A Nurse Is Reviewing the Laboratory Values of a School Age Child Who Has Iron Deficiency Anemia

Therap Adv Gastroenterol. 2011 May; iv(three): 177–184.

Diagnosis and management of iron deficiency anemia in the 21st century

David Y. Graham

Michael E. DeBakey VA Medical Middle, Room 3A-320 (111D), 2002 Holcombe Boulevard, Houston, TX 77030, U.s.

Abstract

Atomic number 26 deficiency is the unmarried almost prevalent nutritional deficiency worldwide. Information technology accounts for anemia in v% of American women and ii% of American men. The goal of this review commodity is to assist practitioners in understanding the physiology of iron metabolism and to aid in accurately diagnosing fe deficiency anemia. The current beginning line of therapy for patients with iron deficiency anemia is oral iron supplementation. Oral supplementation is cheap, safe, and constructive at correcting iron deficiency anemia; nevertheless, it is not tolerated by some patients and in a subset of patients information technology is insufficient. Patients in whom the gastrointestinal claret loss exceeds the abdominal ability to absorb iron (e.g. intestinal angiodysplasia) may develop atomic number 26 deficiency anemia refractory to oral fe supplementation. This population of patients proves to be the most challenging to manage. Historically, these patients have required numerous and frequent blood transfusions and suffer end-organ harm resultant from their refractory anemia. Intravenous iron supplementation fell out of favor secondary to the presence of exceptional but serious side furnishings. Newer and safer intravenous atomic number 26 preparations are now available and are likely currently underutilized. This article discusses the possible use of intravenous iron supplementation in the management of patients with severe iron deficiency anemia and those who have failed oral atomic number 26 supplementation.

Keywords: anemia, blood loss, intravenous iron, iron deficiency, therapy

Introduction

Anemia (from the ancient Greek άναιμία, anaimia, pregnant 'lack of claret') is divers past a decrease in the total amount of hemoglobin or the number of red blood cells. Iron deficiency anemia is a form of anemia due to the lack of sufficient iron to form normal crimson blood cells. Iron deficiency anemia is typically caused by inadequate intake of atomic number 26, chronic blood loss, or a combination of both. Atomic number 26 deficiency anemia is the most mutual cause of anemia in the world. Approximately 5% and 2% of American women and men, respectively, have iron deficiency anemia [Clark, 2009; Looker et al. 1997].

Fe metabolism

Iron is a trace element that is required for numerous cellular metabolic functions. Equally iron is toxic when nowadays in abundance, tight regulation is required to avoid iron deficiency or fe overload [Anderson et al. 2009; Byrnes et al. 2002]. The adult body contains three–4 m of iron. The usual Western nutrition contains approximately 7 mg of iron per thou kcal; however, only 1–ii mg is normally absorbed each mean solar day. The human being nutrition contains two forms of fe: heme iron and nonheme atomic number 26. Heme iron is derived from meat and is well absorbed. Pancreatic enzymes digest heme to costless it from the globin molecule in the intestinal lumen. Iron is and then absorbed into the enterocytes every bit metalloporphyrin and degraded by heme oxygenase-1 to release nonheme iron. Subsequently, fe is exported by ferroportin located on the basolateral aspect of the enterocyte. Nonheme dietary iron, which is found in cereals, beans, and some vegetables, is less well absorbed. Nonheme iron is present as either ferric (Iron^+two) or ferrous (Iron⁺³) iron. The acidic environment of the stomach and certain foods are known to increase the bioavailability of dietary iron [Zhang and Enns, 2009; Schmaier and Petruzzelli, 2003; Conrad and Umbreit, 1993]. Vitamin C, for case, functions to prevent precipitation of ferric fe in the duodenum. Other foods containing plant phytates (grains) and tannins (nonherbal tea) are known to decrease the absorption of nonheme iron [Schmaier and Petruzzelli, 2003; Conrad and Umbreit, 1993]. After entry of ferric iron into the duodenum information technology must first be reduced to the ferrous grade past duodenal cytochrome b prior to absorption. Duodenal cytochrome b is a reductase located in the brush edge of the duodenum and proximal jejunum. Once reduced, the divalent metal transporter 1, the only currently known intestinal iron importer, transports ferrous iron from the proximal pocket-size intestinal lumen into the upmost membrane of the enterocyte [Zhang and Enns, 2009]. Later entry into the prison cell, ferrous iron may either exist stored as ferritin or transverses the cell to the basolateral aspect of the enterocyte where the ferroportin is located. Ferroportin is present in the mucosa of the proximal minor intestine, macrophages, hepatocytes, and syncytiotrophoblasts of the placenta. Ferroportin, along with ceruloplasmin and hephaestin, facilitates the reoxidation of ferrous iron to ferric atomic number 26, which must occur prior to exportation. Transferrin has a loftier affinity for ferric iron and binds it then quickly that in that location is essentially no free atomic number 26 circulating in the plasma. Bounden of iron to transferrin occurs via the apotransferrin receptor pathway [Conrad, 2009; Zhang and Enns, 2009].

Once in the plasma the iron is transported by transferrin to the bone marrow for synthesis of hemoglobin and incorporation into the erythrocytes. Normal erythrocytes circulate for roughly 120 days earlier being degraded. Senescent red blood cells are engulfed by macrophages in the reticuloendothelial system, primarily in the spleen and liver where they are degraded and catabolized by the cytosolic hemeoxygenase-ane to release the bound iron. Recycling of heme iron from senescent red blood cells is the principal source of fe for erythropoiesis and accounts for delivery of 40–60 mg atomic number 26/day to the bone marrow [Hillman and Henderson, 1969]. Some of the iron from senescent scarlet blood cells is also stored in macrophages as ferritin (the major storage form of iron) or hemosiderin (the water-soluble form of atomic number 26), and the majority of it is released via ferroportin into the plasma bound to transferrin for recycling. Around 70% of the total body iron is in heme compounds (e.g. hemoglobin and myoglobin), 29% is stored as ferritin and hemosiderin, <1% is incorporated into heme-containing enzymes (e.g. cytochromes, catalase, peroxidase), and <0.2% is found circulating in the plasma jump to transferrin [Zhang and Enns, 2009; Schmaier and Petruzzelli, 2003]. During states of intravascular hemolysis, cherry-red blood cells are destroyed and hemoglobin is released into the plasma. Haptoglobin is a protein synthesized primarily in the liver and functions to demark gratis hemoglobin. The hemoglobin–haptoglobin complex is and then removed by the reticuloendothelial system and the iron salvaged. The bounden potential of haptoglobin is limited by the amount of circulating molecules and apace becomes saturated in moderate to severe hemolytic states.

No physiologic mechanism for iron excretion exists and only 1–2 mg of fe is lost each day every bit a effect of sloughing of cells (i.e. from the mucosal lining of the gastrointestinal tract, skin, and renal tubules). In women, approximately 0.006 mg iron/kg/solar day is lost during normal menstruation [Schmaier and Petruzzelli, 2003]. Thus, normally iron loss and gain is in residue with the amount lost daily being equal to the amount absorbed daily. The body has the ability to increase abdominal iron absorption dependent on the body fe needs. When the pendulum swings towards more iron being lost than is captivated, iron stores get depleted and the patient develops iron deficiency. If the process continues the patient develops atomic number 26 deficiency anemia. Atomic number 26 deficiency is associated with upregulation of iron absorption from the gut by manner of an increase in the production of key proteins, such equally duodenal cytochrome b, divalent metal transporter one, and ferroportin. Hypoxia-inducible, cistron-mediated signaling and iron regulatory proteins too play critical roles in the local regulation of fe absorption. Hypoxia-inducible gene-signaling upregulates the expression of duodenal cytochrome b and divalent metal transporter 1; iron regulatory proteins upregulate the expression of divalent metal transporter one and ferroportin. These two pathways are vital for the enhancement of iron assimilation associated with iron deficiency [Zhang and Enns, 2009]. Within limits, iron assimilation enhancement is proportional to the caste of iron deficiency (i.e. the synthesis of key proteins, such as transferrin receptor, divalent metal transporter 1, ferritin, and ferroportin, is regulated in an atomic number 26-dependent manner) [Byrnes et al. 2002]. This system is checked past hepcidin, a hormone that is synthesized in the liver, secreted into the blood, and systemically controls the charge per unit of atomic number 26 assimilation also every bit its mobilization from stores (Figure 1). Hepcidin binds to, and negatively modulates, the function of ferroportin. Janus kinase 2 is activated upon binding of hepcidin to ferroportin and results in the internalization, ubiquitination, and deposition of ferroportin. Thus, activation of Janus kinase 2 is associated with limiting fe exportation and ultimately decreasing erythropoiesis [De Domenico et al. 2009]. Hepcidin expression is near notably suppressed by hypoxia, erythropoietin (a hormone essential for erythrocyte differentiation), twisted gastrulation (a protein secreted by young red blood prison cell precursors during the early stages of erythropoiesis), and growth differentiation factor 15 (a protein secreted past erythroblasts during the terminal stages of erythropoiesis). The synthesis of hepcidin is upregulated by inflammatory cytokines (particularly interleukin-half-dozen), irrespective of the total level of fe in the body. This relationship most likely accounts for the evolution of anemia of chronic disease. The anemia of chronic disease is exterior the scope of this discussion [Zhang and Enns, 2009; Schmaier and Petruzzelli, 2003].

An external file that holds a picture, illustration, etc. Object name is 10.1177_1756283X11398736-fig1.jpg

The role of hepcidin in normal iron homeostasis: an increase in plasma iron causes an increment in hepcidin product (yellow arrow). Elevated hepcidin inhibits iron flow into the plasma from the macrophages, hepatocytes, and the duodenum. As the plasma iron continues to be consumed for hemoglobin synthesis, the plasma iron levels decrease and hepcidin production abates, completing the homeostatic loop. (Reprinted with permission from Intrinsic LifeSciences LLC, La Jolla, CA, United states of america: http://www.intrinsiclifesciences.com/iron_reg/).

Laboratory diagnosis of iron deficiency anemia

The Earth Health Organization defines anemia as blood hemoglobin values of less than 7.7 mmol/50 (13 one thousand/dl) in men and seven.4 mmol/fifty (12 g/dl) in women. Typically, the evaluation of the cause of anemia includes a complete claret prison cell count, peripheral smear, reticulocyte count, and serum iron indices. The severity of anemia is based on the patient'south hemoglobin/hematocrit level. Iron deficiency anemia is characterized past microcytic, hypochromic erythrocytes and low iron stores. The mean corpuscular book is the measure of the average red claret jail cell volume and hateful corpuscular hemoglobin concentration is the measure of the concentration of hemoglobin in a given volume of packed red blood cells. The normal reference ranges for mean corpuscular volume is eighty–100 fL and mean corpuscular hemoglobin concentration is 320–360 g/l. The patient'southward cells are said to exist microcytic and hypochromic, respectively, when these values are less than the normal reference range. Of annotation, upwards to 40% of patients with truthful atomic number 26 deficiency anemia volition have normocytic erthrocytes (i.e. a normal hateful corpuscular book does non rule out fe deficiency anemia) [Bermejo and Garcia-Lopez, 2009]. The red cell distribution width is a measure of the variation of red claret cell width and is used in combination with the mean corpuscular volume to distinguish an anemia of mixed cause from that of a single cause. The normal reference range is 11–14%; an elevated carmine cell distribution width value signifies a variation in red cell size, which is known as anisocytosis. The red prison cell distribution width may be elevated in the early on stages of atomic number 26 deficiency anemia or when a patient has both iron deficiency anemia and folate with or without vitamin B12 deficiencies, which both produce macrocytic anemia. It is not uncommon for the platelet count to be greater than 450,000/µl in the presence of atomic number 26 deficiency anemia. Upon examination of a patient's peripheral smear with chronic iron deficiency anemia one will typically encounter hypochromic, microcytic erythrocytes; thrombocytosis may also be apparent. Information technology is important to note that microcytosis visible on the peripheral smear may be seen prior to abnormalities on the complete blood cell count. If the patient has coexistent folate or vitamin B12 deficiency, the peripheral smear volition be a mixture of macrocytic and microcytic hypochromic erythrocytes, along with normalization of the mean corpuscular volume.

Iron studies diagnostic for iron deficiency anemia consist of a low hemoglobin (<7.7 mmol/50 in men and 7.four mmol/50 in women), a depression serum fe (<vii.one µg/l), a low serum ferritin (storage course of iron) (<30 ng/50), a low transferrin saturation (<15%), and a loftier total iron-bounden capacity (>thirteen.1 µmol/l) [Bermejo and Garcia-Lopez, 2009; Clark, 2009]. The ferritin level may be misleading in the presence of astute or chronic inflammation every bit ferritin is too an acute phase reactant and thus one cannot exclude fe deficiency as the cause of anemia when the serum ferritin is normal or even elevated in the presence of an inflammatory process [Bermejo and Garcia-Lopez, 2009; Conrad and Umbreit, 1993]. In the presence of an underlying infection or inflammation other atomic number 26 markers may exist useful including the reticulocyte hemoglobin content which, because reticulocytes are just i–ii days old, is cogitating of the iron available in the bone marrow for erythropoiesis. The culling, which is probable to be more than readily available, is the measurement of soluble transferrin receptor. In the setting of iron deficiency with increased erythroid activeness (e.g. following administration of exogenous erythropoiesis stimulating agents), in that location is increased expression of membrane transferrin receptors in the bone marrow and some of these receptors are detectable in the serum. The limitations are that it is not equally reliable as ferritin, it is not still widely available, and the clinician must exclude other causes of elevated erythroid activeness [Wish, 2006]. When all else fails and it is important to establish whether iron deficiency is present, demonstration of the absenteeism of stainable iron via a bone marrow biopsy remains the golden standard for diagnosis.

Causes of iron deficiency anemia

In developing countries, low iron bioavailability of the diet is the primary cause of iron deficiency anemia [Berger and Dillon, 2002; Yip and Ramakrishnan, 2002]; however, in developed countries, decreased iron absorption and claret loss account for the more likely etiologies of iron deficiency. Decreased atomic number 26 assimilation may also exist the issue of atrophic gastritis or malabsorption syndromes particularly celiac disease [Bermejo and Garcia-Lopez, 2009]. Postsurgical gastrectomy (fractional or total) and intestinal resection or bypass may as well produce atomic number 26 deficiency anemia secondary to decreased atomic number 26 absorption. Chronic claret loss from genitourinary, gynecological, or gastrointestinal tracts accounts for the majority of causes for iron deficiency anemia. The most mutual etiology of iron deficiency anemia in premenopausal women is excessive menstruation.

Gastrointestinal bleeding is a common cause of atomic number 26 deficiency anemia, whether the haemorrhage is acute or chronic. Patients may nowadays with maroon-colored stools or blood in their stools with brisk bleeding but more than often the claret loss is unrecognized by the patient as blood loss up to 100 ml/mean solar day from the gastrointestinal tract may exist associated with normal-appearing stools [Rockey, 2005]. The physiologic response of the minor bowel to bleeding will be to increase iron absorption by twofold to threefold by upregulation of proteins duodenal cytochrome b, divalent metal transporter one, ferroportin, and downregulation of hepcidin. Nonetheless, iron loss greater than 5 mg/mean solar day over a prolonged period of time exceeds this compensatory response; the patient'south iron stores will become depleted and iron deficiency anemia ensues [Rockey, 1999]. Chronic gastrointestinal bleeding is associated with a variety of lesions and can occur at any location within the gastrointestinal tract. Iron deficiency anemia is particularly prone to occur in those taking aspirin or nonsteroidal anti-inflammatory drugs chronically. For those with angiodysplasia or other structural lesions, the site can oftentimes exist visualized by endoscopic evaluation (e.k. video capsule endoscopy) of the gastrointestinal tract. Even so, in 10–40% of patients with occult gastrointestinal bleeding the cause remains obscure [Till and Grundman, 1997; Rockey and Cello, 1993].

Oral iron therapy and its limitations

Traditionally hemodynamically stable patients with iron deficiency anemia resultant from chronic blood loss from the gut are prescribed oral atomic number 26 therapy. The ii categories of iron supplements are those containing the ferrous form of atomic number 26 and those containing the ferric grade of iron. The near widely used iron supplements are those that incorporate the ferrous form of iron given that it is the better captivated of the two. The three commonly administered types of ferrous iron supplements: ferrous fumarate, ferrous sulfate, and ferrous gluconate, which differ in the corporeality of elemental iron (the grade of atomic number 26 in the supplement that is bachelor for assimilation past the body), and contain 33%, xx%, and 12% iron, respectively (NIH, 2010). Recent studies take suggested that these iron preparations are substantially equivalent in terms of bioavailability [Harrington et al. 2011; Navas-Carretero et al. 2007; Lysionek et al. 2003]. The recommended daily dose of handling by the Centers for Disease Control and Prevention (CDC) ranges from 150 mg/24-hour interval to 180 mg/day of elemental fe administered in divided doses two to three times a twenty-four hours [CDC, 1998]. The reticulocyte count begins to increase inside the first week of iron therapy, whereas the hemoglobin unremarkably trails by i–2 weeks [National Institutes of Health, 2010; Provenzano et al. 2009]. Oral atomic number 26 supplements are desirable as first-line therapy as they are rubber, inexpensive, and constructive in restoring iron remainder in the average chronic gastrointestinal bleeder.

Therapy with atomic number 26 supplements may be limited past gastrointestinal side effects, such as abdominal discomfort, nausea, vomiting, constipation, and dark colored stools. Enteric-coated and delayed-release iron supplements accept been developed to increase compliance equally they are associated with fewer side effects; yet, they are non besides absorbed as the nonenteric-coated preparations [Provenzano et al. 2009].

Physicians are often faced with the challenge of managing fe deficiency anemia with oral iron when a patient's fe losses exceed the maximum corporeality of iron that the gut is able to absorb. Information technology is this group of patients that generally requires repeated transfusions and suffers end-organ damage as the patients are not able to replenish their iron stores with oral supplementation lone. One of the near challenging groups of patients is those patients that endure from chronic gastrointestinal bleeding secondary to vascular angiodysplasias. These patients typically have multiple lesions that occur in clusters and/or scattered throughout the gastrointestinal tract, and frequently rebleed resulting in chronic fe deficiency anemia [Boley et al. 1979; Clouse et al. 1985]. When the patient's gastrointestinal blood loss results in more iron loss than that which they are able to absorb from the gut, these patients develop anemia that is clinically refractory to oral iron therapy. It is then that physicians are faced with starting the patient on parenteral iron therapy.

Intravenous iron therapy and its limitations

Intravenously administered iron is ane arroyo to replacing iron losses in patients with chronic gastrointestinal bleeding in which blood loss exceeds 10 ml/day (effectually 5 mg iron). With the use of intravenous iron the desired serum iron levels, in which the marrow product can increase past fourfold to eightfold, can be achieved [Werner et al. 1977]. Hillman and Henderson previously showed that the maximum atomic number 26 delivery from reticuloendothelial iron stores is 40–60 mg of iron/day to the bone marrow for erythropoesis [Hillman and Henderson, 1969]. Supplementation with oral atomic number 26 provides 60–fourscore mg iron/solar day, whereas intravenous atomic number 26 or nonviable cherry-red cells provide lxxx–160 mg iron/day. They found that the maximum reddish blood prison cell product achieved past patients with a mean serum atomic number 26 less than 70 µg/100 ml was betwixt two.5 and 3.5 times normal. With oral iron supplementation, patients were able to attain serum atomic number 26 values between seventy µg/100 ml and 150 µg/100 ml, and carmine blood cell product was able to increase to four to five times normal. Only when nonviable red cells or intravenous iron dextran was administered was the iron supply sufficient to increase the serum fe to values greater than 200 µg/100 ml with a concomitant increase in marrow production to 4.5–7.8 times normal (Figure 2). Information technology is important to note that this response was transient lasting only vii–ten days equally the backlog fe was subsequently sequestered in the reticuloendothelial system. The dr. tin can estimate a patient's total iron deficit and then decide how much to administer intravenously (Table one).

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Response of the bone marrow in relation to the level of serum iron. The marrow response is directly associated to the serum iron level (based on a hematocrit level of 25–27%). A is the response of the bone marrow to the body's physiological increase in iron absorption from the gut in response to iron deficiency. A mean serum iron level <12.5 µmol/l is associated with an increase in RBC production, which ranges from 2.5 to 3.5 times the normal marrow response. B indicates a serum fe level of 12.five–26.8 µmol/l can be accomplished with oral iron supplementation (i.e. 300 mg of ferrous gluconate every 2 h while awake), which is associated with an increase in bone marrow production of RBCs 4–5 times normal. C indicates a serum iron level >35.8 µmol/l was accomplished past administration of intravenous iron dextran or nonviable red cells. This resulted in an increase in RBC production 4.5–7.eight times the normal marrow response. RBC, red blood prison cell.

Table 1.

Formula to calculate iron requirement to replete iron stores in adults.

Formula*

Elemental atomic number 26 (mg) = l × [0.442 (desired Hgb g/L minus observed Hgb g/50) × lean body weight (encounter below for men and women) + 0.26 × lean body weight]

Lean trunk weight

For men: lean body weight = 50 kg + ii.3 kg for each inch in height over sixty inches

For women: lean body weight = 45.five kg + 2.iii kg for each inch in elevation over 60 inches

Note: utilise actual body weight if lean body weight is less than actual weight.

Intravenous iron preparations (mg elemental iron/ml)

Atomic number 26 dextran = l mg

Iron sucrose: = xx mg

Sodium ferric gluconate = 12.v mg

Ferumoxytol = thirty mg

*The formula was derived from: atomic number 26 dextran injection calculator by David McAuley, GlobalRPh http://www.globalrph.com/irondextran.htm with permission

Fe dextran has since been replaced by newer safer iron preparations. Available intravenous fe preparations in the USA include iron dextran (INFeD® or DexFerrum®), atomic number 26 sucrose (Venofer®), sodium ferric gluconate (Ferrlecit®), and ferumoxytol (Feraheme®). Atomic number 26 dextran is the oldest of these and has the reward of total dose infusion (ability to infuse the patient'south total iron requirement in one administration) and lowest price. It vicious out of favor because of its association with fatalities secondary to anaphylactic reactions, with an incidence of 0.half dozen–0.7%. Sodium ferric gluconate and atomic number 26 sucrose are more bioavailable and have a lower incidence of life-threatening anaphylaxis (0.04% and 0.002%, respectively); these preparations are significantly more expensive than iron dextran and require repeated infusions to replace the lost iron stores. Still, information technology is important to note that the assistants of repeated injections has the potential advantage of allowing one to tailor the dose to maintain crimson blood cell production at a maximum with limited sequestration in the reticuloendothelial system. Some of the additional reported agin events associated with each of the iron preparations are hypotension, arthralgias, myalgias, malaise, intestinal pain, nausea, and vomiting. These nonlife-threatening agin reactions are also more than unremarkably associated with iron dextran and less so with iron sucrose or sodium ferric gluconate (50%, 36%, 35%, respectively) (Table 2) [Silverstein and Rodgers, 2004]. Ferumoxytol provides 510 mg of iron per infusion and thus allows the physician to give patients big doses of iron with fewer infusions [De Domenico et al. 2009]. Intravenous iron formulations are now nearly commonly used in hemodialysis patients and in that location is a great deal of literature regarding the use of intravenous iron in patients with endstage renal disease. Regular infusions of intravenous iron may also allow improved management of patients with iron deficiency anemia refractory to oral fe therapy, especially those with anemia every bit a result of chronic gastrointestinal claret loss. However, there is a scarcity of literature in back up of intravenous fe versus oral iron in the medical direction of anemia associated with chronic intestinal haemorrhage and details of administration (doses, interval, factors to assess when the next dose is needed, etc.) are lacking. Comparative studies of the different intravenous fe preparations have not been carried out in terms of sustaining the hemoglobin levels amongst those with chronic blood loss and are sorely needed to provide physicians with good practice-based guidelines.

Table two.

Comparison of intravenous iron preparations bachelor in the United states of america.

	Iron dextran	Atomic number 26 sucrose	Sodium ferric gluconate	Ferumoxytol
Infusion dose	100 mg	100 mg	125 mg	510 mg
Test dose required	Aye	No	No	No
Rate of injection ^*	100 mg given over 2 min (50 mg/min)	100 mg given over 2–5 min (xx–fifty mg/min)	125 mg given over 10 min (12.5 mg/min)	510 mg given over 17 s (30 mg/s)
Rate of infusion (in 0.9% NaCl) ^*	Non FDA approved	100 mg/100 ml 0.9% NaCl given over 15 min	125 mg/100 ml 0.ix% NaCl over 1 h	Non FDA approved

Research questions include the therapeutic doses and frequency of iron infusions indicated, too equally, which indices are best to guide therapy and identify when boosted infusions are necessary. Many physicians remain hesitant in implementing intravenous iron therapy in patients with chronic blood loss from the gut. Until nosotros are able to get answers to these questions, many patients with chronic gastrointestinal bleeding will proceed to receive substandard therapy for fe deficiency anemia and endure end-organ damage because of chronic anemia.

Funding

DYG is supported in part by the Office of Enquiry and Development Medical Research Service Department of Veterans Diplomacy, Public Health Service (grant numbers DK56338, which funds the Texas Medical Center Digestive Diseases Heart, and DK067366, DK067366 and CA116845). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the VA or NIH.

Disharmonize of involvement statement

The authors have no potential conflicts of interest with regard to this work.

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