background Maternal highly-active antiretroviral therapy (HAART) reduces mother-to-child HIV transmission (MTCT), but may increase the risk for infant anemia. Methods The incidence of first severe anemia (Grade 3 or 4, Division of AIDS 2004 Toxicity Table) was assessed among HIV-uninfected infants in the Mashi and Mma Bana MTCT prevention trials in Botswana. Severe anemia rates were compared between 3 groups: infants exposed to maternal HAART in utero and during breastfeeding and 1 month of postnatal zidovudine (HAART-BF); infants exposed to maternal zidovudine (ZDV) in utero, 6 months of postnatal ZDV, and breastfeeding (ZDV-BF); and infants exposed to maternal ZDV in utero, 1 month of postnatal ZDV, and formula-feeding (ZDV-FF). Results A total of 1719 infants were analyzed— 691 HAART-BF, 503 ZDV-BF, and 525 ZDV-FF. Severe anemia was detected in 118 infants (7.4%). By 6 months, 12.5% of HAART-BF infants experienced severe anemia, compared with 5.3% of ZDV-BF (P<0.001) and 2.5% of ZDV-FF infants (P<0.001). In adjusted analysis, HAART-BF infants were at greater risk of severe anemia than ZDV-BF or ZDV-FF infants (adjusted odds ratios 2.6 and 5.8, respectively; P < 0.001). Most anemias were asymptomatic and improved with iron/multivitamin supplementation and cessation of ZDV exposure. However, 11 infants (0.6% of all infants) required transfusion for symptomatic anemia. Microcytosis and hypochromia were common among infants with severe anemia. Conclusions Exposure to maternal HAART starting in utero was associated with severe infant anemia. Confirmation of this finding and possible strategies to mitigate hematologic toxicity warrant further study. Trial Registration ClinicalTrials.gov identifiers: NCT00197587 and NCT00270296. PMID:21266910

Prevalence and associated factors of anemia among pregnant women of Mekelle town: a cross sectional study.

PubMed

Abriha, Abrehet; Yesuf, Melkie Edris; Wassie, Molla Mesele

2014-12-09

Nutritional anemia is the most common type of anemia worldwide and mainly includes iron, folic acid, vitamin B12 and vitamin C deficiencies. Anemia is a global public health problem affecting people in all age groups but the burden of the problem is higher in pregnant women. The study aimed to assess prevalence of anemia and associated factors among pregnant women attending antenatal care in governmental health institutions in mekele town. Institution based cross-sectional study was employed. Systematic random sampling procedure was employed to select 619 study subjects. Pretested questionnaire were used to collect the data. The predictive value of the variable to Anemia was identified by bivariate and multiple logistic regression analysis. The overall prevalence of anemia among pregnant women was 19.7%. Meal frequency less than two per day [AOR 3.93 95% CI (2.0,7.9)], Low Dietary Diversity score [AOR 12.8 95% CI (6.4,25.6)], Medium Dietary Diversity score [AOR 2.4 95% CI (1.2,4.8)], Parity [AOR 2.3 95% CI (1.4,3.8)] and Meat consumption less than once per week [AOR 2.2 95% CI (1.0,4.9)] were found to be factors affecting Anemia in pregnant women. Anemia among pregnant women is found to be mild public health problem in the study area. Parity, meal frequency, dietary diversity and meat consumption were significantly and independently affect anemia of pregnant women. Using family planning methods and improved meat consumption contributes for decreasing prevalence of anemia. Moreover, Diversifying food intake and increasing meal frequency of pregnant women is highly recommended.

An individual-level meta-analysis assessing the impact of community-level sanitation access on child stunting, anemia, and diarrhea: Evidence from DHS and MICS surveys.

PubMed

Larsen, David A; Grisham, Thomas; Slawsky, Erik; Narine, Lutchmie

2017-06-01

A lack of access to sanitation is an important risk factor child health, facilitating fecal-oral transmission of pathogens including soil-transmitted helminthes and various causes of diarrheal disease. We conducted a meta-analysis of cross-sectional surveys to determine the impact that community-level sanitation access has on child health for children with and without household sanitation access. Using 301 two-stage demographic health surveys and multiple indicator cluster surveys conducted between 1990 and 2015 we calculated the sanitation access in the community as the proportion of households in the sampled cluster that had household access to any type of sanitation facility. We then conducted exact matching of children based on various predictors of living in a community with high access to sanitation. Using logistic regression with the matched group as a random intercept we examined the association between the child health outcomes of stunted growth, any anemia, moderate or severe anemia, and diarrhea in the previous two weeks and the exposure of living in a community with varying degrees of community-level sanitation access. For children with household-level sanitation access, living in a community with 100% sanitation access was associated with lowered odds of stunting (adjusted odds ratio [AOR] = 0.97, 95%; confidence interval (CI) = 0.94-1.00; n = 14,153 matched groups, 1,175,167 children), any anemia (AOR = 0.73; 95% CI = 0.67-0.78; n = 5,319 matched groups, 299,033 children), moderate or severe anemia (AOR = 0.72, 95% CI = 0.68-0.77; n = 5,319 matched groups, 299,033 children) and diarrhea (AOR = 0.94; 95% CI = 0.91-0.97); n = 16,379 matched groups, 1,603,731 children) compared to living in a community with < 30% sanitation access. For children without household-level sanitation access, living in communities with 0% sanitation access was associated with higher odds of stunting (AOR = 1.04, 95% CI = 1.02-1.06; n = 14,153 matched groups, 1,175,167 children), any anemia (AOR = 1.05, 95% CI = 1.00-1.09; n = 5,319 matched groups, 299,033 children), moderate or severe anemia (AOR = 1.04, 95% CI = 1.00-1.09; n = 5,319 matched groups, 299,033 children) but not diarrhea (AOR = 1.00, 95% CI = 0.98-1.02; n = 16,379 matched groups, 1,603,731 children) compared to children without household-level sanitation access living in communities with 1-30% sanitation access. Community-level sanitation access is associated with improved child health outcomes independent of household-level sanitation access. The proportion of children living in communities with 100% sanitation access throughout the world is appallingly low. Ensuring sanitation access to all by 2030 will greatly improve child health.

Cardiac Surgery in Children of Jehovah's Witnesses

PubMed Central

Carmichael, Michael J.; Cooley, Denton A.; Kuykendall, R. Craig; Walker, William E.

1985-01-01

A retrospective study was done of 73 consecutive Jehovah's Witness children less than 2 years of age who were operated on for lesions of the heart and major vessels. The series was divided into three groups: (1) neonates less than 31 days old, (2) children between 31 days and 2 years, and (3) children requiring cardiopulmonary bypass. The overall mortality rate for the series was 12.3% (9/73). Only three of the nine deaths were complicated by blood loss and anemia. The mortality rate for Group I was 18.2% (2/11). Only one of the two deaths was partly attributable to anemia. The overall mortality rate for Group II was 14.9% (7/47). Only two of these seven deaths were complicated by anemia. No deaths occurred among the 15 patients in Group III. Bloodless prime hemodilution techniques were used in all patients. Based upon our data, we have concluded that cardiac surgery can be performed when indicated on children of Jehovah's Witnesses with acceptable mortality rates and relatively straightforward perioperative care. PMID:15227042

Impact of moderate intensity aerobic exercise on chemotherapy-induced anemia in elderly women with breast cancer: A randomized controlled clinical trial.

PubMed

Mohamady, Heba M; Elsisi, Hany F; Aneis, Yasser M

2017-01-01

Exercises are often recommended for patients suffering from anemia to improve physical conditioning and hematologic parameters. Hence, the present study aimed to investigate the impact of moderate intensity aerobic exercise on chemotherapy-induced anemia. Thirty elderly women with breast cancer underwent chemotherapy and were randomly assigned into two equal groups; Group A received aerobic exercise for 25-40 min at 50-70% of the maximum heart rate, 3 times/week for 12 weeks in addition to usual daily living activities, medication and nutritional support. Group B who did not train served as controls. Hemoglobin (Hb), and red blood cell count (RBCs) were evaluated pre-treatment and after 12 weeks of training. There were significant declines of both Hb ( t  = 16.30; P  < 0.001) and RBCs ( t  = 10.38; P  < 0.001) in group B relative to group A. Regarding group A, Hb increased from 11.52 ± 0.62 to 12.10 ± 0.59 g/dL with a 5.03% change, while RBCs increased from 4.24 ± 0.37 to 4.49 ± 0.42 million cells/μL with a 5.89% change. Between-group differences were noteworthy regarding Hb ( t  = -5.34; P  < 0.001) and RBCs ( t  = -5.314; P  < 0.001). The results indicate that regular participation in moderate intensity aerobic exercise can enhance chemotherapy-induced anemia.

Partially hydrolyzed guar gum increases intestinal absorption of iron in growing rats with iron deficiency anemia.

PubMed

de Cássia Freitas, Karine; Amancio, Olga Maria Silvério; Ferreira Novo, Neil; Fagundes-Neto, Ulysses; de Morais, Mauro Batista

2006-10-01

The objective of this study was to evaluate the effect of partially hydrolyzed guar gum (PHGG) dietary fiber towards intestinal iron absorption, for dietary intake and on the growth of rats with iron deficiency anemia in comparison to those fed on a diet with cellulose and without dietary fiber. Male Wistar rats (n=24) weaned at 21 days were fed with AIN93-G diet without iron for 2 weeks in order to induce iron deficiency anemia. At 36 days old, the anemic rats were divided into three groups: (1) PHGG group-100g of PHGG per kg of diet; (2) Cellulose group-100g of cellulose per kg of diet; (3) Control group-diet without dietary fiber. All the diets had 25mg of elemental iron/kg of diet added to lead to recovery from iron deficiency anemia. The final hemoglobin values in g/dl, for the PHGG group, the cellulose group and the control group were, respectively: 11.3+/-1.2, 8.6+/-0.7 and 8.1+/-0.9 (P<0.001). The levels of hepatic iron, in mug/g of dry tissue, in the same order, were: 322.2+/-66.6, 217.2+/-59.1 and 203.7+/-42.4 (P<0.001). Apparent iron intestinal absorption was, respectively: 67.5+/-8.9%, 35.4+/-15.3% and 31.3+/-24.9% (P<0.001). The three groups consumed similar quantities of diet. The changes in weight and in body length were similar in the three groups studied. PHGG led to greater intestinal absorption of iron, regeneration of hemoglobin and hepatic levels of iron than diet with cellulose and diet control.

Noninvasive molecular screening for oral precancer in Fanconi anemia patients.

PubMed

Smetsers, Stephanie E; Velleuer, Eunike; Dietrich, Ralf; Wu, Thijs; Brink, Arjen; Buijze, Marijke; Deeg, Dorly J H; Soulier, Jean; Leemans, C René; Braakhuis, Boudewijn J M; Brakenhoff, Ruud H

2015-11-01

LOH at chromosome arms 3p, 9p, 11q, and 17p are well-established oncogenetic aberrations in oral precancerous lesions and promising biomarkers to monitor the development of oral cancer. Noninvasive LOH screening of brushed oral cells is a preferable method for precancer detection in patients at increased risk for head and neck squamous cell carcinoma (HNSCC), such as patients with Fanconi anemia. We determined the prevalence of LOH in brushed samples of the oral epithelium of 141 patients with Fanconi anemia and 144 aged subjects, and studied the association between LOH and HNSCC. LOH was present in 14 (9.9%) nontransplanted patients with Fanconi anemia, whereas LOH was not detected in a low-risk group (n = 50, >58 years, nonsmoking/nonalcohol history) and a group with somewhat increased HNSCC risk (n = 94, >58 years, heavy smoking/excessive alcohol use); Fisher exact test, P = 0.023 and P = 0.001, respectively. Most frequent genetic alteration was LOH at 9p. Age was a significant predictor of LOH (OR, 1.13, P = 0.001). Five patients with Fanconi anemia developed HNSCC during the study at a median age of 39.6 years (range, 24.8-53.7). LOH was significantly associated with HNSCC (Fisher exact test, P = 0.000). Unexpectedly, the LOH assay could not be used for transplanted patients with Fanconi anemia because donor DNA in brushed oral epithelium, most likely from donor leukocytes present in the oral cavity, disturbed the analysis. Noninvasive screening using a LOH assay on brushed samples of the oral epithelium has a promising outlook in patients with Fanconi anemia. However, assays need to be adapted in case of stem cell transplantation, because of contaminating donor DNA. ©2015 American Association for Cancer Research.

2,4,6-Trinitrotoluene (TNT) air concentrations, hemoglobin changes, and anemia cases in respirator protected TNT munitions demilitarization workers.

PubMed

Bradley, Melville D

2011-03-01

2,4,6-Trinitrotoluene (TNT) is an explosive used in munitions production that is known to cause both aplastic and hemolytic anemia in exposed workers. Anemia in a TNT worker is considered a sentinel health event (occupational) (SHE(O)) in the United States (US). Deaths have been reported secondary to aplastic anemia. Studies have shown that TNT systemic absorption is significant by both the respiratory and dermal routes. No studies encountered looked at hemoglobin change or anemia cases in respiratory protected workers. It is hypothesized that respiratory protection is insufficient to protect TNT workers from the risk of anemia development and hemoglobin concentration drop. A records review of eight groups of respiratory protected TNT workers' pre-exposure hemoglobin levels were compared with their during-exposure hemoglobin levels for statistically significant (alpha level 0.05) hemoglobin level changes, and anemia cases were recorded. A curve estimation analysis was performed between mean TNT air concentrations and mean hemoglobin change values. Statistically significant hemoglobin level drops and anemia cases were apparent at TNT air concentrations about the REL and PEL in respiratory protected workers. There were no anemia cases or statistically significant hemoglobin level drops at concentrations about the TLV, however. A statistically significant inverse non-linear regression model was found to be the best fit for regressing hemoglobin change on TNT air concentration. Respiratory protection may be inadequate to prevent workers who are at risk for TNT skin absorption from developing anemia. This study contributes evidence that the TLV should be considered for adoption as the new PEL.

Diagnosis of thalassemia and iron deficiency anemia using confocal and atomic force microscopy

NASA Astrophysics Data System (ADS)

Tariq, Saira; Bilal, Muhammad; Shahzad, Shaheen; Firdous, Shamaraz; Aziz, Uzma; Ahmed, Mushtaq

2017-11-01

Anemia is the most prevalent blood disorder, categorized into thalassemia and iron deficiency anemia. In anemia, the morphology of erythrocytes is disturbed, thus leading to abnormal functioning of the erythrocytes. Globally, thalassemia affects 1.3% of individuals and is one of the most widespread monogenic disorders in Pakistan. All over the World, women and children are most frequently affected by a type of nutritional deficiency known as iron deficiency anemia. The morphological changes that occur in erythrocytes due to these diseases are investigated in this study at the nano-scale level. Fifty samples of blood from individuals suffering from thalassemia or iron deficiency anemia were obtained from different hospitals in Rawalpindi and Islamabad. The blood samples were scanned using atomic force microscopy (AFM) and laser scanning confocal microscopy (LSCM) to check the morphological changes in both types of anemia. According to the present study, thalassemia is most prevalent in females in the age group between 5 and 15 years old, and iron deficiency is most prevalent in females in the age groups of 16-25 and 36-45 years old. Erythrocyte morphology is the significant determinant for diagnosing and discriminating between these two types of diseases. The study reports deformed erythrocytes in anemic patients, which were different from the ones that existed in the control. Thalassemia erythrocytes showed a crenated shape, iron deficiency anemia erythrocytes showed an elliptocyte shape and healthy erythrocytes showed a biconcave disk shape when using AFM and LSCM. These techniques seem to be very promising, cheap and less time consuming in determining the structure-function relationship of erythrocytes of thalassemic and iron deficiency anemic patients. The results of LSCM and AFM are quite useful in determining the morphological changes in erythrocytes and to study the disease at the molecular level within short period of time. Hence, we encourage employing these non-invasive techniques for the effective diagnosis of anemic patients.

Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis.

PubMed

Smuts, Cornelius M; Lombard, Carl J; Benadé, A J Spinnler; Dhansay, Muhammad A; Berger, Jacques; Hop, Le Thi; López de Romaña, Guillermo; Untoro, Juliawati; Karyadi, Elvina; Erhardt, Jürgen; Gross, Rainer

2005-03-01

Diets of infants across the world are commonly deficient in multiple micronutrients during the period of growth faltering and dietary transition from milk to solid foods. A randomized placebo controlled trial was carried out in Indonesia, Peru, South Africa, and Vietnam, using a common protocol to investigate whether improving status for multiple micronutrients prevented growth faltering and anemia during infancy. The results of the pooled data analysis of the 4 countries for growth, anemia, and micronutrient status are reported. A total of 1134 infants were randomized to 4 treatment groups, with 283 receiving a daily placebo (P), 283 receiving a weekly multiple micronutrient supplement (WMM), 280 received a daily multiple micronutrient (DMM) supplement, and 288 received daily iron (DI) supplements. The DMM group had a significantly greater weight gain, growing at an average rate of 207 g/mo compared with 192 g/mo for the WMM group, and 186 g/mo for the DI and P groups. There were no differences in height gain. DMM was also the most effective treatment for controlling anemia and iron deficiency, besides improving zinc, retinol, tocopherol, and riboflavin status. DI supplementation alone increased zinc deficiency. The prevalence of multiple micronutrient deficiencies at baseline was high, with anemia affecting the majority, and was not fully controlled even after 6 mo of supplementation. These positive results indicate the need for larger effectiveness trials to examine how to deliver supplements at the program scale and to estimate cost benefits. Consideration should also be given to increasing the dosages of micronutrients being delivered in the foodlets.

Determination of tissue hypoxia by physicochemical approach in premature anemia.

PubMed

Özdemir, Zeliha; Törer, Birgin; Hanta, Deniz; Cetinkaya, Bilin; Gulcan, Hande; Tarcan, Aylin

2017-10-01

Anemia is a common problem in premature infants and its most rapid and effective therapy is erythrocyte transfusion. However, owing to inherent risks of transfusion in this population, transfusions should be administered only when adequate oxygen delivery to tissues is impaired. The aim of this study was to determine tissue acid levels using Stewart method in an attempt to evaluate the tissue oxygenation level and thereby the accuracy of transfusion timing. This study included 47 infants delivered at gestational age below 34 weeks who required erythrocyte transfusion for premature anemia. Strong ion gap (SIG), unmeasurable anions (UMA), tissue acid levels (TA), and Cl/Na ratios were calculated before and after transfusion. The mean birth weight and gestational age of the study population were 1210 ± 365 g and 29.2 ± 2.7 weeks, respectively. Tissue acid levels were increased (TA ≥ 4) and tissue hypoxia developed in 10 (16.6%) of 60 erythrocyte transfusions administered according to the restrictive transfusion approach. The patients were divided into two groups according to tissue acid levels as low (<4) and high (≥4) tissue acid groups. The group with tissue hypoxia (TA ≥ 4) had significantly higher UMA levels but a significantly lower Cl/Na ratio; and UMA levels decreased and Cl/Na ratio increased after transfusion in this group. Tissue hypoxia secondary to anemia was shown to be improved by erythrocyte transfusion. The results of the present study suggest that the determination of the level of tissue hypoxia by the Stewart approach may be an alternative to restrictive transfusion guidelines for timing of transfusion in premature anemia. It also showed that a low Cl/Na ratio can be used as a simple marker of tissue hypoxia. Copyright © 2017. Published by Elsevier B.V.

Severe anemia in cats with urethral obstruction: 17 cases (2002-2011).

PubMed

Beer, Kari Santoro; Drobatz, Kenneth J

2016-05-01

To characterize clinical parameters of cats with severe anemia due to suspected urinary bladder hemorrhage associated with urethral obstruction. Retrospective case-control study. University teaching hospital. Seventeen cats with urethral obstruction and severe anemia (group "UO-A") that required transfusion were identified via medical record database search. Thirty cats with urethral obstruction and mild or no anemia (group "UO") were included as controls. None. The median PCV of all cases at presentation was 28% (range, 9%-47%). Seven cats had PCV ≤20% at presentation, and all transfused cats had PCV ≤20% at the time of transfusion. Three cats did not receive a transfusion despite PCV ≤18%. Cats in the UO-A group had a significantly longer duration of clinical signs (P = 0.001), and were more likely to have a history of previous urethral obstruction (P = 0.011), have a heart murmur (P = 0.002), have a gallop rhythm (P = 0.005), and have lower blood pressure (P = 0.007) compared to those in the UO group. Additionally, UO-A cats had significantly lower pH, more negative base excess, higher BUN, and higher creatinine compared to UO cats. Duration of urinary catheterization was significantly (P = 0.016) longer in UO-A cats. All UO cats survived to discharge, whereas 4/17 (23.5%) UO-A cats were euthanized (P = 0.013). A history of previous urethral obstruction and longer duration of clinical signs may be important risk factors for severe anemia in UO cats. Additionally, UO-A cats appeared to be more severely affected, as evidenced by lower blood pressure, more severe metabolic acidosis, higher BUN and creatinine, and worse outcome. © Veterinary Emergency and Critical Care Society 2016.

Children with Sickle-Cell Anemia: Parental Relations, Parent-Child Relations, and Child Behavior.

ERIC Educational Resources Information Center

Evans, Robert C.; And Others

1988-01-01

Investigated the influence of a child with sickle-cell anemia on parental affiliation, parent-child relationships, and parents' perception of their child's behavior. In the sickle-cell group, parents' interpersonal relationship suffered; parent-child relationship and child behavior correlated significantly; and single-parent families estimated…

Evaluation of the Efficiency of the Reticulocyte Hemoglobin Content on Diagnosis for Iron Deficiency Anemia in Chinese Adults.

PubMed

Cai, Jie; Wu, Meng; Ren, Jie; Du, Yali; Long, Zhangbiao; Li, Guoxun; Han, Bing; Yang, Lichen

2017-05-02

Our aim was to evaluate the cut-off value and efficiency of using reticulocyte hemoglobin content as a marker to diagnose iron deficiency anemia in Chinese adults. 140 adults who needed bone marrow aspiration for diagnosis at the hematology department of the Peking Union Medical College Hospital were enrolled according to the inclusive and exclusive criteria. Venous blood samples were collected to detect complete blood count, including hemoglobin, reticulocyte hemoglobin content, hematocrit, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, free erythrocyte protoporphyrin; iron indexes of serum ferritin, serum transferrin receptor, and unsaturated iron-binding capacity; and inflammation markers of C-reactive protein and α-acid glycoprotein. Bone marrow samples were obtained for the bone marrow iron staining, which was used as the standard for the evaluation of iron status in this study. Subjects were divided into three groups according to hemoglobin levels and bone marrow iron staining results: the IDA (iron deficiency anemia) group, the NIDA (non-iron deficiency anemia) group, and the control group. The differences of the above-mentioned indexes were compared among the three groups and the effect of inflammation was also considered. The cut-off value of reticulocyte hemoglobin content was determined by receiver operation curves. The IDA group ( n = 56) had significantly lower reticulocyte hemoglobin content, mean cellular volume, corpuscular hemoglobin concentration, hemoglobin content, and serum ferritin; and higher free erythrocyte protoporphyrin, unsaturated iron-binding capacity, and serum transferrin receptor ( p < 0.05) compared with the NIDA group ( n = 38) and control group ( n = 46). Hematocrit, serum ferritin, and unsaturated iron-binding capacity were significantly affected by inflammation while reticulocyte hemoglobin content and other parameters were not. The cut-off value of reticulocyte hemoglobin content for diagnosing iron deficiency anemia was 27.2 pg, with a sensitivity of 87.5% and a specificity of 92.9%. The cut-off values for mean cellular volume, serum ferritin, and serum transferrin receptor were 76.6, 12.9, and 4.89 mg/L, respectively. Reticulocyte hemoglobin content had the largest area under the curve of 0.929, while those for mean cellular volume, serum ferritin, serum transferrin receptor were 0.922, 0.887, and 0.900, respectively. Reticulocyte hemoglobin content has a high sensitivity and specificity in the diagnosis of iron deficiency anemia, and its comprehensive diagnostic efficacy is better than other traditional indicators-such as serum ferritin and serum transferrin receptor.

Multiple TPR motifs characterize the Fanconi anemia FANCG protein.

PubMed

Blom, Eric; van de Vrugt, Henri J; de Vries, Yne; de Winter, Johan P; Arwert, Fré; Joenje, Hans

2004-01-05

The genome protection pathway that is defective in patients with Fanconi anemia (FA) is controlled by at least eight genes, including BRCA2. A key step in the pathway involves the monoubiquitylation of FANCD2, which critically depends on a multi-subunit nuclear 'core complex' of at least six FANC proteins (FANCA, -C, -E, -F, -G, and -L). Except for FANCL, which has WD40 repeats and a RING finger domain, no significant domain structure has so far been recognized in any of the core complex proteins. By using a homology search strategy comparing the human FANCG protein sequence with its ortholog sequences in Oryzias latipes (Japanese rice fish) and Danio rerio (zebrafish) we identified at least seven tetratricopeptide repeat motifs (TPRs) covering a major part of this protein. TPRs are degenerate 34-amino acid repeat motifs which function as scaffolds mediating protein-protein interactions, often found in multiprotein complexes. In four out of five TPR motifs tested (TPR1, -2, -5, and -6), targeted missense mutagenesis disrupting the motifs at the critical position 8 of each TPR caused complete or partial loss of FANCG function. Loss of function was evident from failure of the mutant proteins to complement the cellular FA phenotype in FA-G lymphoblasts, which was correlated with loss of binding to FANCA. Although the TPR4 mutant fully complemented the cells, it showed a reduced interaction with FANCA, suggesting that this TPR may also be of functional importance. The recognition of FANCG as a typical TPR protein predicts this protein to play a key role in the assembly and/or stabilization of the nuclear FA protein core complex.

[Risk factors on anemia among rural elderly women aged 50-75 y in Xinning county, Anhui province, China].

PubMed

Zhang, Jian; Wang, Chun-Rong; Jin, Shao-Hua; Song, Peng-Kun; Meng, Li-Ping; Man, Qing-Qing; Jia, Shang-Chun

2009-03-01

To study the risk factors on anemia among elderly women in rural areas of Xiuning county, Anhui province, China. Xiuning county was selected as working field and elderly women aged 50-75 y were selected as subjects. Finger hemoglobin (Hb) was measured and basic health survey was face-to-face interviewed. 220 elderly women with anemia entered into the case group; and matched by age, another 220 women with normal Hb concentration entered the control group. Survey on diet, questionnaire regarding health and lifestyle and related blood indexes were studied and tested. When comparing the data from both case and control groups, weight was (49.4 +/- 7.3) kg vs. (52.5 +/- 8.4) kg (t = 3.97, P < 0.01), waist circumference was (75.8 +/- 7.8) cm vs. (79.1 +/- 9.3) cm (t = 3.85, P < 0.01), BMI was (21.8 +/- 2.6) kg/m2 vs. (22.9 +/- 3.2) kg/m2 (t = 3.775, P < 0.01), respectively. The total protein was (76.4 +/- 5.0) g/L vs. (78.4 +/- 5.6)g/L (t = 3.83, P < 0.01), albumin was (45.7 +/- 3.1) g/L vs. (47.3 +/- 2.9)g/L (t = 5.24, P < 0.01), serum iron was ( 10.3 +/- 4.1) micromol/L vs. (12.7 +/- 4.6) micromol/L (t = 5.48, P < 0.01), and saturation of transferrin was (19.0 +/- 7.6)% vs. (23.1 +/- 9.1) % (t = 4.90, P < 0.01), respectively. Results from multifactor conditioned logistic regression analysis showed that the odd ratios (OR) for anemia with staple food, BMI and vitamin A were 1.54, 1.89, 1.69, and the OR for anemia with BMI, staple food, animal food, carbohydrate and vitamin A were 2.0, 1.6, 1.6, 1.4, 1.6, with their confidence intervals (CI) as 1.3-2.9, 1.1-2.3, 1.0-2.3, 1.0-2.1, 1.1-2.4, respectively. The quality of diet, health status and related blood indexes on anemia among elderly women were lower than that in control group. Lower BMI, less staple food and animal food, less carbohydrate and vitamin A intake appeared to be risk factors of anemia.

The use of multiplexed MRM for the discovery of biomarkers to differentiate iron-deficiency anemia from anemia of inflammation.

PubMed

Domanski, Dominik; Cohen Freue, Gabriela V; Sojo, Luis; Kuzyk, Michael A; Ratkay, Leslie; Parker, Carol E; Goldberg, Y Paul; Borchers, Christoph H

2012-06-27

In this study we demonstrate the use of a multiplexed MRM-based assay to distinguish among normal (NL) and iron-metabolism disorder mouse models, particularly, iron-deficiency anemia (IDA), inflammation (INFL), and inflammation and anemia (INFL+IDA). Our initial panel of potential biomarkers was based on the analysis of 14 proteins expressed by candidate genes involved in iron transport and metabolism. Based on this study, we were able to identify a panel of 8 biomarker proteins: apolipoprotein A4 (APO4), transferrin, transferrin receptor 1, ceruloplasmin, haptoglobin, lactoferrin, hemopexin, and matrix metalloproteinase-8 (MMP8) that clearly distinguish among the normal and disease models. Within this set of proteins, transferrin showed the best individual classification accuracy over all samples (72%) and within the NL group (94%). Compared to the best single-protein biomarker, transferrin, the use of the composite 8-protein biomarker panel improved the classification accuracy from 94% to 100% in the NL group, from 50% to 72% in the INFL group, from 66% to 96% in the IDA group, and from 79% to 83% in the INFL+IDA group. Based on these findings, validation of the utility of this potentially important biomarker panel in human samples in an effort to differentiate IDA, inflammation, and combinations thereof, is now warranted. This article is part of a Special Section entitled: Understanding genome regulation and genetic diversity by mass spectrometry. Copyright © 2011 Elsevier B.V. All rights reserved.

Anemia and Iron Deficiency in Children With Potential Celiac Disease.

PubMed

Repo, Marleena; Lindfors, Katri; Mäki, Markku; Huhtala, Heini; Laurila, Kaija; Lähdeaho, Marja-Leena; Saavalainen, Päivi; Kaukinen, Katri; Kurppa, Kalle

2017-01-01

Active screening for celiac disease frequently detects seropositive children with normal villous morphology (potential celiac disease). It remains unclear whether these subjects should be treated. We here investigated the prevalence of anemia and iron deficiency in children with potential and mucosal atrophy celiac disease. The prospective study involved 19 children with potential disease, 67 with partial or subtotal villous atrophy (P/SVA), and 16 with total villous atrophy (TVA). Twenty-three healthy children comprised the control group. The groups were compared for various clinical, histological, and laboratory parameters and hepcidin. The prevalence of abnormal parameters was as follows (controls, potential celiac disease, P/SVA, and TVA, respectively): anemia 0%, 15%, 22%, and 63%; low iron 5%, 0%, 14%, and 50%; increased transferrin receptor 1 5%, 16%, 20%, and 47%; low ferritin 0%, 21%, 35%, and 87%; and low transferrin saturation 10%, 11%, 41%, and 71%. One subject had low folate and none had low vitamin B12. The median values for hemoglobin, total iron, ferritin, and transferrin saturation were significantly lower and transferrin receptor 1 values higher in TVA group compared with other groups. After a median of 7 months on a gluten-free diet hemoglobin, total iron, ferritin, and albumin in children with P/SVA exceeded the baseline values in the potential celiac disease group. The development of anemia and iron deficiency in celiac disease is a continuum and may already be present in children with normal villous morphology, advocating an early diagnosis and possible dietary treatment of these patients.

Recombinant human erythropoietin in the prevention of late anemia in intrauterine transfused neonates with Rh-isoimmunization.

PubMed

Zuppa, Antonio Alberto; Alighieri, Giovanni; Calabrese, Valentina; Visintini, Federica; Cota, Francesco; Carducci, Chiara; Antichi, Eleonora; Noia, Giuseppe Antonio; Fortunato, Giuseppe; Romagnoli, Costantino

2010-04-01

The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.

[Trend in the prevalence of anemia in Mexican women of childbearing age from 2006-2016. Ensanut MC 2016].

PubMed

Shamah-Levy, Teresa; Mejía-Rodríguez, Fabiola; Méndez Gómez-Humarán, Ignacio; De la Cruz-Góngora, Vanesa; Mundo-Rosas, Verónica; Villalpando-Hernández, Salvador

2018-01-01

To describe the anemia prevalence among women from 20 to 49 years from 2016-Halfway National Health and Nutrition Survey (Ensanut MC 2016) and compare the trends in 2006, 2012 and 2016 surveys, as well as its association with dietary iron and sociodemographic factors. The methodological design of Ensanut MC is fully comparable with Ensanut 2006 and 2012. Capillary hemoglobin (Hb) was obtained and those values <120 g/L were classified as anemic. Pregnant women were excluded from the analysis. Anemia prevalence is higher in Ensanut MC 2016 when compared with Ensanut 2012 (p<0.001), differences can be found by age-groups, locality (urban-rural) and country region (North, Center, Mexico City and South). Logistic model showed an increase in anemia prevalence in 2016. Anemia decreas from 2006 to 2012 was followed by an increas in 2016. It is necessary to identify potential risk factors that could be promoting anemia prevalence rising as well as estimate the iron-rich foods intake whit 24 hours recall.

Fetal vascular adaptation before and after treatment of severe maternal anemia in pregnancy.

PubMed

Ali, Eram; Kumar, Manisha; Naqvi, Sayyed E H; Trivedi, Shubha S; Singh, Anuradha

2016-06-01

To use color Doppler ultrasonography indices to study the effects on fetal circulation of treating severe maternal anemia. A prospective cohort study enrolled patients who were at 30-34weeks of pregnancy and had hemoglobin levels below 70g/L between November 1, 2011 and March 31, 2013 at a hospital in New Delhi, India. A control group consisting of patients with the same duration of pregnancy and with hemoglobin levels above 110g/L was included. Umbilical artery and middle cerebral artery velocimetry were performed using color Doppler ultrasonography at admission and after 4weeks and 6weeks of treatment. The maternal anemia cohort demonstrated a significantly lower middle cerebral artery resistance index and middle cerebral/umbilical artery resistance ratio (P<0.001) at admission. Following 4weeks of treatment for maternal anemia, significant increases in these parameters were observed (P<0.001). Fetuses of individuals with severe maternal anemia demonstrated altered cerebral and umbilical artery flows. Normal flows were restored following treatment of maternal anemia. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Low prevalence of iron deficiency anemia between 1981 and 2010 in Chilean women of childbearing age.

PubMed

Ríos-Castillo, Israel; Brito, Alex; Olivares, Manuel; López-de Romaña, Daniel; Pizarro, Fernando

2013-01-01

To determine the prevalence of anemia and iron status among Chilean women of childbearing age between 1981 and 2010. Calculation of the prevalence of anemia and iron status was based on multiple cross-sectional iron absorption studies performed in 888 women during this period of time. All studies included measurements of hemoglobin, mean corpuscular volume, zinc protoporphyrin, percentage of transferrin saturation and serum ferritin. Data were grouped by decade (1981-1990, 1991-2000, and 2001-2010). Prevalence of anemia for these decades was 9, 6 and 10%, respectively (p=NS). Iron deficiency anemia was the main cause of anemia in all periods (55, 85 and 75%, respectively; p=NS). A high prevalence of women with normal iron status was observed for all periods (64, 69, and 67, respectively; p=NS). Prevalence of iron deficiency without anemia in 1981-1990, 1991-2000 and 2001-2010 was 7, 20 and 12%, respectively (p<0.05). Finally, prevalence of iron depleted stores was 20, 6 and 10%, respectively (p<0.05). Prevalence of iron deficiency anemia in Chilean women of childbearing age was mild between 1981 and 2010. More than 60% of childbearing age women presented normal iron status in all periods. However, prevalence of iron depleted stores was moderate during 1981-1990, and was mild during 1991-2000 and 2001-2010.

Anemia and malaria in a Yanomami Amerindian population from the southern Venezuelan Amazon.

PubMed

Pérez Mato, S

1998-12-01

The prevalence and age distribution of anemia and malaria among Yanomami Amerindians undergoing sociocultural assimilation are described. Anemia and malaria proportions were determined in 103 individuals randomly selected from 515 villagers in Mavaca in the southern Venezuelan Amazon. The age and sex distribution reflected that of the entire village cluster. Anemia (hematocrit less than World Health Organization/Centers for Disease Control and Prevention reference values) was found in 91% of the study population. As a group, adults (> or = 15 years old) had the highest proportion of anemia (P=0.037). Adult females had lower mean hematocrit values than adult males (P=0.013). The anemia was predominantly hypochromic and microcytic (62%), a finding that could suggest a diagnosis of iron deficiency in the absence of known hereditary hemoglobinopathies in these Amerindians. Malaria was diagnosed in 14% overall. Children (< 10 years old) displayed the highest proportion of Plasmodium falciparum (17%) and P. vivax (14%) parasitemia, splenomegaly (94%), and fever (34%) (P=0.059, 0.039, 0.005, and 0.008, respectively). The high proportions of anemia and splenomegaly observed in the survey may be used as indicators of inadequately controlled malaria in this community. Further studies to assess the epidemiology of risk factors for the high prevalence of anemia, and predominance of P. falciparum infections in the area are urgently needed.

Parameters of oxidative metabolism in neonates suffering from sepsis and anemia.

PubMed

Sanodze, N; Uberi, N; Uberi, E; Kulumbegov, B

2006-11-01

Neonatal sepsis still remains as one of the actual problems in modern medicine due to its high morbidity and mortality rates determined by diagnostic difficulties and absence of sufficient evidence for effective therapy. Literature data have shown that essential role in pathogenesis of sepsis belongs to the cellular oxidation-reduction misballance and development of the oxidative stress. The aim of our work was to assess indices of pro- and antioxidant systems in term neonates with sepsis on the background of anemia and without it. A total of 41 neonates (17 male, 24 female) with the age range from 3 to 7 days, with early sepsis, and in 2003-2005 years treated at the department of neonates' therapy and intensive care unit of pediatric clinics of the Tbilisi State Medical University were under observation. The control group involved 17 practically healthy neonates of the same age range. In consequence of the analyses there was ascertained, that with anemia increases intensification free-radical oxidation process. At the same time, antioxidant system activity was not change significantly in the sepsis with anemia, than other one. Pathogenesis of anemia may was founded undergo hemolitic anemia results by oxidative stress. According to the results of investigations could be concluded that in case of anemia developed at neonatal sepsis supports intensify of oxidative stress and at the same time anemia is the result of the oxidative stress.

Iron status, iron supplementation and anemia in pregnancy: ethnic differences.

PubMed

Baraka, M A; Steurbaut, S; Laubach, M; Coomans, D; Dupont, A G

2012-08-01

To investigate the anemia prevalence during pregnancy and the use of and response to iron supplementation in a multi-ethnic population as well as the possible association between anemia and birth outcomes (pregnancy duration, birth weight). Cross-sectional study conducted in a university hospital (Brussels, Belgium) in 341 women. Hemoglobin, ferritin and iron prescription data were extracted from the patients' electronic dossiers; a questionnaire was used to assess iron intake during pregnancy. Anemia prevalence was higher during the 3rd trimester (24.3%) than in the 1st trimester (6.2%). Arab/Turkish women had a higher prevalence of anemia (9.1%) in the 1st trimester compared to Western women (2.4%; p = 0.044). The frequency of iron prescription was significantly higher among Arab/Turkish (43.7%) compared to Western women (27.9%; p = 0.006). A significantly lower mean birth weight was found among women presenting with anemia in the 1st trimester (3166 g) compared to non anemic women (3442 g; p = 0.036) but no significant difference was detected in mean pregnancy duration between both groups (p = 0.804). Anemia was more prevalent among Arab/Turkish women in spite of receiving more iron prescriptions than Western women. Efficient iron therapy and intensive follow-up are warranted to decrease the anemia prevalence during pregnancy, especially among non-Western women.

Erythropoietin reduces anemia and transfusions after chemotherapy with paclitaxel and carboplatin.

PubMed

Dunphy, F R; Dunleavy, T L; Harrison, B R; Boyd, J H; Varvares, M A; Dunphy, C H; Rodriguez, J J; McDonough, E M; Minster, J R; McGrady, M D

1997-04-15

The authors report on anemia observed during preoperative paclitaxel and carboplatin chemotherapy in patients with advanced head and neck carcinoma and discuss how the use of recombinant human erythropoietin (r-HuEPO) ameliorates this anemia, reducing the need for subsequent packed red blood cell (PRBC) transfusions. Response to r-HuEPO was defined as reduced hemoglobin fall during preoperative chemotherapy and reduced transfusion requirements during surgery. Thirty-six patients with advanced head and neck carcinoma were evaluable after treatment with preoperative chemotherapy using paclitaxel and carboplatin. Group 1 was comprised of 14 patients who empirically received r-HuEPO at a dose of 150 U/kg 3 times per week for 3 weeks; in patients deemed nonresponders, the dose was increased to 300 U/kg and 450 U/kg in the subsequent courses. Group 2 was comprised of 22 patients who did not receive r-HuEPO. During preoperative chemotherapy, the mean hemoglobin fall was 0.5 g/dL in Group 1 (P = 0.40). In Group 2 there was a statistically significant mean hemoglobin fall of 3.3 g/dL (P < 0.0001). There was also a nonstatistically significant trend toward fewer PRBC transfusions: none of 14 patients (0%) in Group 1 versus 4 of 22 patients (18%) in Group 2 (P = 0.141). A significant fall in hemoglobin and an increase in the need for transfusions were observed in head and neck carcinoma patients receiving carboplatin and paclitaxel chemotherapy prior to surgery. Empiric r-HuEPO therapy appeared to prevent anemia and reduced the need for PRBC transfusions.

Prevalence of anemia and associated factors among indigenous children in Brazil: results from the First National Survey of Indigenous People’s Health and Nutrition

PubMed Central

2013-01-01

Background Anemia is the most prevalent nutritional deficiency globally, affecting about a quarter of the world population. In Brazil, about one-fifth of children under five years of age are anemic. Previous case studies indicate prevalence rates much higher among indigenous peoples in the country. The First National Survey of Indigenous People’s Health and Nutrition in Brazil, conducted in 2008–2009, was the first survey based on a nationwide representative sample to study the prevalence of anemia and associated factors among indigenous children in Brazil. Methods The survey assessed the health and nutritional status of indigenous children < 5 years of age based on a representative sample of major Brazilian geopolitical regions. A stratified probabilistic sampling was carried out for indigenous villages. Within villages, children < 5 years of age in sampled households were included in the study. Prevalence rates of anemia were calculated for independent variables and hierarchical multivariate analysis were conducted to assess associations. Results Evaluation of hemoglobin levels was conducted for 5,397 children (88.1% of the total sample). The overall prevalence of anemia was 51.2%. Higher risk of presenting anemia was documented for boys, lower maternal schooling, lower household socioeconomic status, poorer sanitary conditions, presence of maternal anemia, and anthropometric deficits. Regional differences were observed, with the highest rate being observed in the North. Conclusions The prevalence rates of anemia in indigenous children were approximately double than those reported for non-indigenous Brazilian children in the same age group. Similarly notable differences in the occurrence of anemia in indigenous and non-indigenous children have been reported for other countries. Deeper knowledge about the etiology of anemia in indigenous children in Brazil is essential to its proper treatment and prevention. PMID:23714275

Analysis of a FANCE Splice Isoform in Regard to DNA Repair.

PubMed

Bouffard, Frédérick; Plourde, Karine; Bélanger, Simon; Ouellette, Geneviève; Labrie, Yvan; Durocher, Francine

2015-09-25

The FANC-BRCA DNA repair pathway is activated in response to interstrand crosslinks formed in DNA. A homozygous mutation in 1 of the 17 Fanconi anemia (FA) genes results in malfunctions of this pathway and development of FA syndrome. The integrity of this protein network is essential for good maintenance of DNA repair process and genome stability. Following the identification of an alternatively splice isoform of FANCE (Fanconi anemia complementation group E) significantly expressed in breast cancer individuals from high-risk non-BRCA1/2 families, we studied the impact of this FANCE splice isoform (FANCEΔ4) on DNA repair processes. We have demonstrated that FANCEΔ4 mRNA was efficiently translated into a functional protein and expressed in normal and breast cancer cell lines. Following treatment with the crosslinking agent mitomycin C, EUFA130 (FANCE-deficient) cells infected with FANCEΔ4 were blocked into G2/M phase, while cell survival was significantly reduced compared with FANCE-infected EUFA130 cells. In addition, FANCEΔ4 did not allow FANCD2 and FANCI monoubiquitination, which represents a crucial step of the FANC-BRCA functional pathway. As observed for FANCE wild-type protein, localization of FANCEΔ4 protein was confined to the nucleus following mitomycin C treatment. Although FANCEΔ4 protein showed interaction with FANCE, FANCEΔ4 did not support normal function of FANCE protein in this pathway and could have deleterious effects on FANCE protein activity. We have demonstrated that FANCEΔ4 seems to act as a regulator of FANCD2 protein expression level by promoting its degradation. This study highlights the importance of an efficient regulation of alternative splicing expression of FA genes for proper DNA repair. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stem cell gene therapy for fanconi anemia: report from the 1st international Fanconi anemia gene therapy working group meeting.

PubMed

Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

2011-07-01

Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA.

Determinants of Persistent Anemia in Poor, Urban Pregnant Women of Chandigarh City, North India: A Mixed Method Approach.

PubMed

Diamond-Smith, Nadia G; Gupta, Madhu; Kaur, Manmeet; Kumar, Rajesh

2016-06-01

Maternal anemia continues to be a public health problem in India, despite existence of multipronged governmental programs to combat it. This study explores the determinants of persistent anemia in poor pregnant women in an urban population in Chandigarh, India. A mixed method approach was used to examine the causes of maternal anemia. Three focus group discussions with pregnant women from different socioeconomic groups and 2 with female health workers were conducted to explore their perceptions and beliefs about maternal anemia and iron folic acid (IFA) tablets in urban settings in 2009. This was followed by interviews of 120 pregnant women about their nutrition knowledge and practices. Food frequency questionnaires were used to estimate daily consumption of nutrients. Finally, a follow-up survey in health clinics explored issues of stock-outs of IFA. Sixty-five percent of respondents had hemoglobin less than 11g/dL and were anemic. Only 35% respondents obtained free IFA through public health programs. While 53% of respondents knew that they should eat green leafy vegetables, only 8% reported daily consumption of these vegetables. Focus group discussions highlighted issues around lack of food, especially for slum women, and low decision-making power in the household. Stock-outs of IFA in facilities often pushed women to purchase IFA from chemist shops. Clear gaps emerged in pregnant women's knowledge and practice regarding diet and IFA tablet use. Lack of control over decision-making due to their low status of women was also hindering IFA use and healthy eating. © The Author(s) 2016.

[Atypical hemolytic uremic syndrome].

PubMed

Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

2015-11-20

The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The influence of hydroxyurea on oxidative stress in sickle cell anemia

PubMed Central

Torres, Lidiane de Souza; da Silva, Danilo Grünig Humberto; Belini Junior, Edis; de Almeida, Eduardo Alves; Lobo, Clarisse Lopes de Castro; Cançado, Rodolfo Delfini; Ruiz, Milton Artur; Bonini-Domingos, Claudia Regina

2012-01-01

Objective The oxidative stress in 20 sickle cell anemia patients taking hydroxyurea and 13 sickle cell anemia patients who did not take hydroxyurea was compared with a control group of 96 individuals without any hemoglobinopathy. Methods Oxidative stress was assessed by thiobarbituric acid reactive species production, the Trolox-equivalent antioxidant capacity and plasma glutathione levels. Results Thiobarbituric acid reactive species values were higher in patients without specific medication, followed by patients taking hydroxyurea and the Control Group (p < 0.0001). The antioxidant capacity was higher in patients taking hydroxyurea and lower in the Control Group (p = 0.0002 for Trolox-equivalent antioxidant capacity and p < 0.0292 for plasma glutathione). Thiobarbituric acid reactive species levels were correlated with higher hemoglobin S levels (r = 0.55; p = 0.0040) and lower hemoglobin F concentrations(r = -0.52; p = 0.0067). On the other hand, plasma glutathione levels were negatively correlated with hemoglobin S levels (r = -0.49; p = 0.0111) and positively associated with hemoglobin F values (r = 0.56; p = 0.0031). Conclusion Sickle cell anemia patients have high oxidative stress and, conversely, increased antioxidant activity. The increase in hemoglobin F levels provided by hydroxyurea and its antioxidant action may explain the reduction in lipid peroxidation and increased antioxidant defenses in these individuals. PMID:23323065

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

PubMed

Mori, Takehiko; Koh, Hideo; Onishi, Yasushi; Kako, Shinichi; Onizuka, Makoto; Kanamori, Heiwa; Ozawa, Yukiyasu; Kato, Chiaki; Iida, Hiroatsu; Suzuki, Ritsuro; Ichinohe, Tatsuo; Kanda, Yoshinobu; Maeda, Tetsuo; Nakao, Shinji; Yamazaki, Hirohito

2016-04-01

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

Do patients with iron deficiency without anemia benefit from an endoscopic examination?

PubMed

García García de Paredes, Ana; Teruel Sánchez-Vegazo, Carlos; Hernanz Ruiz, Nerea; Ferre Aracil, Carlos; Rodríguez de Santiago, Enrique; Aguilera Castro, Lara; Sierra Morales, María; Albillos, Agustín

2017-07-01

The need for endoscopic investigation in patients with iron deficiency without anemia (ID) is not established. Data from patients with ID (serum ferritin ≤20 ng/mL, normal hemoglobin) studied with upper and lower endoscopies were retrospectively analyzed. Patients evaluated for iron deficiency anemia (IDA) served as controls, matched by sex and age in the proportion of 2:1. The groups were compared for the presence, type, location and age distribution of endoscopic findings. Altogether 109 patients (55% women; mean age 59.6 ± 13.5 years; aged <50 years [27.5%]; 50-69 years [43.1%]; ≥70 years [29.4%]) were included in the ID group and 218 matched controls in the IDA group. Lesions were found in a similar proportion of patients (53.2% in the ID group vs 49.1% in the IDA group, P = 0.48) irrespective of age (P = 0.92). The colonoscopy diagnostic yield was low in both the ID and IDA subgroups of aged <50 years (6.3% vs 4.2%, P = 0.76). Multivariate analysis revealed a significant relationship between age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.06) and male sex (OR 2.28, 95% CI 1.18-4.39) with a positive colonoscopy. Malignancy was significantly less frequent in the ID group (1.8% vs 14.2%, P < 0.05). The prevalence of gastrointestinal lesions in patients with and without anemia was similar but malignancy was eight times less frequent in the ID group. Systematic endoscopic evaluation in patients with ID is therefore questionable. © 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Rapid CO breath test screening of drugs for protective effects on ribavirin-induced hemolysis in a rabbit model: a pilot study.

PubMed

Ma, Yong-Jian; Zhang, Hou-De; Wu, Chuang-Hong; Zhu, Guo-Liang; Ji, Yong-Qiang; Huang, Jia-Liang; Du, Li-Tao; Cao, Ping; Zang, De-Yue; Ji, Kun-Mei

2016-08-10

Hemolytic anemia is a major side effect of ribavirin antiviral treatment for chronic hepatitis C. Ribavirin dose reduction may compromise the antiviral response and erythropoietin can take several weeks to alleviate anemia. The purpose of the present study was to screen potentially protective drugs against ribavirin-induced hemolytic anemia in a rabbit model, using our modified CO breath test for measuring erythrocyte (RBC) lifespan, the gold standard diagnostic index of hemolysis. Fifteen rabbits were divided randomly into five groups (N  =  3/group): one vehicle control group, one ribavirin (only)-treated (RBV) group, and three groups initially treated with ribavirin only, followed by a combination of ribavirin with prednisone (RBV  +  Pred), polyene phosphatidyl choline (RBV  +  PPC), or reduced glutathione (RBV  +  GSH). RBC lifespan was calculated from accumulated CO measured in a closed rebreath apparatus, blood volume measured by the Evan's blue dye (EBD) dilution test, and hemoglobin concentration data. The RBC lifespan was normal in the vehicle control group (44-60 d), but reduced significantly in all of the ribavirin-treated groups before the addition of screened drugs (17-35 d). RBC lifespan rebounded significantly with the addition of glutathione, but not with the addition of prednisone or polyene phosphatidyl choline. A similar overall drug effect pattern was seen in the hemoglobin concentration and reticulocyte count data. In conclusion, the results of this pilot study indicate that reduced glutathione can attenuate ribavirin-induced hemolytic anemia, and that the RBC lifespan measured with our modified rapid CO breath test is feasible and reliable for use in animal studies.

Solid fuel use is associated with anemia in children.

PubMed

Accinelli, Roberto A; Leon-Abarca, Juan A

2017-10-01

Over 3 billion people use solid fuels as a means of energy and heating source, and ~ 50% of households burn them in inefficient, poorly ventilated stoves. In 2010, ~ 43% of the 640 million preschool children in 220 countries suffered from a certain degree of anemia, with iron deficiency as the main cause in developed countries whereas its causes remained multifactorial in the undeveloped group. In this study, we explore the relations of country-wide variables that might affect the people's health status (from socioeconomic status to more specific variables such as water access). We found independent relationship between solid fuel use and anemia in children under five years old (p < 0.0001), taking into account the prevalence of anemia in pregnant woman and the access to improved water sources. Countries in which the population uses solid fuel the most have over three times higher anemia rates in children than countries with the lowest prevalence of solid fuels use. There is still a complex relationship between solid fuels use and anemia, as reflected in its worldwide significance (p < 0.05) controlled for measles immunization, tobacco consumption, anemia in pregnant mothers, girl's primary education, life expectancy and improved water access but not (p > 0.05) when weighing for sanitation access or income per capita. Copyright © 2017 Elsevier Inc. All rights reserved.

Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation.

PubMed

Tran, Ha; Chaudhuri, Abanti; Concepcion, Waldo; Grimm, Paul C

2014-03-01

Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab. An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence. Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.

Micronutrient Deficits Are Still Public Health Issues among Women and Young Children in Vietnam

PubMed Central

Laillou, Arnaud; Pham, Thuy Van; Tran, Nga Thuy; Le, Hop Thi; Wieringa, Frank; Rohner, Fabian; Fortin, Sonia; Le, Mai Bach; Tran, Do Thanh; Moench-Pfanner, Regina; Berger, Jacques

2012-01-01

Background The 2000 Vietnamese National Nutrition Survey showed that the population's dietary intake had improved since 1987. However, inequalities were found in food consumption between socioeconomic groups. As no national data exist on the prevalence of micronutrient deficiencies, a survey was conducted in 2010 to assess the micronutrient status of randomly selected 1526 women of reproductive age and 586 children aged 6–75 mo. Principal Findings In women, according to international thresholds, prevalence of zinc deficiency (ZnD, 67.2±2.6%) and vitamin B12 deficiency (11.7±1.7%) represented public health problems, whereas prevalence of anemia (11.6±1.0%) and iron deficiency (ID, 13.7±1.1%) were considered low, and folate (<3%) and vitamin A (VAD, <2%) deficiencies were considered negligible. However, many women had marginal folate (25.1%) and vitamin A status (13.6%). Moreover, overweight (BMI≥23 kg/m2 for Asian population) or underweight occurred in 20% of women respectively highlighting the double burden of malnutrition. In children, a similar pattern was observed for ZnD (51.9±3.5%), anemia (9.1±1.4%) and ID (12.9±1.5%) whereas prevalence of marginal vitamin A status was also high (47.3±2.2%). There was a significant effect of age on anemia and ID prevalence, with the youngest age group (6–17 mo) having the highest risk for anemia, ID, ZnD and marginal vitamin A status as compared to other groups. Moreover, the poorest groups of population had a higher risk for zinc, anemia and ID. Conclusion The prevalence of anemia and ID in Vietnam has been markedly reduced over the last decade, but a large part of the population is still at risk for other deficiencies such as zinc, vitamin A, folate and vitamin B12 especially the youngest children aged 6–17 mo. Consequently specific interventions to improve food diversity and quality should be implemented, among them food fortification of staple foods and condiments and improvement of complementary feeding. PMID:22529954

Maternal anemia and risk of adverse birth and health outcomes in low- and middle-income countries: systematic review and meta-analysis.

PubMed

Rahman, Md Mizanur; Abe, Sarah Krull; Rahman, Md Shafiur; Kanda, Mikiko; Narita, Saki; Bilano, Ver; Ota, Erika; Gilmour, Stuart; Shibuya, Kenji

2016-02-01

Anemia is a leading cause of maternal deaths and adverse pregnancy outcomes in developing countries. We conducted a systematic review and meta-analysis to estimate the pooled prevalence of anemia, the association between maternal anemia and pregnancy outcomes, and the population-attributable fraction (PAF) of these outcomes that are due to anemia in low- and middle-income countries. PubMed, EMBASE, CINAHL, and the British Nursing Index were searched from inception to May 2015 to identify cohort studies of the association between maternal anemia and pregnancy outcomes. The anemic group was defined as having hemoglobin concentrations <10 or <11 g/dL or hematocrit values <33% or <34% depending on the study. A metaregression and stratified analysis were performed to assess the effects of study and participant characteristics on adverse pregnancy risk. The pooled prevalence of anemia in pregnant women by region and country-income category was calculated with the use of a random-effects meta-analysis. Of 8182 articles reviewed, 29 studies were included in the systematic review, and 26 studies were included in the meta-analysis. Overall, 42.7% (95% CI: 37.0%, 48.4%) of women experienced anemia during pregnancy in low- and middle-income countries. There were significantly higher risks of low birth weight (RR: 1.31; 95% CI: 1.13, 1.51), preterm birth (RR: 1.63; 95% CI: 1.33, 2.01), perinatal mortality (RR: 1.51; 95% CI: 1.30, 1.76), and neonatal mortality (RR: 2.72; 95% CI: 1.19, 6.25) in pregnant women with anemia. South Asian, African, and low-income countries had a higher pooled anemia prevalence than did other Asian and upper-middle-income countries. Overall, in low- and middle-income countries, 12% of low birth weight, 19% of preterm births, and 18% of perinatal mortality were attributable to maternal anemia. The proportion of adverse pregnancy outcomes attributable to anemia was higher in low-income countries and in the South Asian region. Maternal anemia remains a significant health problem in low- and middle-income countries. © 2016 American Society for Nutrition.

Micronutrient supplementation adherence and influence on the prevalences of anemia and iron, zinc and vitamin A deficiencies in preemies with a corrected age of six months

PubMed Central

de Freitas, Brunnella Alcantara Chagas; Lima, Luciana Moreira; Moreira, Maria Elisabeth Lopes; Priore, Silvia Eloiza; Henriques, Bruno David; Carlos, Carla Fernanda Lisboa Valente; Sabino, Jusceli Souza Nogueira; do Carmo Castro Franceschini, Sylvia

2016-01-01

OBJECTIVE: To analyze adherence to the recommended iron, zinc and multivitamin supplementation guidelines for preemies, the factors associated with this adherence, and the influence of adherence on the occurrence of anemia and iron, zinc and vitamin A deficiencies. METHODS: This prospective cohort study followed 58 preemies born in 2014 until they reached six months corrected age. The preemies were followed at a referral secondary health service and represented 63.7% of the preterm infants born that year. Outcomes of interest included high or low adherence to iron, zinc and multivitamin supplementation guidelines; prevalence of anemia; and prevalences of iron, zinc, and vitamin A deficiencies. The prevalence ratios were calculated by Poisson regression. RESULTS: Thirty-eight (65.5%) preemies presented high adherence to micronutrient supplementation guidelines. At six months of corrected age, no preemie had vitamin A deficiency. The prevalences of anemia, iron deficiency and zinc deficiency were higher in the low-adherence group but also concerning in the high-adherence group. Preemies with low adherence to micronutrient supplementation guidelines were 2.5 times more likely to develop anemia and 3.1 times more likely to develop zinc deficiency. Low maternal education level increased the likelihood of nonadherence to all three supplements by 2.2 times. CONCLUSIONS: Low maternal education level was independently associated with low adherence to iron, zinc and vitamin A supplementation guidelines in preemies, which impacted the prevalences of anemia and iron and zinc deficiencies at six months of corrected age. PMID:27626474

Blood levels of toxic metals and rare earth elements commonly found in e-waste may exert subtle effects on hemoglobin concentration in sub-Saharan immigrants.

PubMed

Henríquez-Hernández, Luis Alberto; Boada, Luis D; Carranza, Cristina; Pérez-Arellano, José Luis; González-Antuña, Ana; Camacho, María; Almeida-González, Maira; Zumbado, Manuel; Luzardo, Octavio P

2017-12-01

Pollution by heavy metals and more recently by rare earth elements (REE) and other minor elements (ME) has increased due in part to their high use in technological and electronic devices. This contamination can become very relevant in those sites where e-waste is improperly processed, as it is the case in many countries of the African continent. Exposure to some toxic elements has been associated to certain hematological disorders, specifically anemia. In this study, the concentrations of 48 elements (including REE and other ME) were determined by ICP-MS in whole blood samples of sub-Saharan immigrants with anemia (n=63) and without anemia (n=78). We found that the levels of Fe, Cr, Cu, Mn, Mo, and Se were significantly higher in the control group than in the anemia group, suggesting that anemia was mainly due to nutritional deficiencies. However, since other authors have suggested that in addition to nutritional deficiency, exposure to some elements may influence hemoglobin levels, we wanted to explore the role of a broad panel of toxic and "emerging" elements in hemoglobin deficiency. We found that the levels of Ag, As, Ba, Bi, Ce, Eu, Er, Ga, La, Nb, Nd, Pb, Pr, Sm, Sn, Ta, Th, Tl, U and V were higher in anemic participants than in controls. For most of these elements an inverse correlation with hemoglobin concentration was found. Some of them also correlated inversely with blood iron levels, pointing to the possibility that a higher rate of intestinal uptake of these could exist in relation to a nutritional deficiency of iron. However, the higher levels of Pb, and the group of REE and other ME in anemic participants were independent of iron levels, pointing to the possibility that these elements could play a role in the development of anemia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Craniofacial bone abnormalities and malocclusion in individuals with sickle cell anemia: a critical review of the literature

PubMed Central

Costa, Cyrene Piazera Silva; de Carvalho, Halinna Larissa Cruz Correia; Thomaz, Erika Bárbara Abreu Fonseca; Sousa, Soraia de Fátima Carvalho

2012-01-01

This study aims to critically review the literature in respect to craniofacial bone abnormalities and malocclusion in sickle cell anemia individuals. The Bireme and Pubmed electronic databases were searched using the following keywords: malocclusion, maxillofacial abnormalities, and Angle Class I, Class II and lass III malocclusions combined with sickle cell anemia. The search was limited to publications in English, Spanish or Portuguese with review articles and clinical cases being excluded from this study. Ten scientific publications were identified, of which three were not included as they were review articles. There was a consistent observation of orthodontic and orthopedic variations associated with sickle cell anemia, especially maxillary protrusions. However, convenience sampling, sometimes without any control group, and the lack of estimates of association and hypotheses testing undermined the possibility of causal inferences. It was concluded that despite the high frequency of craniofacial bone abnormalities and malocclusion among patients with sickle cell anemia, there is insufficient scientific proof that this disease causes malocclusion PMID:23049386

Molecular characterization of chicken infectious anemia viruses detected from breeder and broiler chickens in South Korea.

PubMed

Kim, H-R; Kwon, Y-K; Bae, Y-C; Oem, J-K; Lee, O-S

2010-11-01

In South Korea, 32 sequences of chicken infectious anemia virus (CIAV) from various flocks of breeder and commercial chickens were genetically characterized for the first time. Phylogenetic analysis of the viral protein 1 gene, including a hypervariable region of the CIAV genome, indicated that Korean CIAV strains were separated into groups II, IIIa, and IIIb. Strains were commonly identified in great-grandparent and grandparent breeder farms as well as commercial chicken farms. In the field, CIAV strains from breeder farms had no clinical effects, but commercial farm strains were associated with depression, growth retardation, and anemia regardless of the group from which the strain originated. In addition, we identified 7 CIAV genomes that were similar to vaccine strains from vaccinated and unvaccinated breeder flocks. These data suggest that further studies on pathogenicity and vaccine efficacy against the different CIAV group are needed, along with continuous CIAV surveillance and genetic analysis at breeder farms.

Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn.

PubMed

Delaney, Meghan; Matthews, Dana C

2015-01-01

Hemolytic disease of the fetus and newborn (HDFN) affects 3/100 000 to 80/100 000 patients per year. It is due to maternal blood group antibodies that cause fetal red cell destruction and in some cases, marrow suppression. This process leads to fetal anemia, and in severe cases can progress to edema, ascites, heart failure, and death. Infants affected with HDFN can have hyperbilirubinemia in the acute phase and hyporegenerative anemia for weeks to months after birth. The diagnosis and management of pregnant women with HDFN is based on laboratory and radiographic monitoring. Fetuses with marked anemia may require intervention with intrauterine transfusion. HDFN due to RhD can be prevented by RhIg administration. Prevention for other causal blood group specificities is less studied. © 2015 by The American Society of Hematology. All rights reserved.

[Ischemic Changes in the Electrocardiogram and Circulatory Collapse Accompanied by Severe Anemia Owing to the Delay of Red Blood Cell Concentrate Transfusion in Two Patients with Intraoperative Massive Bleeding].

PubMed

Horiuchi, Toshinori; Noguchi, Teruo; Kurita, Naoko; Yamaguchi, Ayako; Takeda, Masafumi; Sha, Keiichi; Nagahata, Toshihiro

2016-01-01

We present two patients developing intraoperative massive bleeding and showed ischemic changes in the electrocardiogram and circulatory collapse accompanied by severe anemia owing to the delay of red blood cell concentrate transfusion. One patient underwent hepatectomy and the other pancreaticoduodenectomy. Their lowest hemoglobin concentration was around 2 g x dl(-1), and they showed ischemic changes in the electrocardiogram and severe decreases in blood pressure. The former received compatible red blood cell concentrate and the latter received uncrossmatched same blood group red blood cell concentrate immediately, and their electrocardiogram and blood pressure quickly improved. To avoid life-threatening anemia, emergency red blood cell concentrate transfusion including compatible different blood group transfusion should be applied for intraoperative massive bleeding.

The science and practice of micronutrient supplementations in nutritional anemia: an evidence-based review.

PubMed

Chan, Lingtak-Neander; Mike, Leigh Ann

2014-08-01

Nutritional anemia is the most common type of anemia, affecting millions of people in all age groups worldwide. While inadequate access to food and nutrients can lead to anemia, patients with certain health status or medical conditions are also at increased risk of developing nutritional anemia. Iron, cobalamin, and folate are the most recognized micronutrients that are vital for the generation of erythrocytes. Iron deficiency is associated with insufficient production of hemoglobin. Deficiency of cobalamin or folate leads to impaired synthesis of deoxyribonucleic acid, proteins, and cell division. Recent research has demonstrated that the status of copper and zinc in the body can significantly affect iron absorption and utilization. With an increasing number of patients undergoing bariatric surgical procedures, more cases of anemia associated with copper and zinc deficiencies have also emerged. The intestinal absorption of these 5 critical micronutrients are highly regulated and mediated by specific apical transport mechanisms in the enterocytes. Health conditions that persistently alter the histology of the upper intestinal architecture, expression, or function of these substrate-specific transporters, or the normal digestion and flow of these key micronutrients, can lead to nutritional anemia. The focus of this article is to review the science of intestinal micronutrient absorption, discuss the clinical assessment of micronutrient deficiencies in relation to anemia, and suggest an effective treatment plan and monitoring strategies using an evidence-based approach. © 2014 American Society for Parenteral and Enteral Nutrition.

National Trends in Hemoglobin Concentration and Prevalence of Anemia among Chinese School-Aged Children, 1995-2010.

PubMed

Song, Yi; Wang, Hai-Jun; Dong, Bin; Wang, Zhiqiang; Ma, Jun; Agardh, Anette

2017-04-01

To assess the trend of sex disparity in hemoglobin concentration and prevalence of anemia among Chinese school-aged children from 1995 to 2010. Data were collected from 360 866 children aged 7, 9, 12, 14, and 17 years during 4 cross-sectional surveys (1995, 2000, 2005, and 2010) of the Chinese National Surveys on Students Constitution and Health. Shifts in hemoglobin concentration distributions were compared by sex. Average shifts and sex differences were calculated with quantile regression models. Logistic regression was used to estimate the prevalence odds ratio of sex for prevalence of anemia in different surveys. The mean hemoglobin concentration increased among Chinese children between 1995 and 2010, from 132.7 to 138.3 g/L in boys, and from 127.7 to 132.3 g/L in girls. The prevalence of anemia decreased from 18.8% in 1995 to 9.9% in 2010. It was higher in rural than urban children among all age groups. The prevalence odds ratios of girls versus boys for anemia increased in both urban and rural areas over time. Hemoglobin concentration and prevalence of anemia improved among Chinese school-aged children over time. Hemoglobin concentration improved faster in boys than girls and as a result the relative prevalence of anemia in girls compared with boys increased. Sex-specific preventive guidelines and public health policies for childhood anemia are needed in China. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of dietary habits on prevalence of anemia in pregnant women of Delhi.

PubMed

Sharma, Jai Bhagwan; Soni, Dimple; Murthy, Nandagudi Srinivasa; Malhotra, Monika

2003-04-01

To see the effect of various dietary habits, such as a vegetarian diet or various types of meat, on the prevalence of anemia in pregnant women. A study was carried out in Delhi to determine the effect of different dietary habits on prevalence of anemia during pregnancy by questioning the women during pregnancy regarding their dietary habits (vegetarian diet, jhatka or halal meat) and assessing their hemoglobin levels. The data was compiled and chi2 test was employed for understanding the associations between the effect of food habits on prevalence of anemia. Mean age was 26.5 years. Most women were in the second (26%) or third trimester (63.2%) of pregnancy. Prevalence of anemia was found to be very high. Of 1150 women, 96% were anemic (89.8% mildly anemic, 5.3% severely anemic). Anemia was seen in 96.18% cases in vegetarian women, 95.3% in halal meat eaters, and 96.2% in jhatka meat eaters (not significant). Although the percentage of women with < 11 g/dL Hb was less in the jhatka group eating meat more than 5 times per month, than in halal meat eaters and vegetarians, the difference was not statistically significant. There is very high prevalence of anemia during pregnancy in Delhi, probably due to very low frequency of meat eating in India. Different types of dietary habits had no effect on the prevalence of anemia in pregnant Indian women.

Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

PubMed

Kim, Sung-Yong; Le Rademacher, Jennifer; Antin, Joseph H; Anderlini, Paolo; Ayas, Mouhab; Battiwalla, Minoo; Carreras, Jeanette; Kurtzberg, Joanne; Nakamura, Ryotaro; Eapen, Mary; Deeg, H Joachim

2014-12-01

A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients. Copyright© Ferrata Storti Foundation.

The Effectiveness of a New Model in Managing Pregnant Women with Iron Deficiency Anemia in Indonesia: A Nonrandomized Controlled Intervention Study.

PubMed

Widyawati, Widyawati; Jans, Suze; Bor, Hans H J; van Dillen, Jeroen; Lagro-Janssen, Antoine L M

2015-12-01

Indonesia has a major problem with iron deficiency anemia among pregnant women. A new model named the Four Pillars Approach was designed to improve antenatal care for these women. This study aimed to measure the effectiveness of the model in managing pregnant women with iron deficiency anemia. We used a nonrandomized controlled intervention study. The study, with the Four Pillars Approach as intervention versus usual care as its control, was conducted in two provinces in Java (Indonesia) during the period from March 2012 until May 2013. Main outcome measures were a difference of Hb level ≥ 0.5 g/dL, the number of women who attended five or more antenatal care visits, and birthing with a skilled birth attendant. Three hundred fifty-four participants were enrolled in the study. Participants in the intervention group had an adjusted odds ratio of 25.0 (95% CI 12.03-52.03, p = 0.001) for increased hemoglobin of ≥ 0.5 g/dL at 35-37 weeks of gestation, compared with the control group. In the intervention group, 95.0 percent of women had five or more antenatal care visits, compared with 57.2 percent (p = 0.001) in the control group. All births in both groups were assisted by skilled birth attendants. The Four Pillars Approach is effective in increasing the hemoglobin level and the frequency of antenatal care visits of participants when compared with the usual care for pregnant women with anemia. © 2015 Wiley Periodicals, Inc.

Impact of iron overload on interleukin-10 levels, biochemical parameters and oxidative stress in patients with sickle cell anemia

PubMed Central

Barbosa, Maritza Cavalcante; dos Santos, Talyta Ellen Jesus; de Souza, Geane Félix; de Assis, Lívia Coêlho; Freitas, Max Victor Carioca; Gonçalves, Romélia Pinheiro

2013-01-01

Objective The aim of this study was to evaluate the impact of iron overload on the profile of interleukin-10 levels, biochemical parameters and oxidative stress in sickle cell anemia patients. Methods A cross-sectional study was performed of 30 patients with molecular diagnosis of sickle cell anemia. Patients were stratified into two groups, according to the presence of iron overload: Iron overload (n = 15) and Non-iron overload (n = 15). Biochemical analyses were performed utilizing the Wiener CM 200 automatic analyzer. The interleukin-10 level was measured by capture ELISA using the BD OptEIAT commercial kit. Oxidative stress parameters were determined by spectrophotometry. Statistical analysis was performed using GraphPad Prism software (version 5.0) and statistical significance was established for p-values < 0.05 in all analyses. Results Biochemical analysis revealed significant elevations in the levels of uric acid, triglycerides, very low-density lipoprotein (VLDL), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), urea and creatinine in the Iron overload Group compared to the Non-iron overload Group and significant decreases in the high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Ferritin levels correlated positively with uric acid concentrations (p-value < 0.05). The Iron overload Group showed lower interleukin-10 levels and catalase activity and higher nitrite and malondialdehyde levels compared with the Non-iron overload Group. Conclusion The results of this study are important to develop further consistent studies that evaluate the effect of iron overload on the inflammatory profile and oxidative stress of patients with sickle cell anemia. PMID:23580881

Phenotypic variability in patients with Fanconi anemia and biallelic FANCF mutations.

PubMed

Tryon, Rebecca; Zierhut, Heather; MacMillan, Margaret L; Wagner, John E

2017-01-01

Fanconi anemia is a heterogeneous genetic disorder that is characterized by progressive bone marrow failure, congenital anomalies, and markedly increased risk for malignancies. Mutations in the FANCF (FA-F) gene represent approximately 2% of affected patients. Currently, information on the phenotypic findings of patients with Fanconi anemia from biallelic mutations in FANCF is limited. Here, we report three patients who illustrate the clinical variability within the FA-F group. This analysis suggests a more severe phenotype for those with the common c.484_485delCT mutation. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Anemia in obstetrics and gynecological surgery].

PubMed

Gredilla Díaz, E

2015-06-01

Iron deficiency is more common in women due to uterine bleeding, which affects them throughout their fertile life. Additionally, iron needs increase physiologically during pregnancy and breastfeeding. Pregnant women therefore constitute one of the risk groups for iron deficiency. During the postpartum period, iron deficiency is the most common cause of anemia. Longer hospital stays and greater susceptibility to infections are potential consequences of postpartum anemia. Copyright © 2015 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Identification of Genes and Genetic Variants Associated with Poor Treatment Response in Patients with Prostate Cancer

DTIC Science & Technology

2012-10-01

influencing the susceptibility of certain promoter regions to hypermethylation (Rappa, et al., 2012; Mori, et al., 2006). The gene FANCF ( Fanconi anemia ...antitumor agent doxorubicin binds to Fanconi anemia group F protein. Bioorg Med Chem. 2012 Nov 1;20(21):6248-55. PMID: 23026082. Mori Y, Cai K

Efficacy of an MFGM-enriched complementary food in diarrhea, anemia, and micronutrient status in infants.

PubMed

Zavaleta, Nelly; Kvistgaard, Anne Staudt; Graverholt, Gitte; Respicio, Graciela; Guija, Henry; Valencia, Norma; Lönnerdal, Bo

2011-11-01

The aim of the present study was to evaluate the efficacy of a milkfat globule membrane (MFGM)-enriched protein fraction in a complementary food, on diarrhea, anemia, and micronutrient status. A randomized, double-blind controlled design to study 550 infants, 6 to 11 months old, who received daily for 6 months a complementary food (40 g/day) with the protein source being either the MFGM protein fraction or skim milk proteins (control). Health and nutritional status of infants were examined monthly in the outpatient clinic; product intake, food patterns, and diarrhea morbidity were assessed by home visits twice per week. Hemoglobin and micronutrient status were measured at 0 and 6 months of intervention. Results are presented as the entire group and as 6 to 8 and 9 to 11 months subgroups. A total of 499 infants completed the study. Global prevalence of diarrhea was 3.84% and 4.37% in the MFGM group and control group, respectively (P < 0.05). Consumption of the MFGM protein fraction reduced episodes of bloody diarrhea (odds ratio 0.54; 95% confidence interval 0.31-0.93, P = 0.025) adjusting for anemia and potable water facilities as covariates. There were no differences between groups in anemia, serum ferritin, zinc, or folate. Addition of an MFGM-enriched protein fraction to complementary food had beneficial effects on diarrhea in infants and may thus help to improve the health of vulnerable populations.

Isolation and Characterization of Mms-Sensitive Mutants of SACCHAROMYCES CEREVISIAE

PubMed Central

Prakash, Louise; Prakash, Satya

1977-01-01

We have isolated mutants sensitive to methyl methanesulfonate (MMS) in Saccharomyces cerevisiae. Alleles of rad1, rad4, rad6, rad52, rad55 and rad57 were found among these mms mutants. Twenty-nine of the mms mutants which complement the existing radiation-sensitive (rad and rev ) mutants belong to 22 new complementation groups. Mutants from five complementation groups are sensitive only to MMS. Mutants of 11 complementation groups are sensitive to UV or X rays in addition to MMS, mutants of six complementation groups are sensitive to all three agents. The cross-sensitivities of these mms mutants to UV and X rays are discussed in terms of their possible involvement in DNA repair. Sporulation is reduced or absent in homozygous diploids of mms mutants from nine complementation groups. PMID:195865

Disparity of anemia prevalence and associated factors among rural to urban migrant and the local children under two years old: a population based cross-sectional study in Pinghu, China

PubMed Central

2014-01-01

Background Number of internal rural to urban migrant children in China increased rapidly. The disparity of anemia prevalence among them and children of local permanent residents has been reported, both in big and middle-size cities. There has been no population-based study to explore the associated factors on feeding behaviors in small size cities of China. This study aimed to identify whether there was a difference in the prevalence of anemia between children of rural to urban migrant families and local children under 2 years old in a small coastal city in China, and to identify the associated factors of any observed difference. Methods A community-based, cross-sectional survey was conducted in Pinghu, a newly-developing city in Zhejiang Province, China, among the caregivers of 988 children (667 who were identified as children of migrants and 321 locals) aged 6–23 months. Disparity of anemia prevalence were reported. Association between anemia prevalence and socio-economic status and feeding behaviors were explored among two groups respectively. Results Anemia prevalence among the migrant and local children was 36.6% and 18.7% respectively (aPR 1.86, 95% CI 1. 40 to 2.47). Results from adjusted Poisson models revealed: having elder sibling/s were found as an associated factor of anemia with the aPR 1.47 (95% CI 1.16 to 1.87) among migrant children and 2.58 (95% CI 1.37 to 4.58) among local ones; anemia status was associated with continued breastfeeding at 6 months (aPR = 1.57, 95% CI 1.15 to 2.14) and lack of iron-rich and/or iron-fortified foods (aPR = 0.68, 95% CI 0.50 to 0.89) among the migrant children but not among local ones. Conclusion Anemia was more prevalent among migrant children, especially those aged 6–11 months. Dislike their local counterparts, migrant children were more vulnerable at early life and seemed sensitive to feeding behaviors, such as, over reliance on breastfeeding for nutrition after aged 6 months, lack of iron-rich and/or iron-fortified foods. Future strategies to narrow the gap of anemia prevalence between the migrant and local children should target more susceptible groups and through improvement of feeding practices among younger children in those kinds of newly-developing areas of China. PMID:24928085

Interactions among micronutrient deficiencies and undernutrition in the Philippines.

PubMed

Florentino, R F; Tanchoco, C C; Rodriguez, M P; Cruz, A J; Molano, W L

1996-09-01

Data gathered from the 1987 National Nutrition Survey in the Philippines provided the opportunity to study the interactions among micronutrient deficiencies and undernutrition in different age groups as basis for program targeting. A randomly selected set of 50% of the households (3,200) covered by the national survey served as source of subjects. Results showed that there was a greater proportion of anemia among the undernourished (as judged by weight for age in children and weight for height in adults) (66.0%) than among the adequately nourished (54.6%) (P < 0.01). However, the observed differences in the proportion of serum vitamin A deficiency and of goiter among the undernourished compared to the adequately nourished were not significant. Also not significant were the observed higher prevalence of anemia among subjects with acceptable serum vitamin A levels for both adequately nourished and undernourished, and the higher prevalence of vitamin A deficiency among the non-anemics. Again there were no significant differences in the prevalence of anemia among goitrous and non-goitrous subjects, as well as the prevalence of goiter among anemic and non-anemic subjects. Neither were there significant differences in the prevalence of vitamin A deficiency among goitrous and non-goitrous subjects, but there were significant differences in the prevalence of goiter among vitamin A deficient and non-vitamin A deficient subjects among the 7-14 years old and among pregnant and lactating women. The study concludes that at the national level, there is apparently an interaction between anemia and protein-energy undernutrition and possibly also between goiter and vitamin A deficiency in the high-risk age groups, but between anemia on the one hand and goiter and vitamin A deficiency in the other, perhaps because of clustering in the latter conditions not found in anemia and general undernutrition. These findings may be useful in targeting communities with high prevalence of micronutrient deficiencies by using prevalence of underweight and goiter as indicators for high prevalence of anemia and vitamin A deficiency, respectively.

Does anemia-polycythemia complicating twin-twin transfusion syndrome affect outcome after fetoscopic laser surgery?

PubMed

Donepudi, R; Papanna, R; Snowise, S; Johnson, A; Bebbington, M; Moise, K J

2016-03-01

Twin anemia-polycythemia sequence (TAPS) can occur as a unique disease or as a complication of twin-twin transfusion syndrome (TTTS). Middle cerebral artery (MCA) Doppler studies are not currently part of the routine evaluation of monochorionic twins since they are not used in the Quintero staging system. As such, the true incidence of TAPS is unknown. We aimed to compare the characteristics and outcomes of twin pregnancies with TTTS complicated by spontaneous anemia-polycythemia vs those with TTTS alone. This was a secondary analysis of data collected prospectively from a cohort of 156 consecutive patients undergoing fetoscopic laser surgery for TTTS, between October 2011 and August 2014. TAPS was defined as discordance in the preoperative MCA peak systolic velocity (PSV), with one twin fetus having MCA-PSV ≤ 1.0 multiples of the median (MoM) and the other having MCA-PSV ≥ 1.5 MoM. Maternal demographics as well as preoperative, operative and postoperative variables were analyzed. Included in the final analysis were 133 patients with complete records: 11 cases with TTTS with anemia-polycythemia and 122 cases with TTTS alone. There was no difference in maternal body mass index, gestational age (GA) at procedure, rate of preterm prelabor rupture of membranes or GA at delivery between the two groups. Patients with TTTS and anemia-polycythemia were more likely to be older (P = 0.03) and parous (P = 0.04) and had a significantly lower number of placental anastomoses (P = 0.01). The dual live-birth rate was similar for both groups (P = 0.76). Cases of TTTS with anemia-polycythemia were more likely to be found in parous and older women and were characterized by fewer vascular anastomoses. TTTS with anemia-polycythemia was not associated with worse perinatal outcome after laser therapy. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Iron Fortified Complementary Foods Containing a Mixture of Sodium Iron EDTA with Either Ferrous Fumarate or Ferric Pyrophosphate Reduce Iron Deficiency Anemia in 12- to 36-Month-Old Children in a Malaria Endemic Setting: A Secondary Analysis of a Cluster-Randomized Controlled Trial.

PubMed

Glinz, Dominik; Wegmüller, Rita; Ouattara, Mamadou; Diakité, Victorine G; Aaron, Grant J; Hofer, Lorenz; Zimmermann, Michael B; Adiossan, Lukas G; Utzinger, Jürg; N'Goran, Eliézer K; Hurrell, Richard F

2017-07-14

Iron deficiency anemia (IDA) is a major public health problem in sub-Saharan Africa. The efficacy of iron fortification against IDA is uncertain in malaria-endemic settings. The objective of this study was to evaluate the efficacy of a complementary food (CF) fortified with sodium iron EDTA (NaFeEDTA) plus either ferrous fumarate (FeFum) or ferric pyrophosphate (FePP) to combat IDA in preschool-age children in a highly malaria endemic region. This is a secondary analysis of a nine-month cluster-randomized controlled trial conducted in south-central Côte d'Ivoire. 378 children aged 12-36 months were randomly assigned to no food intervention ( n = 125; control group), CF fortified with 2 mg NaFeEDTA plus 3.8 mg FeFum for six days/week ( n = 126; FeFum group), and CF fortified with 2 mg NaFeEDTA and 3.8 mg FePP for six days/week ( n = 127; FePP group). The outcome measures were hemoglobin (Hb), plasma ferritin (PF), iron deficiency (PF < 30 μg/L), and anemia (Hb < 11.0 g/dL). Data were analyzed with random-effect models and PF was adjusted for inflammation. The prevalence of Plasmodium falciparum infection and inflammation during the study were 44-66%, and 57-76%, respectively. There was a significant time by treatment interaction on IDA ( p = 0.028) and a borderline significant time by treatment interaction on iron deficiency with or without anemia ( p = 0.068). IDA prevalence sharply decreased in the FeFum (32.8% to 1.2%, p < 0.001) and FePP group (23.6% to 3.4%, p < 0.001). However, there was no significant time by treatment interaction on Hb or total anemia. These data indicate that, despite the high endemicity of malaria and elevated inflammation biomarkers (C-reactive protein or α-1-acid-glycoprotein), IDA was markedly reduced by provision of iron fortified CF to preschool-age children for 9 months, with no significant differences between a combination of NaFeEDTA with FeFum or NaFeEDTA with FePP. However, there was no overall effect on anemia, suggesting most of the anemia in this setting is not due to ID. This trial is registered at clinicaltrials.gov (NCT01634945).

Effects of a Tripeptide Iron on Iron-Deficiency Anemia in Rats.

PubMed

Xiao, Chen; Lei, Xingen; Wang, Qingyu; Du, Zhongyao; Jiang, Lu; Chen, Silu; Zhang, Mingjie; Zhang, Hao; Ren, Fazheng

2016-02-01

This study aims to investigate the effects of a tripeptide iron (REE-Fe) on iron-deficiency anemia rats. Sprague-Dawley rats were randomly divided into seven groups: a normal control group, an iron-deficiency control group, and iron-deficiency groups treated with ferrous sulfate (FeSO4), ferrous glycinate (Fe-Gly), or REE-Fe at low-, medium-, or high-dose groups. The rats in the iron-deficiency groups were fed on an iron-deficient diet to establish iron-deficiency anemia (IDA) model. After the model established, different iron supplements were given to the rats once a day by intragastric administration for 21 days. The results showed that REE-Fe had effective restorative action returning body weight, organ coefficients, and hematological parameters in IDA rats to normal level. In addition, comparing with FeSO4 or Fe-Gly, high-dose REE-Fe was more effective on improving the levels of renal coefficient, total iron-binding capacity, and transferrin. Furthermore, the liver hepcidin messenger RNA (mRNA) expression in the high-dose group was significantly higher (p < 0.05) than that in the FeSO4 or Fe-Gly group and showed no significant difference (p > 0.05) with the normal control group. The findings suggest that REE-Fe is an effective source of iron supplement for IDA rats and might be exploited as a new iron fortifier.

Anemia--prevalence and risk factors in pregnancy.

PubMed

Bencaiova, Gabriela; Burkhardt, Tilo; Breymann, Christian

2012-09-01

To assess the prevalence of decreased iron stores and anemia in pregnant women. To determine whether the risk factors: socio-demographic background, age, BMI, and parity are associated with abnormal hemoglobin concentrations and/or abnormal iron status. A longitudinal study was carried out at the Department of Obstetrics, University Hospital of Zurich to establish the risk factors and prevalence of the decreased iron stores and anemia in early pregnancy. In order to determine the hematological parameters and ferritin levels, venous blood samples of 470 singleton pregnancies between 16 and 20 pregnancy weeks were collected. According to hemoglobin and iron status, the patients were divided into four groups: patients with iron deficiency anemia, patients with decreased iron stores, patients with anemia for other reasons and normal patients. The determinants socio-demographic background, age, BMI and parity were explored using multiple logistic regression analysis. The prevalence of decreased iron stores (ferritin<20 μg/l) was observed in 31.8% of subjects (149/470) and anemia (Hb<110 g/l) in 18.5% (87/470). The prevalence of iron deficiency anemia was higher among women coming from former Yugoslavia and developing countries (p=0.004 and p=0.012). In patients coming from developing countries, a significant increase of anemia for other reasons was observed (p=0.027) and in patients older than 30 years, a significant increase of decreased iron stores (p=0.018). In our study population with low parity, the prevalence of abnormal hemoglobin and abnormal iron status was 50.2% (236/470), and socio-demographic background was the most important risk factor of anemia. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Protocol adherence and the ability to achieve target haemoglobin levels in haemodialysis patients.

PubMed

Chan, Kevin; Moran, John; Hlatky, Mark; Lafayette, Richard

2009-06-01

Anemia management remains complicated in patients with endstage renal disease on hemodialysis. We wished to evaluate the effect of protocol adherence to EPO and intravenous iron dosing on achieving the desired range of hemoglobin levels. A cohort of hemodialysis patients was studied to evaluate the rate of adherence to EPO and iron dosing protocols over a 5 month period. A database was completed to evaluate all known comorbidities, demographic factors, and facility issues that might affect hemoglobin levels. A logistic regression model was employed to evaluate the effect of adherence to the anemia protocols on the probability of achieving a hemoglobin level below, within or above the targeted range of 11-12.5 g/dl. Among 2114 patients, we found that adherence to both the EPO and iron dosing protocol resulted in the greatest probability of achieving the target hemoglobin range (56 +/- 5% in anemia protocol adherent patients versus 42 +/- 7% in non adherent patients). This was predominantly due to a lowered risk of having above target hemoglobin levels rather than below. The use of the anemia protocols was associated with lower rates of hospitalization (9 +/- 0.7 visits/100 months in adherent group vs 15 +/- 2 in non adherent group) and lower utilization of both EPO and intravenous iron. Furthermore, patients in the adherent groups had less variability of their hemoglobin levels month by month, at least as judged by standard deviation. Adherence to anemia protocols, as practiced in the dialysis units included in this cohort, may improve hemodialysis patients' ability to achieve target hemoglobin levels, and by avoiding above target hemoglobin values, lower drug utilization and reduce variability of hemoglobin levels.

Severe anemia in pregnancy in rural Ghana: a case-control study of causes and management.

PubMed

Geelhoed, Diederike; Agadzi, Florence; Visser, Lucia; Ablordeppey, Emelia; Asare, Kofi; O'Rourke, Peter; van Leeuwen, Jules Schagen; van Roosmalen, Jos

2006-01-01

Various factors contribute to severe anemia in pregnancy in low-income countries. This study assesses which of these are of importance in rural Ghana, and evaluates management. Prospective case-control study in two (sub)district hospitals in rural Ghana among 175 severely anemic pregnant women (Hb < 8.0 g/dl), receiving a comprehensive treatment package; and 152 non-anemic pregnant women (Hb > or = 10.9 g/dl), giving birth at the study hospitals, matched for age and parity. Evaluated characteristics were need for treatment for urinary tract infection and schistosomiasis; sickle cell and HIV status; antenatal care characteristics; and Hb increase after treatment. Statistical analysis included Chi square test and general linear modeling. Associated with severe anemia were multiple pregnancy (OR 8.9; 95%CI 1.1-71.0), urinary tract infection (OR 6.2; 95%CI 3.5-11.0), residence outside study (sub)district (OR 2.7; 95%CI 1.7-4.3), body mass index < 20.0 (OR 2.0; 95%CI 1.2-3.4), and less than 4 antenatal clinic visits (OR 1.9; 95%CI 1.2-3.0). No association was found with sickle cell or HIV status, schistosomiasis treatment, blood loss in pregnancy, or gestational age at antenatal care registration. After treatment, mean Hb in the severe anemia group increased by 3.2 g/dl, significantly more than in the control group (0.2 g/dl; p<0.001). Modeling showed that the number of antenatal visits and the lowest Hb together explained approximately 25% of the variability in Hb prior to childbirth among women with severe anemia. Treatable causes contribute considerably to severe anemia in pregnancy in low-income countries. Even with limited resources, a substantial increase of Hb can be achieved.

Diagnosis and treatment of iron deficiency anemia during pregnancy and the postpartum period: Iron deficiency anemia working group consensus report

PubMed Central

Api, Olus; Breyman, Christian; Çetiner, Mustafa; Demir, Cansun; Ecder, Tevfik

2015-01-01

According to the World Health Organization (WHO), anemia is the most common disease, affecting >1.5 billion people worldwide. Furthermore, iron deficiency anemia (IDA) accounts for 50% of cases of anemia. IDA is common during pregnancy and the postpartum period, and can lead to serious maternal and fetal complications. The aim of this report was to present the experiences of a multidisciplinary expert group, and to establish reference guidelines for the optimal diagnosis and treatment of IDA during pregnancy and the postpartum period. Studies and guidelines on the diagnosis and treatment of IDA published in Turkish and international journals were reviewed. Conclusive recommendations were made by an expert panel aiming for a scientific consensus. Measurement of serum ferritin has the highest sensitivity and specificity for diagnosis of IDA unless there is a concurrent inflammatory condition. The lower threshold value for hemoglobin (Hb) in pregnant women is <11 g/dL during the 1st and 3rd trimesters, and <10.5 g/dL during the 2nd trimester. In postpartum period a Hb concentration <10 g/dL indicates clinically significant anemia. Oral iron therapy is given as the first-line treatment for IDA. Although current data are limited, intravenous (IV) iron therapy is an alternative therapeutic option in patients who do not respond to oral iron therapy, have adverse reactions, do not comply with oral iron treatment, have a very low Hb concentration, and require rapid iron repletion. IV iron preparations can be safely used for the treatment of IDA during pregnancy and the postpartum period, and are more beneficial than oral iron preparations in specific indications. PMID:28913064

Ambulatory dysfunction due to unrecognized pernicious anemia.

PubMed

Malizia, Robert W; Baumann, Brigitte M; Chansky, Michael E; Kirchhoff, Michael A

2010-04-01

Pernicious anemia can result in significant hematologic and neurologic impairments due to a reduction in cobalamin absorption. Typically thought to be a disease of elderly whites, a growing body of literature has documented the disease in blacks and in younger age groups. We describe a case of a young black woman with gradually progressive lower extremity paresthesias, weakness, and ataxia as the primary presenting symptoms of pernicious anemia. This case is presented to make emergency physicians aware of pernicious anemia as a cause of ambulatory dysfunction in younger patients. We review the current body of literature on the diagnosis and management as well as evidence that the demographic profile of the disease is changing. Furthermore, in women of reproductive age, there is the potential for significant fetal and infant morbidity. Copyright 2010 Elsevier Inc. All rights reserved.

Phenotypic correction of Fanconi anemia cells in the murine bone marrow after carrier cell mediated delivery of lentiviral vector.

PubMed

Chakkaramakkil Verghese, Santhosh; Goloviznina, Natalya A; Kurre, Peter

2016-11-19

Fanconi anemia (FA) is an autosomal-recessive disorder associated with hematopoietic failure and it is a candidate for hematopoietic stem cell (HSC)-directed gene therapy. However, the characteristically reduced HSC numbers found in FA patients, their ineffective mobilization from the marrow, and re-oxygenation damage during ex vivo manipulation have precluded clinical success using conventional in vitro approaches. We previously demonstrated that lentiviral vector (LV) particles reversibly attach to the cell surface where they gain protection from serum complement neutralization. We reasoned that cellular delivery of LV to the bone marrow niche could avoid detrimental losses during FA HSC mobilization and in vitro modification. Here, we demonstrate that a VSV-G pseudotyped lentivector, carrying the FANCC transgene, can be transmitted from carrier to bystander cells. In cell culture and transplantation models of FA, we further demonstrate that LV carrier cells migrate along SDF-1α gradients and transfer vector particles that stably integrate and phenotypically correct the characteristic DNA alkylator sensitivity in murine and human FA-deficient target bystander cells. Altogether, we demonstrate that cellular homing mechanisms can be harnessed for the functional phenotype correction in murine FA hematopoietic cells.

Overcoming reprogramming resistance of Fanconi anemia cells

PubMed Central

Müller, Lars U. W.; Milsom, Michael D.; Harris, Chad E.; Vyas, Rutesh; Brumme, Kristina M.; Parmar, Kalindi; Moreau, Lisa A.; Schambach, Axel; Park, In-Hyun; London, Wendy B.; Strait, Kelly; Schlaeger, Thorsten; DeVine, Alexander L.; Grassman, Elke; D'Andrea, Alan; Daley, George Q.

2012-01-01

Fanconi anemia (FA) is a recessive syndrome characterized by progressive fatal BM failure and chromosomal instability. FA cells have inactivating mutations in a signaling pathway that is critical for maintaining genomic integrity and protecting cells from the DNA damage caused by cross-linking agents. Transgenic expression of the implicated genes corrects the phenotype of hematopoietic cells, but previous attempts at gene therapy have failed largely because of inadequate numbers of hematopoietic stem cells available for gene correction. Induced pluripotent stem cells (iPSCs) constitute an alternate source of autologous cells that are amenable to ex vivo expansion, genetic correction, and molecular characterization. In the present study, we demonstrate that reprogramming leads to activation of the FA pathway, increased DNA double-strand breaks, and senescence. We also demonstrate that defects in the FA DNA-repair pathway decrease the reprogramming efficiency of murine and human primary cells. FA pathway complementation reduces senescence and restores the reprogramming efficiency of somatic FA cells to normal levels. Disease-specific iPSCs derived in this fashion maintain a normal karyotype and are capable of hematopoietic differentiation. These data define the role of the FA pathway in reprogramming and provide a strategy for future translational applications of patient-specific FA iPSCs. PMID:22371882

[Marked hemosiderosis in myelodysplastic syndrome].

PubMed

Klinz, C

1999-01-29

A 68-year-old man was admitted because of symptoms of lumbar pain. He was known to have chronic anemia with ring sideroblasts and diabetes melitus and to be in heart failure. Three months before he had been given 7 units of red cell concentrate. On admission the outstanding features were brown discoloration of the skin, absent body hair, tachycardia, hepatomegaly and small testicles. He had a normocytic anemia, hyperglycemia and raised transaminases, hypogonadism and vitamin D3 deficiency. The serum levels of iron, transferrin saturation and feritin were markedly elevated. Liver iron content/g dried liver was 4.2 g (by biomagnetometer). Radiology of the lumbar vertebrae showed osteoporosis and sonography confirmed hepatomegaly. The known myelodysplastic syndrome (MDS) had fed to secondary hemosiderosis with heart failure, liver involvement, diabetes mellitus, hypogonadism and osteoporosis. Symptomatic treatment was unsuccessfully complemented by desferoxamine (up to 4 g/12 h) to release iron. But very good iron excretion was then achieved with deferiprone (3 x 1 g/d). The patient later died of the sequelae of hemosiderosis. Even when they have not required transfusions, patients with long-standing MDS should be examined regularly for the possible development of secondary hemosiderosis so that iron-chelating agents can be administered as needed.

Distribution of elements in individual blood cells in metabolic disorders at the cellular level

NASA Astrophysics Data System (ADS)

Johansson, Erland; Lindh, Ulf

1985-08-01

In comparison with controls neutrophil granulocytes from Rheumatoid arthritis (RA), Infantile Neuronal Ceroid Lipofuscinosis (INCL), Chronic Lymphatic Leukemia (L) and Aplastic Anemia (AA) displayed significant alterations in essential and non-essential elements which might be interpreted as fingerprints of these deseases. The neutrophils from RA patients displayed alterations in the concentrations of iron, calcium, strontium, manganese, zinc and copper. INCL displayed alterations in the concentrations of iron and copper but in the INCL disease the iron concentration was about 2 times higher than in RA. In leukemia, aluminium was observed but not in the controls (< 0.5 μg/ g). The zinc concentration was lowered in leukemia. Aplastic anemia displayed alterations in zirconium, arsenic, molybdenum, iron and zinc. The platelets from RA, INCL, L and AA patients also displayed alterations in the elemental profiles. The platelets from AA patients displayed a unique elemental distribution of arsenic, zirconium and molybdenum. The elemental profiles of the thrombocytes and neutrophils might be used as a complement in the diagnosis of the examined diseases and in therapy the elemental profile might be used to monitor drugs at the cellular level.

[Cultural representations about anaemia and supplement with iron].

PubMed

Sammartino, Gloria

2010-10-01

In Argentina, one third of pregnant women and infants suffer from anemia. However, the adherence to the treatment is very low. This study, that is qualitative in nature, tries to show the social representations regarding notions of anemia and the acceptance and reject of iron supplementation among health teams, mothers and pregnant women. Semi-structured and open interviews were applied to professionals and non professionals that worked in health centers, as well as mothers of small children and pregnant users. The 8 health centres that were visited are placed in the City of Buenos Aires and Great Buenos Aires, the provinces of Jujuy and Misiones. Information gathering took place between June 2007 and March 2008; 49 members of health teams and 40 mothers were interviewed. Data analysis was made with the software NUD*IST. The opposing attitudes of the professionals were emphasized. There was a group that did not visualize the anemia problem and that did not consider iron supplementation as necessary, there was another group that, even when considering it as problematic, found that the intake of food was the solution. Finally, there was a third group that had absolutely incorporated fighting and preventing the anemia, for whom iron supplementation had an important place. To follow-up the regulation for iron supplementation depends on the beliefs and the private wishes of health teams members.

A randomized clinical trial of the efficacy of single versus double-daily dose of oral iron for prevention of iron deficiency anemia in women with twin gestations.

PubMed

Ali, Mohammed K; Abbas, Ahmed M; Abdelmagied, Ahmed M; Mohammed, Ghada E; Abdalmageed, Osama S

2017-12-01

The study aims to assess the efficacy of single versus double-daily oral iron dose on prevention of iron deficiency anemia in women with twin gestations. A randomized controlled trial (NCT02858505) conducted at Woman's Health Hospital, Assiut, Egypt, between August 2015 and June 2016 included 120 non-anemic pregnant women with twin gestations in the first trimester. Women were randomly assigned to either group I (27 mg elemental iron) or group II (54 mg elemental iron) daily starting from 12 weeks of pregnancy till 36 weeks. The primary outcomes included the mean level of hemoglobin, hematocrit and serum ferritin at 36 weeks' gestation. Both iron doses maintained the mean hemoglobin and hematocrit within the normal level from 12 weeks to 36 weeks (p = 0.378 and p = 0.244, respectively). However, the mean serum ferritin level was higher in group II than group I (p = 0.000) at 36 weeks' gestation. Moreover, women in group II reported more side effects than group I at 36 weeks' gestation. Doubling the prophylactic iron dose is comparable to single dose in the prevention of iron deficiency anemia among women with twin gestations with more side effects.

[Review by expert group in the diagnosis and treatment of anemia in pregnant women. Federación Mexicana de Colegios de Obstetricia y Ginecología].

PubMed

Montoya Romero, Jose de Jesús; Castelazo Morales, Ernesto; Valerio Castro, Emilio; Velázquez Cornejo, Gerardo; Nava Muñoz, David Antonio; Escárcega Preciado, Jaime Arturo; Montoya Cossío, Javier; Pichardo Villalón, Guadalupe Mireya; Maldonado Aragón, Aristeo; Santana García, Héctor Rogelio; Fajardo Dueñas, Sergio; Mondragón Galindo, César Germán; García Lee, Teresa; García, Angel; Hernández de Morán, Marcela; Chávez Güitrón, Luis Eduardo; Jiménez Gutiérrez, Carlos

2012-09-01

According to data from the World Health Organization and UNICEF from year 2009, iron deficiency is the most widespread nutritional deficiency worldwide. This deficiency causes an imbalance between needs and iron supply, which consequently results in anemia. Around the world, two million people suffer from anemia, half of which is due to iron deficiency. The most impacted groups are children and teenagers, due to their highest requirements derived from the growing process, and women in their reproductive age, due to their loss of iron derived from menstruating or to their highest iron needs during pregnancy. This increase in needs is not satisfied by the regular diet, since it includes an insufficient amount and/or low bioavailability of iron. To share with the medical community treating pregnant women the experience of an expert group so that they always bear in mind the repercussions caused by anemia during pregnancy, know more about the diagnostic possibilities and have a reference point for prescribing iron supplements. The consensus method was used through the expert panel group technique. Two rounds were taken for structuring the clinical questions. The first one was to facilitate working groups their focusing in the clinical topics and the population of interest; the second one was to aid in posing specific questions observing the Patient, Intervention, Compare and Outcome (PICO) structure. The primary and clinical secondary study variables were defined by the working groups from the previously developed questions and during the face-to-face working period, according to the natural history of the disease: risk factors, diagnostic classification, (either pharmacological or non pharmacological) treatment and prognosis. The level of evidence and clinical recommendation was classified based on the Evidence Classification Level and Clinical Recommendation of the Medicine Group based on Evidence from Oxford University. In Mexico, 20.6% of pregnant women suffer from anemia, especially those between 15 and 16 years old, who prevail in 42.4% and 34.3% percent, respectively. Almost half the cases are due to iron deficiency. This type of anemia is associated with a higher risk of pre-term delivery, of low birth weight and perinatal death. The first assessment of an anemic pregnant woman shall include the medical history, a physical examination and the quantification of the erythrocyte indices, serum concentrations of iron and ferritin. The measurement of this last one has the highest sensitivity and specificity for diagnosing iron deficiency. Daily oral iron supplementation, at a 60-to-120 mg dosage, may correct most of mild-to-moderate anemias. The most appropriate treatment is with iron salts (iron sulfate, polimaltose iron complex or iron fumarate). In case of intolerance to iron sulfate or fumarate, polimaltose iron is a better tolerated option. Treatment shall be administered until the hemoglobin values are > 10.5 g and ferritin is between 300 and 360 microg/dL, and such levels shall be observed for at least one year. Parenteral administration is an alternative for patients with a severe intolerance to oral administration; even when the possibility of anaphylaxis shall be considered it is lower when using ferrous sacarate. Transfusion is reserved for patients with hemoglobin lower than 7 g/dL or having an imminent cardio-respiratory decompensation. Iron deficiency is the highest prevailing nutritional deficiency worldwide and its consequences during pregnancy may be highly risky for both the mother and her child. Anemia diagnosis may easily be achieved through a blood analysis including the serum ferritin determination. Serum iron measurement shall not be used as the only marker to set the diagnosis. It is important to rule out other causes, in addition to the deficiencies, which produce anemia in a patient. It is essential to suggest the administration of iron supplements not only during the antenatal period but also after birth o even after a miscarriage to fulfill the need for depleted iron. In severe anemias (hemoglobin being lower than 9.0 g/L), iron doses higher than 120 mg a day may be required. Treatment shall always begin orally, and if this is not well tolerated, parenteral administration shall be used.

Impact of Text Message Reminders on Caregivers’ Adherence to a Home Fortification Program Against Child Anemia in Rural Western China: A Cluster-Randomized Controlled Trial

PubMed Central

Zhou, Huan; Sun, Shuai; Sylvia, Sean; Yue, Ai; Shi, Yaojiang; Zhang, Linxiu; Medina, Alexis; Rozelle, Scott

2016-01-01

Objectives. To test whether text message reminders sent to caregivers improve the effectiveness of a home micronutrient fortification program in western China. Methods. We carried out a cluster-randomized controlled trial in 351 villages (clusters) in Shaanxi Province in 2013 and 2014, enrolling children aged 6 to 12 months. We randomly assigned each village to 1 of 3 groups: free delivery group, text messaging group, or control group. We collected information on compliance with treatments and hemoglobin concentrations from all children at baseline and 6-month follow-up. We estimated the intent-to-treat effects on compliance and child anemia using a logistic regression model. Results. There were 1393 eligible children. We found that assignment to the text messaging group led to an increase in full compliance (marginal effect = 0.10; 95% confidence interval [CI] = 0.03, 0.16) compared with the free delivery group and decrease in the rate of anemia at end line relative to the control group (marginal effect = −0.07; 95% CI = −0.12, −0.01), but not relative to the free delivery group (marginal effect = −0.03; 95% CI = −0.09, 0.03). Conclusions. Text messages improved compliance of caregivers to a home fortification program and children’s nutrition. PMID:27077354

Stem Cell Gene Therapy for Fanconi Anemia: Report from the 1st International Fanconi Anemia Gene Therapy Working Group Meeting

PubMed Central

Tolar, Jakub; Adair, Jennifer E; Antoniou, Michael; Bartholomae, Cynthia C; Becker, Pamela S; Blazar, Bruce R; Bueren, Juan; Carroll, Thomas; Cavazzana-Calvo, Marina; Clapp, D Wade; Dalgleish, Robert; Galy, Anne; Gaspar, H Bobby; Hanenberg, Helmut; Von Kalle, Christof; Kiem, Hans-Peter; Lindeman, Dirk; Naldini, Luigi; Navarro, Susana; Renella, Raffaele; Rio, Paula; Sevilla, Julián; Schmidt, Manfred; Verhoeyen, Els; Wagner, John E; Williams, David A; Thrasher, Adrian J

2011-01-01

Survival rates after allogeneic hematopoietic cell transplantation (HCT) for Fanconi anemia (FA) have increased dramatically since 2000. However, the use of autologous stem cell gene therapy, whereby the patient's own blood stem cells are modified to express the wild-type gene product, could potentially avoid the early and late complications of allogeneic HCT. Over the last decades, gene therapy has experienced a high degree of optimism interrupted by periods of diminished expectation. Optimism stems from recent examples of successful gene correction in several congenital immunodeficiencies, whereas diminished expectations come from the realization that gene therapy will not be free of side effects. The goal of the 1st International Fanconi Anemia Gene Therapy Working Group Meeting was to determine the optimal strategy for moving stem cell gene therapy into clinical trials for individuals with FA. To this end, key investigators examined vector design, transduction method, criteria for large-scale clinical-grade vector manufacture, hematopoietic cell preparation, and eligibility criteria for FA patients most likely to benefit. The report summarizes the roadmap for the development of gene therapy for FA. PMID:21540837

Impacts of anemia on 3-year ischemic events in patients undergoing percutaneous coronary intervention: a propensity-matched study.

PubMed

Wang, Xiaoyan; Qiu, Miaohan; Li, Jing; Wang, Heyang; Qi, Jing; Wang, Geng; Xu, Kai; Liu, Haiwei; Zhao, Xin; Jing, Quanmin; Li, Yi; Han, Yaling

2015-11-01

Anemia correlates with worse outcomes in patients undergoing percutaneous coronary intervention (PCI), improved anemia can improve the outcomes in patients who underwent PCI. But the influence of anemia on long-term ischemic events after PCI remains unknown. We analyzed 8,825 consecutive patients who underwent PCI at General Hospital of Shenyang Military Region and identified 581 patients with anemia. Patients (anemia vs. no anemia) were compared using a propensity score analysis to best match between groups. The main outcome of this study is 3-year ischemic events after PCI, the secondary outcome of this study is 3-year mortality and major adverse cardiac events (MACE) after PCI. Compared with nonanemic patients, anemic patients were often female (38.90% vs. 14.51%) and elder patients (66.44% vs. 34.95%). Anemic patients have lower left ventricular ejection fraction (LVEF) and creatinine clearance (Ccr) and were more likely to have history of cardiovascular and cerebrovascular diseases, hypertension, peripheral vascular diseases (PVD) (P<0.05). However, the prevalences of diabetes and hyperlipidemia were lower in anemic patients (P<0.01). Anemia was an independent predictor for 3-year ischemic events [hazard ratio (HR): 2.20, 95% confidence intervals (CI): 1.61-3.00, P<0.01], 3-year mortality (HR: 3.58, 95% CI: 1.75-7.32, P<0.01) and 3-year MACE (HR: 2.14, 95% CI: 1.64-2.79, P<0.01) after PCI in post-match samples. The incidence of 3-year ischemic events was 41.0% and 19.3% in anemic and nonanemic patients, respectively. Anemia is an independent predictor for 3-year ischemic events, 3-year mortality and 3-year MACE in patients who underwent PCI. Further studies need to explore the impact of the pathogenesis and progress, prevention and therapy of anemia on the outcome of patients undergoing PCI.

[Prevalence and risk factors for anemia in Southern Brazil].

PubMed

Neuman, N A; Tanaka, O Y; Szarfarc, S C; Guimarães, P R; Victora, C G

2000-02-01

To measure the prevalence and evaluate the risk factors of anemia. Cross sectional populational based study of the urban area of Criciuma town, in the state of Santa Catarina, Southern Brazil. The study population was a probabilistic sample of 476 children aged under three years. The prevalence of anemia found in the sample was 60.4% for children aged 0 to 35.9 months according to the Brault-Dubuc criteria and 54% for children aged 6 to 35.9 months according to the OMS criteria. The prevalence of anemia increases with age up to 18 months-old and then decreases. It is less prevalent in families where the father has a higher education level and where there is a higher total family income. Nevertheless, even within the 25% higher income group 40% of the children are anemic. The prevalence of anemia is higher among children living in unfinished and overcrowded houses, where the toilet is not equipped with flush, and among children who have two or more older brothers. It is also higher among teenager mothers (<20 years), and 35 years old or older mothers. The prevalence of anemia is lower among women who had 5 to 9 prenatal visits during pregnancy. Low weight at birth was associated with iron deficiency. The nutritional condition was associated with anemia only according to weight/age criteria. Hospitalizations in the last 12 months were not associated with the disease. In the hierarchical multivariate analysis children age, family income, and crowded house were the only significant variables. Reproductive health history, health service visits, birth weight, breast-feeding, anthropometry, and morbidity did not characterize a risk factor of anemia in the multivariate analysis. The study makes it evident that social inequality is a strong determinant of anemia. The risk imposed by anemia to children in regard to their health and intellectual development requires immediate action.

Effect of NaFeEDTA-Fortified Soy Sauce on Anemia Prevalence in China: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

PubMed

Huo, Jun Sheng; Yin, Ji Yong; Sun, Jing; Huang, Jian; Lu, Zhen Xin; Regina, Moench-Pfanner; Chen, Jun Shi; Chen, Chun Ming

2015-11-01

To assess the effect of sodium iron ethylenediaminetetraacetate (NaFeEDTA)-fortified soy sauce on anemia prevalence in the Chinese population. A systematic review was performed to identify potential studies by searching the electronic databases of PubMed, Cochrane Library, WHO Library, HighWire, CNKI, and other sources. The selection criteria included randomized controlled trials that compared the efficacy of NaFeEDTA-fortified soy sauce with that of non-fortified soy sauce. Anemia rates and hemoglobin levels were the outcomes of interest. Inclusion decisions, quality assessment, and data extraction were performed by two reviewers independently. A total of 16 studies met the inclusion criteria for anemia rate analysis, of which 12 studies met the inclusion criteria for hemoglobin analysis. All included studies assessed the effect of NaFeEDTA-fortified soy sauce on anemia rates and hemoglobin concentrations. After the intervention, the hemoglobin concentration increased and anemia rates decreased significantly as compared with the non-fortified soy sauce groups. For anemia rates, data from 16 studies could be pooled, and the pooled estimate odds ratio was 0.25 (95% CI 0.19-0.35). For hemoglobin concentrations, data from 12 studies could be pooled, and the pooled weighted mean difference was 8.81 g/L (95% CI 5.96-11.67). NaFeEDTA-fortified soy sauce has a positive effect on anemia control and prevention in the at-risk population. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Overview of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project1234

PubMed Central

Suchdev, Parminder S; Namaste, Sorrel ML; Aaron, Grant J; Raiten, Daniel J; Brown, Kenneth H; Flores-Ayala, Rafael

2016-01-01

Anemia remains a widespread public health problem. Although iron deficiency is considered the leading cause of anemia globally, the cause of anemia varies considerably by country. To achieve global targets to reduce anemia, reliable estimates of the contribution of nutritional and non-nutritional causes of anemia are needed to guide interventions. Inflammation is known to affect many biomarkers used to assess micronutrient status and can thus lead to incorrect diagnosis of individuals and to overestimation or underestimation of the prevalence of deficiency in a population. Reliable assessment of iron status is particularly needed in settings with high infectious disease burden, given the call to screen for iron deficiency to mitigate potential adverse effects of iron supplementation. To address these information gaps, in 2012 the CDC, National Institute for Child Health and Human Development, and Global Alliance for Improved Nutrition formed a collaborative research group called Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA). Data from nationally and regionally representative nutrition surveys conducted in the past 10 y that included preschool children and/or women of childbearing age were pooled. Of 25 data sets considered for inclusion, 17 were included, representing ∼30,000 preschool children, 26,000 women of reproductive age, and 21,000 school-aged children from all 6 WHO geographic regions. This article provides an overview of the BRINDA project and describes key research questions and programmatic and research implications. Findings from this project will inform global guidelines on the assessment of anemia and micronutrient status and will guide the development of a research agenda for future longitudinal studies. PMID:26980818

Elevated serum concentration of cardiotoxic lipid peroxidation products in chronic renal failure in relation to severity of renal anemia.

PubMed

Siems, W; Carluccio, F; Grune, T; Jakstadt, M; Quast, S; Hampl, H; Sommerburg, O

2002-07-01

Patients with end-stage renal disease undergoing hemodialysis (HD) are exposed to oxidative stress. Increased levels of malondialdehyde (MDA) and 4-hydroxylnonenal (HNE) were found in plasma of uremic patients indicating accelerated lipid peroxidation (LPO) as a consequence of multiple pathogenetic factors. The catabolism and action of those products was already intensively studied. As highly reactive metabolites they are able to bind to proteins, nucleic acids, and other molecules. Doing so, they exert molecular signal effects in cells and are able to exacerbate tissue and organ damage, e.g. cardiotoxic effects. Since renal anemia was shown to promote oxidative stress as well, the aim of our investigation was to examine its role in HD patients. Therefore, two groups of HD patients were investigated (group I Hb < 10 g/dl, group II Hb > 10 g/dl) and serum concentrations of MDA, HNE, and of protein carbonyls, a marker for protein oxidation, were determined. All HD patients had significantly higher levels of the LPO products MDA and HNE compared with controls. However, group I patients showed higher MDA and HNE concentrations compared to group II patients. The same result could be seen for protein carbonyls. During HD concentration of both LPO products decreased. However, this was not the case for protein carbonyls. These results lead to the conclusion that optimized correction of the renal anemia may result in a significant reduction of oxidative stress and therefore in the reduction of organ tissue damage. In this way correction of renal anemia will reduce the cardiovascular risk and comorbidity of HD patients improving their prognosis.

Dietary Quercetin Reduces Chemotherapy-Induced Fatigue in Mice

PubMed Central

Mahoney, Sara E.; Davis, J. Mark; Murphy, E. Angela; McClellan, Jamie L.; Pena, Marjory M.

2014-01-01

Purpose While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia. Methods Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days −2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia. Results Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001). Conclusion These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia. PMID:24626097

First-Line Matched Related Donor Hematopoietic Stem Cell Transplantation Compared to Immunosuppressive Therapy in Acquired Severe Aplastic Anemia

PubMed Central

Peinemann, Frank; Grouven, Ulrich; Kröger, Nicolaus; Bartel, Carmen; Pittler, Max H.; Lange, Stefan

2011-01-01

Introduction Acquired severe aplastic anemia (SAA) is a rare and progressive disease characterized by an immune-mediated functional impairment of hematopoietic stem cells. Transplantation of these cells is a first-line treatment option if HLA-matched related donors are available. First-line immunosuppressive therapy may be offered as alternative. The aim was to compare the outcome of these patients in controlled trials. Methods A systematic search was performed in the bibliographic databases MEDLINE, EMBASE, and The Cochrane Library. To show an overview of various outcomes by treatment group we conducted a meta-analysis on overall survival. We evaluated whether studies reported statistically significant factors for improved survival. Results 26 non-randomized controlled trials (7,955 patients enrolled from 1970 to 2001) were identified. We did not identify any RCTs. Risk of bias was high except in 4 studies. Young age and recent year of treatment were identified as factors for improved survival in the HSCT group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the IST group. In 19 studies (4,855 patients), summary statistics were sufficient to be included in meta-analysis. Considerable heterogeneity did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. Conclusions Young age and recent year of treatment were identified as factors for improved survival in the transplant group. Advanced age, SAA without very severe aplastic anemia, and combination of anti-lymphocyte globulin with cyclosporine A were factors for improved survival in the immunosuppressive group. Considerable heterogeneity of non-randomized controlled studies did not justify a pooled estimate. Adverse events were inconsistently reported and varied significantly across studies. PMID:21541024

Transient hemolysis due to anti-D and anti-A1 produced by engrafted donor's lymphocytes after allogeneic unmanipulated haploidentical hematopoietic stem cell transplantation.

PubMed

Bailén, Rebeca; Kwon, Mi; Pérez-Corral, Ana María; Pascual, Cristina; Buño, Ismael; Balsalobre, Pascual; Serrano, David; Gayoso, Jorge; Díez-Martín, José Luis; Anguita, Javier

2017-10-01

Development of de novo alloantibodies against recipient's red blood cell (RBC) antigens by engrafted donor's lymphocytes is a known phenomenon in the setting of allogeneic hematopoietic stem cell transplantation (HSCT). This situation is usually clinically insignificant. We report a case of early clinically relevant hemolytic anemia in a blood group A 1 D+ patient, due to a limited production of anti-D and anti-A 1 produced by nonpreviously sensitized newly engrafted donor's immune system. A 31-year-old Caucasian woman, blood group A 1 , D+, with Hodgkin's lymphoma, received an unmanipulated haploidentical allogeneic peripheral blood HSCT after a nonmyeloablative conditioning regimen. Donor blood group was A 2 B, D-. The patient had an uneventful course until Day +34, when she developed clinically significant hemolytic anemia with a positive direct antiglobulin test. Anti-D and anti-A 1 produced by the donor-engrafted lymphocytes were detected both in serum and in eluate. The hemolysis produced an accelerated group change, turning the patient's ABO group into A 2 B 2 weeks after the detection of the alloantibodies. As the residual patient's RBCs progressively disappeared, anti-D and anti-A 1 production decreased and were not detected in serum by Day +41. This case illustrates that de novo alloantibody production against ABO and D antigens by the newly engrafted donor's lymphocytes can occasionally cause clinically significant anemia. To our knowledge, this is the first case reported of clinically significant hemolytic anemia due to a transient anti-D anti-A 1 alloimmunization after T-cell-repleted haploidentical HSCT. © 2017 AABB.

Prevalence of anemia among under-5 children in the Ghanaian population: estimates from the Ghana demographic and health survey

PubMed Central

2014-01-01

Background Anemia in children continues to be a major public health challenge in most developing countries, particularly in Africa. Anemia in the early stages of life leads to severe negative consequences on the cognitive as well as the growth and development of children, which may persist even after treatment. We examine the prevalence of anemia in under-five children in the Ghanaian population to help inform and serve as a guide to health policies and possible interventions. Methods Data from the 2008 Ghana Demographic and Health Survey (GDHS) was used. Data consists of health, demographic and socio-economic factors. Anemia status was determined using hemoglobin level, and prevalence of childhood anemia along with 95% confidence intervals was provided. We also examined the distribution of prevalence across different age and socio-demographic groups as well as the different regions and sub-regions in Ghana. Results The overall prevalence of anemia in under-five children in Ghana was 78.4% (N = 2168, 95% CI: 76.7-80.2), where 7.8% (N = 2168, 95% CI: 6.6-8.9) of the children had severe anemia, 48.0% (N = 2168, 95% CI: 45.9-50.2) moderate anemia and 22.6% (N = 2168, 95% CI: 20.8-24.4) had mild anemia. The highest prevalence regions were the Upper East, 88.9% (N = 158, 95% CI: 80.9-94.0), and Upper West 88.1% (N = 220, 95% CI: 76.4-94.6). The prevalence was also higher among children under 2 years of age, 85.1% (N = 781, 95% CI: 82.6-87.7) than children 2–5 years of age, 74.8% (N = 1387, 95% CI: 72.5-77.1). No significant difference in prevalence between boys and girls was observed. Conclusions Given the high prevalence of childhood anemia observed in Ghana, particularly among those less than 2 years old, and given the negative consequences on their cognitive and behavioral development even in later years, there is an urgent need for effective and efficient public health interventions. PMID:24946725

Prevalence of anemia among under-5 children in the Ghanaian population: estimates from the Ghana demographic and health survey.

PubMed

Ewusie, Joycelyne E; Ahiadeke, Clement; Beyene, Joseph; Hamid, Jemila S

2014-06-19

Anemia in children continues to be a major public health challenge in most developing countries, particularly in Africa. Anemia in the early stages of life leads to severe negative consequences on the cognitive as well as the growth and development of children, which may persist even after treatment. We examine the prevalence of anemia in under-five children in the Ghanaian population to help inform and serve as a guide to health policies and possible interventions. Data from the 2008 Ghana Demographic and Health Survey (GDHS) was used. Data consists of health, demographic and socio-economic factors. Anemia status was determined using hemoglobin level, and prevalence of childhood anemia along with 95% confidence intervals was provided. We also examined the distribution of prevalence across different age and socio-demographic groups as well as the different regions and sub-regions in Ghana. The overall prevalence of anemia in under-five children in Ghana was 78.4% (N = 2168, 95% CI: 76.7-80.2), where 7.8% (N = 2168, 95% CI: 6.6-8.9) of the children had severe anemia, 48.0% (N = 2168, 95% CI: 45.9-50.2) moderate anemia and 22.6% (N = 2168, 95% CI: 20.8-24.4) had mild anemia. The highest prevalence regions were the Upper East, 88.9% (N = 158, 95% CI: 80.9-94.0), and Upper West 88.1% (N = 220, 95% CI: 76.4-94.6). The prevalence was also higher among children under 2 years of age, 85.1% (N = 781, 95% CI: 82.6-87.7) than children 2-5 years of age, 74.8% (N = 1387, 95% CI: 72.5-77.1). No significant difference in prevalence between boys and girls was observed. Given the high prevalence of childhood anemia observed in Ghana, particularly among those less than 2 years old, and given the negative consequences on their cognitive and behavioral development even in later years, there is an urgent need for effective and efficient public health interventions.

E-ADA activity in erythrocytes of lambs experimentally infected with Haemonchus contortus and its possible functional correlations with anemia.

PubMed

Da Silva, Aleksandro S; Schafer, Andressa S; Aires, Adelina R; Tonin, Alexandre A; Pimentel, Victor C; Oliveira, Camila B; Zanini, Daniela; Schetinger, Maria R C; Lopes, Sonia T A; Leal, Marta L R

2013-12-01

The aim of this study was to evaluate the ecto-adenosine deaminase (E-ADA) activity in erythrocytes of lambs experimentally infected with Haemonchus contortus, correlating it with the degrees of anemia of the experimental animals. A total of 14 healthy lambs, with negative fecal exam for parasites, were to carry out the present study. They were divided into two groups, composed by seven animals: Group A represented the healthy animals (uninfected), while in Group B the animals were infected with 15,000 larvae of H. contortus. Blood was drawn on the days 15, 45 and 75 post-infection (PI) in order to perform the hematological analysis, as well as the mensuration of E-ADA activity in erythrocytes. Parasitological stool exam were performed on the same days mentioned above to follow up the evolution of the infection, as well to determine the number of eggs per gram of feces (EPG). On day 15PI, the animals presented negative EPG and there was not significant (P>0.05) difference between groups in relation to E-ADA activity and hematologic parameters. Animals in Group B had positive EPG for helminths on days 45 and 75 PI, accompanied by varying degrees of anemia, when compared to Group A. At the same periods E-ADA activity was significantly (P<0.05) increased in the erythrocytes of animals of Group B when compared with the not-infected ones. Statistically, there was a negative correlation (P<0.01) between activity E-ADA in erythrocytes and hematocrit on days 45 (r = -0.76) and 75 (r = -0.85)PI. Based on these results and in the scientific literature, it is possible to conclude that the E-ADA may participate on mechanisms related with the pathogenesis and host response against anemia caused by H. contortus. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Iron nutrition in Mapuche infants fed with human milk (2d phase)].

PubMed

Franco, E; Hertrampf, E; Rodríguez, E; Illanes, J C; Palacios, L; Llaguno, S; Lettelier, A

1990-01-01

Blood hemoglobin, serum iron, total iron binding capacity (TIBC) and serum ferritin were measured in 140 healthy rural mapuche (southern Chile's indigenous ethnic group) infants aged 8 to 15 months: 90 had been exclusively breast fed for the first 5 or 6 months of life, then solid foods were introduced but cow's milk was never given to them. The remaining 50, which were all weaned at nearly 4 months of age and then given cow's milk and solid foods at the corresponding age, were designated as controls. Anemia was detected in 4.5% of breast fed infants and in 38% of controls. Evidence of iron deficient erythropoiesis was found in 5% and 81% of cases and controls, respectively. Human milk apparently protects this ethnic group from iron deficiency anemia and this protection seems to be better in mapuche infants than in other groups of chilean infants, because these late have shown 30% incidence of anemia around the first year of life in other studies. More studies on differences in iron nutritional state among mapuche and non mapuche are needed and are under way.

Effect of counseling on nutritional status during pregnancy.

PubMed

Garg, Aashima; Kashyap, Sushma

2006-08-01

To assess the nutritional status and dietary practices among underprivileged pregnant women, identify the lacune, outline implement and assess the effect of nutritional counseling on their dietary intake, anthropometric status and anemia status. Hundred pregnant women belonging to low socio-economic status were interviewed. Based on lacune, nutrition education (NE) was given in the form of simple messages to 50 subjects (NE-group) over 10-16 weeks period, while the remaining 50 formed the comparison group (Non-NE group). Tools used were individual counseling, weekly home visits and group meetings. Anthropometric measurements taken were height and weight. Dietary data was collected using 24-hour recall and food frequency questionnaire. Hemoglobin estimation was done. Effect of intervention was assessed by monitoring changes in dietary practices, weight gain, and nutritional status of the subjects. Baseline findings--low mean maternal body weight (51.05 +/- 7.26 kg), 96.3% anemia prevalence and severely sub-optimal dietary intakes. Post-NE results revealed a significant increase in quality and quantity of the diets consumed. Mean hemoglobin levels significantly increased (Post-NE vs Non-NE = 9.65 +/- 0.97 vs 7.85 +/- 1.58, p < 0.001) and anemia prevalence reduced (Post-NE vs Non-NE = 78.7% vs 96%) in post-NE group. Individual counseling with weekly reinforcement can bring about improvement in nutritional status during pregnancy.

Influence of artistic gymnastics on iron nutritional status and exercise-induced hemolysis in female athletes.

PubMed

Sureira, Thaiz Mattos; Amancio, Olga Silverio; Pellegrini Braga, Josefina Aparecida

2012-08-01

This study evaluates the relationship between body iron losses and gains in artistic gymnastics female athletes. It shows that despite the low iron intake and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does not occur, but partial changes in the hematological profile do. The hypothesis that gymnasts' nutritional behavior contributes to anemia, which may be aggravated by exercise-induced hemolysis, led to this cross-sectional study, conducted with 43 female artistic gymnasts 6-16 yr old. The control group was formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin, soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I urine, and parasitologic and occult fecal blood tests were evaluated. The athletes presented mean hematimetric and serum iron values (p = .020) higher than those of the control group. The bilirubin result discarded any hemolytic alteration in both groups. The haptoglobin results were lower in the athlete group (p = .002), confirming the incidence of exercise-induced hemolysis. Both groups presented low iron intake. The results suggest that artistic gymnastics practice leads to exercise-induced hemolysis and partially changes the hematological profile, although not causing iron deficiency or iron-deficiency anemia, even in the presence of low iron intake.

Survival of rats subjected to acute anemia at different levels of erythrocyte 2,3-diphosphoglycerate.

PubMed

Arturson, G; Westman, M

1975-12-01

An experimental procedure was worked out in which rats were subjected to an exchange of erythrocytes, followed by acute anemia by means of hemodilution. One group of rats received erythrocytes with a high concentration of 2,3-diphosphoglycerate (DPG), and the other group was given erythrocytes with a low DPG concentration. The survival rate was equal in the two groups. Irrespective of DPG concentration, the rats whose hemoglobin concentration reached the lowest level died. The rats that died were also more acidotic than the others. The results indicate that the hemoglobin concentration and the pH value were more important determinants for survival than the DPG concentrations.

Determinants of anemia among young children in rural India.

PubMed

Pasricha, Sant-Rayn; Black, James; Muthayya, Sumithra; Shet, Anita; Bhat, Vijay; Nagaraj, Savitha; Prashanth, N S; Sudarshan, H; Biggs, Beverley-Ann; Shet, Arun S

2010-07-01

More than 75% of Indian toddlers are anemic. Data on factors associated with anemia in India are limited. The objective of this study was to determine biological, nutritional, and socioeconomic risk factors for anemia in this vulnerable age group. We conducted a cross-sectional study of children aged 12 to 23 months in 2 rural districts of Karnataka, India. Children were excluded if they were unwell or had received a blood transfusion. Hemoglobin, ferritin, folate, vitamin B(12), retinol-binding protein, and C-reactive protein (CRP) levels were determined. Children were also tested for hemoglobinopathy, malaria infection, and hookworm infestation. Anthropometric measurements, nutritional intake, family wealth, and food security were recorded. In addition, maternal hemoglobin level was measured. Anemia (hemoglobin level < 11.0 g/dL) was detected in 75.3% of the 401 children sampled. Anemia was associated with iron deficiency (low ferritin level), maternal anemia, and food insecurity. Children's ferritin levels were directly associated with their iron intake and CRP levels and with maternal hemoglobin level and inversely associated with continued breastfeeding and the child's energy intake. A multivariate model for the child's hemoglobin level revealed associations with log(ferritin level) (coefficient: 1.20; P < .001), folate level (0.05; P < .01), maternal hemoglobin level (0.16; P < .001), family wealth index (0.02; P < .05), child's age (0.05 per month; P < .005), hemoglobinopathy (-1.51; P < .001), CRP level (-0.18; P < .001), and male gender (-0.38; P < .05). Wealth index and food insecurity could be interchanged in this model. Hemoglobin level was primarily associated with iron status in these Indian toddlers; however, maternal hemoglobin level, family wealth, and food insecurity were also important factors. Strategies for minimizing childhood anemia must include optimized iron intake but should simultaneously address maternal anemia, poverty, and food insecurity.

Epidemiology of aplastic anemia: a prospective multicenter study.

PubMed

Montané, Eva; Ibáñez, Luisa; Vidal, Xavier; Ballarín, Elena; Puig, Ramon; García, Nuria; Laporte, Joan-Ramon

2008-04-01

Aplastic anemia is a rare and severe disease. Its incidence varies considerably worldwide. We aimed at describing the epidemiology of this disease, including the incidence, mortality and survival trends, in a well-defined population. Since 1980, a case-control surveillance study of aplastic anemia has been carried out by a cooperative group, in the metropolitan area of Barcelona. Inclusion is dependent on the patient having at least two of the following features: white blood cell count < or = 3.5 x 10(9)/L, platelet count < or = 50 x 10(9)/L, hemoglobin <10 g/L or hematocrit of <30%; when only one of these last two criteria is fulfilled, a reticulocyte count of < or = 30 x 10(9)/L is also required. The bone marrow biopsy has to be compatible with the diagnosis of aplastic anemia. Between 1980 and 2003, a total of 235 cases of aplastic anemia were identified. The overall incidence was 2.34 per million inhabitants per year and the incidence increased with age. Most of the cases were classified as severe or very severe aplastic anemia. Survival rates at 3 months, and at 2 and 15 years after the diagnosis were 73%, 57%, and 51%, respectively. Advanced age and more severe disease at the time of diagnosis were associated with a lower survival rate. There was a trend to a better 2-year survival rate among patients treated with bone marrow transplantation. Forty-nine cases (20.8%) were exposed to drugs reported to be associated with aplastic anemia, and 21 (8.9%) to toxic agents. The incidence of aplastic anemia in Barcelona is low but the case fatality rate is high. Advanced age and severe disease at the time of diagnosis were associated with decreased survival.

[EFFICIENCY OF HAEMOGLOBIN REGENERATION IN THE NUTRITIONAL FERROPENIC ANAEMIA RECOVERY WITH GOAT MILK-BASED DIETS].

PubMed

Serrano Reina, José Antonio; Nestares Pleguezuelo, Teresa; Muñoz Alférez, Ma José; Díaz Castro, Javier; López Aliaga, Ma Inmaculada

2015-10-01

in spite of the high incidence/prevalence of iron deficiency anemia (IDA) and the beneficial effects derived from the consumption of goat milk, scarce is known about the recovery of the anemia following a balanced diet accompanied by the intake of goat milk of goat. The aim of the current study is to assess, in rats with experimentally induced nutritional iron deficiency anemia, the effects of goat or cow milk-based diets, supplied during 30 days, on the recovery of the anemia and the efficiency of regeneration of the hemoglobin. 40 male Wistar albino rats newly weaned were divided at random in two experimental groups and they were fed ad libitum for 40 days with AIN-93G diet, either with normal iron content (control group, 45 mg/kg diet), or low iron content (anaemic group, 5 mg/kg diet). Samples of blood form the caudal vein were collected for the hematologic control of the anemia. Later, both experimental groups (control and iron deficient) were fed for 30 days with goat or cow milk- based diets. After finishing the experimental period and previous anesthesia the animals were withdrawn by canulation of the abdominal aorta, and the obtained blood was gathered in tubes with EDTA as anticoagulant for the later determination of hematologic parameters and the efficiency of regeneration of the hemoglobin. after the consumption of a diet with low iron content during 40 days, the rats were anaemic, with a concentration of hemoglobin, hematocrit, serum iron, mean corpuscular volume (MCV), serum ferritin and low transferrin (p < 0.001), whereas the levels of platelets and the total iron binding capacity (TIBC) were raised (p < 0.001), findings consistent with the anemia induced experimentally in the animals. The efficiency of regeneration of the hemoglobin was higher in control and anaemic rats fed goat milk-based diet in comparison with those fed cow milk-based diet (p < 0.001) due to, partly, to the major levels of serum iron and hemoglobin, and to the best nutritive utilization of iron in the animals that consumed the goat milk-based diet thanks to the excellent nutritional characteristics of this type of milk. the consumption during 30 days of goat or cow milk-based diets favors the recovery of the iron deficiency anemia, especially with the goat milk, due to the major efficiency of regeneration of the hemoglobin, index that shows the quantity of iron of the diet used for the synthesis of hemoglobin. Therefore, it would be recommendable the consumption of goat milk in the context of a balanced diet in healthy populations and, especially in those at risk of suffering iron deficiency. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Protective environment for marrow transplant recipients. A prospective study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buckner, C.D.; Clift, R.A.; Sanders, J.E.

1978-12-01

Laminar air flow isolation and decontamination procedures were evaluated in a prospective randomized study in patients with aplastic anemia or acute leukemia undergoing marrow transplantation from HLA-matched siblings. Patients transplanted in the laminar air flow group had significantly less septicemia and major local infections than did patients in the control group. Nineteen of 46 laminar air flow patients and six of 44 control patients are alive at present. In patients with aplastic anemia the survival was 13 of 17 in the laminar air flow group compared with four of 17 in the control group. In patients with acute leukemia themore » survival was six of 29 in the laminar air flow group versus two of 27 in the control group. These differences were not statistically significant. Death in both the laminar air flow and control groups was predominantly due to interstitial pneumonitis or recurrent leukemia, which were unaffected by isolation and decontamination.« less

The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder.

PubMed

Walden, Helen; Deans, Andrew J

2014-01-01

Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.

Hematinic deficiencies and anemia statuses in antigastric parietal cell antibody-positive erosive oral lichen planus patients with desquamative gingivitis.

PubMed

Chang, Julia Yu-Fong; Wang, Yi-Ping; Wu, Yang-Che; Wu, Yu-Hsueh; Tseng, Chih-Huang; Sun, Andy

2016-10-01

Erosive oral lichen planus (EOLP) patients with desquamative gingivitis (DG) are sometimes encountered in our oral mucosal disease clinic. This study assessed hematinic deficiencies and anemia statuses in antigastric parietal cell antibody (GPCA)-positive EOLP patients with DG (GPCA + /DG + /EOLP patients). The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations and serum GPCA levels in 92 GPCA + /DG + /EOLP patients and 184 age- and sex-matched healthy controls were measured and compared between the two groups. We found that 27 (29.3%), 16 (17.4%), and 27 (29.3%) of 92 GPCA + /DG + /EOLP patients had hemoglobin (men < 13 g/dL and women < 12 g/dL), iron (< 60 μg/dL), and vitamin B12 (< 200 pg/mL) deficiencies, respectively. Moreover, 37 (40.2%) of 92 GPCA + /DG + /EOLP patients had an abnormally high blood homocysteine level (> 12.1μM). GPCA + /DG + /EOLP patients had a significantly higher frequency of hemoglobin, iron, or vitamin B12 deficiency and an abnormally high blood homocysteine level than healthy control individuals (all p < 0.001). Of 27 anemic GPCA + /DG + /EOLP patients, 13 (48.2%) had pernicious anemia, five (18.5%) had iron deficiency anemia, one (3.7%) had thalassemia trait, and the remaining eight (29.6%) had normocytic anemia. Moreover, of the 92 GPCA + /DG + /EOLP patients, 24 had macrocytosis, and only 13 (54.2%) of these 24 patients had pernicious anemia. We conclude that GPCA + /DG + /EOLP patients may have vitamin B12 deficiency, iron deficiency, and an abnormally high blood homocysteine level. In addition to pernicious anemia, GPCA + /DG + /EOLP patients may sometimes have normocytic anemia or iron deficiency anemia. Copyright © 2016. Published by Elsevier B.V.

[Oral vitamin B12: Efficacy and safety data in 31 patients with pernicious anemia and food-cobalamin malabsorption].

PubMed

Troilo, Arianna; Mecili, Mustapha; Ciobanu, Ecaterina; Boddi, Vieri; D'Elios, Mario M; Andrès, Emmanuel

2010-12-01

The aim of this study is to validate the efficacy and safety of oral cobalamin therapy in the treatment of cobalamin deficiency related to various causes. It's a retrospective study, including 31 patients with documented cobalamin deficiency related to food-cobalamin malabsorption (n=20) and pernicious anemia (n=11). These patients were treated at least for 3 months with oral cyanocobalamin, between 125 to 1000microg per day. Serum cobalamin levels and hematological parameters were compared before and after the therapy and in relation with the nature of cobalamin deficiency. Safety data were also recorded. After 3 months of therapy, the serum cobalamin levels have significantly increased in all the patients, with a mean of +161.6±79.3pg/mL in the food-cobalamin malabsorption group (P<0,00005) and +136.7±67.4pg/mL in the pernicious anemia group (P<0,0001). Hematological parameters have been normalized in 90 % of the patients, independently of the cause of the cobalamin deficiency. Only 1 patient presented an urticarial reaction. This study confirms the efficacy and safety of oral cobalamin therapy in food-cobalamin malabsorption and also in case of pernicious anemia. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Indole 3-acetic acid, indoxyl sulfate and paracresyl-sulfate do not influence anemia parameters in hemodialysis patients.

PubMed

Bataille, Stanislas; Pelletier, Marion; Sallée, Marion; Berland, Yvon; McKay, Nathalie; Duval, Ariane; Gentile, Stéphanie; Mouelhi, Yosra; Brunet, Philippe; Burtey, Stéphane

2017-07-26

The main reason for anemia in renal failure patients is the insufficient erythropoietin production by the kidneys. Beside erythropoietin deficiency, in vitro studies have incriminated uremic toxins in the pathophysiology of anemia but clinical data are sparse. In order to assess if indole 3-acetic acid (IAA), indoxyl sulfate (IS), and paracresyl sulfate (PCS) -three protein bound uremic toxins- are clinically implicated in end-stage renal disease anemia we studied the correlation between IAA, IS and PCS plasmatic concentrations with hemoglobin and Erythropoietin Stimulating Agents (ESA) use in hemodialysis patients. Between June and July 2014, we conducted an observational cross sectional study in two hemodialysis center. Three statistical approaches were conducted. First, we compared patients treated with ESA and those not treated. Second, we performed linear regression models between IAA, IS, and PCS plasma concentrations and hemoglobin, the ESA dose over hemoglobin ratio (ESA/Hemoglobin) or the ESA resistance index (ERI). Third, we used a polytomous logistic regression model to compare groups of patients with no/low/high ESA dose and low/high hemoglobin statuses. Overall, 240 patients were included in the study. Mean age ± SD was 67.6 ± 16.0 years, 55.4% were men and 42.5% had diabetes mellitus. When compared with ESA treated patients, patients with no ESA had higher hemoglobin (mean 11.4 ± 1.1 versus 10.6 ± 1.2 g/dL; p <0.001), higher transferrin saturation (TSAT, 31.1 ± 16.3% versus 23.1 ± 11.5%; p < 0.001), less frequently an IV iron prescription (52.1 versus 65.7%, p = 0.04) and were more frequently treated with hemodiafiltration (53.5 versus 36.7%). In univariate analysis, IAA, IS or PCS plasma concentrations did not differ between the two groups. In the linear model, IAA plasma concentration was not associated with hemoglobin, but was negatively associated with ESA/Hb (p = 0.02; R = 0.18) and with the ERI (p = 0.03; R = 0.17). IS was associated with none of the three anemia parameters. PCS was positively associated with hemoglobin (p = 0.03; R = 0.14), but negatively with ESA/Hb (p = 0.03; R = 0.17) and the ERI (p = 0.02; R = 0.19). In multivariate analysis, the association of IAA concentration with ESA/Hb or ERI was not statistically significant, neither was the association of PCS with ESA/Hb or ERI. Identically, in the subgroup of 76 patients with no inflammation (CRP <5 mg/L) and no iron deficiency (TSAT >20%) linear regression between IAA, IS or PCS and any anemia parameter did not reach significance. In the third model, univariate analysis showed no intergroup significant differences for IAA and IS. Regarding PCS, the Low Hb/High ESA group had lower concentrations. However, when we compared PCS with the other significant characteristics of the five groups to the Low Hb/high ESA (our reference group), the polytomous logistic regression model didn't show any significant difference for PCS. In our study, using three different statistical models, we were unable to show any correlation between IAA, IS and PCS plasmatic concentrations and any anemia parameter in hemodialysis patients. Indolic uremic toxins and PCS have no or a very low effect on anemia parameters.

Relation between Depressive Disorder and Iron Deficiency Anemia among Adults Reporting to a Secondary Healthcare Facility: A Hospital-Based Case Control Study.

PubMed

Shafi, Madiha; Taufiq, Fatima; Mehmood, Humaira; Afsar, Saeed; Badar, Ammarah

2018-06-01

To determine the relationship between iron deficiency anemia and depressive disorder; and identify the correlation between severity of anemia and depressive disorder. Descriptive, analytical study. Department of Psychiatry and Medical Reception Center, Sindh Rangers Hospital, Karachi (a secondaryhealthcare facility), from January to July 2017. Depressive disorder was diagnosed by psychiatrist on ICD 10 criteria and severity of symptoms was assessed on HAM-D rating scale. Hundred cases and equal number of age and gender matched controls were enrolled in the study. A semi-structured proforma was used for documenting the socio-demographic factors and outcome variables. Blood samples were taken for Hemoglobin (Hb) level and peripheral film from both groups. Median Hb levels were 11.9 (IQR=1.27)) for depressed patients versus 12.9 (IQR=1.3) for healthy participants. Significant difference between Hb levels of two groups was found (p<0.001), i.e. depressed participants were found to have higher frequency of anemia (73%) as compared to non depressed participants (16%, p=0.001). Spearman rank correlation coefficient for Hb level and depression was -0.429 (p<0.01), showing significant negative correlation. The odds for Hb level were 0.487 (0.37-0.64), which showed that cases are less likely to be found with higher Hb levels as compared to controls (p<0.001). This study concludes that there is relationship between iron deficiency anemia and depressive disorder; and severity of symptoms of DD increases with degree of IDA.

Long-term and stable correction of uremic anemia by intramuscular injection of plasmids containing hypoxia-regulated system of erythropoietin expression

PubMed Central

Wang, Yarong; Du, Dewei; Li, Zhanting; Wei, Junxia; Yang, Angang

2012-01-01

Relative deficiency in production of glycoprotein hormone erythropoietin (Epo) is a major cause of renal anemia. This study planned to investigate whether the hypoxia-regulated system of Epo expression, constructed by fusing Epo gene to the chimeric phosphoglycerate kinase (PGK) hypoxia response elements (HRE) in combination with cytomegalovirus immediate-early (CMV IE) basal gene promoter and delivered by plasmid intramuscular injection, might provide a long-term physiologically regulated Epo secretion expression to correct the anemia in adenine-induced uremic rats. Plasmid vectors (pHRE-Epo) were synthesized by fusing human Epo cDNA to the HRE/CMV promoter. Hypoxia-inducible activity of this promoter was evaluated first in vitro and then in vivo in healthy and uremic rats (n = 30 per group). The vectors (pCMV-Epo) in which Epo expression was directed by a constitutive CMV gene promoter served as control. ANOVA and Student's t-test were used to analyze between-group differences. A high-level expression of Epo was induced by hypoxia in vitro and in vivo. Though both pHRE-Epo and pCMV-Epo corrected anemia, the hematocrit of the pCMV-Epo-treated rats exceeded the normal (P < 0.05), but that of the pHRE-Epo-treated rats didn't. Hypoxia-regulated system of Epo gene expression constructed by fusing Epo to the HRE/CMV promoter and delivered by plasmid intramuscular injection may provide a long-term and stable Epo expression and secretion in vivo to correct the anemia in adenine-induced uremic rats. PMID:22990115

IgG red blood cell autoantibodies in autoimmune hemolytic anemia bind to epitopes on red blood cell membrane band 3 glycoprotein

DOE Office of Scientific and Technical Information (OSTI.GOV)

Victoria, E.J.; Pierce, S.W.; Branks, M.J.

1990-01-01

Red blood cell (RBC) autoantibodies from patients with IgG warm-type autoimmune hemolytic anemia were labeled with iodine 125 and their RBC binding behavior characterized. Epitope-bearing RBC membrane polypeptides were identified after autoantibody immunoprecipitation of labeled membranes and immunoblotting. Immunoaffinity isolation of labeled membrane proteins with 12 different IgG hemolytic autoantibodies with protein A-agarose revealed a major polypeptide at Mr 95 to 110 kd, which coelectrophoresed on sodium dodecylsulfate-polyacrylamide gel electrophoresis with a membrane component isolated with sheep IgG anti-band 3. Immunoprecipitation studies with chymotrypsinized RBCs resulted in the recovery of two labeled membrane polypeptides with molecular weights characteristically resulting frommore » the chymotryptic fragmentation of band 3. Immunoblotting with sheep IgG anti-band 3 of the immunoprecipitated polypeptides confirmed that hemolytic autoantibody binding led to recovery of band 3 or its fragments. Two 125I-labeled IgG hemolytic autoantibodies showed binding behavior consistent with epitope localization on band 3. The labeled RBC autoantibodies bound immunospecifically to all types of human RBC tested, including those of rare Rh type (Rh-null, D--) at a site density of approximately 10(6) per RBC. The 125I-IgG in two labeled autoantibodies was 84% and 92% adsorbable by human and higher nonhuman primate RBCs. Antigen-negative animal RBC bound less than 10%, consistent with immunospecific RBC binding. IgG-1 was the major subclass in five autoantibodies tested; one of six fixed complement; and autoantibody IgG appeared polyclonal by isoelectric focusing. We conclude that IgG eluted from RBCs of patients with autoimmune hemolytic anemia consists predominantly of a single totally RBC-adsorbable antibody population that binds to antigenic determinants on band 3.« less

Live-born diploid fetus complicated with partial molar pregnancy presenting with pre-eclampsia, maternal anemia, and seemingly huge placenta: A rare case of confined placental mosaicism and literature review.

PubMed

Kawasaki, Kaoru; Kondoh, Eiji; Minamiguchi, Sachiko; Matsuda, Fumihiko; Higasa, Koichiro; Fujita, Kohei; Mogami, Haruta; Chigusa, Yoshitsugu; Konishi, Ikuo

2016-08-01

A partial molar pregnancy almost always ends in miscarriage due to a triploid fetus. We describe a rare case of a singleton, partial molar pregnancy with a seemingly huge placenta, which continued to delivery of a live-born diploid baby. A 27-year-old primigravida suffered from severe pre-eclampsia and progressive anemia. The uterus was enormously enlarged for the gestational age. A cesarean section was performed because of deterioration of maternal status at 25 weeks' gestation, when more than 3000 mL blood spouted concurrently with the delivery of the placenta. The histological examination showed congestion in the decidua, which indicated disturbance of maternal venous return from the intervillous space. The chromosome complement of the placenta and the neonate were 69,XXX and 46,XX, respectively. We also reviewed all published cases of a singleton, partial molar pregnancy. A literature search yielded 18 cases of a singleton, diploid fetus with partial molar pregnancy. The mean gestational age at delivery was 24.5 ± 6.2 weeks, and fetuses survived outside the uterus in only four cases (22.2%). Intriguingly, previous reports numbered 10 cases with diploid placenta as well as five cases with no karyotyping of the placenta, indicating that they may have included a complete mole in a twin pregnancy or placental mesenchymal dysplasia. In conclusion, this was the first case of placentomegaly that presented manifestations of excessive abdominal distension and maternal severe anemia, and the second case of a singleton, partial molar pregnancy confirmed by chromosome analysis resulting in a diploid living baby. © 2016 Japan Society of Obstetrics and Gynecology.

Iron Therapy Challenges for the Treatment of Nondialysis CKD Patients

PubMed Central

Mazzaferro, Sandro; Yee, Jerry

2016-01-01

The clinical consequences of untreated, severe anemia in patients with nondialysis CKD can be significant, but disparities exist in the anemia treatment guidelines and position papers issued from working groups and associations across the world. These differ in hemoglobin target and iron levels and their emphasis on various iron markers and other clinical outcomes. Not surprisingly, disparities are observed in anemia treatment strategies among patients with nondialysis CKD across different areas of the world. Over the past decade, the prescription and dosage of both iron therapies and erythropoiesis-stimulating agents have shifted, with notable regional differences observed. Moreover, there is ongoing debate regarding oral versus intravenous administration of iron. Compared with oral iron therapy, which often leads to gastrointestinal adverse events, low patient adherence, and low efficacy, intravenous iron administration has been associated with potential serious adverse events, such as anaphylaxis. New iron–based compounds and drugs currently under development are reviewed to describe their potential benefits in the treatment of anemia in patients with CKD. New oral compounds, including iron–based phosphate binders, heme iron polypeptide, and liposomal iron, show different rates of absorption with possibly different efficacy and improved tolerability. These new potential therapies offer health care providers additional anemia treatment options for their patients with CKD; however, the management of anemia in the CKD population continues to present challenges that require prospective studies to identify the optimal iron therapy for patients. PMID:27185524

[Anemia in public school first graders in the city of Maceió, Alagoas, Brazil].

PubMed

Santos, Célia Dias dos; Santos, Leonor Maria Pacheco; Figueiroa, José Natal; Marroquim, Pajuçara Maria Guimarães; Oliveira, Maria Alice Araújo

2002-01-01

A cross-sectional study was conducted in a representative sample of 426 randomly selected first graders (ages 6 to 10 years) from public schools in Maceió, State of Alagoas, Brazil. The aim was to determine the prevalence of anemia, as well as its association with growth retardation. Data were collected from May to July 2000, and determination of hemoglobin (HGB) employed an STKS Coulter counter. Two cut-off points were used to classify anemia, both established by the World Health Organization: HGB < 11.5g/dl and HGB < 12.0g/dl. The indicators height/age (H/A), weight/age (W/A), and weight/height (W/H) below -2.0 standard deviations from the NCHS reference were diagnosed as growth retardation. Prevalence of anemia was 9.9% when HGB < 11.5g/dl was used, and 25.4% when the cut-off point was HGB < 12.0g/dl. Growth retardation was detected in 6.2% of children according to H/A, 4.0% for W/A, and 3.0% for W/H. There was no statistically significant association between the variables in the study. These findings confirm results of previous surveys where prevalence of anemia was much higher than that of growth retardation. The severe consequences of anemia in this age group justify the implementation of broad public policies to overcome this nutritional deficiency.

Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome

PubMed Central

Delvaeye, Mieke; Noris, Marina; De Vriese, Astrid; Esmon, Charles T.; Esmon, Naomi L.; Ferrell, Gary; Del-Favero, Jurgen; Plaisance, Stephane; Claes, Bart; Lambrechts, Diether; Zoja, Carla; Remuzzi, Giuseppe; Conway, Edward M.

2012-01-01

BACKGROUND The hemolytic–uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxin–producing bacteria and has a favorable outcome. The less common form of the syndrome, called atypical hemolytic–uremic syndrome, accounts for about 10% of cases, and patients with this form of the syndrome have a poor prognosis. Approximately half of the patients with atypical hemolytic–uremic syndrome have mutations in genes that regulate the complement system. Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic–uremic syndrome. METHODS We sequenced the entire thrombomodulin gene (THBD) in 152 patients with atypical hemolytic–uremic syndrome and in 380 controls. Using purified proteins and cell-expression systems, we investigated whether thrombomodulin regulates the complement system, and we characterized the mechanisms. We evaluated the effects of thrombomodulin missense mutations associated with atypical hemolytic–uremic syndrome on complement activation by expressing thrombomodulin variants in cultured cells. RESULTS Of 152 patients with atypical hemolytic–uremic syndrome, 7 unrelated patients had six different heterozygous missense THBD mutations. In vitro, thrombomodulin binds to C3b and factor H (CFH) and negatively regulates complement by accelerating factor I–mediated inactivation of C3b in the presence of cofactors, CFH or C4b binding protein. By promoting activation of the plasma procarboxypeptidase B, thrombomodulin also accelerates the inactivation of anaphylatoxins C3a and C5a. Cultured cells expressing thrombomodulin variants associated with atypical hemolytic–uremic syndrome had diminished capacity to inactivate C3b and to activate procarboxypeptidase B and were thus less protected from activated complement. CONCLUSIONS Mutations that impair the function of thrombomodulin occur in about 5% of patients with atypical hemolytic–uremic syndrome. PMID:19625716

Hemoglobin levels and prevalence of anemia in pregnant women assisted in primary health care services, before and after fortification of flour.

PubMed

Araújo, Claudia Regina Marchiori Antunes; Uchimura, Taqueco Teruya; Fujimori, Elizabeth; Nishida, Fernanda Shizue; Veloso, Giovanna Batista Leite; Szarfarc, Sophia Cornblutz

2013-06-01

We evaluated hemoglobin-Hb levels and prevalence of anemia in pregnant women before and after fortification of flour. It was developed a study to evaluate intervention, of the type before and after, with independent population samples. Study was conducted in primary health care services in Maringá, PR. We assessed 366 and 419 medical records, Before and After implementation of fortification. Pregnant women with Hb < 11g/dL were considered anemic. Data were submitted to multiple linear regression analysis. There was low prevalence of anemia affecting 12.3% and 9.4% pregnant women Before and After fortification (p > 0.05), but the Group After the fortification had higher Hb levels (p < 0.05). Hb levels associated with Group, gestational age, previous pregnancy number, employment and marital status (p < 0.05). Although the fortification of flour may have had role in increasing the mean hemoglobin, we need consider the contribution of other variables not investigated.

Fruit and vegetable consumption and anemia among adult non-pregnant women: Ghana Demographic and Health Survey.

PubMed

Ghose, Bishwajit; Yaya, Sanni

2018-01-01

Anemia is the most widely prevalent form of micronutrient deficiency that affects over a quarter of the global population. Evidence suggests that the burden of anemia is higher in the developing countries with women of reproductive age and children being the most at-risk groups. The most common causes are believed to be malnutrition and low bioavailability of micronutrients, which usually result from poor dietary habits and inadequate intake of food rich in micronutrients such as fresh fruits and vegetables. Regular consumption of F&V was shown to have protective effect against NCDs; however, evidence on this protective effect against micronutrient deficiency diseases are limited. (1) To measure the prevalence of anemia among adult non-pregnant women in Ghana, and (2) to investigate if there is any cross-sectional relationship between F&V consumption and anemia. This is a cross-sectional study based on data extracted from the Ghana Demographic and Health Survey, 2008. Subjects were 4,290 non-pregnant women aged between 15 and 49 years. Hemoglobin levels were measured by HemoCue ® hemoglobin-meter. Association between anemia and F&V consumption was assessed by multivariable regression methods. Findings indicate that well over half (57.9%) of the women were suffering from anemia of some level. The percentage of women consuming at least five servings of fruits and vegetables a day were 5.4% and 2.5% respectively. Results of multivariable analysis indicated that among urban women, consumption of <5 servings fruits/day was associated with significantly higher odds of severe [AOR = 9.27; 95% CI [5.15-16.70

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

PubMed Central

Tonelli, Marcello; Hemmelgarn, Brenda; Reiman, Tony; Manns, Braden; Reaume, M. Neil; Lloyd, Anita; Wiebe, Natasha; Klarenbach, Scott

2009-01-01

Background Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. Methods We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. Results We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25). Interpretation Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer. PMID:19407261

Interleukin-6 and Interleukin-8 Levels Correlate With the Severity of Aplastic Anemia in Children.

PubMed

Gupta, Vineeta; Kumar, Sushil; Sonowal, Rimjhim; Singh, Surya K

2017-04-01

The aim of this study was to evaluate the levels of interleukin (IL)-6 and IL-8 in patients with aplastic anemia and its correlation with severity of the disease. IL-6 and IL-8 levels were measured in 40 patients with aplastic anemia in the age group of 4 to 14 years. A total of 40 healthy children served as controls. Quantitative estimation of IL-6 and IL-8 was performed using a solid-phase sandwich ELISA kit. Results were presented as IL-6 and IL-8 concentrations in pg/mL. Patients received immunosuppressive therapy per the British Committee for Standards in Haematology Guidelines 2009. Mean age of the patients was 9.78±2.74 years. IL-6 level of patients was elevated compared with controls (193.48±352.3 vs. 4.58±3.39; P<0.001). IL-8 levels were also significantly elevated in patients compared with controls (15.58±18.0 vs. 1.85±0.95; P<0.001). IL levels were also assessed in relation to severity of the disease. Levels were the highest in patients with very severe aplastic anemia (724.33±519.42), followed by severe aplastic anemia (80.51±66.28 pg/mL), and non-severe aplastic anemia (6.01±1.89). Differences were statistically significant. A similar trend was also observed for IL-8 levels, where the levels were 41.02±24.23, 11.34±8.0, and 1.67±0.71 for very severe aplastic anemia, severe aplastic anemia, and non-severe aplastic anemia, respectively. The differences were again statistically significant. IL levels were also correlated with the treatment outcome. Responders had lower levels compared with nonresponders, but the difference was not statistically significant (186.36±322.45 vs. 198.74±368.10). Levels of ILs decreased in responders, but were not comparable with that of controls 6 months after therapy. High levels of IL-6 and IL-8 were observed in children with aplastic anemia. Increased levels showed correlation with disease severity and therefore appear to play an important role in aplastic anemia. However, levels had no significant correlation with the treatment outcome.

A Micronutrient Fortified Beverage Given at Different Dosing Frequencies Had Limited Impact on Anemia and Micronutrient Status in Filipino Schoolchildren.

PubMed

Angeles-Agdeppa, Imelda; Magsadia, Clarita R; Aaron, Grant J; Lloyd, Beate B; Hilmers, David C; Bhutta, Zulfiqar A

2017-09-12

This study evaluated the effects of a multi-micronutrient fortified juice drink given in different frequencies of consumption on hemoglobin (Hb) concentration of schoolchildren. Hb was measured in 2423 schoolchildren aged 6- to 9-years-old at baseline. All anemic children ( n = 246) were randomly allocated into groups: Daily dose (HD: high dose), 5X/week (MD: Moderate Dose), 3X/week (LD: Low Dose) and unfortified (Control). Pre- and post-study measurements of micronutrients were collected from 228 children. At the endpoint, significant Hb increases were observed in all groups, but there was no significant difference between groups. There was a significant reduction in anemia prevalence in all groups from 100% to 36% (Control), 30% (LD), 23% (MD) and 26% (HD). No dose-response effect was observed in Hb in this population. Most likely, this resulted from better than expected micronutrient status and lower than expected severity of anemia and micronutrient deficiencies in this cohort. It is unlikely that the addition of a fortified beverage to school feeding programs in this population would have a positive impact. Whether such an intervention would be cost-effective as a preventative approach needs to be assessed. This study demonstrates the importance of targeting such interventions to appropriate populations.

A Micronutrient Fortified Beverage Given at Different Dosing Frequencies Had Limited Impact on Anemia and Micronutrient Status in Filipino Schoolchildren

PubMed Central

Angeles-Agdeppa, Imelda; Magsadia, Clarita R.; Aaron, Grant J.; Lloyd, Beate B.; Hilmers, David C.; Bhutta, Zulfiqar A.

2017-01-01

This study evaluated the effects of a multi-micronutrient fortified juice drink given in different frequencies of consumption on hemoglobin (Hb) concentration of schoolchildren. Hb was measured in 2423 schoolchildren aged 6- to 9-years-old at baseline. All anemic children (n = 246) were randomly allocated into groups: Daily dose (HD: high dose), 5X/week (MD: Moderate Dose), 3X/week (LD: Low Dose) and unfortified (Control). Pre- and post-study measurements of micronutrients were collected from 228 children. At the endpoint, significant Hb increases were observed in all groups, but there was no significant difference between groups. There was a significant reduction in anemia prevalence in all groups from 100% to 36% (Control), 30% (LD), 23% (MD) and 26% (HD). No dose-response effect was observed in Hb in this population. Most likely, this resulted from better than expected micronutrient status and lower than expected severity of anemia and micronutrient deficiencies in this cohort. It is unlikely that the addition of a fortified beverage to school feeding programs in this population would have a positive impact. Whether such an intervention would be cost-effective as a preventative approach needs to be assessed. This study demonstrates the importance of targeting such interventions to appropriate populations. PMID:28895887

Factors associated with anemia in refugee children.

PubMed

Hassan, K; Sullivan, K M; Yip, R; Woodruff, B A

1997-11-01

A nutrition survey was performed in 1990 among children 6 through 35 mo of age living in Palestinian refugee camps in Syria, Jordan, the West Bank, Gaza Strip and Lebanon. Overall, 67% [95% confidence interval (CI): 66, 68] were anemic (hemoglobin <110 g/L), ranging from 54% in the West Bank to 75% in Syria. The following factors were significantly associated with anemia in one or more of three age groups (6-11.9, 12-23.9 and 24-35.9 mo) by logistic regression: living in Syria, Lebanon, or Gaza [with prevalence odds ratios (POR) in the range of 1.4-2.6 depending on the age group and area, relative to children living in Jordan]; never having been breast-fed (POR = 1.7); male sex (POR = 1.2); maternal illiteracy (POR = 1.4 relative to those with >/=6 y of education); having a recent (within 2 wk) or current episode of fever or diarrhea; and stunting. Recent or current illness and stunting interacted in two age groups with the general trend of stunted children with recent or current illness having high POR. Early childhood anemia is associated with factors reflecting poor socioeconomic status and recent diarrheal and febrile illnesses in Palestinian refugee camps.

Efficacy of different strategies to treat anemia in children: a randomized clinical trial

PubMed Central

2010-01-01

Background Anemia continues to be a major public health problem among children in many regions of the world, and it is still not clear which strategy to treat it is most effective. Objective To evaluate the efficacy and children's acceptance of several recognized strategies to treat anemia. Methods Non-breastfed children (n = 577), 6 to 43 mo of age, were screened for the trial; 267 were anemic (hemoglobin < 11.7 g/dL), and 266 of those were randomized into 1 of 5 treatments to received daily either: an iron supplement (IS), an iron+folic acid supplement (IFS), a multiple micronutrient supplement (MMS), a micronutrient-fortified complementary food as porridge powder (FCF), or zinc+iron+ascorbic acid fortified water (FW). The iron content of each daily dose was 20, 12.5, 10, 10 and 6.7 mg respectively. Hemoglobin (Hb), ferritin, total iron, weight and height were measured at baseline and after 4 months of treatment. Morbidity, treatment acceptability and adherence were recorded during the intervention. Results All treatments significantly increased Hb and total iron concentration; ferritin did not change significantly. Groups MMS, IS and IFS increased Hb (g/dL) [1.50 (95%CI: 1.17, 1.83), 1.48 [(1.18, 1.78) and 1.57 (1.26, 1.88), respectively] and total iron ((μg/dL) [0.15 (0.01, 0.29), 0.19 (0.06, 0.31) and 0.12(-0.01, 0.25), respectively] significantly more than FCF [0.92 (0.64, 1.20)] but not to FW group [0.14 (0.04, 0.24)]. The prevalence of anemia was reduced to a greater extent in the MMS and IFS groups (72% and 69%, respectively) than in the FCF group (45%) (p < 0.05). There were no significant differences in anthropometry or in the number of episodes of diarrhea and respiratory infections among treatment groups. The supplements MMS and IS were less acceptable to children, than IFS, FCF and FW. Conclusion The three supplements IS, ISF and MMS increased Hb more than the FCF; the supplements that contained micronutrients (IFS and MMS) were more effective for reducing the prevalence of anemia. In general, fortified foods were better accepted by the study participants than supplements. ClinicalTrial.gov Identifier NCT00822380 PMID:20863398

A diffuse mixed histiocytic-lymphocytic lymphoma associated with immunological abnormalities.

PubMed

Syrjänen, K J

1979-01-01

A diffuse generalized lymphoma histologically classified as mixed histiocytic-lymphocytic type and associated with profound immunologie abnormalities is reported. The patient had an autoimmune hemolytic anemia, an autoimmune thrombocytopenia, polyclonally increased IgG and IgM, polyclonal secretion of kappa and lamda chains into urine, very low serum complement C3 and antibodies against glomerulus and smooth muscle. When studied with the modern surface-marker techniques, the lesion was found to be composed of entirely lymphoid cells of the B-lymphocyte series. The proper classification of this tumor could be a primitive immunoblastic sarcoma. The relationship of the present tumor to the non-neoplastic angioimmunoblastic lymphadenopathia is discussed. The necessity of applying the surface-marker techniques in the classification of malignant lymphomas is emphasized.

Scope and design of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements (FREEDOM) Study.

PubMed

Jaber, Bertrand L; Finkelstein, Fredric O; Glickman, Joel D; Hull, Alan R; Kraus, Michael A; Leypoldt, John K; Liu, Jiannong; Gilbertson, David; McCarthy, James; Miller, Brent W; Moran, John; Collins, Allan J

2009-02-01

Conventional thrice-weekly hemodialysis (HD) has limited the ability to generate further improvements in patient quality of life, morbidity, and mortality. Daily HD (DHD) offers the promise of providing clinical and economic benefits. The objectives of the Following Rehabilitation, Economics and Everyday-Dialysis Outcome Measurements Study are to evaluate outcomes of DHD (6 times/wk) with the NxStage System One (NxStage Medical Inc, Lawrence, MA) device. Cohort study with matched control group. The DHD group will include up to 500 participants at 70 clinical sites, enrolling for 3 years with a minimum of 1-year follow-up. Study candidates include adult patients (age >or= 18 years) with end-stage renal disease who are considered suitable candidates for DHD with the NxStage System One device by the treating physician and who have Medicare as their primary insurance payer. The control group will consist of a matched thrice-weekly in-center HD cohort derived from the US Renal Data System database using a 10:1 ratio, totaling 5,000 patients. Treatment with DHD and "standard of care" thrice-weekly HD. The primary intent-to-treat analysis compares hospitalization days/patient-year between the DHD and thrice-weekly HD groups. Other outcomes recorded in both groups include non-treatment-related medical expenditures. In addition, in the DHD cohort, changes in quality-of-life measures (baseline, 4 and 12 months, and every 6 months thereafter); urea kinetics; parameters related to anemia, bone and mineral metabolism, and nutrition; vascular access interventions; and use of medications will be examined. This study has the potential to elucidate the health and economic benefits of DHD and complement results of current clinical trials.

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients

PubMed Central

2014-01-01

Background Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. Methods We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Results Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients’ clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Conclusions Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology. PMID:24885126

Whole exome sequencing reveals concomitant mutations of multiple FA genes in individual Fanconi anemia patients.

PubMed

Chang, Lixian; Yuan, Weiping; Zeng, Huimin; Zhou, Quanquan; Wei, Wei; Zhou, Jianfeng; Li, Miaomiao; Wang, Xiaomin; Xu, Mingjiang; Yang, Fengchun; Yang, Yungui; Cheng, Tao; Zhu, Xiaofan

2014-05-15

Fanconi anemia (FA) is a rare inherited genetic syndrome with highly variable clinical manifestations. Fifteen genetic subtypes of FA have been identified. Traditional complementation tests for grouping studies have been used generally in FA patients and in stepwise methods to identify the FA type, which can result in incomplete genetic information from FA patients. We diagnosed five pediatric patients with FA based on clinical manifestations, and we performed exome sequencing of peripheral blood specimens from these patients and their family members. The related sequencing data were then analyzed by bioinformatics, and the FANC gene mutations identified by exome sequencing were confirmed by PCR re-sequencing. Homozygous and compound heterozygous mutations of FANC genes were identified in all of the patients. The FA subtypes of the patients included FANCA, FANCM and FANCD2. Interestingly, four FA patients harbored multiple mutations in at least two FA genes, and some of these mutations have not been previously reported. These patients' clinical manifestations were vastly different from each other, as were their treatment responses to androstanazol and prednisone. This finding suggests that heterozygous mutation(s) in FA genes could also have diverse biological and/or pathophysiological effects on FA patients or FA gene carriers. Interestingly, we were not able to identify de novo mutations in the genes implicated in DNA repair pathways when the sequencing data of patients were compared with those of their parents. Our results indicate that Chinese FA patients and carriers might have higher and more complex mutation rates in FANC genes than have been conventionally recognized. Testing of the fifteen FANC genes in FA patients and their family members should be a regular clinical practice to determine the optimal care for the individual patient, to counsel the family and to obtain a better understanding of FA pathophysiology.

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia

PubMed Central

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-01-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was −0.99 standard deviation (SD) (range −4.01–+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. PMID:26315930

Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia.

PubMed

Narita, Atsushi; Muramatsu, Hideki; Sekiya, Yuko; Okuno, Yusuke; Sakaguchi, Hirotoshi; Nishio, Nobuhiro; Yoshida, Nao; Wang, Xinan; Xu, Yinyan; Kawashima, Nozomu; Doisaki, Sayoko; Hama, Asahito; Takahashi, Yoshiyuki; Kudo, Kazuko; Moritake, Hiroshi; Kobayashi, Masao; Kobayashi, Ryoji; Ito, Etsuro; Yabe, Hiromasa; Ohga, Shouichi; Ohara, Akira; Kojima, Seiji

2015-12-01

Acquired aplastic anemia is an immune-mediated disease characterized by severe defects in stem cell number resulting in hypocellular marrow and peripheral blood cytopenias. Minor paroxysmal nocturnal hemoglobinuria populations and a short telomere length were identified as predictive biomarkers of immunosuppressive therapy responsiveness in aplastic anemia. We enrolled 113 aplastic anemia patients (63 boys and 50 girls) in this study to evaluate their response to immunosuppressive therapy. The paroxysmal nocturnal hemoglobinuria populations and telomere length were detected by flow cytometry. Forty-seven patients (42%) carried a minor paroxysmal nocturnal hemoglobinuria population. The median telomere length of aplastic anemia patients was -0.99 standard deviation (SD) (range -4.01-+3.01 SD). Overall, 60 patients (53%) responded to immunosuppressive therapy after six months. Multivariate logistic regression analysis identified the absence of a paroxysmal nocturnal hemoglobinuria population and a shorter telomere length as independent unfavorable predictors of immunosuppressive therapy response at six months. The cohort was stratified into a group of poor prognosis (paroxysmal nocturnal hemoglobinuria negative and shorter telomere length; 37 patients) and good prognosis (paroxysmal nocturnal hemoglobinuria positive and/or longer telomere length; 76 patients), respectively. The response rates of the poor prognosis and good prognosis groups at six months were 19% and 70%, respectively (P<0.001). The combined absence of a minor paroxysmal nocturnal hemoglobinuria population and a short telomere length is an efficient predictor of poor immunosuppressive therapy response, which should be considered while deciding treatment options: immunosuppressive therapy or first-line hematopoietic stem cell transplantation. The trial was registered in www.umin.ac.jp with number UMIN000017972. Copyright© Ferrata Storti Foundation.

The hematological effects of nitrous oxide anesthesia in pediatric patients.

PubMed

Duma, Andreas; Cartmill, Christopher; Blood, Jane; Sharma, Anshuman; Kharasch, Evan D; Nagele, Peter

2015-06-01

Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients. This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide-free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macrocytosis/microcytosis, anisocytosis, hyperchromatosis/hypochromatosis, thrombocytopenia, and leukopenia. The change (Δ) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW). No pancytopenia was present in any patient after surgery. All patients had postoperative anemia, and none had macrocytosis. Postoperative MCV (mean [99% confidence interval]) peaked at 86 fL (85-88 fL), 85 fL (81-89 fL), and 88 fL (80-96 fL) and postoperative RDW at 13.2% (12.8-13.5%), 13.3% (12.7-13.8%), and 13.0% (11.4-14.6%) for the maintenance group, the induction/emergence group, and the nitrous oxide-free group. Two patients in the maintenance group (5%) developed anisocytosis (RDW >14.6%), but none in the induction/emergence group or in the nitrous oxide-free group (P = 0.43). Both ΔMCV (P = 0.52) and ΔRDW (P = 0.16) were similar across all groups. Nitrous oxide exposure for up to 8 hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery.

The Hematological Effects of Nitrous Oxide Anesthesia in Pediatric Patients

PubMed Central

Duma, Andreas; Cartmill, Christopher; Blood, Jane; Sharma, Anshuman; Kharasch, Evan; Nagele, Peter

2016-01-01

Background Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear if nitrous oxide doses used in clinical practice cause adverse hematological effects in pediatric patients. Methods This retrospective study included 54 pediatric patients undergoing elective spinal surgery: 41 received nitrous oxide throughout anesthesia (maintenance group), 9 received nitrous oxide for induction and/or emergence (induction/emergence group), and 4 did not receive nitrous oxide (nitrous oxide-free group). Complete blood counts obtained before and up to 4 days after surgery were assessed for anemia, macro-/microcytosis, anisocytosis, hyper-/hypochromatosis, thrombocytopenia and leucopenia. The change (Δ) from preoperative to the highest postoperative value was calculated for mean corpuscular volume (MCV) and red cell distribution width (RDW). Results No pancytopenia was present in any patient after surgery. All patients had postoperative anemia; none had macrocytosis. Postoperative MCV (mean [99% CI]) peaked at 86 [85 to 88] fL, 85 [81 to 89] fL, and 88 [80 to 96] fL, and postoperative RDW at 13.2 [12.8 to 13.5] %, 13.3 [12.7 to 13.8] %, and 13.0 [11.4 to 14.6] % for the maintenance group, the induction/emergence group, and the nitrous oxide-free group. Two patients in the maintenance group (5 %) developed anisocytosis (RDW>14.6%), but none in the induction/emergence group or in the nitrous oxide-free group (P = 0.43). Both ΔMCV (P=0.52) and ΔRDW (P=0.16) were similar across all groups. Conclusions Nitrous oxide exposure for up to eight hours is not associated with megaloblastic anemia in pediatric patients undergoing major spinal surgery. PMID:25658315

Acute Liver Failure in a Pediatric Patient with Congenital Dysery-Thropoietic Anemia Type I Treated with Deferasirox.

PubMed

Ling, Galina; Pinsk, Vered; Golan-Tripto, Inbal; Ling, Eduard

2015-09-23

Congenital dyserythropoietic anemias (CDA) represent a heterogeneous group of disorders characterized by morphological abnormalities of erythroid precursor cells and various degrees of hemolysis. Iron overload is a result of continuous hemolysis and recurrent transfusions. It is treated with iron chelators, including deferasirox. We present here a case of acute liver failure in a 12 years old girl with CDA type I treated with deferasirox and discuss the approach to treatment.

Hematopoietic Stem Cell Transplant in Adolescent and Young Adults With Fanconi Anemia Is Feasible With Acceptable Toxicity, With Those Surviving 100 Days Posttransplant Having Excellent Outcomes.

PubMed

Alhuraiji, Ahmad; Alzahrani, Hazza; Al Mohareb, Fahad; Chaudhri, Naeem; Alsharif, Fahad; Mohamed, Said; Rasheed, Walid; Aldawsari, Ghuzayel; Ahmed, Syed Osman; Aljurf, Mahmoud

2016-12-01

Fanconi anemia is a congenital bone marrow failure syndrome that is associated with congenital anomalies and increased risk of cancer. Hematopoietic stem cell transplant is a potentially curative modality for bone marrow failure in Fanconi anemia patients. Here, we report our center's experience regarding adolescent and young adult patients with Fanconi anemia and hematopoietic stem cell transplant. We conducted a retrospective patient record analyses of patients who presented at our center from 1988 to 2014. We included patients greater than 14 years old with confirmed Fanconi anemia based on positive chromosome breakage study and who underwent hematopoietic stem cell transplant at our institution. Our study group comprised 12 patients with Fanconi anemia who underwent hematopoietic stem cell transplant at our institution. The median age was 20 years (range, 14-31 y) with a female predominance of 83%. Low-dose cyclophosphamide (20-80 mg/kg)-based conditioning regimens were used with different combinations that included fludarabine, antithymocyte globulin, or total body irradiation. All patients had HLA-matched sibling grafts. In all patients, stem cell source was the bone marrow. All patients showed engraftment. Four patients (33%) developed acute graft-versus-host disease. Three patients (25%) died early before day 100 after hematopoietic stem cell transplant due to infectious complications, with 1 patient having steroid refractory acute graft-versus-host disease. Overall survival was 75% at a median follow-up of 43 months. All patients who survived are well and remained transfusion independent without evidence of secondary malignancy. Our findings support the feasibility of reduced intensity conditioning allogeneic hematopoietic stem cell transplant in older and more heavily pretreated patients with Fanconi anemia, especially for those who are engrafted.

Effectiveness evaluation of the food fortification program of Costa Rica: impact on anemia prevalence and hemoglobin concentrations in women and children.

PubMed

Martorell, Reynaldo; Ascencio, Melany; Tacsan, Luis; Alfaro, Thelma; Young, Melissa F; Addo, O Yaw; Dary, Omar; Flores-Ayala, Rafael

2015-01-01

Food fortification is one approach for addressing anemia, but information on program effectiveness is limited. We evaluated the impact of Costa Rica's fortification program on anemia in women aged 15-45 y and children aged 1-7 y. Reduced iron, an ineffective fortificant, was replaced by ferrous fumarate in wheat flour in 2002, and ferrous bisglycinate was added to maize flour in 1999 and to liquid and powdered milk in 2001. We used a one-group pretest-posttest design and national survey data from 1996 (baseline; 910 women, 965 children) and 2008-2009 (endline; 863 women, 403 children) to assess changes in iron deficiency (children only) and anemia. Data were also available for sentinel sites (1 urban, 1 rural) for 1999-2000 (405 women, 404 children) and 2008-2009 (474 women, 195 children), including 24-h recall data in children. Monitoring of fortification levels was routine. Foods were fortified as mandated. Fortification provided about one-half the estimated average requirement for iron in children, mostly and equally through wheat flour and milk. Anemia was reduced in children and women in national and sentinel site comparisons. At the national level, anemia declined in children from 19.3% (95% CI: 16.8%, 21.8%) to 4.0% (95% CI: 2.1%, 5.9%) and in women from 18.4% (95% CI: 15.8%, 20.9%) to 10.2% (95% CI: 8.2%, 12.2%). In children, iron deficiency declined from 26.9% (95% CI: 21.1%, 32.7%) to 6.8% (95% CI: 4.2%, 9.3%), and iron deficiency anemia, which was 6.2% (95% CI: 3.0%, 9.3%) at baseline, could no longer be detected at the endline. A plausible impact pathway suggests that fortification improved iron status and reduced anemia. Although unlikely in the Costa Rican context, other explanations cannot be excluded in a pre/post comparison. © 2015 American Society for Nutrition.

Methodologic approach for the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

PubMed Central

Aaron, Grant J; Varadhan, Ravi

2017-01-01

Background: The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project is a multiagency and multicountry collaboration that was formed to improve micronutrient assessment and to better characterize anemia. Objectives: The aims of the project were to 1) identify factors associated with inflammation, 2) assess the relations between inflammation, malaria infection, and biomarkers of iron and vitamin A status and compare adjustment approaches, and 3) assess risk factors for anemia in preschool children (PSC) and women of reproductive age (WRA). Design: The BRINDA database inclusion criteria included surveys that 1) were conducted after 2004, 2) had target groups of PSC, WRA, or both, and 3) used a similar laboratory methodology for the measurement of ≥1 biomarker of iron [ferritin or soluble transferrin receptor or vitamin A status (retinol-binding protein or retinol)] and ≥1 biomarker of inflammation (α-1-acid glycoprotein or C-reactive protein). Individual data sets were standardized and merged into a BRINDA database comprising 16 nationally and regionally representative surveys from 14 countries. Collectively, the database covered all 6 WHO geographic regions and contained ∼30,000 PSC and 27,000 WRA. Data were analyzed individually and combined with the use of a meta-analysis. Results: The methods that were used to standardize the BRINDA database and the analytic approaches used to address the project’s research questions are presented in this article. Three approaches to adjust micronutrient biomarker concentrations in the presence of inflammation and malaria infection are presented, along with an anemia conceptual framework that guided the BRINDA project’s anemia analyses. Conclusions: The BRINDA project refines approaches to interpret iron and vitamin A biomarker values in settings of inflammation and malaria infection and suggests the use of a new regression approach as well as proposes an anemia framework to which real-world data can be applied. Findings can inform guidelines and strategies to prevent and control micronutrient deficiencies and anemia globally. PMID:28615254

Is anemia associated with cognitive impairment and delirium among older acute surgical patients?

PubMed

Myint, Phyo Kyaw; Owen, Stephanie; McCarthy, Kathryn; Pearce, Lyndsay; Moug, Susan J; Stechman, Michael J; Hewitt, Jonathan; Carter, Ben

2018-03-01

The determinants of cognitive impairment and delirium during acute illness are poorly understood, despite being common among older people. Anemia is common in older people, and there is ongoing debate regarding the association between anemia, cognitive impairment and delirium, primarily in non-surgical patients. Using data from the Older Persons Surgical Outcomes Collaboration 2013 and 2014 audit cycles, we examined the association between anemia and cognitive outcomes in patients aged ≥65 years admitted to five UK acute surgical units. On admission, the Confusion Assessment Method was carried out to detect delirium. Cognition was assessed using the Montreal Cognitive Assessment, and two levels of impairment were defined as Montreal Cognitive Assessment <26 and <20. Logistic regression models were constructed to examine these associations in all participants, and individuals aged ≥75 years only. A total of 653 patients, with a median age of 76.5 years (interquartile range 73.0-80.0 years) and 53% women, were included. Statistically significant associations were found between anemia and age; polypharmacy; hyperglycemia; and hypoalbuminemia. There was no association between anemia and cognitive impairment or delirium. The adjusted odds ratios of cognitive impairment were 0.95 (95% CI 0.56-1.61) and 1.00 (95% CI 0.61-1.64) for the Montreal Cognitive Assessment <26 and <20, respectively. The adjusted odds ratio of delirium was 1.00 (95% CI 0.48-2.10) in patients with anemia compared with those without. Similar results were observed for the ≥75 years age group. There was no association between anemia and cognitive outcomes among older people in this acute surgical setting. Considering the retrospective nature of the study and possible lack of power, findings should be taken with caution. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 The Authors Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.

Iron deficiency and anemia are prevalent in women with multiple gestations.

PubMed

Ru, Yuan; Pressman, Eva K; Cooper, Elizabeth M; Guillet, Ronnie; Katzman, Philip J; Kent, Tera R; Bacak, Stephen J; O'Brien, Kimberly O

2016-10-01

Little attention has been placed on the unique iron demands that may exist in women with multiple gestations. This merits attention because iron deficiency (ID) during pregnancy is associated with adverse pregnancy outcomes that are known to be more prevalent in multiple births. We characterized longitudinal changes in iron status across pregnancy in a cohort of healthy women with multiple gestations and identified determinants of maternal ID and anemia. A group of 83 women carrying twins, triplets, or quadruplets (aged 20-46 y) was recruited from 2011 to 2014. Blood samples obtained during pregnancy (∼24 wk; n = 73) and at delivery (∼35 wk; n = 61) were used to assess hemoglobin, serum ferritin (SF), soluble transferrin receptor (sTfR), hepcidin, serum iron, erythropoietin, serum folate, vitamin B-12, C-reactive protein, and interleukin-6. The prevalence of tissue ID (sTfR >8.5 mg/L) increased significantly from pregnancy to delivery (9.6% compared with 23%, P = 0.03). Women with depleted iron stores (SF <12 μg/L, n = 20) during pregnancy had a 2-fold greater risk of anemia at delivery, and 25% (n = 5) developed iron deficiency anemia (IDA). Overall, 44.6% of women studied (n = 37/83) were anemic at delivery, and 18% of women (n = 11/61) had IDA. Erythropoietin during pregnancy was significantly negatively associated with hemoglobin at delivery. Women with erythropoietin >75th percentile during pregnancy exhibited a 3-fold greater risk of anemia, suggesting that erythropoietin is a sensitive predictor of anemia at delivery. Inflammation was present at delivery, which limited the utility of ferritin or hepcidin as iron-status indicators at delivery. ID and anemia are highly prevalent in women with multiple gestations. Additional screening and iron supplementation may be warranted in this high-risk population given the known associations between ID anemia and adverse maternal and neonatal outcomes. This trial was registered at clinicaltrials.gov as NCT01582802. © 2016 American Society for Nutrition.

Language and theory of mind in autism spectrum disorder: the relationship between complement syntax and false belief task performance.

PubMed

Lind, Sophie E; Bowler, Dermot M

2009-06-01

This study aimed to test the hypothesis that children with autism spectrum disorder (ASD) use their knowledge of complement syntax as a means of "hacking out" solutions to false belief tasks, despite lacking a representational theory of mind (ToM). Participants completed a "memory for complements" task, a measure of receptive vocabulary, and traditional location change and unexpected contents false belief tasks. Consistent with predictions, the correlation between complement syntax score and location change task performance was significantly stronger within the ASD group than within the comparison group. However, contrary to predictions, complement syntax score was not significantly correlated with unexpected contents task performance within either group. Possible explanations for this pattern of results are considered.

The effects of malaria and HIV co-infection on hemoglobin levels among pregnant women in Sekondi-Takoradi, Ghana.

PubMed

Orish, Verner N; Onyeabor, Onyekachi S; Boampong, Johnson N; Acquah, Samuel; Sanyaolu, Adekunle O; Iriemenam, Nnaemeka C

2013-03-01

To assess the burden of maternal malaria and HIV among pregnant women in Ghana and to determine the risk of anemia among women with dual infection. A cross-sectional study was conducted at 4 hospitals in the Sekondi-Takoradi metropolis, Ghana. The study group comprised 872 consenting pregnant women attending prenatal care clinics. Venous blood samples were screened for malaria, HIV, and hemoglobin level. Multivariate logistic regression analysis was performed to determine the association between malaria, HIV, and risk of anemia. In all, 34.4% of the study cohort had anemia. Multivariate logistic regression analysis indicated that pregnant women with either malaria (odds ratio 1.99; 95% confidence interval, 1.43-2.77; P=<0.001) or HIV (odds ratio 1.78; 95% confidence interval, 1.13-2.80; P=0.014) had an increased risk of anemia. In adjusted models, pregnant women co-infected with both malaria and HIV displayed twice the risk of anemia. The adjusted odds ratio was 2.67 (95% confidence interval, 1.44-4.97; P=0.002). Pregnant women infected with both malaria and HIV are twice as likely to be anemic than women with a single infection or no infection. Measures to control malaria, HIV, and anemia during pregnancy are imperative to improve birth outcomes in this region of Ghana. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

The double burden of undernutrition and excess body weight in Mexico.

PubMed

Kroker-Lobos, Maria F; Pedroza-Tobías, Andrea; Pedraza, Lilia S; Rivera, Juan A

2014-12-01

In Mexico, stunting and anemia have declined but are still high in some regions and subpopulations, whereas overweight and obesity have increased at alarming rates in all age and socioeconomic groups. The objective was to describe the coexistence of stunting, anemia, and overweight and obesity at the national, household, and individual levels. We estimated national prevalences of and trends for stunting, anemia, and overweight and obesity in children aged <5 y and in school-aged children (5-11 y old) and anemia and overweight and obesity in women aged 20-49 y by using the National Health and Nutrition Surveys conducted in 1988, 1999, 2006, and 2012. With the use of the most recent data (2012), the double burden of malnutrition at the household level was estimated and defined as the coexistence of stunting in children aged <5 y and overweight or obesity in the mother. At the individual level, double burden was defined as concurrent stunting and overweight and obesity in children aged 5-11 y and concurrent anemia and overweight or obesity in children aged 5-11 y and in women. We also tested if the coexistence of the conditions corresponded to expected values, under the assumption of independent distributions of each condition. At the household level, the prevalence of concurrent stunting in children aged <5 y and overweight and obesity in mothers was 8.4%; at the individual level, prevalences were 1% for stunting and overweight or obesity and 2.9% for anemia and overweight or obesity in children aged 5-11 y and 7.6% for anemia and overweight or obesity in women. At the household and individual levels in children aged 5-11 y, prevalences of double burden were significantly lower than expected, whereas anemia and the prevalence of overweight or obesity in women were not different from that expected. Although some prevalences of double burden were lower than expected, assuming independent distributions of the 2 conditions, the coexistence of stunting, overweight or obesity, and anemia at the national, household, and intraindividual levels in Mexico calls for policies and programs to prevent the 3 conditions. © 2014 American Society for Nutrition.

Use of nandrolone decanoate as an adjuvant for erythropoietin dose reduction in treating anemia in patients on hemodialysis.

PubMed

Sheashaa, Hussein; Abdel-Razek, Waleed; El-Husseini, Amr; Selim, Amal; Hassan, Nabil; Abbas, Tarek; El-Askalani, Hassan; Sobh, Mohamed

2005-01-01

Use of androgen as an adjuvant therapy to treat anemia in patients on hemodialysis is debated. Our target is to assess the safety and the efficacy of nandrolone decanoate (ND) as an effective adjunctive therapy to treat such anemia. This study included 32 anemic adult hemodialysis patients who had adequate iron stores. They were randomized into two equal groups: the first group received subcutaneously a low dose of erythropoietin (EPO) 1,000 U three times weekly combined with ND, 50 mg intramuscularly twice weekly, and the second group received only the same low dose of EPO for the 6-month study period. All patients were subjected to a serial follow-up of hemoglobin (Hb), hematocrit % (Hct%), iron store indices, serum insulin-like growth factor-1 (IGF-1) concentration and liver function tests. A significant rise of both Hb and Hct in both groups was found at the end of the study (p < 0.001). Although the rise of both Hb and Hct was higher in the androgen group, it was not rated as being statistically significant. Both groups showed a significant rise of serum IGF-1 concentration at the end of the study in comparison to its initial value. Moreover, the androgen group attained a more statistically significant rise of IGF-1 serum concentration. Four female patients discontinued ND because of related adverse effects, principally distressing hirsutism and hepatic dysfunction. Addition of ND to a low-dose EPO regimen does not offer a significant benefit. Androgen-related side effects limit its use in female patients.

Prevalence of anaemia in pregnant women during the last trimester: consequense for birth weight.

PubMed

Demmouche, A; Lazrag, A; Moulessehoul, S

2011-04-01

Iron deficiency continues to be one of the most prevalent single-nutrient deficiencies in the world. The current study aimed to estimate the prevalence of iron deficiency anemia (IDA) among pregnant women who attend Antenatal Care Centers in Sidi Bel Abbes, Algeria. The effect of anaemia on infant birth weight was also examined. The study was conducted during the period March-Mai, 2010 and the sample consisted of 207 pregnant women (in the third trimesters) in the age group (17-41) years. The subjects were not taking iron, folate or vitamin B12 supplements at the time of the study. Blood samples were collected from each pregnant woman and a questionnaire was completed at the time of blood collection. A series of determinations was conducted to determine hemoglobin concentration (Hb); packed cell volume (PCV); corpuscular hemoglobin concentration (MCHC), corpuscular volume (MCV). The effect of anemia on the weight of new born babies was examined by calculating the correlation coefficient of birth weight and hematological indexes. The overall prevalence of anemia was found to be 46.86%. According to the severity anemia was 36.08% mild, 49.48% moderate and 14.43% severe anemia. The mean values (+/- SD) of haematological indexes were as follows: Hb 9.00 +/- 1.57 g/dl; PCV 27 +/- 5.37%; mean corpuscular haemoglobin concentration (MCHC) 33.75 +/- 2.69 g/dl and mean corpuscular volume (MCV) 75.7 +/- 10.4 fl. The results have shown that 46.39% of the subjects had MCV values less than standard value of 75 fl suggesting a microcytic anemia. The mean haemoglobin concentration was 9 +/- 1.57 g/dl while the mean birth weight was 3201.54 +/- 566.71 g. There was a not significant correlation between the Hb level and the birth weight of the infants (r = 0.28, p > 0.05). The prevalence of low birth weight was 9.2%. There was no statistically significant haemoglobin concentration /foetal birth weight difference among the various hemoglobin concentration (Chi square test = 0.34, p > 0.05). Anemia had no significant obstetric adverse effects in our pregnant population (Fischer test = 0.06, p > 0.05). There was no statistically significant difference in mean birth weight among the various haemoglobin groups suggesting that other parameters may play important roles in influencing the birth weight than the maternal haemoglobin concentration.

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification1234

PubMed Central

Morris, Martha Savaria; Jacques, Paul F; Rosenberg, Irwin H; Selhub, Jacob

2007-01-01

Background Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. Objective We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <34) in senior participants in the 1999–2002 US National Health and Nutrition Examination Survey. Design The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration <148 pmol/L or a serum methylmalonic acid concentration >210 nmol/L—the maximum of the reference range for serum vitamin B-12–replete participants with normal creatinine. Results After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate ≤59 nmol/L (80th percentile), as opposed to ≤59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were <1.0 (Pinteraction <0.05), but significantly <1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). Conclusion In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment. PMID:17209196

Effects of separate delivery of zinc or zinc and vitamin A on hemoglobin response, growth, and diarrhea in young Peruvian children receiving iron therapy for anemia.

PubMed

Alarcon, Karl; Kolsteren, Patrick W; Prada, Ana M; Chian, Ana M; Velarde, Ruth E; Pecho, Iris L; Hoeree, Tom F

2004-11-01

Anemia is the most prevalent nutritional deficiency in the world. Attempts to improve iron indexes are affected by deficiency of and interaction between other micronutrients. Our goal was to assess whether zinc added to iron treatment alone or with vitamin A improves iron indexes and affects diarrheal episodes. This was a randomized, placebo-controlled, double-blind trial conducted in Peru. Anemic children aged 6-35 mo were assigned to 3 treatment groups: ferrous sulfate (FS; n = 104), ferrous sulfate and zinc sulfate (FSZn; n = 109), and ferrous sulfate, zinc sulfate, and vitamin A (FSZnA; n = 110). Vitamin A or its placebo was supplied only once; iron and zinc were provided under supervision >/=1 h apart 6 d/wk for 18 wk. The prevalence of anemia was 42.97%. The increase in hemoglobin in the FS group (19.5 g/L) was significantly less than that in the other 2 groups (24.0 and 23.8 g/L in the FSZn and FSZnA groups, respectively). The increase in serum ferritin in the FS group (24.5 mug/L) was significantly less than that in the other 2 groups (33.0 and 30.8 mug/L in the FSZn and FSZnA groups, respectively). The median duration of diarrhea and the mean number of stools per day was significantly higher in the FS group than in other 2 groups (P < 0.005). Adding zinc to iron treatment increases hemoglobin response, improves iron indexes, and has positive effects on diarrhea. No additional effect of vitamin A was found.

Effect of Pretreatment Anemia on Treatment Outcome of Concurrent Radiochemotherapy in Patients With Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fortin, Andre; Wang Changshu; Vigneault, Eric

2008-09-01

Purpose: To investigate the effect of anemia on outcome of treatment with radiochemotherapy in patients with head-and-neck cancer. Methods and Materials: The data of 196 patients with Stage II-IV head-and-neck cancer treated with concomitant cisplatin-based radiochemotherapy were retrospectively reviewed. Anemia was defined according to World Health Organization criteria as hemoglobin <130 g/L in men and <120 g/L in women. Results: Fifty-three patients were classified as anemic, 143 as nonanemic. The 3-year local control rate of anemic and nonanemic patients was 72% and 85%, respectively (p = 0.01). The 3-year overall survival rate of anemic and nonanemic patients was 52% andmore » 77%, respectively (p = 0.004). In multivariate analysis, anemia was the most significant predictor of local control (hazard ratio, 0.37, p = 0.009) and survival (hazard ratio, 0.47, p = 0.007). A dose-effect relationship was also found for local control (p = .04) and survival (0.04) when grouping by hemoglobin concentration: <120, 120-140, and >140 g/L. Conclusions: Anemia was strongly associated with local control and survival in this cohort of patients with head-and-neck cancer receiving radiochemotherapy.« less

Meta-analysis of treatment with rabbit and horse antithymocyte globulin for aplastic anemia.

PubMed

Hayakawa, Jin; Kanda, Junya; Akahoshi, Yu; Harada, Naonori; Kameda, Kazuaki; Ugai, Tomotaka; Wada, Hidenori; Ishihara, Yuko; Kawamura, Koji; Sakamoto, Kana; Ashizawa, Masahiro; Sato, Miki; Terasako-Saito, Kiriko; Kimura, Shun-Ichi; Kikuchi, Misato; Yamazaki, Rie; Kako, Shinichi; Kanda, Yoshinobu

2017-05-01

Aplastic anemia patients who received rabbit antithymocyte globulin exhibited response and survival rates inferior to those who received horse antithymocyte globulin in several studies. Therefore, we conducted a meta-analysis to compare rabbit and horse antithymocyte globulin as immunosuppressive therapy for aplastic anemia. We searched online databases for studies that compared antithymocyte globulin regimens as first-line treatment for aplastic anemia, including both randomized and non-randomized controlled trials. The early mortality rate at 3 months and overall response rate at 6 months were evaluated. Thirteen studies were included in the analysis. The risk ratio (RR) of early mortality for rabbit vs. horse antithymocyte globulin was 1.33 [95% confidence interval (CI) 0.69-2.57; P = 0.39], with significant heterogeneity. A sensitivity analysis suggested higher early mortality rate in patients who received rabbit antithymocyte globulin. The overall response rate was significantly higher in patients who received horse antithymocyte globulin (RR 1.27; 95% CI 1.05-1.54; P = 0.015). In conclusion, in aplastic anemia patients treated with ATG, early mortality rate was not significantly different in patients receiving horse or rabbit ATG, although a sensitivity analysis showed higher early mortality in the rabbit ATG group. Horse ATG was associated with significantly higher response rate than rabbit ATG.

A short review of malabsorption and anemia

PubMed Central

Fernández-Bañares, Fernando; Monzón, Helena; Forné, Montserrat

2009-01-01

Anemia is a frequent finding in most diseases which cause malabsorption. The most frequent etiology is the combination of iron and vitamin B12 deficiency. Celiac disease is frequently diagnosed in patients referred for evaluation of iron deficiency anemia (IDA), being reported in 1.8%-14.6% of patients. Therefore, duodenal biopsies should be taken during endoscopy if no obvious cause of iron deficiency (ID) can be found. Cobalamin deficiency occurs frequently among elderly patients, but it is often unrecognized because the clinical manifestations are subtle; it is caused primarily by food-cobalamin malabsorption and pernicious anemia. The classic treatment of cobalamin deficiency has been parenteral administration of the vitamin. Recent data suggest that alternative routes of cobalamin administration (oral and nasal) may be useful in some cases. Anemia is a frequent complication of gastrectomy, and has been often described after bariatric surgery. It has been shown that banding procedures which maintain digestive continuity with the antrum and duodenum are associated with low rates of ID. Helicobacter pylori (H pylori) infection may be considered as a risk factor for IDA, mainly in groups with high demands for iron, such as some children and adolescents. Further controlled trials are needed before making solid recommendations about H pylori eradication in these cases. PMID:19787827

Complement component 4

MedlinePlus

... of a certain protein. This protein is part of the complement system. The complement system is a group of proteins ... system and play a role in the development of inflammation. The complement system protects the body from infections, dead cells and ...

[Clinical and experimental study of treating aplastic anemia with fetal liver cell suspension and fetal liver cell-free suspension].

PubMed

Han, J R; Yuan, S W; Ren, Q F

1990-06-01

Fresh fetal liver obtained from 3- to 6-month fetus was prepared. Fetal liver cell suspension (FLC) or fetal liver cell-free suspension (FLCF) were then transfused into two groups of patient of aplastic anemia. 15 of 21 patients of aplastic anemia treated with FLC showed reconstitution of haemopoietic function or improvement of peripheral blood pictures, while 27 of 30 patients treated with FLCF showed reconstitution or improvement. It is verified that there is a stimulating factor for CFU-CM, BFU-E, and CFU-E and also a immunologic stimulant for improving the nonspecific immunologic function of the organism as shown by clinical analysis and experimental study. It is obvious that the therapeutic effect of FLCF is much better than that of the FLC.

Hb Alesha [β67(E11)Val→Met (GTG>ATG); HBB: c.202G > A] Found in a Chinese Girl.

PubMed

Jiang, Hua; Yan, Jin-Mei; Zhou, Jian-Ying; Li, Dong-Zhi

2016-11-01

Mutations that cause destabilization of the hemoglobin (Hb) tetramer are a rare cause of hemolytic anemia. In contrast to the hemolytic anemia caused by enzyme deficiencies, a dominant mode of inheritance characterizes the unstable Hbs. Hb Alesha [β67(E11)Val→Met; HBB: c.202G>A] is caused by a G>A mutation at codon 67 of the β-globin gene, resulting in a valine to methionine substitution at helix E11. This replacement disrupts the apolar bonds between valine and the heme group, producing an unstable Hb and severe hemolysis. We report this rare hemoglobinopathy in a Chinese girl with severe hemolytic anemia, splenomegaly and frequent requirement for red blood cell (RBC) transfusions.

Reticulocyte hemoglobin equivalent as a potential marker for diagnosis of iron deficiency.

PubMed

Toki, Yasumichi; Ikuta, Katsuya; Kawahara, Yoshie; Niizeki, Noriyasu; Kon, Masayuki; Enomoto, Motoki; Tada, Yuko; Hatayama, Mayumi; Yamamoto, Masayo; Ito, Satoshi; Shindo, Motohiro; Kikuchi, Yoko; Inoue, Mitsutaka; Sato, Kazuya; Fujiya, Mikihiro; Okumura, Toshikatsu

2017-07-01

Evaluation of parameters relating to serum ferritin and iron is critically important in the diagnosis of iron deficiency anemia (IDA). The recent development of automated systems for hematology analysis has made it possible to measure reticulocyte hemoglobin equivalent (RET-He), which is thought to reflect iron content in reticulocytes, in the same sample used for complete blood count tests. If RET-He is, indeed, capable of evaluating iron deficiency (ID), it would be useful for immediate diagnosis of IDA. In the present study, we examined the usefulness of RET-He for diagnosis of ID. Blood samples were obtained from 211 patients. Anemia was defined as hemoglobin (Hb) level of <12 g/dL. Iron deficiency was defined as serum ferritin level of <12 ng/mL. Patients were classified into four groups: IDA, ID, control, and non-ID with anemia. Patients in the IDA group had significantly lower RET-He levels than those in the control group. RET-He correlated with serum ferritin in the IDA and ID groups. The area under the curve for RET-He was 0.902, indicating that RET-He facilitates the diagnosis of ID with high accuracy. RET-He changed in parallel with changes in Hb during iron administration for 21 IDA patients. Our results indicate that RET-He may be a clinically useful marker for determining ID in the general population.

Association Between Atopic Disease and Anemia in US Children.

PubMed

Drury, Kerry E; Schaeffer, Matt; Silverberg, Jonathan I

2016-01-01

Atopic disease is associated with chronic inflammation, food allergen avoidance, and use of systemic immunosuppressant medications. All these factors have been shown to be associated with anemia. To investigate whether atopic disease is associated with increased risk of childhood anemia. A cross-sectional survey and laboratory assessment were conducted using data from the 1997-2013 US National Health Interview Survey (NHIS) that included 207,007 children and adolescents and the 1999-2012 National Health and Nutrition Examination Survey (NHANES) that included 30,673 children and adolescents. Analysis of the data was conducted between August 1, 2014, and August 28, 2015. Caregiver-reported history of eczema, asthma, hay fever, and/or food allergy. Anemia was defined by caregiver report in the NHIS and by hemoglobin levels for age and sex in the NHANES. Data were collected on 207,007 children and adolescents from NHIS, representing all pediatric age, sex, racial/ethnic, household educational level, and income groups. The US prevalence was 9.5% (95% CI, 9.4%-9.7%) from all years of the NHIS for health care-diagnosed eczema, 12.8% (95% CI, 12.6%-13.0%) for asthma, 17.1% (95% CI, 16.9%-17.3%) for hay fever, 4.2% (95% CI, 4.1%-4.3%) for food allergy, and 1.1% (95% CI, 1.1%-1.2%) for anemia. In multivariable logistic regression models controlling for age, sex, race/ethnicity, annual household income, highest educational level in the family, insurance coverage, number of persons in the household, birthplace in the United States, and history of asthma, hay fever, and food allergy, anemia was associated with eczema in 14 of 17 studies, asthma in 11, hay fever in 12, and food allergy in 12. In multivariable analysis across the NHIS (with results reported as adjusted odds ratios [95% CIs]), children with any eczema (1.83; 1.58-2.13), asthma (1.31; 1.14-1.51), hay fever (1.57; 1.36-1.81), and food allergy (2.08; 1.71-2.52) had higher odds of anemia (P < .001 for all). In the NHANES, current history of asthma (1.33; 1.04-1.70; P = .02) and eczema (1.93; 1.04-3.59; P = .04) were associated with higher odds of anemia, particularly microcytic anemia (asthma: 1.61; 1.09-2.38; P = .02; eczema: 2.03; 1.20-3.46; P = .009) while history of hay fever was not associated with anemia (0.85; 0.62-1.17; P = .33). The association between atopic disease and anemia was reproducible in multiple cohorts. Future studies are needed to identify the determinants of association between atopic disease and anemia.

Term babies with delayed cord clamping: an approach in preventing anemia (.).

PubMed

Ertekin, Arif Aktug; Nihan Ozdemir, Nilufer; Sahinoglu, Zeki; Gursoy, Tugba; Erbil, Nazan; Kaya, Erdal

2016-09-01

We investigated the effects of delayed and early clamping of the cord on the hematologic status of the baby at birth and at the end of second month. Umbilical cord of 74 babies were clamped in the first 30 s (Group 1) and 76 were clamped at 90-120 s (Group 2). Levels of hemoglobin, hematocrit, iron and ferritin were analyzed from the umbilical cord blood at birth and from the venous samples at the end of second month. Hemoglobin, hematocrit, iron and ferritin levels of cord blood were similar in both groups. However, their levels other than ferritin were higher in Group 2 at the end of second month. Two babies had respiratory distress and twelve neonates received phototherapy in Group 2 whereas only five neonates received phototherapy in Group 1. Term babies to whom delayed cord clamping was performed had improved hematological parameters at the end of second month. Therefore, delaying cord clamping in these babies may be a favorible approach in preventing anemia.

Non-transfusion Dependent Thalassemias: A Developing Country Perspective.

PubMed

Mukherjee, Somnath; Das, Rashmi R; Raghuwanshi, Babita

2015-01-01

Non-transfusion-dependent thalassemias (NTDT) encompass a group of hereditary chronic hemolytic anemia, which, as the name indicates, not require regular blood transfusion for survival. These include β-thalassemia intermedia, hemoglobin E/β-thalassemia, and Hemoglobin H disease (α- thalassemia intermedia). Individuals with structural variant of hemoglobin especially Hemoglobin S and Hemoglobin C associated with "α" or "β" thalassemia in heterozygous condition may also present with similar features of NTDT. NTDT patients are not immune to the development of transfusion unrelated complications in the long run. These hereditary chronic hemolytic anemias are still under-recognized in developing countries like India, where the disease burden might be high causing significant morbidity. The pathophysiologic hallmark that characterizes this group of disorders (ineffective erythropoiesis, hemolysis, chronic anemia) leads to a number of serious complications, similar to transfusion dependent thalassemia. So, timely diagnosis and institution of appropriate preventive/remedial measures as well as education of patient population can help decrease the morbidity to a significant extent. In the present review, focus will be on the pathophysiological mechanisms and available management options of NTDT from a developing country perspective like India.

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... immunochemical techniques the complement C3b inactivator (a plasma protein) in serum. Complement is a group of serum proteins that destroy infectious agents. Measurement of complement C3b inactivator aids in the...

Complement component 3 (C3)

MedlinePlus

... of a certain protein. This protein is part of the complement system. The complement system is a group of proteins ... system and play a role in the development of inflammation. The complement system protects the body from infections, dead cells and ...

The Role of Chlorogenic Acid Supplementation in Anemia and Mineral Disturbances Induced by 4-Tert-Octylphenol Toxicity.

PubMed

Koriem, Khaled M M; Arbid, Mahmoud S S; Gomaa, Nawal E

2018-01-02

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 ml saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

Effect of scaling and root planing on erythrocyte count, hemoglobin and hematocrit in patients with chronic periodontal disease.

PubMed

Malhotra, Ranjan; Kapoor, Anoop; Grover, Vishakha; Grover, Deepak; Kaur, Aaswin

2012-01-01

Anemia of chronic disease, a cytokine-mediated anemia, is a frequent complication of many chronic inflammatory conditions. The present clinical trial was aimed to evaluate the effect of chronic periodontal disease on erythrocyte count, hemoglobin and hematocrit and the changes produced in these parameters after the provision of periodontal therapy. 40 systemically healthy non-smoker male subjects in the age group of 25 to 50 years suffering with chronic periodontal disease were selected and categorized into 2 groups. Group A was categorized as chronic generalized gingivitis, and Group B was categorized as chronic generalized periodontitis on the basis of clinical findings. The clinical parameters Gingival Index (GI), Probing Pock et Depth (PPD) and Relative Attachment Level (RAL) and laboratory blood investigations viz erythrocyte count (EC), hemoglobin (Hb), hematocrit (HCT) and red cell indices (MCV, MCH, MCHC) were recorded at baseline. Complete oral prophylaxis was performed for all patients. Patients were recalled after 3 weeks and 3 months. The clinical and hematological parameters were re-evaluated to analyze the changes after provision of phase I therapy. The mean values of EC, Hb and HCT were significantly lower in Group B in comparison to Group A, and showed a significantly greater increase at 3 months of observation. However, the values of MCV, MCH and MCHC showed a non significant change during the same observation period in both the groups. Lower values of EC, Hb and HCT in Group B showed that mild anemia is associated with chronic generalized periodontitis, which tends to improve after provision of periodontal therapy. Minimal changes in MCV, MCH and MCHC indicated that the lower values are not due to any vitamin and mineral deficiencies, but secondary to the chronic inflammatory changes associated with chronic periodontal disease.

Micronutrient Fortified Milk Improves Iron Status, Anemia and Growth among Children 1–4 Years: A Double Masked, Randomized, Controlled Trial

PubMed Central

Sazawal, Sunil; Dhingra, Usha; Dhingra, Pratibha; Hiremath, Girish; Sarkar, Archana; Dutta, Arup; Menon, Venugopal P.; Black, Robert E.

2010-01-01

Background Multiple micronutrient deficiencies are highly prevalent among preschool children and often lead to anemia and growth faltering. Given the limited success of supplementation and health education programs, fortification of foods could be a viable and sustainable option. We report results from a community based double-masked, randomized trial among children 1–4 years evaluating the effects of micronutrients (especially of zinc and iron) delivered through fortified milk on growth, anemia and iron status markers as part of a four group study design, running two studies simultaneously. Methods and Findings Enrolled children (n = 633) were randomly allocated to receive either micronutrients fortified milk (MN = 316) or control milk (Co = 317). Intervention of MN milk provided additional 7.8 mg zinc, 9.6 mg iron, 4.2 µg selenium, 0.27 mg copper, 156 µg vitamin A, 40.2 mg vitamin C, and 7.5 mg vitamin E per day (three serves) for one year. Anthropometry was recorded at baseline, mid- and end-study. Hematological parameters were estimated at baseline and end-study. Both groups were comparable at baseline. Compliance was over 85% and did not vary between groups. Compared to children consuming Co milk, children consuming MN milk showed significant improvement in weight gain (difference of mean: 0.21 kg/year; 95% confidence interval [CI] 0.12 to 0.31, p<0.001) and height gain (difference of mean: 0.51 cm/year; 95% CI 0.27 to 0.75, p<0.001). Mean hemoglobin (Hb) (difference of 13.6 g/L; 95% CI 11.1 to 16.0, p<0.001) and serum ferritin levels (difference of 7.9 µg/L; 95% CI 5.4 to 10.5, p<0.001) also improved. Children in MN group had 88% (odds ratio = 0.12, 95% CI 0.08 to 0.20, p<0.001) lower risk of iron deficiency anemia. Conclusions/Significance Milk provides an acceptable and effective vehicle for delivery of specific micronutrients, especially zinc and iron. Micronutrient bundle improved growth and iron status and reduced anemia in children 1–4 years old. Trial Registration ClinicalTrials.gov NCT00255385 PMID:20730057

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence

PubMed Central

Arcanjo, C. P. C.; Santos, P. R.

2016-01-01

Background. In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods. The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t-test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results. Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions. In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without. PMID:27703806

Schoolchildren with Learning Difficulties Have Low Iron Status and High Anemia Prevalence.

PubMed

Arcanjo, F P N; Arcanjo, C P C; Santos, P R

2016-01-01

Background . In developing countries there is high prevalence of iron deficiency anemia, which reduces cognitive performance, work performance, and endurance; it also causes learning difficulties and negative impact on development for infant population. Methods . The study concerns a case-control study; data was collected from an appropriate sample consisting of schoolchildren aged 8 years. The sample was divided into two subgroups: those with deficient initial reading skills (DIRS) (case) and those without (control). Blood samples were taken to analyze hemoglobin and serum ferritin levels. These results were then used to compare the two groups with Student's t -test. Association between DIRS and anemia was analyzed using odds ratio (OR). Results . Hemoglobin and serum ferritin levels of schoolchildren with DIRS were statistically lower when compared to those without, hemoglobin p = 0.02 and serum ferritin p = 0.04. DIRS was statistically associated with a risk of anemia with a weighted OR of 1.62. Conclusions . In this study, schoolchildren with DIRS had lower hemoglobin and serum ferritin levels when compared to those without.

The production of recombinant human erythropoietin.

PubMed

Inoue, N; Takeuchi, M; Ohashi, H; Suzuki, T

1995-01-01

Erythropoietin (EPO) is the glycoprotein hormone that promotes differentiation of erythroid progenitor cells in bone marrow. The normal kidney produces EPO to maintain erythrocyte for oxygen supply. This hormone activity was found in the serum of anemic animals in the 1890s. Renal failure results in severe anemia because of reduced EPO production, therefore anemia patients expected EPO treatment for long time. However, this was difficult due to the limited amount of EPO. Many researchers have tried to isolate EPO since the 1950s. Finally Miyake and Goldwasser purified highly active EPO from the urine of aplastic anemia patients. Since then, the characteristics and structural information from the purified material accelerated the cloning of the EPO gene. Mammalian cells were essential to produce EPO, because EPO contains 40% carbohydrate that plays some important roles in its activity, stability and biosynthesis. In 1984, two groups succeeded in cloning the EPO gene and expressing this gene in mammalian cells. Recombinant human EPO is currently available for anemia treatment. In this paper, we review production in mammalian cells, molecular characterization, especially carbohydrate moieties, and clinical applications of recombinant EPO.

Whole-exome analysis to detect congenital hemolytic anemia mimicking congenital dyserythropoietic anemia.

PubMed

Hamada, Motoharu; Doisaki, Sayoko; Okuno, Yusuke; Muramatsu, Hideki; Hama, Asahito; Kawashima, Nozomu; Narita, Atsushi; Nishio, Nobuhiro; Yoshida, Kenichi; Kanno, Hitoshi; Manabe, Atsushi; Taga, Takashi; Takahashi, Yoshiyuki; Miyano, Satoru; Ogawa, Seishi; Kojima, Seiji

2018-06-23

Congenital dyserythropoietic anemia (CDA) is a heterogeneous group of rare congenital disorders characterized by ineffective erythropoiesis and dysplastic changes in erythroblasts. Diagnosis of CDA is based primarily on the morphology of bone marrow erythroblasts; however, genetic tests have recently become more important. Here, we performed genetic analysis of 10 Japanese patients who had been diagnosed with CDA based on laboratory findings and morphological characteristics. We examined 10 CDA patients via central review of bone marrow morphology and genetic analysis for congenital bone marrow failure syndromes. Sanger sequencing for CDAN1, SEC23B, and KLF1 was performed for all patients. We performed whole-exome sequencing in patients without mutation in these genes. Three patients carried pathogenic CDAN1 mutations, whereas no SEC23B mutations were identified in our cohort. WES unexpectedly identified gene mutations known to cause congenital hemolytic anemia in two patients: canonical G6PD p.Val394Leu mutation and SPTA1 p.Arg28His mutation. Comprehensive genetic analysis is warranted for more effective diagnosis of patients with suspected CDA.

Diagnosis and classification of pernicious anemia.

PubMed

Bizzaro, Nicola; Antico, Antonio

2014-01-01

Pernicious anemia (PA) is a complex disorder consisting of hematological, gastric and immunological alterations. Diagnosis of PA relies on histologically proven atrophic body gastritis, peripheral blood examination showing megaloblastic anemia with hypersegmented neutrophils, cobalamin deficiency and antibodies to intrinsic factor and to gastric parietal cells. Anti-parietal cell antibodies are found in 90% of patients with PA, but have low specificity and are seen in atrophic gastritis without megaloblastic anemia as well as in various autoimmune disorders. Anti-intrinsic factor antibodies are less sensitive, being found in only 60% of patients with PA, but are considered highly specific for PA. The incidence of PA increases with age and is rare in persons younger than 30 years of age. The highest prevalence is seen in Northern Europeans, especially those in the United Kingdom and Scandinavia, although PA has been reported in virtually every ethnic group. Because of the complexity of the diagnosis, PA prevalence is probably underestimated and no reliable data are available on the risk of gastric cancer as the end-stage evolution of atrophic gastritis in these patients. Copyright © 2014 Elsevier B.V. All rights reserved.

A 2-year integrated agriculture and nutrition and health behavior change communication program targeted to women in Burkina Faso reduces anemia, wasting, and diarrhea in children 3-12.9 months of age at baseline: a cluster-randomized controlled trial.

PubMed

Olney, Deanna K; Pedehombga, Abdoulaye; Ruel, Marie T; Dillon, Andrew

2015-06-01

Among young children in Burkina Faso, anemia and chronic and acute undernutrition are widespread. This study assessed the impact of Helen Keller International's (HKI) 2-y integrated agriculture [homestead food production (HFP)] and nutrition and health behavior change communication (BCC) program, targeted to women, on children's (3-12.9 mo old at baseline) anthropometry (stunting, wasting, and underweight), mean hemoglobin (Hb), anemia (Hb < 11 g/dL), and diarrhea prevalence. We used a cluster-randomized controlled trial, with 55 villages randomly assigned to a control group (n = 25) or 1 of 2 treatment groups (n = 15 each), which differed by who delivered the BCC messages [older women leaders or health committee (HC) members]. We used difference-in-difference (DID) estimates to assess impacts on child outcomes. We found marginally significant (P < 0.10) impacts on Hb (DID: 0.51 g/dL; P = 0.07) and wasting [DID: -8.8 percentage point (pp); P = 0.08] and statistically significant (P < 0.05) impacts on diarrhea (-15.9 pp; P = 0.00) in HC compared with control villages among children aged 3-12.9 mo and larger impacts for anemia (DID: -14.6 pp; P = 0.03) and mean Hb (DID: 0.74 g/dL; P = 0.03) among younger children (aged 3-5.9 mo). However, we found no significant impacts on stunting or underweight prevalence. Plausibility was supported by greater improvements in women's agricultural production and maternal infant and young child feeding and care knowledge and practices in HC compared with control villages. HKI's 2-y integrated HFP+BCC program (HC group) significantly improved several child outcomes, including wasting (marginal), diarrhea, Hb, and anemia, especially among the youngest children. This is the first cluster-randomized controlled trial of an HFP program that documents statistically significant positive effects on these child nutrition outcomes. This trial was registered at clinicaltrials.gov as NCT01825226. © 2015 American Society for Nutrition.

Randomized controlled trial assessing the efficacy of a reusable fish-shaped iron ingot to increase hemoglobin concentration in anemic, rural Cambodian women.

PubMed

Rappaport, Aviva I; Whitfield, Kyly C; Chapman, Gwen E; Yada, Rickey Y; Kheang, Khin Meng; Louise, Jennie; Summerlee, Alastair J; Armstrong, Gavin R; Green, Timothy J

2017-08-01

Background: Anemia affects 45% of women of childbearing age in Cambodia. Iron supplementation is recommended in populations in which anemia prevalence is high. However, there are issues of cost, distribution, and adherence. A potential alternative is a reusable fish-shaped iron ingot, which, when added to the cooking pot, leaches iron into the fluid in which it is prepared. Objective: We sought to determine whether there was a difference in hemoglobin concentrations in rural Cambodian anemic women (aged 18-49 y) who cooked with the iron ingot or consumed a daily iron supplement compared with a control after 1 y. Design: In Preah Vihear, 340 women with mild or moderate anemia were randomly assigned to 1 ) an iron-ingot group, 2 ) an iron-supplement (18 mg/d) group, or 3 ) a nonplacebo control group. A venous blood sample was taken at baseline and at 6 and 12 mo. Blood was analyzed for hemoglobin, serum ferritin, and serum transferrin receptor. Hemoglobin electrophoresis was used to detect structural hemoglobin variants. Results: Anemia prevalence was 44% with the use of a portable hemoglobinometer during screening. At baseline, prevalence of iron deficiency was 9% on the basis of a low serum ferritin concentration. There was no significant difference in mean hemoglobin concentrations between the iron-ingot group (115 g/L; 95% CI: 113, 118 g/L; P = 0.850) or iron-supplement group (115 g/L; 95% CI: 113, 117 g/L; P = 0.998) compared with the control group (115 g/L; 95% CI: 113, 117 g/L) at 12 mo. Serum ferritin was significantly higher in the iron-supplement group (73 μg/L; 95% CI: 64, 82 μg/L; P = 0.002) than in the control group at 6 mo; however, this significance was not maintained at 12 mo (73 μg/L; 95% CI: 58, 91 μg/L; P = 0.176). Conclusions: Neither the iron ingot nor iron supplements increased hemoglobin concentrations in this population at 6 or 12 mo. We do not recommend the use of the fish-shaped iron ingot in Cambodia or in countries where the prevalence of iron deficiency is low and genetic hemoglobin disorders are high. This trial was registered at clinicaltrials.gov as NCT02341586. © 2017 American Society for Nutrition.

Maize porridge enriched with a micronutrient powder containing low-dose iron as NaFeEDTA but not amaranth grain flour reduces anemia and iron deficiency in Kenyan preschool children.

PubMed

Macharia-Mutie, Catherine W; Moretti, Diego; Van den Briel, Natalie; Omusundi, Agnes M; Mwangi, Alice M; Kok, Frans J; Zimmermann, Michael B; Brouwer, Inge D

2012-09-01

Few studies have evaluated the impact of fortification with iron-rich foods such as amaranth grain and multi-micronutrient powder (MNP) containing low doses of highly bioavailable iron to control iron deficiency anemia (IDA) in children. We assessed the efficacy of maize porridge enriched with amaranth grain or MNP to reduce IDA in Kenyan preschool children. In a 16-wk intervention trial, children (n = 279; 12-59 mo) were randomly assigned to: unrefined maize porridge (control; 4.1 mg of iron/meal; phytate:iron molar ratio 5:1); unrefined maize (30%) and amaranth grain (70%) porridge (amaranth group; 23 mg of iron/meal; phytate:iron molar ratio 3:1); or unrefined maize porridge with MNP (MNP group; 6.6 mg iron/meal; phytate:iron molar ratio 2.6:1; 2.5 mg iron as NaFeEDTA). Primary outcomes were anemia and iron status with treatment effects estimated relative to control. At baseline, 38% were anemic and 30% iron deficient. Consumption of MNP reduced the prevalence of anemia [-46% (95% CI: -67, -12)], iron deficiency [-70% (95% CI: -89, -16)], and IDA [-75% (95% CI: -92, -20)]. The soluble transferrin receptor [-10% (95% CI: -16, -4)] concentration was lower, whereas the hemoglobin (Hb) [2.7 g/L (95% CI: 0.4, 5.1)] and plasma ferritin [40% (95% CI: 10, 95)] concentrations increased in the MNP group. There was no significant change in Hb or iron status in the amaranth group. Consumption of maize porridge fortified with low-dose, highly bioavailable iron MNP can reduce the prevalence of IDA in preschool children. In contrast, fortification with amaranth grain did not improve iron status despite a large increase in iron intake, likely due to high ratio of phytic acid:iron in the meal.

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy.

PubMed

Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-Ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

2014-12-01

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86-90) versus 92% (90-94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54-59) versus 87% (85-90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992-1999 versus 2000-2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia. Copyright© Ferrata Storti Foundation.

First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy

PubMed Central

Yoshida, Nao; Kobayashi, Ryoji; Yabe, Hiromasa; Kosaka, Yoshiyuki; Yagasaki, Hiroshi; Watanabe, Ken-ichiro; Kudo, Kazuko; Morimoto, Akira; Ohga, Shouichi; Muramatsu, Hideki; Takahashi, Yoshiyuki; Kato, Koji; Suzuki, Ritsuro; Ohara, Akira; Kojima, Seiji

2014-01-01

The current treatment approach for severe aplastic anemia in children is based on studies performed in the 1980s, and updated evidence is required. We retrospectively compared the outcomes of children with acquired severe aplastic anemia who received immunosuppressive therapy within prospective trials conducted by the Japanese Childhood Aplastic Anemia Study Group or who underwent bone marrow transplantation from an HLA-matched family donor registered in the Japanese Society for Hematopoietic Cell Transplantation Registry. Between 1992 and 2009, 599 children (younger than 17 years) with severe aplastic anemia received a bone marrow transplant from an HLA-matched family donor (n=213) or immunosuppressive therapy (n=386) as first-line treatment. While the overall survival did not differ between patients treated with immunosuppressive therapy or bone marrow transplantation [88% (95% confidence interval: 86–90) versus 92% (90–94)], failure-free survival was significantly inferior in patients receiving immunosuppressive therapy than in those undergoing bone marrow transplantation [56% (54–59) versus 87% (85–90); P<0.0001]. There was no significant improvement in outcomes over the two time periods (1992–1999 versus 2000–2009). In multivariate analysis, age <10 years was identified as a favorable factor for overall survival (P=0.007), and choice of first-line immunosuppressive therapy was the only unfavorable factor for failure-free survival (P<0.0001). These support the current algorithm for treatment decisions, which recommends bone marrow transplantation when an HLA-matched family donor is available in pediatric severe aplastic anemia. PMID:25193958

The association of prenatal nutrition and educational services with low birth weight rates in a Florida program.

PubMed Central

Taren, D L; Graven, S N

1991-01-01

Nutrition services and education, provided as components of normal prenatal care, have a key role in preventing preterm delivery and low birth weight (LBW). To determine the influence of these components on a woman's risk of having a LBW infant, the authors examined groups of patients who were receiving the services. Bivariate analyses were made of 9,024 prenatal charts of single births. Most women received nutrition education, prescriptions for nutrient supplements, screenings for anemia, and dietary assessments. A greater proportion of the women at high risk received the interventions than did women at lower risk. The presence of educational components and assays for anemia were associated with a lower risk of a LBW delivery in the total group and in the high risk groups. PMID:1908594

Complementation studies in Niemann-Pick disease type C indicate the existence of a second group.

PubMed Central

Steinberg, S J; Ward, C P; Fensom, A H

1994-01-01

Niemann-Pick disease type C is a clinically heterogeneous storage disorder with an unknown primary metabolic defect. We have undertaken somatic cell hybridisation experiments using skin fibroblast strains from 12 patients representing a wide clinical spectrum. Preliminary experiments using filipin staining of free cholesterol as a marker for complementation indicated the existence of one major group (group alpha) and one minor group (group beta) represented by one mutant strain. Subsequent experiments in which sphingomyelinase activity was measured as a marker for complementation using five mutant strains showing activity consistently < 40% control levels confirmed the existence of the second group. Images PMID:8071958

Mendelian diseases among Roman Jews: implications for the origins of disease alleles.

PubMed

Oddoux, C; Guillen-Navarro, E; Ditivoli, C; Dicave, E; Cilio, M R; Clayton, C M; Nelson, H; Sarafoglou, K; McCain, N; Peretz, H; Seligsohn, U; Luzzatto, L; Nafa, K; Nardi, M; Karpatkin, M; Aksentijevich, I; Kastner, D; Axelrod, F; Ostrer, H

1999-12-01

The Roman Jewish community has been historically continuous in Rome since pre-Christian times and may have been progenitor to the Ashkenazi Jewish community. Despite a history of endogamy over the past 2000 yr, the historical record suggests that there was admixture with Ashkenazi and Sephardic Jews during the Middle Ages. To determine whether Roman and Ashkenazi Jews shared common signature mutations, we tested a group of 107 Roman Jews, representing 176 haploid sets of chromosomes. No mutations were found for Bloom syndrome, BRCA1, BRCA2, Canavan disease, Fanconi anemia complementation group C, or Tay-Sachs disease. Two unrelated individuals were positive for the 3849 + 10C->T cystic fibrosis mutation; one carried the N370S Gaucher disease mutation, and one carried the connexin 26 167delT mutation. Each of these was shown to be associated with the same haplotype of tightly linked microsatellite markers as that found among Ashkenazi Jews. In addition, 14 individuals had mutations in the familial Mediterranean fever gene and three unrelated individuals carried the factor XI type III mutation previously observed exclusively among Ashkenazi Jews. These findings suggest that the Gaucher, connexin 26, and familial Mediterranean fever mutations are over 2000 yr old, that the cystic fibrosis 3849 + 10kb C->T and factor XI type III mutations had a common origin in Ashkenazi and Roman Jews, and that other mutations prevalent among Ashkenazi Jews are of more recent origin.

Clinical outcome in neonates with twin anemia-polycythemia sequence.

PubMed

Lopriore, Enrico; Slaghekke, Femke; Oepkes, Dick; Middeldorp, Johanna M; Vandenbussche, Frank P; Walther, Frans J

2010-07-01

The purpose of this study was to evaluate neonatal outcome of monochorionic twin pregnancies complicated by twin anemia-polycythemia sequence (TAPS). A cohort of consecutive monochorionic twins with TAPS with double survivors was included in the study. Each twin pair with TAPS was compared with 2 monochorionic twin pairs who were unaffected by TAPS or twin-to-twin transfusion syndrome and who were matched for gestational age at birth. Neonatal death, severe morbidity, and cerebral injury were studied. We included 19 twin pairs in the TAPS group and 38 control twin pairs. The incidence of neonatal death and severe neonatal morbidity was similar in the TAPS group and control group (3% [1/38] vs 1% [1/76] and 24% [9/38] vs 28% [21/76], respectively). Severe cerebral injury was detected in 1 infant (5%) in the TAPS group and 1 infant (2%) in the control group. Neonatal mortality and morbidity rates in a select population of TAPS neonates are similar to control neonatal rates. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Impact of the International Prognostic Scoring System cytogenetic risk groups on the outcome of patients with primary myelodysplastic syndromes undergoing allogeneic stem cell transplantation from human leukocyte antigen-identical siblings: a retrospective analysis of the European Society for Blood and Marrow Transplantation-Chronic Malignancies Working Party.

PubMed

Onida, Francesco; Brand, Ronald; van Biezen, Anja; Schaap, Michel; von dem Borne, Peter A; Maertens, Johan; Beelen, Dietrich W; Carreras, Enric; Alessandrino, Emilio P; Volin, Liisa; Kuball, Jürgen H E; Figuera, Angela; Sierra, Jorge; Finke, Jürgen; Kröger, Nicolaus; de Witte, Theo

2014-10-01

Acquired chromosomal abnormalities are important prognostic factors in patients with myelodysplastic syndromes treated with supportive care and with disease-modifying therapeutic interventions, including allogeneic hematopoietic stem cell transplantation. To assess the prognostic impact of cytogenetic characteristics after hematopoietic stem cell transplantation accurately, we investigated a homogeneous group of 523 patients with primary myelodysplastic syndromes who have received stem cells from human leukocyte antigen-identical siblings. Overall survival at five years from transplantation in good, intermediate, and poor cytogenetic risk groups according to the International Prognostic Scoring System was 48%, 45% and 30%, respectively (P<0.01). Both the disease status (complete remission vs. not in complete remission) and the morphological classification at transplant in the untreated patients were significantly associated with probability of overall survival and relapse-free survival (P<0.01). The cytogenetic risk groups have no prognostic impact in untreated patients with refractory anemia ± ringed sideroblasts (P=0.90). However, combining the good and intermediate cytogenetic risk groups and comparing them to the poor-risk group showed within the other three disease-status-at-transplant groups a hazard ratio of 1.86 (95%CI: 1.41-2.45). In conclusion, this study shows that, in a large series of patients with primary myelodysplastic syndromes, poor-risk cytogenetics as defined by the standard International Prognostic Scoring System is associated with a relatively poor survival after allogeneic stem cell transplantation from human leukocyte antigen-identical siblings except in patients who are transplanted in refractory anemia/refractory anemia with ringed sideroblasts stage before progression to higher myelodysplastic syndrome stages. Copyright© Ferrata Storti Foundation.

Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany – a real-world evidence analysis

PubMed Central

Haas, Jennifer Scarlet; Ong, Siew Hwa; Borchert, Kathrin; Hardt, Thomas; Lechat, Elmira; Nip, Kerry; Foerster, Douglas; Braun, Sebastian; Baumgart, Daniel C

2018-01-01

Background Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. Aim This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. Methods IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. Results In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). Conclusion IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains. PMID:29440920

Oral versus intravenous iron therapy in patients with inflammatory bowel disease and iron deficiency with and without anemia in Germany - a real-world evidence analysis.

PubMed

Stein, Jürgen; Haas, Jennifer Scarlet; Ong, Siew Hwa; Borchert, Kathrin; Hardt, Thomas; Lechat, Elmira; Nip, Kerry; Foerster, Douglas; Braun, Sebastian; Baumgart, Daniel C

2018-01-01

Iron-deficiency anemia and iron deficiency are common comorbidities associated with inflammatory bowel disease (IBD) resulting in impaired quality of life and high health care costs. Intravenous iron has shown clinical benefit compared to oral iron therapy. This study aimed to compare health care outcomes and costs after oral vs intravenous iron treatment for IBD patients with iron deficiency or iron deficiency anemia (ID/A) in Germany. IBD patients with ID/A were identified by ICD-10-GM codes and newly commenced iron treatment via ATC codes in 2013 within the InGef (formerly Health Risk Institute) research claims database. Propensity score matching was performed to balance both treatment groups. Non-observable covariates were adjusted by applying the difference-in-differences (DID) approach. In 2013, 589 IBD patients with ID/A began oral and 442 intravenous iron treatment. After matching, 380 patients in each treatment group were analyzed. The intravenous group had fewer all-cause hospitalizations (37% vs 48%) and ID/A-related hospitalizations (5% vs 14%) than the oral iron group. The 1-year preobservation period comparison revealed significant health care cost differences between both groups. After adjusting for cost differences by DID method, total health care cost savings in the intravenous iron group were calculated to be €367. While higher expenditure for medication (€1,876) was observed in the intravenous iron group, the inpatient setting achieved most cost savings (€1,887). IBD patients receiving intravenous iron were less frequently hospitalized and incurred lower total health care costs compared to patients receiving oral iron. Higher expenditures for pharmaceuticals were compensated by cost savings in other domains.

Pregnancy Complications: Anemia

MedlinePlus

... online community Home > Complications & Loss > Pregnancy complications > Anemia Anemia E-mail to a friend Please fill in ... anemia at a prenatal care visit . What causes anemia? Usually, a woman becomes anemic (has anemia) because ...

Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates123

PubMed Central

Zhao, Gengli; Xu, Guobin; Zhou, Min; Jiang, Yaping; Richards, Blair; Clark, Katy M; Kaciroti, Niko; Georgieff, Michael K; Zhang, Zhixiang; Tardif, Twila; Li, Ming; Lozoff, Betsy

2015-01-01

Background: Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status. Objective: The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status. Methods: Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 μg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 μg/L or zinc protoporphyrin/heme >118 μmol/mol). Results: A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P < 0.05). Conclusions: Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752. PMID:26063068

Prenatal Iron Supplementation Reduces Maternal Anemia, Iron Deficiency, and Iron Deficiency Anemia in a Randomized Clinical Trial in Rural China, but Iron Deficiency Remains Widespread in Mothers and Neonates.

PubMed

Zhao, Gengli; Xu, Guobin; Zhou, Min; Jiang, Yaping; Richards, Blair; Clark, Katy M; Kaciroti, Niko; Georgieff, Michael K; Zhang, Zhixiang; Tardif, Twila; Li, Ming; Lozoff, Betsy

2015-08-01

Previous trials of prenatal iron supplementation had limited measures of maternal or neonatal iron status. The purpose was to assess effects of prenatal iron-folate supplementation on maternal and neonatal iron status. Enrollment occurred June 2009 through December 2011 in Hebei, China. Women with uncomplicated singleton pregnancies at ≤20 wk gestation, aged ≥18 y, and with hemoglobin ≥100 g/L were randomly assigned 1:1 to receive daily iron (300 mg ferrous sulfate) or placebo + 0.40 mg folate from enrollment to birth. Iron status was assessed in maternal venous blood (at enrollment and at or near term) and cord blood. Primary outcomes were as follows: 1) maternal iron deficiency (ID) defined in 2 ways as serum ferritin (SF) <15 μg/L and body iron (BI) <0 mg/kg; 2) maternal ID anemia [ID + anemia (IDA); hemoglobin <110 g/L]; and 3) neonatal ID (cord blood ferritin <75 μg/L or zinc protoporphyrin/heme >118 μmol/mol). A total of 2371 women were randomly assigned, with outcomes for 1632 women or neonates (809 placebo/folate, 823 iron/folate; 1579 mother-newborn pairs, 37 mothers, 16 neonates). Most infants (97%) were born at term. At or near term, maternal hemoglobin was significantly higher (+5.56 g/L) for iron vs. placebo groups. Anemia risk was reduced (RR: 0.53; 95% CI: 0.43, 0.66), as were risks of ID (RR: 0.74; 95% CI: 0.69, 0.79 by SF; RR: 0.65; 95% CI: 0.59, 0.71 by BI) and IDA (RR: 0.49; 95% CI: 0.38, 0.62 by SF; RR: 0.51; 95% CI: 0.40, 0.65 by BI). Most women still had ID (66.8% by SF, 54.7% by BI). Adverse effects, all minor, were similar by group. There were no differences in cord blood iron measures; >45% of neonates in each group had ID. However, dose-response analyses showed higher cord SF with more maternal iron capsules reported being consumed (β per 10 capsules = 2.60, P < 0.05). Prenatal iron supplementation reduced anemia, ID, and IDA in pregnant women in rural China, but most women and >45% of neonates had ID, regardless of supplementation. This trial was registered at clinicaltrials.gov as NCT02221752. © 2015 American Society for Nutrition.

Structural and biophysical properties of h-FANCI ARM repeat protein.

PubMed

Siddiqui, Mohd Quadir; Choudhary, Rajan Kumar; Thapa, Pankaj; Kulkarni, Neha; Rajpurohit, Yogendra S; Misra, Hari S; Gadewal, Nikhil; Kumar, Satish; Hasan, Syed K; Varma, Ashok K

2017-11-01

Fanconi anemia complementation groups - I (FANCI) protein facilitates DNA ICL (Inter-Cross-link) repair and plays a crucial role in genomic integrity. FANCI is a 1328 amino acids protein which contains armadillo (ARM) repeats and EDGE motif at the C-terminus. ARM repeats are functionally diverse and evolutionarily conserved domain that plays a pivotal role in protein-protein and protein-DNA interactions. Considering the importance of ARM repeats, we have explored comprehensive in silico and in vitro approach to examine folding pattern. Size exclusion chromatography, dynamic light scattering (DLS) and glutaraldehyde crosslinking studies suggest that FANCI ARM repeat exist as monomer as well as in oligomeric forms. Circular dichroism (CD) and fluorescence spectroscopy results demonstrate that protein has predominantly α- helices and well-folded tertiary structure. DNA binding was analysed using electrophoretic mobility shift assay by autoradiography. Temperature-dependent CD, Fluorescence spectroscopy and DLS studies concluded that protein unfolds and start forming oligomer from 30°C. The existence of stable portion within FANCI ARM repeat was examined using limited proteolysis and mass spectrometry. The normal mode analysis, molecular dynamics and principal component analysis demonstrated that helix-turn-helix (HTH) motif present in ARM repeat is highly dynamic and has anti-correlated motion. Furthermore, FANCI ARM repeat has HTH structural motif which binds to double-stranded DNA.

FANCD2 protects against bone marrow injury from ferroptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Song, Xinxin; Xie, Yangchun; Kang, Rui

Bone marrow injury remains a serious concern in traditional cancer treatment. Ferroptosis is an iron- and oxidative-dependent form of regulated cell death that has become part of an emerging strategy for chemotherapy. However, the key regulator of ferroptosis in bone marrow injury remains unknown. Here, we show that Fanconi anemia complementation group D2 (FANCD2), a nuclear protein involved in DNA damage repair, protects against ferroptosis-mediated injury in bone marrow stromal cells (BMSCs). The classical ferroptosis inducer erastin remarkably increased the levels of monoubiquitinated FANCD2, which in turn limited DNA damage in BMSCs. FANCD2-deficient BMSCs were more sensitive to erastin-induced ferroptosismore » (but not autophagy) than FANCD2 wild-type cells. Knockout of FANCD2 increased ferroptosis-associated biochemical events (e.g., ferrous iron accumulation, glutathione depletion, and malondialdehyde production). Mechanically, FANCD2 regulated genes and/or expression of proteins involved in iron metabolism (e.g., FTH1, TF, TFRC, HAMP, HSPB1, SLC40A1, and STEAP3) and lipid peroxidation (e.g., GPX4). Collectively, these findings indicate that FANCD2 plays a novel role in the negative regulation of ferroptosis. FANCD2 could represent an amenable target for the development of novel anticancer therapies aiming to reduce the side effects of ferroptosis inducers.« less

The functional interactome of GSTP: A regulatory biomolecular network at the interface with the Nrf2 adaption response to oxidative stress.

PubMed

Bartolini, Desirée; Galli, Francesco

2016-04-15

Glutathione S-transferase P (GSTP), and possibly other members of the subfamily of cytosolic GSTs, are increasingly proposed to have roles far beyond the classical GSH-dependent enzymatic detoxification of electrophilic metabolites and xenobiotics. Emerging evidence suggests that these are essential components of the redox sensing and signaling platform of cells. GSTP monomers physically interact with cellular proteins, such as other cytosolic GSTs, signaling kinases and the membrane peroxidase peroxiredoxin 6. Other interactions reported in literature include that with regulatory proteins such as Fanconi anemia complementation group C protein, transglutaminase 2 and several members of the keratin family of genes. Transcription factors downstream of inflammatory and oxidative stress pathways, namely STAT3 and Nrf2, were recently identified to be further components of this interactome. Together these pieces of evidence suggest the existence of a regulatory biomolecular network in which GSTP represents a node of functional convergence and coordination of signaling and transcription proteins, namely the "GSTP interactome", associated with key cellular processes such as cell cycle regulation and the stress response. These aspects and the methodological approach to explore the cellular interactome(s) are discussed in this review paper. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive behavioral therapy in patients with sickle cell disease.

PubMed

Daniels, Sheena

2015-01-01

Sickle cell disease (SCD) is an inherited autosomal recessive disorder. In the United States, most individuals with SCD are African Americans, withan incidence of 1 in 400 to 1 in 500 live births. SCD is a lifelong disorder with no known cure. SCD causes anemia, frequent painful episodes, and reduced life ex- pectancy. The most disturbing clinical problem associated with SCD is severe pain episodes, the most common reason for hospitalization. Pharmacological interventions have been the mainstream for treatment; however, psychological interventions such as cognitive behavioral therapy (CBT) may complement current medical treatment, lead- ing to better coping and overall improved quality of life. In a quasi-experimental one-group pretest-posttest study, 9 African American individuals with SCD completed 3 weekly educational sessions learning CBT methods. Participants demonstrated increased frequency of use of CBT methods post-intervention, including diverting attention, coping self-statements, and behavioral activities, leading to better pain control. However, quality of life and role limitation did not show significant improvement. CBT may be beneficial to those suffering from SCD when combined with conventional treatment options; however, there are still barriers to incorporating psychological interventions into practice. CBT shows promise for individuals with chronic conditions such as SCD, but more investigation into its efficacy is needed with larger sample sizes over longer periods of time.

Helicase-inactivating mutations as a basis for dominant negative phenotypes

PubMed Central

Wu, Yuliang

2010-01-01

There is ample evidence from studies of both unicellular and multicellular organisms that helicase-inactivating mutations lead to cellular dysfunction and disease phenotypes. In this review, we will discuss the mechanisms underlying the basis for abnormal phenotypes linked to mutations in genes encoding DNA helicases. Recent evidence demonstrates that a clinically relevant patient missense mutation in Fanconi Anemia Complementation Group J exerts detrimental effects on the biochemical activities of the FANC J helicase, and these molecular defects are responsible for aberrant genomic stability and a poor DNA damage response. The ability of FANC J to use the energy from AT P hydrolysis to produce the force required to unwind duplex or G-quadruplex DNA structures or destabilize protein bound to DNA is required for its DNA repair functions in vivo. Strikingly, helicase-inactivating mutations can exert a spectrum of dominant negative phenotypes, indicating that expression of the mutant helicase protein potentially interferes with normal DNA metabolism and has an effect on basic cellular processes such as DNA replication, the DNA damage response and protein trafficking. This review emphasizes that future studies of clinically relevant mutations in helicase genes will be important to understand the molecular pathologies of the associated diseases and their impact on heterozygote carriers. PMID:20980836

Anemia in Chronic Kidney Disease

MedlinePlus

... Heart Disease Mineral & Bone Disorder Anemia in Chronic Kidney Disease What is anemia? Anemia is a condition ... they should. How is anemia related to chronic kidney disease? Anemia commonly occurs in people with chronic ...

Effect of 131I on the anemia of hyperthyroidism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perlman, J.A.; Sternthal, P.M.

1983-01-01

Data from the National Thyrotoxicosis Therapy Follow-Up Study (NTTFS) are presented here to document the existence of anemia in hyperthyroidism, a mild and reversible anemia that is simultaneously ameliorated with reversal of the hyperthyroid state. Among 20,600 women entered into the NTTF study with no previous history of hematological disorders, the prevalence of anemia was found to range from 10-15%, appearing to be higher in those selected for treatment with 131I when compared to those selected for surgery. An attempt is made to verify the recent hypothesis that thyroid hormone levels in the supraphysiologic range may suppress erythrogenesis. Two statisticallymore » significant regression models are consistent with a hypothesis of thyrotoxic bone marrow suppression. However, both associations are weak enough to suggest that some other physiologic improvement underlies the amelioration of anemia when hyperthyroidism is reversed. The degree of improvement in hematological status is similar for women in both treatment groups. Among 4464 women for whom serial hematological tests are obtained, over 3/4 of anemic patients are no longer anemic after an average 6.2 yr of follow-up. Clinicians are reassured that radioactive iodine exposure causes no further insult to the bone marrow, no matter what the cumulative dosage. The highly fractionated low dose bone marrow exposures to radiation account for the minimal hematological risks of 131I treatment.« less

Predictive factors for anemia response to erythropoiesis-stimulating agents in myelofibrosis.

PubMed

Hernández-Boluda, Juan-Carlos; Correa, Juan-Gonzalo; García-Delgado, Regina; Martínez-López, Joaquín; Alvarez-Larrán, Alberto; Fox, María-Laura; García-Gutiérrez, Valentín; Pérez-Encinas, Manuel; Ferrer-Marín, Francisca; Mata-Vázquez, María-Isabel; Raya, José-María; Estrada, Natalia; García, Silvia; Kerguelen, Ana; Durán, María-Antonia; Albors, Manuel; Cervantes, Francisco

2017-04-01

Erythropoiesis-stimulating agents (ESAs) are commonly used to treat the anemia of myelofibrosis (MF), but information on the predictors of response is limited. Results of ESA therapy were analyzed in 163 MF patients with severe anemia, most of whom had inadequate erythropoietin (EPO) levels (<125 U/L) at treatment start. According to the revised criteria of the International Working Group for Myelofibrosis Treatment and Research, anemia response was achieved in 86 patients (53%). Median response duration was 19.3 months. In multivariate analysis, baseline factors associated with a higher response rate were female sex (P=.007), leukocyte count ≥10×10 9 /L (P=.033), and serum ferritin <200 ng/mL (P=.002). Patients with 2 or 3 of the above features had a significantly higher response rate than the remainder (73% vs 28%, respectively; P<.001). Over the 373 patient-years of follow-up on ESA treatment, nine patients developed thrombotic complications (six arterial, three venous), accounting for 2.41 events per 100 patient-years. Survival time from ESA start was longer in anemia responders than in non-responders (P=.011). Besides the already established predictive value of EPO levels, these data can help to identify which MF patients are more likely to benefit from ESA treatment. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association of Preoperative Anemia With Postoperative Mortality in Neonates.

PubMed

Goobie, Susan M; Faraoni, David; Zurakowski, David; DiNardo, James A

2016-09-01

Neonates undergoing noncardiac surgery are at risk for adverse outcomes. Preoperative anemia is a strong independent risk factor for postoperative mortality in adults. To our knowledge, this association has not been investigated in the neonatal population. To assess the association between preoperative anemia and postoperative mortality in neonates undergoing noncardiac surgery in a large sample of US hospitals. Using data from the 2012 and 2013 pediatric databases of the American College of Surgeons National Surgical Quality Improvement Program, we conducted a retrospective study of neonates undergoing noncardiac surgery. Analysis of the data took place between June 2015 and December 2015. All neonates (0-30 days old) with a recorded preoperative hematocrit value were included. Anemia defined as hematocrit level of less than 40%. Receiver operating characteristics analysis was used to assess the association between preoperative hematocrit and mortality, and the Youden J Index was used to determine the specific hematocrit cutoff point to define anemia in the neonatal population. Demographic and postoperative outcomes variables were compared between anemic and nonanemic neonates. Univariate and multivariable logistic regression analyses were used to determine factors associated with postoperative neonatal mortality. An external validation was performed using the 2014 American College of Surgeons National Surgical Quality Improvement Program database. Neonates accounted for 2764 children (6%) in the 2012-2013 American College of Surgeons National Surgical Quality Improvement Program databases. Neonates inlcuded in the study were predominately male (64.5%), white (66.3%), and term (69.9% greater than 36 weeks' gestation) and weighed more than 2 kg (85.0%). Postoperative in-hospital mortality was 3.4% in neonates and 0.6% in all age groups (0-18 years). A preoperative hematocrit level of less than 40% was the optimal cutoff (Youden) to predict in-hospital mortality. Multivariable regression analysis demonstrated that preoperative anemia is an independent risk factor for mortality (OR, 2.62; 95% CI, 1.51-4.57) in neonates. The prevalence of postoperative in-hospital mortality was significantly higher in neonates with a preoperative hematocrit level less than 40%; being 7.5% (95% CI, 1%-10%) vs 1.4% (95% CI, 0%-4%) for preoperative hematocrit levels 40%, or greater. The relationship between anemia and in-hospital mortality was confirmed in our validation cohort (National Surgical Quality Improvement Program 2014). To our knowledge, this is the first study to define the incidence of preoperative anemia in neonates, the incidence of postoperative in-hospital mortality in neonates, and the association between preoperative anemia and postoperative mortality in US hospitals. Timely diagnosis, prevention, and appropriate treatment of preoperative anemia in neonates might improve survival.

[Clinical hematological symptoms of vitamin B12 deficiency in old age : Summarized overview of this year's symposium of the Working Group "Anemia in the Aged" on the occasion of the annual conference of the German Geriatric Society (DGG) in Frankfurt].

PubMed

Röhrig, Gabriele; Gütgemann, Ines; Kolb, Gerald; Leischker, Andreas

2018-05-23

The interdisciplinary symposium of the working group "anemia in the aged" on the occasion of the annual conference of the German Society of Geriatrics focused this year on vitamin B 12 deficiency in aged patients. Experts from hematopathology, clinical geriatrics and geriatric hematology presented the case of a 78-year-old woman and an interdisciplinary discussion was held on the epidemiology, clinical aspects as well as diagnostic and therapeutic steps. This article reviews the symposium on vitamin B 12 deficiency in the aged in the context of the currently available literature.

Gene for ataxia-telangiectasia complementation group D (ATDC)

DOEpatents

Murnane, John P.; Painter, Robert B.; Kapp, Leon N.; Yu, Loh-Chung

1995-03-07

Disclosed herein is a new gene, an AT gene for complementation group D, the ATDC gene and fragments thereof. Nucleic acid probes for said gene are provided as well as proteins encoded by said gene, cDNA therefrom, preferably a 3 kilobase (kb) cDNA, and recombinant nucleic acid molecules for expression of said proteins. Further disclosed are methods to detect mutations in said gene, preferably methods employing the polymerase chain reaction (PCR). Also disclosed are methods to detect AT genes from other AT complementation groups.

Women's perceptions of iron deficiency and anemia prevention and control in eight developing countries.

PubMed

Galloway, Rae; Dusch, Erin; Elder, Leslie; Achadi, Endang; Grajeda, Ruben; Hurtado, Elena; Favin, Mike; Kanani, Shubhada; Marsaban, Julie; Meda, Nicolas; Moore, K Mona; Morison, Linda; Raina, Neena; Rajaratnam, Jolly; Rodriquez, Javier; Stephen, Chitra

2002-08-01

The World Health Organization estimates that 58% of pregnant women in developing countries are anemic. In spite of the fact that most ministries of health in developing countries have policies to provide pregnant women with iron in a supplement form, maternal anemia prevalence has not declined significantly where large-scale programs have been evaluated. During the period 1991-98, the MotherCare Project and its partners conducted qualitative research to determine the major barriers and facilitators of iron supplementation programs for pregnant women in eight developing countries. Research results were used to develop pilot program strategies and interventions to reduce maternal anemia. Across-region results were examined and some differences were found but the similarity in the way women view anemia and react to taking iron tablets was more striking than differences encountered by region, country or ethnic group. While women frequently recognize symptoms of anemia, they do not know the clinical term for anemia. Half of women in all countries consider these symptoms to be a priority health concern that requires action and half do not. Those women who visit prenatal health services are often familiar with iron supplements, but commonly do not know why they are prescribed. Contrary to the belief that women stop taking iron tablets mainly due to negative side effects, only about one-third of women reported that they experienced negative side effects in these studies. During iron supplementation trials in five of the countries, only about one-tenth of the women stopped taking the tablets due to side effects. The major barrier to effective supplementation programs is inadequate supply. Additional barriers include inadequate counseling and distribution of iron tablets, difficult access and poor utilization of prenatal health care services, beliefs against consuming medications during pregnancy, and in most countries, fears that taking too much iron may cause too much blood or a big baby, making delivery more difficult. Facilitators include women's recognition of improved physical well being with the alleviation of symptoms of anemia, particularly fatigue, a better appetite, increased appreciation of benefits for the fetus, and subsequent increased demand for prevention and treatment of iron deficiency and anemia.

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway.

PubMed

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

2017-01-01

The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination.

Pernicious anemia associated with autoimmune hemolytic anemia and alopecia areata.

PubMed

Zafad, Saadia; Madani, Abdellah; Harif, Mhamed; Quessar, Asmaa; Benchekroun, Said

2007-12-01

We report a 16-year-old male with a combination of pernicious anemia, auto-immune hemolytic anemia and alopecia areata. Autoimmune hemolytic anemia coexisted with pernicious anemia but was diagnosed only when the anemia failed to respond to cobalamin therapy. Alopecia areata occurred 9 years later. 2007 Wiley-Liss, Inc

Chronic restraint stress after injury and shock is associated with persistent anemia despite prolonged elevation in erythropoietin levels.

PubMed

Bible, Letitia E; Pasupuleti, Latha V; Gore, Amy V; Sifri, Ziad C; Kannan, Kolenkode B; Mohr, Alicia M

2015-07-01

Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (chronic stress [CS]) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia and prolong the initial anemia, despite elevated erythropoietin (EPO) levels. Male Sprague-Dawley rats (n = 6-8 per group) underwent lung contusion (LC) or combined LC/hemorrhagic shock (LCHS) followed by 6 days of CS. CS consisted of a 2-hour restraint period interrupted with repositioning and alarms every 30 minutes. At 7 days, urine was assessed for norepinephrine (NE) levels, blood for EPO and hemoglobin (Hgb), and BM for erythroid progenitor growth. Animals undergoing LC or combined LCHS predictably recovered by Day 7; urine NE, EPO, and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on Day 6. The addition of CS to LC led to a persistent 20% to 25% decrease in the growth of BM hematopoietic progenitor cells. These findings were further exaggerated when CS was added following LCHS, resulting in a 20%q to 40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared with LCHS alone. Exposing injured animals to CS results in prolonged elevation of NE and EPO, which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating CS after severe injury is a potential therapeutic target to improve BM dysfunction and anemia.

High Oxygen Partial Pressure Decreases Anemia-Induced Heart Rate Increase Equivalent to Transfusion

PubMed Central

Feiner, John R.; Finlay-Morreale, Heather E.; Toy, Pearl; Lieberman, Jeremy A.; Viele, Maurene K.; Hopf, Harriet W.; Weiskopf, Richard B.

2011-01-01

Background Anemia is associated with morbidity and mortality and frequently leads to transfusion of erythrocytes. We sought to compare directly the effect of high inspired oxygen fraction vs. transfusion of erythrocytes on the anemia-induced increased heart rate (HR) in humans undergoing experimental acute isovolemic anemia. Methods We combined HR data from healthy subjects undergoing experimental isovolemic anemia in seven studies performed by our group. We examined HR changes associated with breathing 100% oxygen by non-rebreathing face mask vs. transfusion of erythrocytes at their nadir hemoglobin (Hb) concentration of 5 g/dL. Data were analyzed using a mixed-effects model. Results HR had an inverse linear relationship to hemoglobin concentration with a mean increase of 3.9 beats per minute per gram of Hb (beats/min/g Hb) decrease (95% confidence interval [CI], 3.7 – 4.1 beats/min/g Hb), P < 0.0001. Return of autologous erythrocytes significantly decreased HR by 5.3 beats/min/g Hb (95% CI, 3.8 – 6.8 beats/min/g Hb) increase, P < 0.0001. HR at nadir Hb of 5.6 g/dL (95% CI, 5.5 – 5.7 g/dL) when breathing air (91.4 beats/min; 95% CI, 87.6 – 95.2 beats/min) was reduced by breathing 100% oxygen (83.0 beats/min; 95% CI, 79.0 -87.0 beats/min), P < 0.0001. The HR at hemoglobin 5.6 g/dL when breathing oxygen was equivalent to the HR at Hb 8.9 g/dL when breathing air. Conclusions High arterial oxygen partial pressure reverses the heart rate response to anemia, probably owing to its usability, rather than its effect on total oxygen content. The benefit of high arterial oxygen partial pressure has significant potential clinical implications for the acute treatment of anemia and results of transfusion trials. PMID:21768873

The Impact of Integrated Infant and Young Child Feeding and Micronutrient Powder Intervention on Feeding Practices and Anemia in Children Aged 6-23 Months in Madagascar.

PubMed

Locks, Lindsey M; Reerink, Ietje; Tucker Brown, Amal; Gnegne, Smaila; Ramalanjaona, Noelimanjaka; Nanama, Simeon; Duggan, Christopher P; Garg, Aashima

2017-06-07

This study assesses the impact of an integrated infant and young child feeding (IYCF) and micronutrient powder (MNP) intervention on children's risk of anemia and IYCF practices in Madagascar. Quantitative baseline and endline surveys were conducted in representative households with children 6-23 months from two districts, where an 18-month IYCF-MNP intervention was implemented. Relative risks comparing children's risk of anemia and maternal IYCF knowledge and practices at baseline versus endline, and also at endline among MNP-users versus non-users were estimated using log-binomial regression models. 372 and 475 children aged 6-23 months were assessed at baseline and endline respectively. Prevalence of anemia fell from 75.3% to 64.9% from baseline to endline ( p = 0.002); the reduction in the risk of anemia remained significant in models adjusting for sociodemographic characteristics (ARR (95% CI): 0.86 (0.78, 0.95), p = 0.003). In endline assessments, 229 out of 474 (48.3%) of children had consumed MNPs. MNP-users had a lower risk of anemia (ARR (95% CI): 0.86 (0.74, 0.99), p = 0.04) than non-users, after controlling for child's dietary diversity and morbidity, maternal counseling by community-health-workers, and sociodemographic characteristics. Mothers interviewed at endline also had greater nutrition knowledge and were more likely to feed their children ≥4 food groups (ARR (95% CI): 2.92 (2.24, 3.80), p < 0.001), and the minimum acceptable diet (ARR (95% CI): 2.88 (2.17, 3.82), p < 0.001) than mothers interviewed at baseline. Integration of MNP into IYCF interventions is a viable strategy for improving children's consumption of micronutrients and reducing risk of anemia. The addition of MNP does not negatively impact, and may improve, IYCF practices.

Elimination of Iron Deficiency Anemia and Soil Transmitted Helminth Infection: Evidence from a Fifty-four Month Iron-Folic Acid and De-worming Program

PubMed Central

Casey, Gerard J.; Montresor, Antonio; Cavalli-Sforza, Luca T.; Thu, Hoang; Phu, Luong B.; Tinh, Ta T.; Tien, Nong T.; Phuc, Tran Q.; Biggs, Beverley-Ann

2013-01-01

Background Intermittent iron-folic acid supplementation and regular de-worming are effective initiatives to reduce anemia, iron deficiency, iron deficiency anemia, and soil transmitted helminth infections in women of reproductive age. However, few studies have assessed the long-term effectiveness of population-based interventions delivered in resource-constrained settings. Methodology/Principal Findings The objectives were to evaluate the impact of weekly iron-folic acid supplementation and de-worming on mean hemoglobin and the prevalence of anaemia, iron deficiency, and soil transmitted helminth infection in a rural population of women in northern Vietnam and to identify predictive factors for hematological outcomes. A prospective cohort design was used to evaluate a population-based supplementation and deworming program over 54 months. The 389 participants were enrolled just prior to commencement of the intervention. After 54 months 76% (95% CI [68%, 84%]) were taking the iron-folic acid supplement and 95% (95% CI [93%, 98%]) had taken the most recently distributed deworming treatment. Mean hemoglobin rose from 122 g/L (95% CI [120, 124]) to 131 g/L (95% CI [128, 134]) and anemia prevalence fell from 38% (95% CI [31%, 45%]) to 18% (95% CI [12%, 23%]); however, results differed significantly between ethnic groups. Iron deficiency fell from 23% (95% CI [17%, 29%]) to 8% (95% CI [4%, 12%]), while the prevalence of iron deficiency anemia was reduced to 4% (95% CI [1%, 7%]). The prevalence of hookworm infection was reduced from 76% (95% CI [68%, 83%]) to 11% (95% CI [5%, 18%]). The level of moderate or heavy infestation of any soil-transmitted helminth was reduced to less than 1%. Conclusions/Significance Population-based interventions can efficiently and effectively reduce anemia and practically eliminate iron deficiency anemia and moderate to heavy soil transmitted helminth infections, maintaining them below the level of public health concern. PMID:23593517

Prevalence of anemia and associated factors in older adults: evidence from the SABE Study

PubMed Central

Corona, Ligiana Pires; Duarte, Yeda Aparecida de Oliveira; Lebrão, Maria Lucia

2014-01-01

OBJECTIVE To assess the prevalence of anemia and associated factors in older adults. METHODS The prevalence and factors associated with anemia in older adults were studied on the basis of the results of the Saúde, Bem-Estar e Envelhecimento (SABE – Health, Welfare and Aging) study. A group of 1,256 individuals were interviewed during the third wave of the SABE study performed in Sao Paulo, SP, in 2010. The study included 60.4% females; the mean age of the participants was 70.4 years, and their average education was 5.3 years. The dependent variable was the presence of anemia (hemoglobin levels: 12 g/dL in women and 13 g/dL in men). Descriptive analysis and hierarchical logistic regression were performed. The independent variables were as follows: a) demographics: gender, age, and education and b) clinical characteristics: self-reported chronic diseases, presence of cognitive decline and depression symptoms, and body mass index. RESULTS The prevalence of anemia was 7.7% and was found to be higher in oldest adults. There was no difference between genders, although the hemoglobin distribution curve in women showed a displacement toward lower values in comparison with the distribution curve in men. Advanced age (OR = 1.07; 95%CI 0.57;1.64; p < 0.001), presence of diabetes (OR = 2.30; 95%CI 1.33;4.00; p = 0.003), cancer (OR = 2.72; 95%CI 1.2;6.11; p = 0.016), and presence of depression symptoms (OR = 1.75; 95%CI 1.06;2.88; p = 0.028) remained significant even after multiple analyses. CONCLUSIONS The prevalence of anemia in older adults was 7.7% and was mainly associated with advanced age and presence of chronic diseases. Thus, anemia can be an important marker in the investigation of health in older adults because it can be easily diagnosed and markedly affects the quality of life of older adults. PMID:25372162

Chronic Restraint Stress after Injury and Shock is Associated with Persistent Anemia despite Prolonged Elevation in Erythropoietin Levels

PubMed Central

Bible, Letitia E.; Pasupuleti, Latha V.; Gore, Amy V.; Sifri, Ziad C.; Kannan, Kolenkode B.; Mohr, Alicia M.

2015-01-01

Background Following severe traumatic injury, critically ill patients have a prolonged hypercatacholamine state that is associated with bone marrow (BM) dysfunction and persistent anemia. However, current animal models of injury and shock result in a transient anemia. Daily restraint stress (CS) has been shown to increase catecholamines. We hypothesize that adding CS following injury or injury and shock in rats will prolong the hypercatecholaminemia, and prolong the initial anemia, despite elevated erythropoietin levels. Methods Male Sprague-Dawley Rats (N=6–8/group) underwent lung contusion (LC) or combined lung contusion/hemorrhagic shock (LCHS) followed by six days of chronic stress (CS). CS consisted of a two hour restraint period interrupted with repositioning and alarms every 30 minutes. At seven days, urine was assessed for norepinephrine (NE) levels, blood for erythropoietin (EPO) and hemoglobin (Hgb), and BM for erythroid progenitor growth. Results Animals undergoing LC or combined LCHS predictably recovered by day seven; urine NE, EPO and Hgb levels were normal. The addition of CS to LC and LCHS models was associated with a significant elevation in NE on day six. The addition of CS to LC led to a persistent 20–25% decrease in the growth of BM HPCs. These findings were further exaggerated when CS was added following LCHS, resulting in a 20–40% reduction in BM erythroid progenitor colony growth and a 20% decrease in Hgb when compared to LCHS alone. Conclusions Exposing injured animals to CS results in prolonged elevation of norepinephrine and erythropoietin which is associated with worsening BM erythroid function and persistent anemia. Chronic restraint stress following injury and shock provides a clinically relevant model to further evaluate persistent injury-associated anemia seen in critically ill trauma patients. Furthermore, alleviating chronic stress after severe injury is a potential therapeutic target to improve BM dysfunction and anemia. PMID:26091320

Multiple micronutrient-fortified rice affects physical performance and plasma vitamin B-12 and homocysteine concentrations of Indian school children.

PubMed

Thankachan, Prashanth; Rah, Jee Hyun; Thomas, Tinku; Selvam, Sumithra; Amalrajan, Vani; Srinivasan, Krishnamachari; Steiger, Georg; Kurpad, Anura V

2012-05-01

Fortifying rice with multiple micronutrients could be a promising strategy for combat micronutrient deficiencies in developing countries. We determined the efficacy of extruded rice grains fortified with multiple micronutrients on the prevalence of anemia, micronutrient status, and physical and cognitive performance in 6- to 12-y-old, low-income school children in Bangalore, India. In a randomized, double-blind, controlled trial, 258 children were assigned to 1 of 3 intervention groups to receive rice-based lunch meals fortified with multiple micronutrients with either low-iron (6.25 mg) or high-iron (12.5 mg) concentrations or identical meals with unfortified rice. The meals were provided 6 d/wk for 6 mo. Anthropometric, biochemical, physical performance, and cognitive assessments were taken at baseline and endpoint. At baseline, study groups were comparable, with 61% of the children being anemic. However, only <10% were deficient in iron, vitamin A, and zinc. After 6 mo, plasma vitamin B-12 and homocysteine concentrations (both P < 0.001) as well as physical performance (P < 0.05) significantly improved in the intervention arms. No between-group differences were observed in hemoglobin concentration, anemia, and deficiencies of other micronutrients or cognitive function after 6 mo, but paired analyses revealed a small reduction in anemia prevalence in children in the low-iron group. The fortified rice was efficacious in improving vitamin B-12 status and physical performance in Indian school children.

Frequency and Genotype of Human Parvovirus B19 among Iranian Hemodialysis and Peritoneal Dialysis Patients.

PubMed

Sharif, Alireza; Aghakhani, Arezoo; Velayati, Ali Akbar; Banifazl, Mohammad; Sharif, Mohammad Reza; Razeghi, Effat; Kheirkhah, Davood; Kazemimanesh, Monireh; Bavand, Anahita; Ramezani, Amitis

2016-01-01

The aim of this study was to evaluate the frequency and genotype of human parvovirus B19 and its relation with anemia among Iranian patients under dialysis. Fifty hemodialysis (HD) and 33 peritoneal dialysis (PD) patients were enrolled. B19 IgG and IgM antibodies were assessed by ELISA, and the presence of B19 DNA was evaluated by nested PCR. PCR products were sequenced directly and phylogenetic analysis was performed. In the HD group, the prevalence of B19 antibodies was 54% for IgG and 4% for IgM. B19 DNA was detected in 10% of the cases, and 10% showed B19 IgG and viremia simultaneously. In the PD group, the prevalence of B19 IgG and IgM was 57.6 and 0% respectively, whereas B19 DNA was found in 12.1% of the group. A total of 9.1% showed B19 IgG and viremia concurrently. There was no significant difference regarding anemia and B19 infection in either group. All B19 isolates were clustered in genotype 1A. Our findings indicate that B19 infection plays no role in leading chronic anemia in dialysis patients. However, persistent B19 viremia and the circulation of the same strains in dialysis patients may indicate a potential risk for the contamination of dialysis equipment and nosocomial spread of B19 infection within dialysis units. © 2017 S. Karger AG, Basel.

Pathological and immunohistochemical studies of subclinical infection of chicken anemia virus in 4-week-old chickens.

PubMed

Haridy, Mohie; Sasaki, Jun; Ikezawa, Mitsutaka; Okada, Kosuke; Goryo, Masanobu

2012-06-01

Subclinical infection of chicken anemia virus (CAV) at 4 to 6 weeks of age, after maternal antibodies have waned, is implicated in several field problems in broiler flocks. In order to understand the pathogenesis of subclinical infection with CAV, an immunopathological study of CAV-inoculated 4-week-old SPF chickens was performed. Sixty 4-week-old SPF chickens were equally divided into CAV and control groups. The CAV group was inoculated intramuscularly with the MSB1-TK5803 strain of CAV. Neither mortality nor anemia was detected in the CAV and control groups. In the CAV group, no signs were observed, except that some chickens were grossly smaller compared with the control group. Sporadic thymus lobes appeared to be reddening and atrophied. Within the first two weeks p.i. of CAV, there was a mild to moderate depletion of lymphocytes in the thymus cortex and spleen in some chickens. Moreover, lymphoid depletion of the bursa of Fabricius, proventriculus and cecal tonsils was observed. Hyperplastic lymphoid foci were observed in the liver, lungs, kidneys and heart at the 4th week p.i. of CAV. Immunohistochemically, a moderate lymphoid depletion of CD4(+)and CD8(+) T cells in the thymus cortex and spleen was observed in some chickens within two weeks p.i. of CAV. CAV inclusions and antigens were detected infrequently in the thymus cortex and spleen. It could be concluded that the immunosuppression in subclinical infection with CAV occurs as a result of reduction of cellular immunity.

Group Counseling: Health Related.

ERIC Educational Resources Information Center

McFadden, Johnnie

1979-01-01

Diabetes and sickle cell anemia (SCA) are two health-related characteristics that distinguish young people from their peers. This article outlines the problems of children with diabetes and SCA and presents the goals and format for group counseling of these populations and their parents. (Author/BEF)

[Characterization of anemia in children under five years of age from urban areas of Huancavelica and Ucayali, Peru].

PubMed

Gonzales, Elena; Huamán-Espino, Lucio; Gutiérrez, César; Aparco, Juan Pablo; Pillaca, Jenny

2015-01-01

Characterize anemia in children aged between 12 and 59 months from urban areas in the provinces of Coronel Portillo and Huancavelica in Peru. Cross-sectional study carried out in two stages: a) population-based study to identify children with anemia using multistage probability sampling, and b) characterization of the serum levels of ferritin, vitamin B12, intraerythrocytic folic acid and presence of parasitosis in children with anemia. For the statistical analysis, expansion factors calculated from the sampling plan were applied. The prevalence of anemia was 55.9% in Huancavelica and 36.2% in Coronel Portillo. In Huancavelica, the coexistence of anemia with iron deficiency was 22.8% and anemia with vitamin B12 deficiency was 11%. In Coronel Portillo, the coexistence of anemia with iron deficiency and vitamin B12 deficiency was 15.2% and 29.7%, respectively. The most common types of anemia in Huancavelica were anemia with concurrent parasitosis (50.9%), iron deficiency anemia and parasitosis (12.3%), and iron deficiency alone (6.4%). In Coronel Portillo, it was anemia and parasitosis (54.4%), vitamin B12 deficiency and parasitosis (18.4%), and iron deficiency anemia and parasitosis (6.3%). The prevalence of anemia is higher than the national average, with anemia concurrent with parasitosis and anemia concurrent with two or more causes as the most common type. Consideration should be given to different causes other than iron deficiency in the programs of anemia contol for Peruvian children.

Changes in the choroidal thickness in reproductive-aged women with iron-deficiency anemia.

PubMed

Yumusak, Erhan; Ciftci, Aydin; Yalcin, Selim; Sayan, Cemile Dayangan; Dikel, Nevin Hande; Ornek, Kemal

2015-12-29

The aim of this study was to investigate the potential significance of the central macular thickness (foveal thickness-FT) and choroidal thickness (CT) in the eyes of patients with iron-deficiency anemia, the most common form of the anemia, via enhanced-depth imaging optical coherence tomography (EDI-OCT). We also investigated whether such changes might serve as an early indicator of underlying hematological disease. This prospective clinical study compared 96 female patients with iron-deficiency anemia and 60 healthy female control subjects. The macular and choroidal thicknesses in the temporal and nasal subfoveal areas were measured using enhanced-depth imaging optical coherence tomography (EDI-OCT) at 500 and 1500 microns and in five different regions (FCT, T1500, T500, N500, and N1500). The mean ages of the patients and healthy controls were 34.08 ± 10.39 years and 32.29 ± 8.28 years, respectively (P =0.232). There were no significant changes in macular thickness between the groups (225.58 ± 19.76 vs. 222.45 ± 13.51, P =0.2). The choroidal thickness was significantly reduced in the patient group relative to the controls at all measured points (foveal choroidal thickness, P = 0.042; nasal-500 microns, P = 0.033; temporal-500 microns, P = 0.033; and temporal-1500 microns, P = 0.019). At some points, the choroidal thickness findings correlated with the hemoglobin values (temporal-500 microns, r = -0.287, P = 0.001; nasal-500 microns, r = -0.287, P = 0.005; nasal-1500 microns, r = -0.245, P = 0.016; and temporal-1500 microns, r = -0.280, P = 0.06). Patients with iron-deficiency anemia had a significantly reduced choroidal thickness.

Anemia and mortality in older persons: does the type of anemia affect survival?

PubMed

Shavelle, Robert M; MacKenzie, Ross; Paculdo, David R

2012-03-01

Anemia is a common condition among community-dwelling older adults. The present study investigates the effect of type of anemia on subsequent mortality. We analyzed data from participants of the Third National Health and Nutrition Survey who were aged ≥50 and had valid hemoglobin levels determined by laboratory measurement. Anemia was defined by World Health Organization criteria. 7,171 subjects met our inclusion criterion. Of those with anemia (n = 862, deaths = 491), 24% had nutritional anemia, 11% had anemia of chronic renal disease, 26% had anemia of chronic inflammation, and 39% had unexplained anemia. We found an overall relative risk (RR) for mortality of 1.8 (p < 0.001) comparing those with anemia to those without, after adjusting for age, sex, and race. After we controlled for a number of chronic medical conditions, the overall RR was 1.6. Compared to persons without anemia, we found the following RRs for the type of anemia: nutritional (2.34, p < 0.0001), chronic renal disease (1.70, p < 0.0001), chronic inflammation (1.48, p < 0.0001), and unexplained (1.26, p < 0.01). Anemia is common although not severe in older non-institutionalized adults. When compared with non-anemic older adults, those with nutritional anemia or anemia due to chronic renal disease have the highest mortality risk.

Hemoglobin status of non-school going adolescent girls in three districts of Orissa, India.

PubMed

Bulliyy, Gandham; Mallick, Gitanjali; Sethy, Girija Sankar; Kar, Santanu Kumar

2007-01-01

Anemia is a major public health problem in young children and pregnant women in SouthEast Asia, but a paucity of data on anemia in adolescent girls in India. Studies are lacking on the entire non-school going adolescent population. To determine the prevalence of anemia in non-school going adolescent girls and the association between hemoglobin (Hb) concentration and socioeconomic and nutritional factors. A cross-sectional community study conducted on a sample of 1937 healthy adolescent girls aged 11-19 years from three districts of Orissa, India. Sample size was determined using a probability proportionate to size cluster sampling. The adolescent girls were interviewed and anthropometric measurements were collected. The Hb estimation was carried out in capillary blood samples using the cyanmethemoglobin method. Anemia and nutritional status were evaluated according to standard procedures. The mean Hb concentration was 9.7 +/- 1.4 g/dL (range, 4.5-13.4 g/dL). Of the total adolescent girls, 1869 (96.5%) were anemic (Hb < 12.0 g/dL), of which, 45.2%, 46.9% and 4.4% had mild, moderate, and severe anemia, respectively. A significant curvilinear relation was found between Hb concentration and age, with the nadir of the curve occurring in the 12-14 years age group. Girls from Bargarh district had significantly lower mean Hb levels than those from the Jajpur and Khurda districts. Significant positive associations were found between Hb concentration and pre-menarche, community, education levels of girls and their parents' family income, body mass index, and mid-upper arm circumference. This study revealed that prevalence of anemia was extremely high in non-school going adolescent girls (most were moderately anemic) and stressed the need for more research and public health interventions.

Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000–2011

PubMed Central

Vaht, Krista; Göransson, Magnus; Carlson, Kristina; Isaksson, Cecilia; Lenhoff, Stig; Sandstedt, Anna; Uggla, Bertil; Winiarski, Jacek; Ljungman, Per; Brune, Mats; Andersson, Per-Ola

2017-01-01

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70–80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000–2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06–2.64) cases per million inhabitants per year. Median age was 60 years (range: 2–92), and median follow up was 76 (0–193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0–18 years, 90.5% in patients aged 19–39 years, 70.7% in patients aged 40–59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40–59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted. PMID:28751565

Incidence and outcome of acquired aplastic anemia: real-world data from patients diagnosed in Sweden from 2000-2011.

PubMed

Vaht, Krista; Göransson, Magnus; Carlson, Kristina; Isaksson, Cecilia; Lenhoff, Stig; Sandstedt, Anna; Uggla, Bertil; Winiarski, Jacek; Ljungman, Per; Brune, Mats; Andersson, Per-Ola

2017-10-01

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged ≥60 years. Multivariate analysis showed that age (both 40-59 and ≥60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients ≥60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted. Copyright© 2017 Ferrata Storti Foundation.

Hemodialysis patients' preferences for the management of anemia.

PubMed

Hauber, Brett; Caloyeras, John; Posner, Joshua; Brommage, Deborah; Tzivelekis, Spiros; Pollock, Allan

2017-07-28

Patient engagement in end-stage renal disease (ESRD) is expected to result in a more patient-centered approach to care that aligns with patients' values, preferences, and goals for treatment. Nevertheless, no previous studies of which we are aware have evaluated patients' benefit-risk preferences for the management of anemia associated with ESRD. The primary objective of this study was to quantify the tradeoffs patients are willing to make between cardiovascular risks associated with some anemia medicines and red blood cell (RBC) transfusions. A secondary objective was to quantify the importance of avoiding transfusion-related risks. A survey instrument was developed from the clinical literature, clinician input, patient-education resources, and a patient focus group. The survey instrument was qualitatively pretested before its administration to a broader sample of patients. The National Kidney Foundation invited individuals in the United States to participate in the survey. In a discrete-choice experiment (DCE), respondents chose between two hypothetical anemia medications in a series of questions. Each medication was defined by symptom relief, frequency of transfusions, cardiovascular risk, mode of administration, and out-of-pocket cost. The survey also included a best-worst scaling (BWS) exercise to quantify the importance of avoiding attributes of blood transfusions. Results from the DCE were used to estimate relative importance and marginal willingness to pay. Results from the BWS were converted to relative importance weights. A total of 200 individuals completed the survey. Patients were willing to accept a 6% medication-related risk of heart attack to avoid having two RBC transfusions per month. Symptom relief and mode of administration were of moderate importance. The most important transfusion-related risk to avoid was transfusion-related lung injury. Patients with ESRD and anemia have measurable treatment preferences and are willing to accept risks associated with anemia medications to avoid transfusions.

Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

PubMed

Barone, Angelica; Lucarelli, Annunziata; Onofrillo, Daniela; Verzegnassi, Federico; Bonanomi, Sonia; Cesaro, Simone; Fioredda, Francesca; Iori, Anna Paola; Ladogana, Saverio; Locasciulli, Anna; Longoni, Daniela; Lanciotti, Marina; Macaluso, Alessandra; Mandaglio, Rosalba; Marra, Nicoletta; Martire, Baldo; Maruzzi, Matteo; Menna, Giuseppe; Notarangelo, Lucia Dora; Palazzi, Giovanni; Pillon, Marta; Ramenghi, Ugo; Russo, Giovanna; Svahn, Johanna; Timeus, Fabio; Tucci, Fabio; Cugno, Chiara; Zecca, Marco; Farruggia, Piero; Dufour, Carlo; Saracco, Paola

2015-06-01

Acquired aplastic anemia (AA) is a rare heterogeneous disease characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3/million inhabitants/year, in Europe, but higher in East Asia. Survival in severe aplastic anemia (SAA) has markedly improved in the past 2 decades because of advances in hematopoietic stem cell transplantation, immunosuppressive and biologic drugs, and supportive care. In SAA hematopoietic stem cell transplant (HSCT) from a matched sibling donor (MSD) is the treatment of choice. If a MSD is not available, the options include immunosuppressive therapy (IST) or unrelated donor HSCT. The objective of this guideline is to provide healthcare professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary, evidence-based document issued by a group of pediatric hematologists was discussed, modified and approved during a series of "Consensus Conferences" according to procedures previously validated by the AIEOP Board. The guidelines highlight the importance of referring pediatric patients with AA to pediatric centers with long experience in diagnosis, differential diagnosis, management, supportive care and follow-up of AA. Copyright © 2015. Published by Elsevier Inc.

[Iron nutritional status in pregnant adolescents at the beginning of gestation].

PubMed

Hertrampf, E; Olivares, M; Letelier, A; Castillo, C

1994-12-01

The frequency of anemia and iron nutrition deficiency was assessed in 342 low socioeconomic level pregnant teenagers at entry to prenatal care in 5 outpatient clinics from a South Orient area of Santiago Chile. According to the Center for Disease Control Criteria, 1.2% of women had iron deficiency anemia. Iron stores were insufficient (defined as a serum ferritin lower than 20 g/L) in 55% for women and depleted (serum ferritin lower than 10 g/L) in 21%. Women with more than 14 weeks of gestation had lower packed red cell volumes, hemoglobin, mean corpuscular volumes and ferritin levels than women with less than 14 of gestation. It is concluded that the prevalence of iron deficiency anemia is lower than that predicted for a highly vulnerable group but the high frequency of low iron stores should encourage the use of iron supplementation in these teenagers.

Parvovirus B19 Infection and Severe Anemia in Renal Transplant Recipients

PubMed Central

Carraturo, Antonio; Catalani, Valentina; Ottaviani, Donatella; Menichelli, Patrizia; Rossini, Maurizio; Terella, Delia; Biondi, Brunello

2012-01-01

Kidney transplant (KT) recipients can develop symptomatic Parvovirus (PV) B19 infections, frequently associated with persistent anemia. The aim of this study was to evaluate the prevalence and clinical significance of PV B19 infection in anemic and non-anemic KT patients. Overall, out of 64 patients monitored for the presence of PV B19 by real-time PCR, 2 (3.12%) had an active PV B19 infection, in absence of other viral coinfections. The 2 cases occurred in nonanemic kidney transplant patients group (2/50, 4%), while none of the anemic transplant patients (0/14) was found to suffer from this infection. Moreover, patients affected by active PV B19 infection showed viral loads not exceeding 1 × 105 genome copies/reaction. In conclusion, in this study, PV B19 infection was not common in renal transplant population and wasn't associated with severe anemia. PMID:22619569

Hematological characteristics in neonates with twin anemia-polycythemia sequence (TAPS).

PubMed

Lopriore, E; Slaghekke, F; Oepkes, D; Middeldorp, J M; Vandenbussche, F P H A; Walther, F J

2010-03-01

To evaluate the neonatal hematological features of monochorionic twins with twin anemia-polycythemia sequence (TAPS) and to determine the additional diagnostic value of reticulocyte count measurement. A cohort of consecutive monochorionic twins with TAPS (n = 19) was included in the study and each twin pair was compared with two monochorionic twin pairs (n = 38) unaffected by TAPS or twin-twin transfusion syndrome (TTTS), matched for gestational age at birth. We measured full blood counts on day 1 and determined the incidence of anemia, polycythemia, reticulocytosis and thrombocytopenia. Median inter-twin hemoglobin (Hb) difference in monochorionic twins with and without TAPS was 13.7 g/dL and 2.4 g/dL, respectively (p < 0.01). Median inter-twin reticulocyte count ratio in twins with and without TAPS was 3.1 and 1.0, respectively (p < 0.01). Thrombocytopenia (platelet count < 150 x 10(9)/L) occurred more often in the TAPS group than in the control group, 45% (17/38) versus 11% (11/38), respectively (p < 0.01). In the TAPS group, mean platelet count was significantly lower in recipients than in donors, 133 x 10(9)/L versus 218 x 10(9)/L, respectively (p < 0.01). TAPS twins have a large inter-twin Hb difference in combination with a large inter-twin reticulocyte count ratio. Recipients are more often thrombocytopenic than donors, probably due to polycythemia. Copyright (c) 2010 John Wiley & Sons, Ltd.

The Production of Complement Clauses in Children with Language Impairment

ERIC Educational Resources Information Center

Steel, Gillian; Rose, Miranda; Eadie, Patricia

2016-01-01

Purpose: The purpose of this research was to provide a comprehensive description of complement-clause production in children with language impairment. Complement clauses were examined with respect to types of complement structure produced, verb use, and both semantic and syntactic accuracy. Method: A group of 17 children with language impairment…

Treatment of Anemia in Heart Failure: Potential Risks and Benefits of Intravenous Iron Therapy in Cardiovascular Disease

PubMed Central

Jelani, Qurat-ul-ain; Katz, Stuart D.

2010-01-01

Iron-deficiency anemia is common is patients with heart failure (HF), but the optimum diagnostic tests to detect iron deficiency and the treatment options to replete iron have not been fully characterized. Recent studies in patients with HF indicate that intravenous iron can rapidly replenish iron stores in patients having iron-deficiency anemia, with resultant increased hemoglobin levels and improved functional capacity. Preliminary data from a sub-group analysis also suggests that supplemental intravenous iron therapy can improve functional capacity even in those subjects without anemia. The mechanisms responsible for this observation are not fully characterized, but may be related to beneficial effects of iron supplementation on mitochondrial respiration in skeletal muscle. The long-term safety of using intravenous iron supplementation in HF populations is not known. Iron is a known pro-oxidant factor that can inhibit nitric oxide signaling and irreversibly injury cells. Increased iron stores are associated with vascular endothelial dysfunction and increased risk of coronary heart disease events. Additional clinical trials are needed to more fully characterize the therapeutic potential and safety of intravenous iron in HF patients. PMID:20699672

Iron deficiency and cognitive functions.

PubMed

Jáuregui-Lobera, Ignacio

2014-01-01

Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%-6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups.

Dialysis in rats with acute renal failure: evaluation of three different dialyzer membranes.

PubMed

Kränzlin, B; Gretz, N; Kirschfink, M; Mujais, S K

1996-11-01

Exposure to complement-activating cellulosic dialysis membranes has been claimed to adversely affect the course of acute renal failure (ARF). To test this hypothesis, male Sprague-Dawley rats were allocated to 2 groups: in Group 1, ARF was induced by bilateral renal artery clamping whereas in Group 2, animals underwent a sham procedure. In each group, rats were further allocated to undergo hemodialysis with either a Cuprophan, a Hemophan, or a polyacrylonitrile minidialyzer on Days 4 and 8 after surgery, or no dialysis. Renal function was measured by inulin clearance on the days after dialysis. Additionally, total complement activity (CH50) was estimated on Days 1, 2, 4, and 8, and complement factor C3 was detected immunohistochemically. The degree of renal failure and the rate of recovery of renal function were similar in all the ARF groups irrespective of whether they had undergone dialysis or not, or of the type of the dialysis membrane. Furthermore, there were no significant differences in the course of CH50 or in the amount and distribution of complement factor C3 in the kidney tissue between the rats of Groups 1 and 2. Our findings refute the hypothesis that in ischemic ARF exposure to complement-activating cellulosic dialysis membranes impairs the recovery of renal function in rats.

Hematological and biochemical investigations on the effect of vitamin E and C on Oreochromis niloticus exposed to zinc oxide nanoparticles.

PubMed

Alkaladi, Ali; El-Deen, Nasr A M Nasr; Afifi, Mohamed; Zinadah, Osama A Abu

2015-09-01

This study was carried out to determine the LC50 of zinc oxide nanoparticles (ZnONPs) on Oreochromis niloticus and to investigate the effect of vitamin E and C on hematological and biochemical alterations induced by two sublethal concentrations (1 and 2 mg/L) of ZnONPs. One hundred and eighty fish were used for studying the lethal concentrations of ZnONPs. For sublethal study two hundred and twenty-five males of O. niloticus were equally divided into five groups, control, the second and the third were treated with 1 and 2 mg/L ZnONPs respectively. The fourth and fifth were exposed to the same concentrations of ZnONPs plus vitamins E and C. The results revealed that the 96 h LC50 of ZnONPs was 3.1 ± 0.4 mg/L. The sublethal study revealed the presence of normocytic normochromic anemia in groups (2, 3 and 5) along the experiment period. The 4th group showed normocytic normochromic anemia at the 7th day and microcytic hypochromic anemia at the 15th day. Leukocytosis, heterophilia, lymphopenia and monocytopenia were recorded at the 7th day in all treated groups compared with the normal control. At the 15th day heteropenia, lymphopenia and monocytopenia were reported in all treated groups. A significant increase in the serum levels of alkaline phosphatase, aminotransferases, urea, creatinine and erythrocytic nuclear and morphological abnormalities along the experimental periods in all treated groups compared with the normal control. Serum total protein and albumin levels were significantly decreased at the same period in the same groups. Addition of vitamin E and C to the diet (groups 4 and 5) significantly improved all measured parameters compared with groups (2 and 3) which treated with ZnONPs only.

Gene for ataxia-telangiectasia complementation group D (ATDC)

DOEpatents

Murnane, J.P.; Painter, R.B.; Kapp, L.N.; Yu, L.C.

1995-03-07

Disclosed herein is a new gene, an AT gene for complementation group D, the ATDC gene and fragments thereof. Nucleic acid probes for the gene are provided as well as proteins encoded by the gene, cDNA therefrom, preferably a 3 kilobase (kb) cDNA, and recombinant nucleic acid molecules for expression of the proteins. Further disclosed are methods to detect mutations in the gene, preferably methods employing the polymerase chain reaction (PCR). Also disclosed are methods to detect AT genes from other AT complementation groups. 30 figs.

Alpha-thalassemia (3.7 kb deletion) in a population from the Brazilian Amazon region: Santarém, Pará State.

PubMed

Souza, A E S; Cardoso, G L; Takanashi, S Y L; Guerreiro, J F

2009-04-28

The ethnic composition of the Brazilian population favors high frequencies of the -alpha3.7 deletion, responsible for alpha-thalassemia, because this mutation is very common in African populations. In spite of its importance, this hemoglobinopathy has been poorly investigated in Brazil, especially at the molecular level. We investigated the prevalence of the -alpha3.7 mutation in 220 individuals attended at the Municipal Hospital of Santarém, in the state of Pará. These patients were distributed into three different groups: i) 103 individuals with anemia who had microcytosis and hypochromia, ii) 11 individuals without anemia who had microcytosis and hypochromia, and iii) 106 individuals with no hematological alterations. We examined the usefulness of investigating alpha-thalassemia carrier status for microcytosis. Among the 103 patients with anemia, 20 (19.4%) were heterozygotes (-alpha3.7/alphaalpha) and one (1.0%) was a homozygote (-alpha3.7/-alpha3.7). Among the 11 patients without anemia, one heterozygote (-alpha3.7/alphaalpha) was identified; in the third group, composed of normal individuals (106 samples), deletion -alpha3.7 was found in seven samples (6.6%), all of which were heterozygotes (-alpha/alphaalpha).These frequencies are within the expected range, given available data on the distribution of this hemoglobin disorder in human populations and the ethnic composition of the population of Santarém. We found that alpha-thalassemia is a common cause of microcytosis, given that a high proportion (19.2%) of the microcytic population carried alpha-globin gene deletions.

Arsenic exposures alter clinical indicators of anemia in a male population of smokers and non-smokers in Bangladesh.

PubMed

Parvez, Faruque; Medina, Sebastian; Santella, Regina M; Islam, Tariqul; Lauer, Fredine T; Alam, Nur; Eunus, Mahbubul; Rahman, Mizanour; Factor-Litvak, Pam; Ahsan, Habib; Graziano, Joseph H; Liu, Ke Jian; Burchiel, Scott W

2017-09-15

Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh. The participants are part of an ongoing study focused on evaluating the influence of As and smoking on immune function. Samples were collected at recruitment and analyzed for water As, urinary As (UAs) and UAs metabolites to assess As exposure. Blood samples were also collected at recruitment and assayed immediately for hematological parameters. We found that increased WAs levels were associated with decreased red blood cell counts [β=-0.13, p<0.0001] as well as hematocrit packed cell volumes [β=-0.68, p=0.008] following adjustment for age, smoking, body mass index and polycyclic aromatic hydrocarbon-DNA adducts. Other measures of As exposure (UAs and its metabolites) demonstrated similar associations. Slightly stronger effects were observed among smokers. We also observed an effect of As on hemoglobin among smokers in relation to UAs [β=-0.54, p<0.05]. Our analysis revealed effects of As exposure on hematological indicators of anemia in a group of healthy male smokers and non-smokers. Copyright © 2017 Elsevier Inc. All rights reserved.

Hydroxyurea Use in Young Children With Sickle Cell Anemia in New York State.

PubMed

Anders, David G; Tang, Fei; Ledneva, Tatania; Caggana, Michele; Green, Nancy S; Wang, Ying; Sturman, Lawrence S

2016-07-01

This study examined hydroxyurea usage in young children with sickle cell anemia within New York State (NYS). The cohort was 273 children with sickle cell anemia born in NYS in 2006-2009 and enrolled essentially continuously in Medicaid for the first 4 years of life. Medicaid data were used to examine hydroxyurea usage in this group by age at first prescription fill, persistence, region, treatment institution, and year. Log-binomial regression models were used to estimate the likelihood of receiving hydroxyurea treatment. Data from birth through 2014 for all members of the study group were assembled and analyzed in 2015. About 25% of the cohort had at least one filled hydroxyurea prescription by their fifth birthday, and nearly 40% by the end of the study period. The mean proportion of days covered for the first year of therapy was 56.3%. Adherence was also assessed by calculating medication possession ratios for individual treatment periods. Slightly more than one third of treated children showed 80% coverage by these measures. There was a consistent, but not statistically significant, trend toward younger age at first fill. Significant regional and treatment center differences in initiation of hydroxyurea use, but not in persistence after initiation, were noted among NYS centers. Subsequent to clinical studies demonstrating safety, current NYS-wide use of hydroxyurea in young children with sickle cell anemia appears to be widespread and increasing. However, practice differences between treatment centers and inadequate adherence may limit the full disease-modifying effects of hydroxyurea. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Theory of mind in SLI revisited: links with syntax, comparisons with ASD.

PubMed

Durrleman, Stephanie; Burnel, Morgane; Reboul, Anne

2017-11-01

According to the linguistic determinism approach, knowledge of sentential complements such as: John says that the earth is flat plays a crucial role in theory of mind (ToM) development by providing a means to represent explicitly people's mental attitudes and beliefs. This approach predicts that mastery of complements determines successful belief reasoning across explicit ToM tasks, even low-verbal ones, and across populations. (1) To investigate the link between a low-verbal ToM-task and complements in Specific Language Impairment (SLI), (2) To determine whether this population shows similar ToM performance to that of children with Autism Spectrum Disorder (ASD) or those with Typical Development (TD) once these groups are matched on competency for complements, (3) To explore whether complements conveying a falsehood without jeopardizing the veracity of the entire sentence, such as complements of verbs of communication, are more crucial for belief attribution than complements which do not have this property, namely complements of verbs of perception, (?John sees that the earth is flat). Children with SLI (n = 20), with ASD (n = 34) and TD (n = 30) completed sentence-picture-matching tasks assessing complementation with communication and perception verbs, as well as a picture-sequencing task assessing ToM. Children were furthermore evaluated for general grammatical and lexical abilities and non-verbal IQ. Results reveal that competency on complements relates to ToM performance with a low-verbal task in SLI, and that SLI, ASD and TD groups of equivalent performance on complements also perform similarly for ToM. Results further suggest that complements with an independent truth-value are the only ones to show a significant relation to ToM performance after teasing out the impact of non-verbal reasoning. This study suggests that clinical groups of different aetiologies as well as TD children perform comparably for ToM once they have similar complementation skills. Findings further highlight that specific types of complements, namely those with an independent truth value, relate in a special way to mentalizing. Future work should determine whether these specific structures could be effective in ToM remediation programmes. © 2017 Royal College of Speech and Language Therapists.

Patterns and Predictors of Severe Postpartum Anemia after Cesarean Section

PubMed Central

Butwick, Alexander. J.; Walsh, Eileen. M.; Kuzniewicz, Michael; Li, Sherian.X.; Escobar, Gabriel.J.

2016-01-01

Background Postpartum anemia is associated with maternal and perinatal morbidity. Population-level data may inform guideline development for postpartum anemia screening. Our objectives were to evaluate the associations between potential predictors (predelivery anemia and postpartum hemorrhage (PPH)) with severe postpartum anemia after cesarean section. Study Design and Methods Data were collected from 70,939 hospitalizations for cesarean section performed at Kaiser Permanente Northern California facilities between 2005 and 2013. Severe postpartum anemia was defined as a hemoglobin < 8 g/dl before hospital discharge. Using multivariable logistic regression, we assessed the associations between predelivery anemia and PPH with severe postpartum anemia. Distributions of these characteristics among women with severe postpartum anemia were evaluated. Results The overall rate of severe postpartum anemia was 7.3%; 95% confidence interval (CI) = 7.1 – 7.4. Severe postpartum anemia was strongly associated with a predelivery hemoglobin between 10 and 10.9 g/dl (adjusted odds ratio (aOR) 5.4; 95% CI = 4.89– 5.91), predelivery hemoglobin <10 g/dl (aOR 30.6; 95% CI = 27.21– 34.6, and PPH (aOR 8.45; 95% CI = 7.8–9.16). The proportions of women with severe postpartum anemia were highest for those experiencing PPH but no predelivery anemia (12.2%; 95% CI = 11.0 – 13.6), and those who did not incur PPH nor predelivery anemia (10.7%; 95% CI = 9.6 – 12.0). Conclusions Our findings suggest that PPH and predelivery anemia are strong independent risk factors for severe postpartum anemia. Optimization of patients’ hemoglobin prior to delivery may reduce the incidence of severe anemia after cesarean section. PMID:27618767

Evasion Mechanisms Used by Pathogens to Escape the Lectin Complement Pathway

PubMed Central

Rosbjerg, Anne; Genster, Ninette; Pilely, Katrine; Garred, Peter

2017-01-01

The complement system is a crucial defensive network that protects the host against invading pathogens. It is part of the innate immune system and can be initiated via three pathways: the lectin, classical and alternative activation pathway. Overall the network compiles a group of recognition molecules that bind specific patterns on microbial surfaces, a group of associated proteases that initiates the complement cascade, and a group of proteins that interact in proteolytic complexes or the terminal pore-forming complex. In addition, various regulatory proteins are important for controlling the level of activity. The result is a pro-inflammatory response meant to combat foreign microbes. Microbial elimination is, however, not a straight forward procedure; pathogens have adapted to their environment by evolving a collection of evasion mechanisms that circumvent the human complement system. Complement evasion strategies features different ways of exploiting human complement proteins and moreover features different pathogen-derived proteins that interfere with the normal processes. Accumulated, these mechanisms target all three complement activation pathways as well as the final common part of the cascade. This review will cover the currently known lectin pathway evasion mechanisms and give examples of pathogens that operate these to increase their chance of invasion, survival and dissemination. PMID:28553281

Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

PubMed

Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

2015-06-01

Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p < 0.03) higher incidence of C4d deposition was observed in placentas from women with preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p < 10th percentile) compared with the preeclamptic OD group. In addition, the placental mRNA expression level of complement regulatory proteins was significantly lower in uncomplicated and preeclamptic OD compared with the autologous pregnancies. In line with autologous preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Pernicious Anemia with Autoimmune Hemolytic Anemia: A Case Report and Literature Review

PubMed Central

Manchandani, Raj Pal; Oneal, Patricia

2016-01-01

Pernicious anemia is a common cause of vitamin B12 deficiency. Here, we discuss a case of a young woman who presented with severe anemia along with a history of iron deficiency anemia. After a review of her clinical presentation and laboratory data, we identified an autoimmune hemolytic anemia and a concomitant pernicious anemia. The concurrence of both these hematological diagnoses in a patient is rare. PMID:27559485

Iron metabolism in critically ill patients developing anemia of inflammation: a case control study.

PubMed

Boshuizen, Margit; Binnekade, Jan M; Nota, Benjamin; van de Groep, Kirsten; Cremer, Olaf L; Tuinman, Pieter R; Horn, Janneke; Schultz, Marcus J; van Bruggen, Robin; Juffermans, Nicole P

2018-05-02

Anemia occurring as a result of inflammatory processes (anemia of inflammation, AI) has a high prevalence in critically ill patients. Knowledge on changes in iron metabolism during the course of AI is limited, hampering the development of strategies to counteract AI. This case control study aimed to investigate iron metabolism during the development of AI in critically ill patients. Iron metabolism in 30 patients who developed AI during ICU stay was compared with 30 septic patients with a high Hb and 30 non-septic patients with a high Hb. Patients were matched on age and sex. Longitudinally collected plasma samples were analyzed for levels of parameters of iron metabolism. A linear mixed model was used to assess the predictive values of the parameters. In patients with AI, levels of iron, transferrin and transferrin saturation showed an early decrease compared to controls with a high Hb, already prior to the development of anemia. Ferritin, hepcidin and IL-6 levels were increased in AI compared to controls. During AI development, erythroferrone decreased. Differences in iron metabolism between groups were not influenced by APACHE IV score. The results show that in critically ill patients with AI, iron metabolism is already altered prior to the development of anemia. Levels of iron regulators in AI differ from septic controls with a high Hb, irrespective of disease severity. AI is characterized by high levels of hepcidin, ferritin and IL-6 and low levels of iron, transferrin and erythroferrone.

The sociodemographic correlates of nutritional status of school adolescents in Jiangsu Province, China.

PubMed

Shi, Zumin; Lien, Nanna; Kumar, Bernadette Nirmal; Dalen, Ingvild; Holmboe-Ottesen, Gerd

2005-10-01

The objective of this article was to describe the relationship between sociodemographic factors and nutritional status (body mass index [BMI], height for age, and anemia) in adolescents. In 2002, a cross-sectional study comprising 824 students aged 12 to 14 years from 8 schools in 2 prefectures in Jiangsu province of China had their height, weight, and hemoglobin level measured. Self-administered questionnaires were used to collect sociodemographic information. The prevalence of underweight was low in the overall sample (5.2%). The prevalence of stunting also was low (2.9%), and the differences between residential areas and sociodemographic groups were small. The percentage of overweight/obesity was higher among boys (17.9%) than girls (8.9%). Male students having fathers with a high educational level had the highest percentage of overweight and obesity (27.8%). Household socioeconomic status (SES) was associated positively with BMI. Family size, gender, and the father's level of education also were related to BMI. The percentage of anemia was somewhat higher among girls (23.4%) than boys (17.2%). Anemia coexisted with underweight. No urban/rural or SES differences in the percentage of students with anemia were observed in the sample, but differences between regions and schools were very significant. Undernutrition was not a problem in the research area. Nutritional status was associated with SES and region. Overnutrition and anemia in adolescents are important nutritional problems in Jiangsu, China. Intervention programs are needed to address these problems.

Iron-deficiency anemia in infancy and social emotional development in preschool-aged Chinese children.

PubMed

Chang, Suying; Wang, Li; Wang, Yuying; Brouwer, Inge D; Kok, Frans J; Lozoff, Betsy; Chen, Chunming

2011-04-01

We aimed to compare affect and behavior of 3 groups of nonanemic 4-year-old children: children with iron-deficiency anemia (IDA) in infancy whose anemia was not corrected before 24 months (chronic IDA) (n = 27); children with IDA in infancy whose anemia was corrected before 24 months (corrected IDA) (n = 70); and children who were nonanemic in infancy and at 24 months (n = 64). Mother and child dyads were invited to a local clinic room. Children's social referencing, wariness, frustration-tolerance behavior, and affect were observed during a set of situations encountered in the laboratory, including free play, stranger approach, novel toy, and delay of gratification. The whole procedure was videotaped. The children's affective and behavioral displays were coded by using a time-sampling (5-second segments) code scheme. Iron status of children was determined on the basis of hemoglobin concentration measured with the cyanomethemoglobin method in blood samples obtained by fingerstick in infancy and at the ages of 24 months and 4 years. Children who had chronic IDA in infancy displayed less positive affect, less frustration tolerance, more passive behavior, and more physical self-soothing in the stranger approach and delay of gratification. In contrast, the behavior and affect of children whose anemia was corrected before the age of 24 months were comparable to those of children who were nonanemic throughout infancy. The results point to the potential benefits of preventing iron deficiency in infancy and treating it before it becomes chronic or severe.

About Anemia (For Kids)

MedlinePlus

... Safe Videos for Educators Search English Español About Anemia KidsHealth / For Kids / About Anemia What's in this ... to every cell in your body. What Is Anemia? Anemia happens when a person doesn't have ...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernstein, S.E.

Hereditary anemias of mice are the chief objects of investigation, specificially four macrocytic anemias, 3 types of hemolytic anemia, nonhemolytic microcytic anemia, transitory siderocytic anemia, sex-linked iron-transport anemia, the autoimmune hemolytic anemia of NZB mice, an ..cap alpha..-thalassemia and a new hypochromic anemia with hemochromatosis. New types of anemia may be analyzed as new mutations appear. Three new mutations have been identified during the past 18 months. These anemias are studied through characterization of peripheral blood values, determinations of radiosensitivity under a variety of conditions, measurements of iron metabolism and heme synthesis, study of normal and abnormal erythrocyte membrane proteins,more » histological and biochemical characterization of blood-forming tissue, functional tests of the stem-cell component, examination of responses to erythroid stimuli, and transplantation of tissue and parabiosis between individuals of differently affected genotypes. 31 refs.« less

Effects of Adjuvant Androgen on Anemia and Nutritional Parameters in Chronic Hemodialysis Patients Using Low-dose Recombinant Human Erythropoietin

PubMed Central

Lee, Myeung Su; Ahn, Seon Ho; Song, Ju Hung

2002-01-01

Background: Recombinant human erythropoietin (epoetin) has greatly contributed to improvement of the anemia of chronic renal failure patients on hemodialysis. However, the reduced erythropoietic effect to epoetin and its high cost have induced lots of supplementary treatments. Therefore, we performed a prospective study to evaluate the effects of adjuvant low-dose androgen therapy in patients using a lower-dose of epoetin than the commonly recommended dose on anemia and the nutritional parameters. Methods : 17 patients of hemoglobin (Hgb) less than 9 g/dL even after being treated with 1,000 U epoetin subcutaneously (s.c.) 3 times per week on a stable status for more than 6 months, who were on hemodialysis at our institution were examined. They were injected with the same dose of epoetin s.c. and nandrolone decanoate 100 mg intramuscularly (i.m) weekly for another 6 months. Blood test was performed every month before therapy for 6 months and after therapy for 6 months and the mean values were reviewed for comparison. Results: Hgb (7.75±0.9 vs 8.99±1.39 g/dL, p <0.01) and hematocrit (Hct) (23.68±2.85 vs 26.66±3.91%, p <0.01) were apparently changed before and after adjuvant therapy. Hgb and Hct, weekly dose of epoetin were not statistically different in 9 male patients before and after adjuvant therapy. The weekly dose of epoetin was not statistically different in 8 female patients, but Hgb and Hct (8.02±0.6 vs 9.72±1.31 g/dL, 24.54±1.7 vs 28.74±3.06%, p <0.01) were statistically different before and after adjuvant therapy. In comparison between male and female groups, weekly doses of epoetin and nandrolone decanoate were significantly greater in the female group than the male group (epoetin: 50.66±6.23 vs 61.18±8.76 U/kg/week, nandrolone decanoate: 1.69±0.2 vs 2.04±0.29 mg/kg/week, p <0.05). Conclusion : Our data show that the adjuvant androgen therapy is effective for the anemia of hemodialysis patients who did not recover from anemia even after being continuously treated with low-dose epoetin. PMID:12298427

Potential Contribution of Iron Deficiency and Multiple Factors to Anemia among 6- to 72-Month-Old Children in the Kokang Area of Myanmar

PubMed Central

Zhao, Ai; Gao, Hongchong; Li, Bo; Yu, Kai; Win, Naing Naing; Zhang, Yumei; Wang, Peiyu

2015-01-01

The prevalence of anemia among children in Myanmar has been reported to be among the highest in the world. This study was conducted to determine 1) the prevalence of anemia in preschool children and 2) risk factors associated with anemia. A total of 138 children aged from 6 to 72 months were recruited through cluster sampling from six villages in Kokang. Hemoglobin (Hb) concentration, blood trace elements, and anthropometric indicators were measured. Feces samples were collected to examine for the presence of ascarid eggs. The overall prevalence of anemia in children was 61.6%, including 10.9% with severe anemia. Meanwhile, high prevalence of stunting (40.0%), underweight (22.4%), wasting (6.3%), and small head circumference (6.7%) was found. Children with anemia were more prone to stunting. Children with severe anemia and moderate anemia had significantly lower blood iron and zinc levels than children without anemia (P < 0.001 and P = 0.007). The prevalence of ascarid infection was 64.9%; however, it was not associated with anemia. Drinking spring water was positively associated with anemia (odds ratio [OR] = 6.368). This study demonstrated that anemia is an important public health problem among children from the Kokang area. Iron deficiency and drinking spring water may be the important causes of anemia among children. PMID:26195457

Anemia (For Teens)

MedlinePlus

... Staying Safe Videos for Educators Search English Español Anemia KidsHealth / For Teens / Anemia What's in this article? ... Enough Iron Print en español Anemia What Is Anemia? Lots of teens are tired. With all the ...

Beta Thalassemia (For Parents)

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... July 2015 More on this topic for: Parents Kids Teens Blood Transfusions Iron Iron-Deficiency Anemia Blood Test: Hemoglobin Electrophoresis Sickle Cell Disease Alpha Thalassemia Anemia Word! Anemia About Anemia Stem Cell Transplants Blood Transfusions Anemia Sickle Cell Disease ...

The Relationship between Strategies of Coping and Perception of Pain in Three Chronic Pain Groups.

ERIC Educational Resources Information Center

Anderson, Louis P.; Rehm, Lynn P.

1984-01-01

Examined the relationship between perception of pain, personality, coping, and the reaction of family members in three chronic pain groups (sickle cell anemia, arthritis, and low back pain) (N=60). Analyses suggested that the three groups were not distinguishable in coping, personality, or in their experience of pain. (LLL)

6-Month Mortality and Cardiac Catheterization in Non-ST Elevation Myocardial Infarction Patients with Anemia

PubMed Central

Wu, Wen-Chih; Waring, Molly E.; Lessard, Darleen; Yarzebski, Jorge; Gore, Joel; Goldberg, Robert J.

2011-01-01

Background It is unknown how anemia influences the invasive management of patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and associated mortality. We investigated whether receipt of cardiac catheterization relates to 6-month death rates among patients with different severity of anemia. Methods We used data from the population-based Worcester Heart Attack Study, which included 2,634 patients hospitalized with confirmed NSTEMI, from 3 PCI-capable medical centers in the Worcester (MA) metropolitan area, during 5 biennial periods between 1997 and 2005. Severity of anemia was categorized using admission hematocrit levels: ≤30.0% (moderate-to-severe anemia), 30.1–39.0% (mild anemia), and >39.0% (no anemia). Propensity matching and conditional logistic regression adjusting for hospital use of aspirin, heparin, and plavix compared 6-month post-admission all-cause mortality rates in relation to cardiac catheterization during NSTEMI hospitalization. Results Compared to patients without anemia, patients with anemia were less likely to undergo cardiac catheterization (adjusted odds ratio [AOR] 0.79 [95% confidence interval [CI]: 0.67–0.95] for mild anemia and 0.45 [95%CI: 0.42–0.49] for moderate-to-severe anemia). After propensity matching, cardiac catheterization was associated with lower 6-month death rates only in patients without anemia (AOR 0.26 [95%CI: 0.09–0.79]) but not in patients with mild anemia (AOR 0.55 [95%CI: 0.25–1.23]). The small number of patients rendered data inconclusive for patients with moderate-to-severe anemia. Conclusions Anemia at the time of hospitalization for NSTEMI was associated with lower utilization of cardiac catheterization. However, cardiac catheterization use was associated with a decreased risk of dying at 6 months post hospital admission only in patients without anemia. PMID:21738102

Effects and Predictive Factors of Immunosuppressive Therapy Combined with Umbilical Cord Blood Infusion in Patients with Severe Aplastic Anemia.

PubMed

Zhang, Xia; Li, Zhangzhi; Geng, Wei; Song, Bin; Wan, Chucheng

2018-07-01

To investigate the efficacy and safety of umbilical cord blood (UCB) infusion (UCBI) plus immunosuppressive therapy (IST) treatment in comparison to IST treatment, as well as predictive factors for clinical responses, in severe aplastic anemia (SAA) patients. Totally, 93 patients with SAA were enrolled in this cohort study. In the IST group, rabbit antithymocyte globulin (r-ATG) combined with cyclosporine A (CsA) was administered, while in the IST+UBCI group, r-ATG, CsA, and UCB were used. After 6 months of treatment, UCBI+IST achieved a higher complete response (CR) rate (p=0.002) and an elevated overall response rate (ORR) (p=0.004), compared to IST. Regarding hematopoietic recovery at month 6, platelet responses in the UCBI+IST group were better than those in the IST group (p=0.002), and UCBI+IST treatment facilitated increasing trends in absolute neutrophil count (ANC) response (p=0.056). Kaplan-Meier curves illuminated UCBI+IST achieved faster ANC response (p<0.001) and platelet response (p<0.001), compared with IST therapy. There was no difference in overall survival (OS) between the two groups (p=0.620). Furthermore, logistic regression analysis demonstrated that UCBI+IST was an independent predicting factor for both CR (p=0.001) and ORR (p<0.001), compared to IST; meanwhile, very severe aplastic anemia (VSAA) and ANC could predict clinical responses as well. However, Cox proportional hazard regression indicated that VSAA (p=0.003), but not UCBI+IST, affected OS. Safety profiles showed that UCBI+IST therapy did not elevate adverse events, compared with IST treatment. UCBI+IST achieved better clinical responses and hematopoietic recovery than IST, and was well tolerated in SAA patients. © Copyright: Yonsei University College of Medicine 2018.

Increased risk of pernicious anemia following scabies: a nationwide population-based matched-cohort study.

PubMed

Liu, Jui-Ming; Hsu, Ren-Jun; Chang, Fung-Wei; Chiu, Feng-Hsiang; Yeh, Chia-Lun; Huang, Chun-Fa; Chang, Shu-Ting; Lee, Hung-Chang; Chi, Hsin; Lin, Chien-Yu

2017-01-01

Scabies is a common and annoying disorder. Pernicious anemia (PA) is a serious disease which, when untreated, leads to death. Mounting evidence suggests that immune-mediated inflammatory processes play a role in the pathophysiology of both diseases. The relationship between these two diseases has not been investigated. We conducted this study to explore the potential relationship between scabies and PA. This nationwide, population-based study was conducted using the National Health Insurance Research Database of Taiwan. In total, 5,407 patients with scabies were identified as a study group and 20,089 matched patients were randomly selected as a control group. We tracked patients in both groups for a 7-year period to identify the incidence of PA. The demographic characteristics and comorbidities of the patients were analyzed, and Cox proportional hazards regression was used to calculate the hazard ratios for PA. Of the 25,496 patients in this study, 183 (0.7%) patients with newly diagnosed PA were identified during the 7-year follow-up period; 71 of 5,407 (1.3%) from the scabies group and 112 of 20,089 (0.6%) from the control group. Patients with scabies had a higher risk of subsequent PA, with a crude hazard ratio of 2.368. After adjusting for covariates, the adjusted hazard ratio was 1.51 (95% confidence interval: 1.09-2.08). This study demonstrated an increased risk of PA (adjusted hazard ratio 1.51) among patients with scabies. Immune-mediated inflammatory processes may contribute to this association. Further studies are warranted to investigate the entire pathological mechanisms between these two diseases. Physicians should pay attention to patients with history of scabies presented with anemia. Further confirmative tests of PA may contribute to correct diagnosis and initiation of vitamin B12 supplement.

Delivery of iron-fortified yoghurt, through a dairy value chain program, increases hemoglobin concentration among children 24 to 59 months old in Northern Senegal: A cluster-randomized control trial.

PubMed

Le Port, Agnes; Bernard, Tanguy; Hidrobo, Melissa; Birba, Ousmane; Rawat, Rahul; Ruel, Marie T

2017-01-01

Innovative strategies are needed to enhance the nutritional impact of agriculture. Value chain approaches, which use supply chains to add value (usually economic) to products as they move from producers to consumers, can be used to increase access to nutritious foods and improve nutritional status. This study tested whether a dairy value chain could be used to distribute a micronutrient-fortified yoghurt (MNFY) (conditional upon the producer supplying a minimum amount of cow milk/day) to improve hemoglobin and reduce anemia among preschool children in a remote area in Northern Senegal. A cluster randomized control trial was used to compare 204 children (24 to 59 months of age at baseline) from households who received the MNFY coupled to a behavior change communication (BCC) campaign focusing on anemia prevention to 245 children from a control group (receiving BCC only) after one year. Randomization was done at the level of the family concession (households from the same family) (n = 321). Eligible households had a child of the target age and were willing to deliver milk to the dairy factory. Changes in anemia and hemoglobin between groups were assessed using mixed regression models. Anemia prevalence was very high at baseline (80%) and dropped to close to 60% at endline, with no differences between intervention groups. Hemoglobin increased by 0.55 g/dL, 95%CI (0.27; 0.84) more in the intervention compared to the control group after one year, in models that controlled for potentially confounding factors. The impact was greater (0.72 g/dL, 95%CI (0.34; 1.12)) for boys, compared to girls (0.38 g/dL, 95%CI (-0.03; 0.80)). The dairy value chain was a successful strategy to distribute MNFY among pastoralists in Northern Senegal, and increase Hb concentrations among their children. This study is one of the first proofs of concept showing that a nutrition-sensitive agriculture value chain approach can contribute to improved child nutrition in a remote pastoralist population. ClinicalTrials.gov NCT02079961.

Delivery of iron-fortified yoghurt, through a dairy value chain program, increases hemoglobin concentration among children 24 to 59 months old in Northern Senegal: A cluster-randomized control trial

PubMed Central

Le Port, Agnes; Bernard, Tanguy; Hidrobo, Melissa; Birba, Ousmane; Rawat, Rahul; Ruel, Marie T.

2017-01-01

Background Innovative strategies are needed to enhance the nutritional impact of agriculture. Value chain approaches, which use supply chains to add value (usually economic) to products as they move from producers to consumers, can be used to increase access to nutritious foods and improve nutritional status. This study tested whether a dairy value chain could be used to distribute a micronutrient-fortified yoghurt (MNFY) (conditional upon the producer supplying a minimum amount of cow milk/day) to improve hemoglobin and reduce anemia among preschool children in a remote area in Northern Senegal. Methods A cluster randomized control trial was used to compare 204 children (24 to 59 months of age at baseline) from households who received the MNFY coupled to a behavior change communication (BCC) campaign focusing on anemia prevention to 245 children from a control group (receiving BCC only) after one year. Randomization was done at the level of the family concession (households from the same family) (n = 321). Eligible households had a child of the target age and were willing to deliver milk to the dairy factory. Changes in anemia and hemoglobin between groups were assessed using mixed regression models. Key findings Anemia prevalence was very high at baseline (80%) and dropped to close to 60% at endline, with no differences between intervention groups. Hemoglobin increased by 0.55 g/dL, 95%CI (0.27; 0.84) more in the intervention compared to the control group after one year, in models that controlled for potentially confounding factors. The impact was greater (0.72 g/dL, 95%CI (0.34; 1.12)) for boys, compared to girls (0.38 g/dL, 95%CI (-0.03; 0.80)). Conclusion The dairy value chain was a successful strategy to distribute MNFY among pastoralists in Northern Senegal, and increase Hb concentrations among their children. This study is one of the first proofs of concept showing that a nutrition-sensitive agriculture value chain approach can contribute to improved child nutrition in a remote pastoralist population. Trial registration ClinicalTrials.gov NCT02079961 PMID:28245227

Anemia of Inflammation and Chronic Disease

MedlinePlus

Anemia of Inflammation and Chronic Disease National Hematologic Diseases Information Service What is anemia? Anemia is a condition in which a person has ... also cause low blood iron levels. People with anemia may feel tired because their blood does not ...

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation

PubMed Central

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W.; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C.; Currier, Judith S.; Tang, Alice M.; Semba, Richard D.; Christian, Parul; Campbell, Thomas B.; Gupta, Amita

2015-01-01

Background. Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. Methods. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥10 mg/L) with clinical failure were assessed using multivariable Cox models. Results. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82–14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37–1.58) for anemia without inflammation, and 0.45 (95% CI, .11–1.80) for inflammation without anemia compared to those without anemia and inflammation. Conclusions. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening. PMID:25828994

Subchronic and chronic toxicity of ingested 1,3-dichloropropene in dogs.

PubMed

Stebbins, K E; Quast, J F; Haut, K T; Stott, W T

1999-12-01

The potential toxicologic effects to dogs of 1,3-dichloropropene (1, 3-D), a soil fumigant used for the control of nematodes, were investigated. The 13-week subchronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) given approximately 0, 5, 15, or 41 mg 1,3-D/kg body wt/day (approximately equivalent amounts of cis and trans isomers) via their diets. The 1-year chronic toxicity study consisted of male and female beagle dogs (4/sex/dose group) provided diets delivering approximately 0, 0.5, 2. 5, or 15 mg/kg body wt/day. The test material was stabilized in the feed by microencapsulation in a starch/sucrose matrix (80/20). In both the 13-week and the 1-year studies, the primary effect of 1,3-D in male and female dogs ingesting a dosage of >/=15 mg/kg/day was hypochromic, microcytic anemia. The anemia was regenerative, with increased erythropoietic activity characterized by polychromasia of erythrocytes and increased numbers of reticulocytes in peripheral blood. In the 13-week study, the anemia in dogs given 41 mg/kg/day progressively worsened over time, while the anemia in dogs given 15 mg/kg/day remained relatively constant between 42 and 90 days of dosing. Partial reversal of the anemia of high-dose animals occurred during a 5-week recovery period following the 13-week dosing regimen. In the 13-week study, terminal fasted body weights of males given 15 or 41 mg/kg/day were decreased 3 and 28%, respectively, and body weights of females given 5, 15, or 41 mg/kg/day were decreased 4.5, 12, and 24%, respectively, relative to controls. Males given 5 mg/kg/day for 13 weeks had no change in body weights relative to controls. In the 1-year study, the hypochromic microcytic anemia in dogs given 15 mg/kg/day remained relatively constant in severity between 3 and 12 months of treatment. Histopathologic alterations associated with anemia in the 1-year study consisted of increased hematopoiesis of the bone marrow and increased extramedullary hematopoiesis of the spleen. Body weights of males given 15 mg/kg/day were 5-12% lower than controls during the first 13 weeks of the study and 13-19% lower than controls during the remaining 9 months. Body weights of females given 15 mg/kg/day were 5-14% lower than controls over the majority of the dosing period. Males and females given 0.5 or 2.5 mg/kg/day for 1 year had no change in body weights relative to controls. A no-observed-effect level of 2.5 mg/kg/day was established for male and female dogs from the 1-year study. Copyright 1999 Academic Press.

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.

PubMed

Chandrasekharappa, Settara C; Chinn, Steven B; Donovan, Frank X; Chowdhury, Naweed I; Kamat, Aparna; Adeyemo, Adebowale A; Thomas, James W; Vemulapalli, Meghana; Hussey, Caroline S; Reid, Holly H; Mullikin, James C; Wei, Qingyi; Sturgis, Erich M

2017-10-15

Patients with Fanconi anemia (FA) have an increased risk for head and neck squamous cell carcinoma (HNSCC). The authors sought to determine the prevalence of undiagnosed FA and FA carriers among patients with HNSCC as well as an age cutoff for FA genetic screening. Germline DNA samples from 417 patients with HNSCC aged <50 years were screened for sequence variants by targeted next-generation sequencing of the entire length of 16 FA genes. The sequence revealed 194 FA gene variants in 185 patients (44%). The variant spectrum was comprised of 183 nonsynonymous point mutations, 9 indels, 1 large deletion, and 1 synonymous variant that was predicted to effect splicing. One hundred eight patients (26%) had at least 1 rare variant that was predicted to be damaging, and 57 (14%) had at least 1 rare variant that was predicted to be damaging and had been previously reported. Fifteen patients carried 2 rare variants or an X-linked variant in an FA gene. Overall, an age cutoff for FA screening was not identified among young patients with HNSCC, because there were no significant differences in mutation rates when patients were stratified by age, tumor site, ethnicity, smoking status, or human papillomavirus status. However, an increased burden, or mutation load, of FA gene variants was observed in carriers of the genes FA complementation group D2 (FANCD2), FANCE, and FANCL in the HNSCC patient cohort relative to the 1000 Genomes population. FA germline functional variants offer a novel area of study in HNSCC tumorigenesis. FANCE and FANCL, which are components of the core complex, are known to be responsible for the recruitment and ubiquitination, respectively, of FANCD2, a critical step in the FA DNA repair pathway. In the current cohort, the increased mutation load of FANCD2, FANCE, and FANCL variants among younger patients with HNSCC indicates the importance of the FA pathway in HNSCC. Cancer 2017;123:3943-54. © 2017 American Cancer Society. © 2017 American Cancer Society.

The Association of Parasitic Infections in Pregnancy and Maternal and Fetal Anemia: A Cohort Study in Coastal Kenya

PubMed Central

McClure, Elizabeth M.; Meshnick, Steven R.; Mungai, Peter; Malhotra, Indu; King, Christopher L.; Goldenberg, Robert L.; Hudgens, Michael G.; Siega-Riz, Anna Maria; Dent, Arlene E.

2014-01-01

Background Relative contribution of these infections on anemia in pregnancy is not certain. While measures to protect pregnant women against malaria have been scaling up, interventions against helminthes have received much less attention. In this study, we determine the relative impact of helminthes and malaria on maternal anemia. Methods A prospective observational study was conducted in coastal Kenya among a cohort of pregnant women who were recruited at their first antenatal care (ANC) visit and tested for malaria, hookworm, and other parasitic infections and anemia at enrollment. All women enrolled in the study received presumptive treatment with sulfadoxine-pyrimethamine, iron and multi-vitamins and women diagnosed with helminthic infections were treated with albendazole. Women delivering a live, term birth, were also tested for maternal anemia, fetal anemia and presence of infection at delivery. Principal Findings Of the 706 women studied, at the first ANC visit, 27% had moderate/severe anemia and 71% of women were anemic overall. The infections with highest prevalence were hookworm (24%), urogenital schistosomiasis (17%), trichuria (10%), and malaria (9%). In adjusted and unadjusted analyses, moderate/severe anemia at first ANC visit was associated with the higher intensities of hookworm and P. falciparum microscopy-malaria infections. At delivery, 34% of women had moderate/severe anemia and 18% of infants' cord hemoglobin was consistent with fetal anemia. While none of the maternal infections were significantly associated with fetal anemia, moderate/severe maternal anemia was associated with fetal anemia. Conclusions More than one quarter of women receiving standard ANC with IPTp for malaria had moderate/severe anemia in pregnancy and high rates of parasitic infection. Thus, addressing the role of co-infections, such as hookworm, as well as under-nutrition, and their contribution to anemia is needed. PMID:24587473

Acute and chronic anemia and short- and long-term outcome of patients with peripheral arterial disease and critical limb ischemia.

PubMed

Lüders, Florian; Engelbertz, Christiane; Meyborg, Matthias; Freisinger, Eva; Malyar, Nasser M; Zeller, Thomas; Reinecke, Holger

2016-06-01

Evident data about the additive effect of "the fifth cardiovascular risk factor" (anemia) and peripheral arterial disease (PAD) focused on morbidity and outcome of patients with PAD are currently still missing. A total of 41,882 PAD patients were included. Of these, 5566 (13.3%) suffered from anemia. Patients with anemia were older (P<0.001), suffered more often from chronic kidney disease (P<0.001), coronary artery disease (P<0.001), and more severe PAD (P<0.001). However, they received significantly less endovascular revascularizations (P<0.001), had higher amputation rates (acute anemia: 3.7-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 2.9-fold, P<0.001), higher in-hospital mortality rates (acute anemia: 6.4-fold, P<0.001; nutritional, aplastic, and anemia in chronic disease: 4.6-fold; P<0.001), had significantly higher in-hospital complications (P<0.001) compared to those without anemia. During a follow-up time up to 4years (until Dec. 31st, 2012, median 775days, 25th-75th percentiles 469-1120days) nutritional, aplastic, and anemia in chronic disease and acute anemia were high significant predictors of long-term mortality and amputation (each P<0.001). Lengths of hospital stay and reimbursement costs were higher (nutritional, aplastic, and anemia in chronic disease: 2-fold higher (P<0.001), acute anemia: 3-fold higher (P<0.001)) than in patients without anemia. This study illustrates from a large, comprehensive database the association of acute, nutritional, aplastic, and anemia in chronic disease on morbidity, in-hospital treatment and complications, short- and long term outcome, and costs of patients with PAD. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Salivary Iron (Fe) Ion Levels, Serum Markers of Anemia and Caries Activity in Pregnant Women.

PubMed

Costa, Elisa Miranda; Azevedo, Juliana Aires Paiva de; Martins, Rafiza Félix Marão; Rodrigues, Vandilson Pereira; Alves, Cláudia Maria Coêlho; Ribeiro, Cecília Cláudia Costa; Thomaz, Erika Bárbara Abreu Fonseca

2017-03-01

Introduction  Anemia is a very frequent event among pregnant women. There are evidences of differences in the incidence of dental caries between pregnant and non-pregnant women, but the relationship between salivary iron (Fe) and serum markers of anemia and caries development has not been investigated. Objective  To evaluate the correlation between salivary (Fe) and serum iron (Fe, ferritin and hemoglobin) parameters in pregnant women with the development of dental caries. Methods  A prospective cohort was conducted with 59 women. The outcome of interest was represented by new dental caries lesions during pregnancy, using the Nyvad criteria. Pregnant women were evaluated at three clinical times: up to the 16th week of gestational age (GA) (T1), in the last trimester of pregnancy (T2), and postpartum (T3), at the Mother and Child Unit of University Hospital of the Universidade Federal do Maranhão. A stimulated saliva sample was collected for biochemical analysis of salivary Fe, and a blood sample was collected early in the morning. The correlation between salivary and serum Fe was evaluated through the Pearson correlation test. Analysis of variance (ANOVA) and Kruskal-Wallis were used to compare the means of anemia parameters at different times. The Student's t and Mann-Whitney tests were used to compare the anemia parameters between the groups of pregnant women (with and without new caries lesions). Results  Serum Fe concentrations were higher in the first trimester of pregnancy and lower after delivery ( p  = 0.036). It was also observed that the ferritin concentrations were higher in the first trimester and lower at the end of gestation ( p  = 0.011). There was no association between the expositions of salivary iron and anemia, and the development of dental caries. There was a positive correlation between serum Fe in T1 and salivary Fe in T2 ( p  < 0.05). Conclusion  The serum markers of anemia were more prevalent in the last trimester of pregnancy. Thieme-Revinter Publicações Ltda Rio de Janeiro, Brazil.

Lactoferrin or ferrous salts for iron deficiency anemia in pregnancy: A meta-analysis of randomized trials.

PubMed

Abu Hashim, Hatem; Foda, Osama; Ghayaty, Essam

2017-12-01

This systematic review and meta-analysis aimed to evaluate the efficacy of daily oral bovine lactoferrin versus daily oral ferrous iron preparations for treatment of iron deficiency anemia (IDA) during pregnancy. Searches were conducted on PubMed, ScienceDirect, ClinicalTrials.gov and CENTRAL databases from inception to February 2017 and the bibliographies of retrieved articles were screened. The PRISMA Statement was followed. Published English language randomized trials comparing lactoferrin with oral ferrous iron preparations in pregnant women with iron deficiency anemia were included. Quasi-randomized, non- randomized or studies including other known cause of anemia, gestational or pre-existent maternal diseases were excluded. Accordingly, 4 eligible trials (600 women) were analyzed. Primary outcome was change in hemoglobin level at 4 weeks of treatment. Secondary outcomes were; change in serum ferritin and iron, rates of gastrointestinal side effects, preterm birth, low birthweight, neonatal death and mean birthweight. Quality assessment was performed by the Cochrane risk of bias tool. Odds ratio and mean difference were used to integrate dichotomous and continuous outcomes respectively. Pooled estimates for change in hemoglobin levels at four weeks favored daily oral lactoferrin over daily oral ferrous sulphate (mean difference 0.77; 95% confidence interval [CI] 0.04-1.55; P=0.04, 4 trials, 600 women). However, after subgroup analysis (degree of anemia), no significant difference in hemoglobin levels were found between both groups in mild anemia (mean difference 0.80; 95% CI -0.21 to 1.82, 3 trials, 372 women), but a significant increase favoring lactoferrin was reported in moderate anemia (mean difference 0.68; 95% CI 0.53-0.83; P<0.00001, one trial, 228 women). Significantly less gastrointestinal side effects were reported with lactoferrin treatment. No significant differences existed with regard to other outcomes. In conclusion, for pregnant women with IDA, daily oral bovine lactoferrin is just as good as ferrous sulfate in improving hematological parameters with fewer gastrointestinal side effects. Thereby, lactoferrin should be the iron replacement agent of choice for treatment of IDA in pregnancy. Copyright © 2017 Elsevier B.V. All rights reserved.

Gross and microscopic characteristics of stomach cancer with microangiopathic hemolytic anemia and/or disseminated intravascular coagulopathy.

PubMed

Morimatsu, M; Shirouzu, K; Irie, K; Tokunaga, O; Sasaguri, Y

1985-07-01

We described gross and microscopic characteristics of 11 autopsied cases of stomach cancer with microangiopathic hemolytic anemia and/or disseminated intravascular coagulopathy. They were divided into two groups grossly. One was superficial carcinoma and the other diffuse infiltrating and fungating carcinoma. Superficial carcinoma arose multicentrically and showed figures of signet ring cell carcinoma. This condition was accompanied by marked pulmonary tumor emboli and bone marrow dissemination in the initial stage of cancer evolution. Diffuse infiltrating and fungating carcinoma arose in the corpus and showed variable histological features. Dissemination of tumor cells to the bone marrow was seen in the terminal stage. Stomach cancer in this series consisted of two different groups on gross, microscopic and metastatic features. Signet ring cell of superficial carcinoma showed characteristic biological features with respect to local extension and metastasis.

[Relationship between lethality of hemodialysis patients, erythropoietin dosage for renal anemia treatment and hemodialysis quality].

PubMed

Ziginskiene, Edita; Kuzminskis, Vytautas; Bumblyte, Inga Arūne

2003-01-01

In December of 1999 and 2000 we visited all hemodialysis centers of Lithuania and collected data about all hemodialysis patients, using special questionnaires. The aim of the study was to evaluate the relationship between lethality of hemodialysis patients, erythropoietin dosage for renal anemia treatment and hemodialysis quality. The patients with higher Kt/V, higher levels of iron and albumin, normal levels of phosphorus and parathyroid hormone (PTH) requested lower doses of erythropoietin (analysis of the patients who were on hemodialysis in 2000 more than 6 months). So, we can conclude that adequate hemodialysis procedure and good management of hemodialysis patient are leading to the decrease request of erythropoietin doses for anemia treatment. We compared two groups of patients in order to examine relationship between hemodialysis quality and lethality of hemodialysis patients. We selected incident patients registered in December of 1999 and we divided these patients in December of 2000 in two groups: a) 175 patients, who continued hemodialysis treatment and b) 41 patients, who died in 2000. The results revealed, that dead patients were elder, their duration of weekly hemodialysis was shorter, Hb concentration lower, they had worse nutritional status (blood albumin level was lower). Lethality was associated with underlying diseases such as diabetes, hypertensive nephropathy and renal amyloidosis.

Modified immunosuppressive therapy with porcine antilymphocyte globulin plus delayed cyclosporine A in children with severe aplastic anemia.

PubMed

Cui, Qingya; Sha, Pingping; Chen, Haifei; Shen, Hongshi; Qin, Longmei; Li, Zhengyang; Wu, Tianqin; Wang, Zhaoyue

2018-01-01

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine (CsA) is the standard treatment for children with severe aplastic anemia (SAA) with no human leukocyte antigen-matched siblings. Due to the unavailability of horse ATG in China, porcine antilymphocyte globulin (p-ALG), which is less expensive and more effective than rabbit ATG, is widely used. We sought to evaluate the efficacy and safety profile of modified IST with p-ALG plus delayed CsA at day 21 in 50 SAA children. Eighteen SAA patients who progressed from nonsevere aplastic anemia (NSAA) were classified as SAA-II; the other 32 patients were classified as SAA-I. Overall response (OR) rates at 3, 6 and 12 months were 56, 64 and 62%, respectively. The 10-year overall survival (OS) rate and disease-free survival (DFS) rate were 80 and 56%. The OR, OS and DFS rates in the SAA-I group were clearly better than those in the SAA-II group. Death rate from infection within 30 days was 4%. Modified IST with p-ALG plus delayed CsA is a reliable and well-tolerated treatment for children with SAA, and reduces early death due to infection. Modified IST is more suitable for children with SAA-I.

Double-blind randomized controlled trial of rolls fortified with microencapsulated iron.

PubMed

Barbosa, Teresa Negreira Navarro; Taddei, José Augusto de Aguiar Carrazedo; Palma, Domingos; Ancona-Lopez, Fábio; Braga, Josefina Aparecida Pellegrini

2012-01-01

To evaluate the impact of the fortification of rolls with microencapsulated iron sulfate with sodium alginate on the hemoglobin levels in preschoolers as compared to controls. Double-blind randomized controlled trial comprised of children aged 2 to 6 years with initial hemoglobin exceeding 9 g/dL from four not-for-profit daycares randomly selected in the city of São Paulo - Brazil. Children of 2 daycares (n = 88) received rolls with fortified wheat flour as the exposed group (EC) and children of 2 daycares (n = 85) received rolls without fortification as the control group (CG) over a 24-week period. Rolls with 4 mg iron each were offered once a day, five days a week. Hemoglobin concentrations were determined in capillary blood by HemoCue® at three moments of trial: baseline (Ml), after 12 and 24 weeks of intervention (M2, M3). Hemoglobin concentration presented significant increase up to M3 in EG (11.7-12.5-12.6 g/dL) and in CG (11.1-12.4-12.3 g/dL) with higher elevations in children initially with anemia. There was significant reduction in the occurrence of anemia from 22% to 9% in EG and from 47% to 8.2% in CG at M3. Rolls fortified with microencapsulated iron sulfate were well tolerated, increased hemoglobin levels and reduced the occurrence of anemia, but with no difference compared to the control group.

Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

PubMed

Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

2016-05-01

Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

Syngeneic transplantation in aplastic anemia: pre-transplant conditioning and peripheral blood are associated with improved engraftment: an observational study on behalf of the Severe Aplastic Anemia and Pediatric Diseases Working Parties of the European Group for Blood and Marrow Transplantation

PubMed Central

Gerull, Sabine; Stern, Martin; Apperley, Jane; Beelen, Dietrich; Brinch, Lorentz; Bunjes, Donald; Butler, Andrew; Ganser, Arnold; Ghavamzadeh, Ardeshir; Koh, Mickey B; Komarnicki, Mieczyslaw; Kröger, Nicolaus; Maertens, Johan; Maschan, Alexei; Peters, Christina; Rovira, Montserrat; Sengeløv, Henrik; Socié, Gerard; Tischer, Johanna; Oneto, Rosi; Passweg, Jakob; Marsh, Judith

2013-01-01

Aplastic anemia is usually treated with immunosuppression or allogeneic transplant, depending on patient and disease characteristics. Syngeneic transplant offers a rare treatment opportunity with minimal transplant-related mortality, and offers an insight into disease mechanisms. We present here a retrospective analysis of all syngeneic transplants for aplastic anemia reported to the European Group for Blood and Marrow Transplantation. Between 1976 and 2009, 88 patients received 113 transplants. Most transplants (n=85) were preceded by a conditioning regimen, 22 of these including anti-thymocyte globulin. About half of transplants with data available (39 of 86) were followed by posttransplant immunosuppression. Graft source was bone marrow in the majority of cases (n=77). Transplant practice changed over time with more transplants with conditioning and anti-thymocyte globulin as well as peripheral blood stem cells performed in later years. Ten year overall survival was 93% with 5 transplant-related deaths. Graft failure occurred in 32% of transplants. Risk of graft failure was significantly increased in transplants without conditioning, and with bone marrow as graft source. Lack of posttransplant immunosuppression also showed a trend towards increased risk of graft failure, while anti-thymocyte globulin did not have an influence. In summary, syngeneic transplant is associated with a significant risk of graft failure when no conditioning is given, but has an excellent long-term outcome. Furthermore, our comparatively large series enables us to recommend the use of pre-transplant conditioning rather than not and possibly to prefer peripheral blood as a stem cell source. PMID:23894010

Risk Factors of Pulmonary Hypertension in Brazilian Patients with Sickle Cell Anemia.

PubMed

Lobo, Clarisse Lopes de Castro; do Nascimento, Emilia Matos; Abelha, Renato; Queiroz, Ana Maria Mach; Connes, Philippe; Cardoso, Gilberto Perez; Ballas, Samir K

2015-01-01

This study was a prospective cross-sectional cohort study of 125 patients with sickle cell anemia (SS) between the ages of 16 to 60 years. Enrolled patients were followed-up prospectively for 15 months. Demographic, clinical, hematological and routine biochemical data were obtained on all patients. Six-minute walk test and Doppler Echocardiography were performed on all patients. A tricuspid regurgitant jet velocity (TRJV) < 2.5 m/sec was considered normal, 2.5 ≤ TRJV ≤ 3.0 was considered mild-moderate and > 3.0 m/sec, severe. Patients with abnormal TRJV were significantly older and more anemic, had significantly higher lactate dehydrogenase (LDH) levels, reticulocyte count and incidence of death. The logistic multimodal model implemented for the 125 patients indicated that age was the covariate that influenced the outcome of normal or abnormal TRJV with a cutoff age of thirty-two years. The survival rate for the group of patients with creatinine (Cr) > 1.0 mg/dL was lower than the group with Cr ≤ 1 and normal TRJV. A coefficient matrix showed that the LDH values were weakly correlated with the reticulocyte count but strongly correlated with hemoglobin suggesting that the TRJV values were not correlated with the hemolytic rate but with anemia. Ten patients died during the follow-up of whom 7 had TRJV > 2.5 m/sec. Acute chest syndrome was the most common cause of death followed by sepsis. In conclusion, this study shows that patients with SS older than thirty-two years with high LDH, elevated TRJV, severe anemia and Cr > 1 have poor prognosis and may be at risk of having pulmonary hypertension and should undergo RHC.

Approval summary: azacitidine for treatment of myelodysplastic syndrome subtypes.

PubMed

Kaminskas, Edvardas; Farrell, Ann; Abraham, Sophia; Baird, Amy; Hsieh, Li-Shan; Lee, Shwu-Luan; Leighton, John K; Patel, Hasmukh; Rahman, Atiqur; Sridhara, Rajeshwara; Wang, Yong-Cheng; Pazdur, Richard

2005-05-15

This article summarizes data submitted to the U.S. Food and Drug Administration for marketing approval of azacitidine as injectable suspension (Vidaza, Pharmion Corporation, Boulder, CO) for treatment of patients with myelodysplastic syndrome. In one phase 3 controlled trial, 191 study subjects were randomized to treatment with azacitidine or to observation; an additional 120 patients were treated with azacitidine in two phase 2 single arm studies. The primary efficacy end point was the overall response rate, defined as complete or partial normalization of peripheral blood counts and bone marrow blast percentages for at least 4 weeks. In the controlled trial, the overall response rate was 15.7% in the azacitidine treatment group; there were no responders in the observation group (P < 0.0001). Response rates were similar in the two single arm studies. During response patients stopped being red cell or platelet transfusion dependent. Median duration of responses was at least 9 months. An additional 19% of azacitidine-treated patients had less than partial responses, most becoming transfusion independent. The most common adverse events attributed to azacitidine were gastrointestinal, hematologic, local (injection site), and constitutional. There were no azacitidine-related deaths. On May 19, 2004 the U.S. Food and Drug Administration approved azacitidine as injectable suspension for treatment of patients with the following myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Full prescribing information is available at http://www.fda.gov/cder/foi/label/2004/050794lbl.pdf. Azacitidine is the first agent approved for treatment of myelodysplastic syndrome.

Multivitamin supplementation improves hematologic status in HIV-infected women and their children in Tanzania.

PubMed

Fawzi, Wafaie W; Msamanga, Gernard I; Kupka, Roland; Spiegelman, Donna; Villamor, Eduardo; Mugusi, Ferdinand; Wei, Ruilan; Hunter, David

2007-05-01

Anemia is a frequent complication among HIV-infected persons and is associated with faster disease progression and mortality. We examined the effect of multivitamin supplementation on hemoglobin concentrations and the risk of anemia among HIV-infected pregnant women and their children. HIV-1-infected pregnant women (n = 1078) from Dar es Salaam, Tanzania, were enrolled in a double-blind trial and provided daily supplements of preformed vitamin A and beta-carotene, multivitamins (vitamins B, C, and E), preformed vitamin A and beta-carotene + multivitamins, or placebo. All women received iron and folate supplements only during pregnancy according to local standard of care. The median follow-up time for hemoglobin measurement for mothers was 57.3 mo [interquartile range (IQR): 28.6-66.8] and for children it was 28.0 mo (IQR: 5.3-41.7). During the whole period, hemoglobin concentrations among women who received multivitamins were 0.33 g/dL higher than among women who did not receive multivitamins (P=0.07). Compared with placebo, multivitamin supplementation resulted in a hemoglobin increase of 0.59 g/dL during the first 2 y after enrollment (P=0.0002). Compared with placebo, the children born to mothers who received multivitamins had a reduced risk of anemia. In this group, the risk of macrocytic anemia was 63% lower than in the placebo group (relative risk: 0.37: 95% CI: 0.18, 0.79; P=0.01). Multivitamin supplementation provided during pregnancy and in the postpartum period resulted in significant improvements in hematologic status among HIV-infected women and their children, which provides further support for the value of multivitamin supplementation in HIV-infected adults.

Plasma hepcidin levels and anemia in old age. The Leiden 85-Plus Study

PubMed Central

den Elzen, Wendy P.J.; de Craen, Anton J.M.; Wiegerinck, Erwin T.; Westendorp, Rudi G.J.; Swinkels, Dorine W.; Gussekloo, Jacobijn

2013-01-01

Hepcidin, an important regulator of iron homeostasis, is suggested to be causally related to anemia of inflammation. The aim of this study was to explore the role of plasma hepcidin in anemia among older persons from the general population. The Leiden 85-Plus Study is a population-based study of 85-year olds in Leiden, the Netherlands. Eighty-five-year old inhabitants of Leiden were enrolled between September 1997 and September 1999. At the age of 86, plasma hepcidin was determined with time of flight mass spectrometry in 490 participants [160 (32.7%) male, 114 (23.3%) with anemia]. Anemia was defined according to criteria of the World Health Organization (hemoglobin level <13 g/dL for men and hemoglobin <12 g/dL for women). The median plasma hepcidin level was 3.0 nM [interquartile range (IQR) 1.8–4.9]. We found strong correlations between plasma hepcidin and body iron status, C-reactive protein and erythropoietin levels. Significantly higher hepcidin levels were found in participants with anemia of inflammation (P<0.01), in participants with anemia of kidney disease (P=0.01), and in participants with unexplained anemia (P=0.01) than in participants without anemia. Participants with iron-deficiency anemia had significantly lower plasma hepcidin levels than participants without anemia (P<0.01). In conclusion, older persons with anemia of inflammation have higher hepcidin levels than their counterparts without anemia. The potential clinical value of hepcidin in future diagnostic algorithms for anemia has to be explored. PMID:23065507

G6PD deficiency and absence of α-thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia.

PubMed

Joly, Philippe; Garnier, Nathalie; Kebaili, Kamila; Renoux, Céline; Dony, Arthur; Cheikh, Nathalie; Renard, Cécile; Ceraulo, Antony; Cuzzubbo, Daniela; Pondarré, Corinne; Martin, Cyril; Pialoux, Vincent; Francina, Alain; Bertrand, Yves; Connes, Philippe

2016-04-01

The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

IRON DEFICIENCY AND INFANT MOTOR DEVELOPMENT

PubMed Central

Shafir, Tal; Angulo-Barroso, Rosa; Jing, Yuezhou; Lu Angelilli, Mary; Jacobson, Sandra W.; Lozoff, Betsy

2011-01-01

Background Iron deficiency (ID) during early development impairs myelination and basal ganglia function in animal models. Aims To examine the effects of iron deficiency anemia (IDA) and iron deficiency (ID) without anemia on infant motor skills that are likely related to myelination and basal ganglia function. Study design Observational study. Subjects Full-term inner-city African-American 9- to 10-month-old infants who were free of acute or chronic health problems with iron status indicators ranging from IDA to iron sufficiency (n = 106). Criteria for final iron status classification were met by 77 of these infants: 28 IDA, 28 non-anemic iron-deficient (NA ID), and 21 iron-sufficient (IS). Outcome measures Gross motor developmental milestones, Peabody Developmental Motor Scale, Infant Neurological International Battery (INFANIB), motor quality factor of the Bayley Behavioral Rating Scale, and a sequential/bi-manual coordination toy retrieval task. General linear model analyses tested for linear effects of iron status group and thresholds for effects. Results There were linear effects of iron status on developmental milestones, Peabody gross motor (suggestive trend), INFANIB standing item, motor quality, and toy retrieval. The threshold for effects was ID with or without anemia for developmental milestones, INFANIB standing item, and motor quality and IDA for toy retrieval. Conclusions Using a comprehensive and sensitive assessment of motor development, this study found poorer motor function in ID infants with and without anemia. Poorer motor function among non-anemic ID infants is particularly concerning, since ID without anemia is not detected by common screening procedures and is more widespread than IDA. PMID:18272298

Mortality in children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil.

PubMed

Lobo, Clarisse Lopes de Castro; Nascimento, Emilia Matos do; Jesus, Leonardo José Carvalho de; Freitas, Thiago Gotelip de; Lugon, Jocemir Ronaldo; Ballas, Samir K

To determine the mortality rate of children, adolescents and adults with sickle cell anemia in Rio de Janeiro, Brazil. The number of deaths, the mortality rate and the causes of deaths in patients with sickle cell anemia who were treated and followed up at our institution for 15 years were determined and compared to data available for the Brazilian population. The overall number of deaths was 281 patients with a mortality rate of 16.77%. Survival probability was significantly higher in females. The number of deaths and the mortality rate were age-specific with a significant increase in the 19- to 29-year-old age group. The remaining life expectancy of the patients with sickle cell anemia was less than that of Brazilians at large. The gap between the two was about 20 years for ages between one and five years with this gap decreasing to ten years after the age of 65 years. The most common causes of death were infection, acute chest syndrome, overt stroke, organ damage and sudden death during painful crises. To the best of our knowledge, this is the first Brazilian study in a single institution in Rio de Janeiro; the mortality rate was 18.87% among adult patients with sickle cell anemia. The mortality rates in children and adults are higher than those reported in developed countries of the northern hemisphere. Copyright © 2017 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Iron deficiency anemia among children: Addressing a global public health problem within a Canadian context

PubMed Central

Christofides, Anna; Schauer, Claudia; Zlotkin, Stanley H

2005-01-01

Despite current Canadian pre- and perinatal nutrition programs, the prevalence of both iron deficiency and iron deficiency anemia (IDA) is very high among young Aboriginal children from Canada’s remote north. The major risk factors for IDA include prolonged consumption of evaporated cow’s milk, chronic infection and prolonged exclusive breastfeeding. In the present article, the authors discuss IDA as a significant public health problem in Canadian Aboriginal communities. Whereas the prevalence of IDA in Canadian children is between 3.5% and 10.5% in the general population, in two Northern Ontario First Nations communities and one Inuit community, the anemia rate was 36%, with 56% having depleted iron stores. Traditional methods of preventing IDA, including targeted fortification, dietary diversification and supplementation, have not solved the problem. The authors’ research group at The Hospital for Sick Children in Toronto, Ontario, conceived of the strategy of ‘home fortification’ with ‘Sprinkles’ – single-dose sachets containing micronutrients in a powder form, which are easily sprinkled onto any foods prepared in the household. In Sprinkles, the iron (ferrous fumarate) is encapsulated within a thin lipid layer to prevent the iron from interacting with food. Sprinkles have been shown to be efficacious in the treatment of anemia in many developing countries. Their use in Aboriginal communities to treat and prevent anemia is described in the present paper. The authors believe that children in Aboriginal communities across Canada would potentially benefit if Sprinkles were incorporated into Health Canada’s current distribution system, in combination with a social marketing strategy to encourage their use. PMID:19668671

Relationship between Schistosoma japonicum and nutritional status among children and young adults in Leyte, the Philippines.

PubMed

Friedman, Jennifer F; Kanzaria, Hemal K; Acosta, Luz P; Langdon, Gretchen C; Manalo, Daria L; Wu, Haiwei; Olveda, Remigio M; McGarvey, Stephen T; Kurtis, Jonathan D

2005-05-01

The objectives of this study were 1) to provide more accurate estimates of the relationship between Schistosoma japonicum infection and both protein energy malnutrition (PEM) and anemia through better adjustment for potential confounders such as socioeconomic status (SES) and geo-helminth infections and 2) to assess the role of occult blood loss in mediating S. japonicum-associated anemia. We examined cross-sectionally 729 individuals (86.7% S. japonicum-infected and 13.3% S. japonicum-uninfected) aged 7-30 years in Leyte, The Philippines. The main outcome measures were height-for-age Z-score (HAZ), body-mass-index Z-score (BMIZ), triceps skinfold Z-score, hemoglobin, and fecal occult blood loss. Multivariate models were created to assess the relationship between S. japonicum infection and nutritional status after adjusting for age, gender, other helminths, and SES. After controlling for confounders, intensity of S. japonicum infection was inversely related to hemoglobin in all age groups (P < 0.0001) and HAZ among children

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study

PubMed Central

Zulfiqar, AA; Andres, E

2017-01-01

Objective: To investigate the association between pernicious anemia and other autoimmune diseases. Methods: This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. Results: A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. Conclusion: We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b. PMID:29362601

[Pernicious anemia in an adolescent with type 1 diabetes mellitus].

PubMed

Carneiro, M; Dumont, C

2009-04-01

The most frequent organ-specific autoimmune diseases associated with type 1 diabetes mellitus in children are hypothyroidism and celiac disease. Among adults, other associations exist, notably with pernicious anemia, which is extremely rare in children. We relate the observation of an adolescent with type 1 diabetes mellitus and hypothyroidism, admitted for severe anemia in addition to chronic anemia caused by autoimmune gastritis. Blood cell count showed severe aregenerative anemia with pancytopenia, with signs of non-autoimmune hemolysis. Vitamin B12 levels were low, bone marrow aspiration revealed erythroid hyperplasia, and anti-intrinsic factor antibodies were positive, providing the diagnosis of pernicious anemia. Treatment with intramuscular vitamin B12 produced brisk reticulosis after 6 days, with a subsequent rapid resolution of the anemia. Follow-up of type 1 diabetes mellitus in children requires screening for organ-specific autoimmune diseases; in case of unexplained anemia, autoimmune gastritis must be suggested. It can evolve into pernicious anemia.

Association pernicious anemia and autoimmune polyendocrinopathy: a retrospective study.

PubMed

Zulfiqar, A A; Andres, E

2017-01-01

To investigate the association between pernicious anemia and other autoimmune diseases. This retrospective and bicentric study was conducted at Reims and Strasbourg University Hospitals and involved 188 patients with pernicious anemia examined between 2000 and 2010 in order to search for other autoimmune diseases and to evaluate the role of pernicious anemia in autoimmune polyglandular syndrome. A total of 74 patients with a combination of pernicious anemia and other autoimmune diseases were included in the study. Our study revealed the privileged association of pernicious anemia with autoimmune thyroiditis. The association of pernicious anemia and autoimmune thyroiditis are a part of the autoimmune polyglandular syndrome type 3b. We suggest undertaking a systematic clinical examination and laboratory investigations in search of autoimmune thyroiditis in patient(s) with the diagnosis of pernicious anemia. The association of pernicious anemia and autoimmune thyroiditis is frequent and a part of autoimmune polyglandular 3b.

Concurrent Anemia and Elevated C-Reactive Protein Predicts HIV Clinical Treatment Failure, Including Tuberculosis, After Antiretroviral Therapy Initiation.

PubMed

Shivakoti, Rupak; Yang, Wei-Teng; Gupte, Nikhil; Berendes, Sima; Rosa, Alberto La; Cardoso, Sandra W; Mwelase, Noluthando; Kanyama, Cecilia; Pillay, Sandy; Samaneka, Wadzanai; Riviere, Cynthia; Sugandhavesa, Patcharaphan; Santos, Brento; Poongulali, Selvamuthu; Tripathy, Srikanth; Bollinger, Robert C; Currier, Judith S; Tang, Alice M; Semba, Richard D; Christian, Parul; Campbell, Thomas B; Gupta, Amita

2015-07-01

Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models. Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation. ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Prevalence of preoperative anemia, abnormal mean corpuscular volume and red cell distribution width among surgical patients in Singapore, and their influence on one year mortality

PubMed Central

Wee, Hide Elfrida; Ang, Ai Leen; Ranjakunalan, Niresh; Ong, Biauw Chi; Abdullah, Hairil Rizal

2017-01-01

Introduction Preoperative anemia and high red cell distribution width (RDW) are associated with higher perioperative mortality. Conditions with high RDW levels can be categorized by mean corpuscular volume (MCV). The relationship between RDW, anemia and MCV may explain causality between high RDW levels and outcomes. We aim to establish the prevalence of preoperative anemia and distribution of RDW and MCV among pre-surgical patients in Singapore. In addition, we aim to investigate the association between preoperative anemia, RDW and MCV levels with one-year mortality after surgery. Methods Retrospective review of 97,443 patients aged > = 18 years who underwent cardiac and non-cardiac surgeries under anesthesia between January 2012 and October 2016. Patient demographics, comorbidities, priority of surgery, surgical risk classification, perioperative transfusion, preoperative hemoglobin, RDW, MCV were collected. WHO anemia classification was used. High RDW was defined as >15.7%. Multivariate regression analyses were done to identify independent risk factors for mild or moderate/severe anemia and high RDW (>15.7). Multivariate cox regression analysis was done to determine the effect of preoperative anemia, abnormal RDW and MCV values on 1-year mortality. Results Our cohort comprised of 94.7% non-cardiac and 5.3% cardiac surgeries. 88.7% of patients achieved 1 year follow-up. Anemia prevalence was 27.8%—mild anemia 15.3%, moderate anemia 12.0% and severe anemia 0.5%. One-year mortality was 3.5%. Anemia increased with age in males, while in females, anemia was more prevalent between 18–49 years and > = 70 years. Most anemics were normocytic. Normocytosis and macrocytosis increased with age, while microcytosis decreased with age. Older age, male gender, higher ASA-PS score, anemia (mild- aHR 1.98; moderate/severe aHR 2.86), macrocytosis (aHR 1.47), high RDW (aHR 2.34), moderate-high risk surgery and emergency surgery were associated with higher hazard ratios of one-year mortality. Discussion Preoperative anemia is common. Anemia, macrocytosis and high RDW increases one year mortality. PMID:28777814

Epigenetic silencing of MicroRNA-503 regulates FANCA expression in non-small cell lung cancer cell.

PubMed

Li, Ning; Zhang, Fangfang; Li, Suyun; Zhou, Suzhen

2014-02-21

It is reported that MicroRNA-503 (miR-503) regulates cell apoptosis, and thus modulates the resistance of non-small cell lung cancer cells (NSCLC) to cisplatin. However, the exact role of miR-503 in NSCLC remains unknown. In the present study, the level of miR-503 expression in NSCLC was evaluated using realtime PCR, and the DNA methylation status within miR-503 promoter was analyzed by Combined Bisulfite Restriction Analysis (COBRA) or bisulfite-treated DNA sequencing assays (BSP). We found that the expression of miR-503 was significantly decreased in NSCLC tissues compared to normal tissues. A statistically significant inverse association was found between miR-503 methylation status and expression of the miR-503 in tumor tissues (P<0.001), and expression of miR-503 was restored by the demethylating agent 5-aza-2'-deoxycytidine, suggesting that methylation was associated with the transcriptional silencing. Then, we show that miR-503 targets a homologous DNA region in the 3'-UTR region of the Fanconi anemia complementation group A protein (FANCA) gene and represses its expression at the transcriptional level. Taken together, our results suggest that miR-503 regulates the resistance of non-small cell lung cancer cells to cisplatin at least in part by targeting FANCA. Copyright © 2014 Elsevier Inc. All rights reserved.

Fatal warm autoimmune hemolytic anemia in a child due to IgM-type autoantibodies.

PubMed

Takahashi, Hiroyuki; Tanaka, Fumiko; Sakuma, Hiroyuki; Sato, Mutsumi; Inaba, Shoichi; Kai, Sumio

2016-08-01

Herein is described a case of immunoglobulin M (IgM) warm autoimmune hemolytic anemia (AIHA) in a child who consequently died within 3 days of clinical onset. A previously healthy 11-year-old boy presented with fever, anemia, jaundice, and deteriorating consciousness. On direct agglutination test against group O red blood cells, agglutination was seen even at 37°C in saline, which was abolished on dithiothreitol treatment of the serum, indicating that the responsible autoantibody was IgM and had a warm-reactive capacity. A diagnosis of IgM warm AIHA was therefore made. Hemagglutination in the visceral capillaries was considered as the direct cause of organ dysfunction. The patient died due to respiratory failure. IgM warm AIHA is a very severe condition that is difficult to reverse in an advanced state. Both prompt, definite diagnosis and intervention are therefore vital to prevent severe multi-organ dysfunction in cases of IgM warm AIHA. © 2016 Japan Pediatric Society.

[Prevalence of anemia and its association with nutritional status among Chinese students of ethnic minorities in 2010].

PubMed

Song, Y; Zhang, B; Hu, P J; Ma, J

2016-06-18

To analyze the prevalence of anemia and its proportions of severity, and to examine the association between anemia and nutritional status among Chinese students of ethnic minorities, so as to provide bases for the prevention and treatment of anemia. The subjects were Mongolian, Hui, Zhuang and Korean students aged 7, 9, 12, 14 and 17 years, sampled from the 2010 Chinese National Surveys on Students' Constitution and Health. World Health Organization (WHO) criteria for screening anemia (2001) was used, and the proportion rates of mild, moderate and severe were analyzed. The nutritional status was defined according to the growth references of body mass index (BMI)-for-age z-score for 5-19 years developed by the WHO. Stepwise Logistic regression was used to assess the association between anemia and nutritional status, gender, urban/rural areas, age and ethnic minorities. The prevalences of anemia were 4.4%, 26.4%, 6.6% and 5.8% in Mongolian, Hui, Zhuang and Korean students, respectively, of whom, the prevalence of anemia was highest in rural girls and reached 4.8%, 42.0%, 9.0% and 6.7%, respectively. Most of the ethnic minorities' students belonged to mild anemia, and the prevalence of severe anemia was 1.4%, 12.9%, 1.6% and 1.9% in Mongolian, Hui, Zhuang and Korean students, respectively. Stepwise Logistic regression showed that the girls, rural students, students aged 12 years and 17 years, Hui, Zhuang and Korean students were more likely to develop anemia than the boys, urban students, students aged 7 years and Mongolian students. The overweight students were less likely to develop anemia compared with the normal students and there was no significant association between anemia and thinness or obesity when the other factors were controlled (P>0.05). The epidemic of anemia was different in the different ethnic minorities and the prevalence of anemia in Hui students was of moderate public health concern according to the WHO's criteria. We should pay more attention to the prevention and treatment of anemia for Hui and ethnic minorities in rural areas, especially for rural girls. The nutritional status of students could not be a basis or judgement for anemia as there was no significant association between anemia and nutritional status.

Iron chelated cyclic peptide, ferrichrysin, for oral treatment of iron deficiency: solution properties and efficacy in anemic rats.

PubMed

Suzuki, Sachiko; Fukuda, Katsuharu; Irie, Motoko; Hata, Yoji

2007-01-01

Ferrichrysin (Fcy), which is produced by Aspergillus oryzae and is present in foods used for human consumption, belongs to a group of hydroxamate siderophore ferric iron chelators. Fcy (100 mg/mL) dissolves completely at both pH 2.0 and 7.0, being very stable at a wide range of pH, high temperatures and pressures, with little reactivity to dietary iron absorption inhibitors, phytic acid, tannic acid, and catechin. We studied the effect of Fcy in male Sprague-Dawley rats with iron-deficiency anemia, which were separated into three different dietary groups (n=5) and supplementing diets as follows: (i) ferric citrate, (ii) heme iron concentrate, and (iii) Fcy (35 mg Fe/kg diet) for three weeks. Fcy exhibited the same beneficial effect in improving iron deficiency anemia as ferric citrate, being significantly greater than the effect of heme iron. The iron concentration of liver in the Fcy group was 35% greater than that in the ferric citrate group. These findings indicate that Fcy could be an efficient oral iron supplement to prevent or treat iron deficiency.

Respiratory and systemic infections in children with severe aplastic anemia on immunosuppressive therapy.

PubMed

Pawelec, Katarzyna; Salamonowicz, Malgorzata; Panasiuk, Anna; Matysiak, Michal; Demkow, Urszula

2013-01-01

In the present study we investigated the occurrence of systemic and respiratory infections in a cohort of 123 children with severe acquired aplastic anemia (SAA) on immunosuppressive therapy (IST). We recorded 101 episodes of infection in 77 patients (62.6 %). Pneumonia was among the most frequently observed clinical forms of infection (17 cases - 16.8 %). In the entire group, 23 children died, mostly in the course of fatal sepsis (15/23) and in 3 cases because of pneumonia complications. All patients were treated with horse (h-ATG) or rabbit antithymocyte globulin (r-ATG) supplemented with cyclosporine and corticosteroids. The crude incidence rate for serious infections in h-ATG group and r-ATG group was comparable. The relative risk of infectious complications was lower in patients treated with granulocyte colony stimulating factors (G-CSF) by 36 % (RR 0.64; p < 0.0001). The analysis confirmed that respiratory tract and disseminated infections comprise a very serious clinical problem and are the leading cause of death of SAA children. Active surveillance and the analysis of associated risk factors are required to detect opportunistic infections in this group of patients.

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study.

PubMed

El-Ghamrawy, Mona Kamal; Hanna, Wagdi Maurice; Abdel-Salam, Amina; El-Sonbaty, Marwa M; Youness, Eman R; Adel, Ahmed

2014-01-01

the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r=-0.3, p=0.04). PON level was found to be positively correlated with patients' weight and BMI (r=-0.4, p=0.01; r=-0.7, p<0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p=0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. Copyright © 2014 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

The anemia of primary autonomic failure and its reversal with recombinant erythropoietin

NASA Technical Reports Server (NTRS)

Biaggioni, I.; Robertson, D.; Krantz, S.; Jones, M.; Haile, V.

1994-01-01

OBJECTIVE: To determine if chronic sympathetic deprivation is associated with anemia and a low erythropoietin response. DESIGN: Survey of the prevalence and characteristics of anemia in patients with severe primary autonomic failure. SETTING: A referral service for autonomic failure in a tertiary teaching hospital. PATIENTS: 84 patients with primary autonomic failure who had symptomatic orthostatic hypotension. INTERVENTION: Open-label trial with human recombinant erythropoietin. RESULTS: Anemia was present in 32 of 84 patients (38%; 95% Cl, 27% to 50%). Plasma norepinephrine levels, measured in patients standing upright, were lower in the patient group with lower hemoglobin levels. Mean values in 22 patients with a hemoglobin level of less than 120 g/L were as follows: hemoglobin, 108 g/L (range, 87 to 118 g/L); hematocrit, 0.33; corrected reticulocyte counts, 0.008; mean corpuscular volume, 89 fL (89 microns 3); serum iron, 16.5 mumol/L (92 micrograms/dL); total iron binding capacity, 43.3 mumol/L (242 micrograms/dL); ferritin, 184 micrograms/L; serum vitamin B12, 410 pmol/L (556 pg/mL); and serum folate, 22.7 nmol/L (10 ng/mL). No relation was found between serum erythropoietin and blood hemoglobin levels. In seven of nine patients with autonomic failure who had hemoglobin levels less than 120 g/L, serum erythropoietin levels decreased below the 95% confidence interval corresponding to patients with iron deficiency anemia. Therapy with recombinant erythropoietin improved mean hemoglobin levels (from 108 to 133 g/L) in all patients treated (n = 5) at relatively low doses (25 to 50 units/kg body weight, subcutaneously, three times a week). CONCLUSIONS: Our data support the hypothesis that the sympathetic nervous system stimulates erythropoiesis in humans because anemia is a frequent occurrence in patients with severe autonomic failure and is associated with a blunted erythropoietin response.

Sickle cell anemia - resources

MedlinePlus

Resources - sickle cell anemia ... The following organizations are good resources for information on sickle cell anemia : American Sickle Cell Anemia Association -- www.ascaa.org US National Library of Medicine -- ghr.nlm. ...

Effects of partial replacement of fish meal by yeast hydrolysate on complement system and stress resistance in juvenile Jian carp (Cyprinus carpio var. Jian).

PubMed

Yuan, Xiang-Yang; Liu, Wen-Bin; Liang, Chao; Sun, Cun-Xin; Xue, Yun-Fei; Wan, Zu-De; Jiang, Guang-Zhen

2017-08-01

A 10-week feeding trial was carried out to investigate the effects of dietary fish meal replacement by yeast hydrolysate (YH) on growth performance, complement system and stress resistance of juvenile Jian carp (Cyprinus carpio var. Jian) (initial average weight 19.44 ± 0.06 g). In the study, there were five groups: one control group was fed with a basal diet (YH0), and four treatment groups were fed with dietary fish meal replaced by 1% YH (YH1), 3% (YH3), 5% (YH5) and 7% (YH7), respectively. Each group had four replicates. At the end of feeding trial, twelve fish from each group (three fish per replicate) were randomly selected for assessing the growth and immunity. Meanwhile, 20 fish per replicate were injected by Aeromonas hydrophila. The results showed that (1) Replacement levels of YH significantly affected the growth of the fish with the highest values of weight gain (WG) occurred in fish fed YH3 diet. However, no significant difference in feed conversion ratios (FCR) was observed among all groups. (2) Pre-stressed plasma lysozyme activity, total protein and albumin contents and complement component 3 (C3) and complement component 4 (C4) levels of fish fed YH3 diet were significantly higher than those of fish fed YH0 diet. However, post-stressed immune parameters of fish in all groups were significantly lower. (3) There was a trend that the expression levels of the complement-related genes (c1r/s-A, c4-1, c3-H1, c5-1, fb/c2-A, mbl-2 and masp) initially increased and then decreased except mbl-2 and masp, with the maximum values observed in fish fed YH3 diet. Before stress, the expression levels of the inflammation-related genes (alp, il-1β and tnf-α) in the hepatopancreas and spleen of fish fed YH1 diet and YH7 diet were significant higher than that of fish fed YH0 diet. After stress, no significant difference in the expression levels of those genes was observed among all groups. These results indicated that FM replacement by YH could improve growth performance, enhance innate immunity, and activate complement via the alternative complement pathway (ACP) and the classical complement pathway (CCP). Copyright © 2017 Elsevier Ltd. All rights reserved.

Burden and Determinants of Severe Anemia among HIV-Infected Adults: Results from a Large Urban HIV Program in Tanzania, East Africa

PubMed Central

Makubi, Abel; Okuma, James; Spiegelman, Donna; Hawkins, Claudia; Darling, Anne Marie; Jackson, Elizabeth; Mugusi, Ferdinand; Chalamilla, Guerino; Fawzi, Wafaie

2017-01-01

Background and Methods This cross-sectional study aimed at determining the prevalence and risk factors for severe anemia, severe microcytic anemia, and severe normocytic anemia among HIV-infected individuals aged >15 years. Univariate and multivariate analyses were performed to identify the risk factors for anemia. Results Data from 40 408 patients were analyzed, showing an overall prevalence of 22% for severe anemia. The risk of developing severe anemia increased by 49% among patients with a body mass index of <18.5 kg/m2, by approximately 2-fold among patients with the World Health Organization (WHO) stage III, and by 3-fold among patients with WHO stage IV illness. Severe normocytic anemia was uniquely increased among patients aged ≥50 years, among those with chronic diarrhea and Kaposi’s sarcoma, and those taking cotrimoxazole. Conclusion There was a high prevalence of severe anemia among adults infected with HIV. Focused identification of anemia should be based on the hemoglobin and mean corpuscular volume measurements. PMID:23792708

Language and False-Belief Task Performance in Children With Autism Spectrum Disorder.

PubMed

Jeffrey Farrar, M; Seung, Hye Kyeung; Lee, Hyeonjin

2017-07-12

Language is related to false-belief (FB) understanding in both typically developing children and children with autism spectrum disorder (ASD). The current study examined the role of complementation and general language in FB understanding. Of interest was whether language plays similar or different roles in the groups' FB performance. Participants were 16 typically developing children (mean age = 5.0 years; mental age = 6.7) and 18 with ASD (mean age = 7.3 years; mental age = 8.3). Children were administered FB and language tasks (say- and think-complements), receptive and expressive vocabulary tests, and relative clauses. When mental age and receptive and expressive vocabulary were used as separate covariates, the typical control group outperformed the children with ASD in FB task performance. Chi-square analyses indicated that passing both complementation tasks was linked to the FB understanding of children with ASD. Children with ASD who passed FB tasks all passed say- and think-complement tasks. However, some children in the control group were able to pass the FB tasks, even if they failed the say- and think-complement tasks. The results indicate that children with ASD relied more on complement understanding to pass FB than typically developing children. Results are discussed regarding the developmental pathways for FB understanding.

Variants in Complement Factor H and Complement Factor H-Related Protein Genes, CFHR3 and CFHR1, Affect Complement Activation in IgA Nephropathy.

PubMed

Zhu, Li; Zhai, Ya-Ling; Wang, Feng-Mei; Hou, Ping; Lv, Ji-Cheng; Xu, Da-Min; Shi, Su-Fang; Liu, Li-Jun; Yu, Feng; Zhao, Ming-Hui; Novak, Jan; Gharavi, Ali G; Zhang, Hong

2015-05-01

Complement activation is common in patients with IgA nephropathy (IgAN) and associated with disease severity. Our recent genome-wide association study of IgAN identified susceptibility loci on 1q32 containing the complement regulatory protein-encoding genes CFH and CFHR1-5, with rs6677604 in CFH as the top single-nucleotide polymorphism and CFHR3-1 deletion (CFHR3-1∆) as the top signal for copy number variation. In this study, to explore the clinical effects of variation in CFH, CFHR3, and CFHR1 on IgAN susceptibility and progression, we enrolled two populations. Group 1 included 1178 subjects with IgAN and available genome-wide association study data. Group 2 included 365 subjects with IgAN and available clinical follow-up data. In group 1, rs6677604 was associated with mesangial C3 deposition by genotype-phenotype correlation analysis. In group 2, we detected a linkage between the rs6677604-A allele and CFHR3-1∆ and found that the rs6677604-A allele was associated with higher serum levels of CFH and lower levels of the complement activation split product C3a. Furthermore, CFH levels were positively associated with circulating C3 levels and negatively associated with mesangial C3 deposition. Moreover, serum levels of the pathogenic galactose-deficient glycoform of IgA1 were also associated with the degree of mesangial C3 deposition in patients with IgAN. Our findings suggest that genetic variants in CFH, CFHR3, and CFHR1 affect complement activation and thereby, predispose patients to develop IgAN. Copyright © 2015 by the American Society of Nephrology.

Microinjection of cytoplasm as a test of complementation in Paramecium

PubMed Central

1982-01-01

Mutants in Paramecium tetraurelia, unable to generate action potentials, have been isolated as cells which show no backward swimming in response to ionic stimulation. These "pawn" mutants belong to at least three complementation groups designated pwA, pwB, and pwC. We have found that microinjection of cytoplasm from a wild-type donor into a pawn recipient of any of the three complementation groups restores the ability of the pawn to generate action potentials and hence swim backward. In addition, the cytoplasm from a pawn cannot restore a recipient of the same complementation group, but that from a pawn of a different group can. Electrophysiological analysis had demonstrated that the restoration of backward swimming is not due to a simple addition of ions but represents a profound change in the excitable membrane of the recipient pawn cells. Using known pawn mutants and those which had previously been unclassified, we have been able to establish a perfect concordance of genetic complementation and complementation by cytoplasmic transfer through microinjection. This method has been used to classify pawn mutants that are sterile or hard- to-mate and to examine the ability of cytoplasms from different species of ciliated protozoa to restore the ability to swim backward in the pawn mutants of P. tetraurelia. A cell homogenate has also been fractionated by centrifugation to further purify the active components. These results demonstrate that transfer of cytoplasm between cells by microinjection can be a valid and systematic method to classify mutants. This test is simpler to perform than the genetic complementation test and can be used under favorable conditions in mutants that are sterile and in cells of different species. PMID:7061597

A Genetic and Molecular Analysis of the 46c Chromosomal Region Surrounding the Fmrfamide Neuropeptide Gene in Drosophila Melanogaster

PubMed Central

O'Brien, M. A.; Roberts, M. S.; Taghert, P. H.

1994-01-01

We have analyzed the FMRFamide neuropeptide gene region of Drosophila melanogaster. This gene maps to the 46C region of chromosome 2R; this interval previously was not well characterized. For this genetic and molecular analysis, we have used X-ray mutagenesis, EMS mutagenesis, and the recently reported local P element transposition method. We identified four overlapping deletions, two of which have proximal breakpoints that define a 50-60-kb region surrounding the FMRFamide gene in 46C. To this small region, we mapped three lethal complementation groups; 10 additional lethal complementation groups were mapped to more distal regions of 46CD. One of these groups corresponds to even-skipped, the other 12 are previously unidentified. Using various lines of evidence we excluded the possibility that FMRFamide corresponds to any of the three lethal complementation groups mapping to its immediate 50-60-kb vicinity. The positions of two of the three lethal complementation groups were identified with P elements using a local transposition scheme. The third lethal complementation group was excluded as being FMRFamide mutants by sequence analysis and by immunocytochemistry with proFMRFamide precursor-specific antibodies. This analysis has (1) provided a genetic map of the 46CD chromosomal region and a detailed molecular map of a portion of the 46C region and (2) provided additional evidence of the utility of local transposition for targeting nearby genes. PMID:8056304

Assessment of red blood cell parameters and peripheral smear at different temperatures in case of cold agglutination disease.

PubMed

Gupta, V

2014-03-01

Cold agglutination disease (CAD) is characterized by an auto-antibody which is able to agglutinate red blood cells (RBCs) at temperatures lower than that of the body, and subsequently to activate the complement system responsible for lysis of RBCs. Patients show hemolytic anemia of varying degrees of severity, which arise or worsen upon exposure to low temperatures. We describe a case who presented with fever and symptoms of asthenia. His investigations yielded bizarre RBC parameters which led to suspicion of a rare CAD, which was confirmed on reviewing RBC parameters, peripheral smear and direct Coomb's test at different temperatures. Hence, we suggest assessment of bizarre RBC parameters and peripheral smear can help in laboratory testing and diagnosis of CAD. It should also not pose embarrassment in laboratory testing to the pathologist for making an early and accurate diagnosis, thus emphasizing the need for an early treatment of CAD.

Magnitude of Anemia at Discharge Increases 30-Day Hospital Readmissions.

PubMed

Koch, Colleen G; Li, Liang; Sun, Zhiyuan; Hixson, Eric D; Tang, Anne; Chagin, Kevin; Kattan, Michael; Phillips, Shannon C; Blackstone, Eugene H; Henderson, J Michael

2017-12-01

Anemia during hospitalization is associated with poor health outcomes. Does anemia at discharge place patients at risk for hospital readmission within 30 days of discharge? Our objectives were to examine the prevalence and magnitude of anemia at hospital discharge and determine whether anemia at discharge was associated with 30-day readmissions among a cohort of hospitalizations in a single health care system. From January 1, 2009, to August 31, 2011, there were 152,757 eligible hospitalizations within a single health care system. The endpoint was any hospitalization within 30 days of discharge. The University HealthSystem Consortium's clinical database was used for demographics and comorbidities; hemoglobin values are from the hospitals' electronic medical records, and readmission status was obtained from the University HealthSystem Consortium administrative data systems. Mild anemia was defined as hemoglobin of greater than 11 to less than 12 g/dl in women and greater than 11 to less than 13 g/dl in men; moderate, greater than 9 to less than or equal to 11 g/dl; and severe, less than or equal to 9 g/dl. Logistic regression was used to assess the association of anemia and 30-day readmissions adjusted for demographics, comorbidity, and hospitalization type. Among 152,757 hospitalizations, 72% of patients were discharged with anemia: 31,903 (21%), mild; 52,971 (35%), moderate; and 25,522 (17%), severe. Discharge anemia was associated with severity-dependent increased odds for 30-day hospital readmission compared with those without anemia: for mild anemia, 1.74 (1.65-1.82); moderate anemia, 2.76 (2.64-2.89); and severe anemia, 3.47 (3.30-3.65), P < 0.001. Anemia at discharge is associated with a severity-dependent increased risk for 30-day readmission. A strategy focusing on anemia treatment care paths during index hospitalization offers an opportunity to influence subsequent readmissions.

The care of a child with multiple trauma and severe anemia who was a Jehovah's Witness.

PubMed

Digieri, Luciana Andrea; Pistelli, Ivan Pollastrini; de Carvalho, Cid Eduardo

2006-06-01

Jehovah's Witness followers do not accept blood derived transfusions and available methods for avoiding transfusion have been used with degrees of success, demonstrating that the probability of death after trauma in these patients may not be significantly different from religious groups. In this report, we describe the case of a child victim of a multiple trauma with severe anemia due to blood loss, whose family would not authorize blood transfusion because of their Jehovah's Witness faith. We discuss the current indications for restricting transfusion, as well as highlighting new tools that contribute to the success of minimizing blood loss, thus avoiding transfusion.

Prevalence of anemia and malnutrition and their association in elderly nursing home residents.

PubMed

Sahin, Sevnaz; Tasar, Pinar Tosun; Simsek, Hatice; Çicek, Zeynep; Eskiizmirli, Hulya; Aykar, Fisun Senuzun; Sahin, Fahri; Akcicek, Fehmi

2016-10-01

Malnutrition is one of the most important geriatric syndromes in the elderly. The aim of this study was to investigate the association between anemia and malnutrition in elderly nursing home residents. Local nursing home residents over 60 years old in the Izmir were included in the study. Blood samples were taken from study participants for hemogram, iron, ferritin, total iron-binding capacity, vitamin B12 and folic acid analysis. WHO criteria were used to define anemia. Causes of anemia were classified as iron deficiency, vitamin B12 or folic acid deficiency, anemia of chronic disease or other hematologic causes. Anemia was defined as the dependent variable and malnutrition was defined as the independent variable. Correlation between MNA scores and Hb levels was determined using Pearson correlation analysis. The slope of causality between malnutrition and anemia was determined using the χ (2) test and logistic regression analysis. The study included 257 elderly nursing home residents with a mean age of 78.5 ± 7.8 years. The overall prevalence of anemia was 54.9 %; 35.8 % of the study participants were at risk of malnutrition and 8.2 % were malnourished. Anemia risk was 2.12-fold higher in participants at risk of malnutrition and 5.05-fold higher in those with malnutrition. In the participants with malnutrition or malnutrition risk, the most common cause of anemia was anemia of chronic disease (57.1 and 46.5 %, respectively). The prevalence of anemia among elderly nursing home residents is high in Turkey. Malnutrition and malnutrition risk increase the incidence of anemia.

Elevated Levels of Somatic Mutation as a Biomarker of Environmental Effects Contributing to Breast Carcinogenesis

DTIC Science & Technology

2006-07-01

abnormalities in constitutional aplastic anemia . NEng JMed 274:8–14. Callen E, Samper E, Ramirez MJ, Creus A, Marcos R, Ortega JJ, Olive T, Badell I, Blasco... anemia , ‘‘idiopathic’’ aplastic anemia , and Fanconi anemia heterozy- gotes. Am J Med Genet 15:211–223. Chaganti RSK, Houldsworth J. 1991. Fanconi anemia : A...allows us to apply the GPA assay, regardless of genotype, for diagnosis of the cancer-prone diseases ataxia telangiectasia (9), Fanconi anemia (8

Locally Sustainable School Lunch Intervention Improves Hemoglobin and Hematocrit Levels and Body Mass Index among Elementary Schoolchildren in Rural West Java, Indonesia

PubMed Central

Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

2017-01-01

School lunch is not provided in public elementary schools in Indonesia, and students frequently buy and eat snacks at school. We hypothesized that providing a traditional Sundanese meal as school lunch would be beneficial for children in rural West Java. To test this hypothesis, we evaluated the effect of a 1-month school lunch intervention aiming at sustainability and based on children’s nutritional intake, hemoglobin and hematocrit levels, and body mass index (BMI). A lunch (including rice, vegetable dish, animal protein dish, plant protein dish, and fruit) containing one-third of the recommended daily allowance of energy was offered every school day for 1 month, targeting 68 fourth-grade elementary schoolchildren. At baseline, the prevalence of anemia was 33.3%. The prevalence of stunting and underweight were 32.4% and 2.9%, respectively, whereas that of overweight and obesity combined was 17.6%, indicating a double burden of malnutrition among the subjects. During the intervention, intakes of protein (p < 0.05), calcium (p < 0.05), and vitamin C (p < 0.001) significantly increased, while that of fat significantly decreased (p < 0.001). After the intervention, hemoglobin (p < 0.05) and hematocrit (p < 0.05) levels were significantly improved, thereby almost halving the rate of anemia. These changes were significantly larger in the baseline anemic group than the non-anemic group (p < 0.01). BMI significantly increased in the baseline underweight/normal group (p < 0.001) but not in the overweight/obese group. The school lunch intervention significantly improved nutritional intakes and health statuses, implying its potential for reducing anemia and resolving the double burden of malnutrition among rural Indonesian schoolchildren. PMID:28805668

Locally Sustainable School Lunch Intervention Improves Hemoglobin and Hematocrit Levels and Body Mass Index among Elementary Schoolchildren in Rural West Java, Indonesia.

PubMed

Sekiyama, Makiko; Roosita, Katrin; Ohtsuka, Ryutaro

2017-08-12

School lunch is not provided in public elementary schools in Indonesia, and students frequently buy and eat snacks at school. We hypothesized that providing a traditional Sundanese meal as school lunch would be beneficial for children in rural West Java. To test this hypothesis, we evaluated the effect of a 1-month school lunch intervention aiming at sustainability and based on children's nutritional intake, hemoglobin and hematocrit levels, and body mass index (BMI). A lunch (including rice, vegetable dish, animal protein dish, plant protein dish, and fruit) containing one-third of the recommended daily allowance of energy was offered every school day for 1 month, targeting 68 fourth-grade elementary schoolchildren. At baseline, the prevalence of anemia was 33.3%. The prevalence of stunting and underweight were 32.4% and 2.9%, respectively, whereas that of overweight and obesity combined was 17.6%, indicating a double burden of malnutrition among the subjects. During the intervention, intakes of protein ( p < 0.05), calcium ( p < 0.05), and vitamin C ( p < 0.001) significantly increased, while that of fat significantly decreased ( p < 0.001). After the intervention, hemoglobin ( p < 0.05) and hematocrit ( p < 0.05) levels were significantly improved, thereby almost halving the rate of anemia. These changes were significantly larger in the baseline anemic group than the non-anemic group ( p < 0.01). BMI significantly increased in the baseline underweight/normal group ( p < 0.001) but not in the overweight/obese group. The school lunch intervention significantly improved nutritional intakes and health statuses, implying its potential for reducing anemia and resolving the double burden of malnutrition among rural Indonesian schoolchildren.

Efficacy and safety of subcutaneous administration of lyophilized powder of alfa-erythropoietin to maintain hemoglobin concentrations among hemodialysis patients.

PubMed

Satirapoj, Bancha; Dispan, Rattanawan; Supasyndh, Ouppatham

2017-01-01

Anemia associated with chronic kidney disease (CKD) often requires treatment with recombinant human erythropoietin (EPO). This study investigated the therapeutic equivalence between lyophilized powder and standard liquid EPO alfa by subcutaneous (SC) administration in hemoglobin maintenance among patients on hemodialysis. This was a single-blinded, randomized, controlled, single-center, parallel-group study regarding the treatment of anemia among CKD patients on hemodialysis and being treated with stable doses of EPO alfa at least for 12 weeks. Anemic hemodialysis patients (n=63) received standard liquid or lyophilized powder EPO alfa for 24 weeks by SC administration. Achievement of the target hemoglobin concentration and safety and tolerability end points were documented. Baseline mean hemoglobin level was 11.1±0.7 g/dL using lyophilized powder EPO alfa and 11.2±0.9 g/dL using standard liquid EPO alfa. The baseline median dose of EPO alfa was 126.4 (interquartile range [IQR] 81.6-163.6) U/kg/week in the lyophilized powder EPO alfa group and 116.9 (IQR 76.5-144.1) U/kg/week in the standard liquid EPO alfa group. Treatment with SC lyophilized powder EPO alfa maintained mean hemoglobin and hematocrit concentrations after switching from standard liquid EPO alfa. No statistical significance between groups was reported for hemoglobin concentrations and weekly dose of EPO alfa during the study. No safety concerns were raised, including positive anti-EPO antibodies. In this study of anemia therapy among patients with end-stage renal disease on hemodialysis therapy, the SC injection of lyophilized powder EPO alfa was well tolerated and effectively maintained hemoglobin levels. Future studies of larger size and longer duration will be required to assess safety profiles.

Nutritional causes of anemia in Mexican children under 5 years. Results from the 2006 National Health and Nutrition Survey.

PubMed

De la Cruz-Góngora, Vanessa; Villalpando, Salvador; Rebollar, Rosario; Shamah-Levy, Teresa; Méndez-Gómez Humarán, Ignacio

2012-01-01

To describe the frequency and severity of anemia and the nutritional variables associated to hemoglobin levels (Hb) in children <5 years of age. We studied 981 children measuring hemoglobin and serum concentrations of ferritin, soluble transferrin receptors (sTfR), C-reactive protein (CRP), zinc, iron, copper, magnesium, folate and vitamin B12. Ordinal logit or multiple regression models were constructed to assess the risk for anemia and the associations among nutritional variables. The overall prevalence of anemia was 20.6%, of which 14% were mild cases and 6.38% moderate. Anemia was associated with iron deficiency (ID) in 42.17% of the cases, whereas ID coexisted with either folate or vitamin B12 deficiency in 9%. Only 2% of cases of anemia were associated with either folate or vitamin B12 deficiencies. CRP (coef: 0.17 g/dl) and third tertile of s-copper (coef: -0.85 g/dl) were associated to unexplained anemia (p<0.05). ID is the main cause of anemia in children <5 y. Folate and vitamin B12 concentrations were associated with anemia. CRP was associated to unexplained anemia. However, vitamin A deficiency, which is associated with anemia, was not studied.

[Single center survey of the relationship between pregnancy anemia and prepregnancy lifestyle].

PubMed

Akase, Tomoko; Hihara, Emiko; Uematsu, Kazuko; Kodaka, Masanobu; Akase, Tomohide; Tashiro, Shin-Ichi

2008-07-01

Physiologically, anemia often occurs during pregnancy because of an increase in circulating plasma volume. Pregnancy anemia is found prenatally in 50-75% of women. Based on the present survey performed in our obstetrics and gynecology ward, 52% of women experienced anemia during their pregnancy. This suggests that normal physiological changes due to pregnancy alone are not the only factors contributing to pregnancy anemia. Therefore to study the influence of lifestyle on pregnancy anemia, we investigated prepregnancy lifestyles on the assumption that the accumulation of several factors over a long period is usually the cause of anemia. The present results suggest that (i) the probability of anemia is slight in late pregnancy, if a normal Hb concentration is maintained in early pregnancy; (ii) the menstrual cycle is involved in the onset of anemia during early pregnancy; (iii) the number of meals taken and the level of alcohol consumption influence Hb concentration in late pregnancy. We believe that these findings provide a useful information source for advising patients on avoiding pregnancy anemia, which we can also use as guidance for outpatients at puberty. In conclusion, to prevent pregnancy anemia it is important to keep a regular menstrual cycle before pregnancy, and to take 3 meals/day and abstain from alcohol before and during pregnancy.

Anemia among pregnant women in Southeast Ethiopia: prevalence, severity and associated risk factors.

PubMed

Kefiyalew, Filagot; Zemene, Endalew; Asres, Yaregal; Gedefaw, Lealem

2014-11-03

Anemia is a significant public health problem in developing countries, particularly in pregnant women. It may complicate pregnancy, sometimes resulting in tragic outcomes. There is a lack of information on the magnitude of anemia among pregnant women in Southeast Ethiopia. The aim of this study is, therefore, to determine the prevalence of anemia and assess associated factors among pregnant women attending antenatal care (ANC) at Bisidimo Hospital in Southeast Ethiopia. A facility-based cross-sectional study, involving 258 pregnant women, was conducted from March to June 2013. Socio-demographic, medical and obstetric data of the study participants were collected using structured questionnaire. Hemoglobin was measured using a hematology analyzer and faecal specimens were examined to detect intestinal parasites. Anemia in pregnancy was defined as hemoglobin <11 g/dl. Overall, prevalence of anemia was 27.9%, of which 55% had mild anemia. Rural residence (AOR =3.3, 95% CI: 1.5-7.4), intestinal parasitic infection (IPI) (AOR = 2.5, 95% CI: 1.3-4.8) and history of heavy cycle (AOR =2.7, 95% CI: 1.3-1.7) were predictors of anemia. This study showed moderate prevalence of anemia among the pregnant women, with a sizable proportion having severe anemia. Routine testing of pregnant women for IPIs and creating awareness on factors predisposing to anemia is recommended.

Hemolytic anemia

MedlinePlus

Anemia - hemolytic ... bones that helps form all blood cells. Hemolytic anemia occurs when the bone marrow isn't making ... destroyed. There are several possible causes of hemolytic anemia. Red blood cells may be destroyed due to: ...

Association of anemia with the risk of cardiovascular adverse events in overweight/obese patients.

PubMed

Winther, S A; Finer, N; Sharma, A M; Torp-Pedersen, C; Andersson, C

2014-03-01

Anemia is associated with increased cardiovascular risks. Obesity may cause anemia in several ways, for example, by low-grade inflammation and relative iron deficit. The outcomes associated with anemia in overweight/obese patients at high cardiovascular risk are however not known. Therefore, we investigated the cardiovascular prognosis in overweight/obese subjects with anemia. A total of 9,687 overweight/obese cardiovascular high-risk patients from the Sibutramine Cardiovascular OUTcomes trial were studied. Patients were stratified after baseline hemoglobin level and followed for the risks of primary event (comprising nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality. Risk estimates (hazard ratios (HR) with 95% confidence intervals (CI)) were calculated using Cox regression models. Anemia was unadjusted associated with increased risk for the primary event, HR 1.73 (CI 1.37-2.18) and HR 2.02 (CI 1.34-3.06) for patients with mild or moderate-to-severe anemia, respectively, compared with patients without anemia. Adjusted for several confounders, anemia remained of prognostic importance. Increased risk of the primary events appeared to be driven by risk of cardiovascular death, adjusted HR 1.82 (CI 1.33-2.51) for mild anemia and adjusted HR 1.65 (CI 0.90-3.04) for moderate-to-severe anemia, and all-cause mortality, adjusted HR 1.50 (CI 1.17-1.93) for mild and adjusted HR 1.61 (CI 1.04-2.51) for moderate-to-severe anemia. While adding serum creatinine to the models, the increased risk of mild anemia was still a significant predictor for mortality (cardiovascular and all-cause), whereas moderate-to-severe anemia was not. For the primary events, anemia was no longer of independent prognostic importance when including serum creatinine. Anemia is associated with an increased risk of long-term adverse cardiovascular events and deaths among overweight/obese cardiovascular high-risk patients. The increased risk appeared to be driven by the risk of cardiovascular death and all-cause mortality, and renal impairments seemed to have a role in the increased risk.