Iron Deficiency Anemia:

A Clinical Case Study

Iron deficiency anemia (IDA) is

the result of low iron stores in

the body due to decreased red

blood cell (RBC) production (Short

& Domagalski, 2013). Api, Breyman,

Çetiner, Demir, and Ecder (2015)

indicated 50% of cases of anemia

are related to iron deficiency.

According to the World Health

Organization (2018), approximately

30% of the world’s population (2

billion people) has anemia; the con-

dition affects mostly females and

children.

Management of IDA is important

because of its link to increased mor-

bidity and mortality (Shander et al.,

2014). For example, IDA may cause

permanent cognitive impairment in

children, fatigue or heart failure in

adults, and serious maternal and

fetal complications (Api et al., 2015;

Hennek et al., 2016). Empirical

research found understanding the

etiology, diagnosis, treatment, man-

agement, and evaluation of IDA is

key to effective care (Short &

Domagalski, 2013). A clinical case

study is presented, followed by the

discussion of implications for

patient care in clinical practice.

Subjective Data

History of Present Illness

Chief complaint. A 68-year-old

African-American female came to

the clinic because of progressive

lethargy, dizziness, and fatigue that

began 3 months earlier.

Medical and surgical history. The

patient has a history of type 2 dia-

betes mellitus (DM), hypertension

(HTN), coronary artery disease

(CAD), and osteoporosis. She had a

Caesarean section 23 years ago.

Allergies. She is allergic to sulfa,

which caused hives when she took

it 4 years ago.

Medications. Medications include

the following: lisinopril/hydrochlor-

othiazide (Prinzide®) 20 mg/12.5

mg by mouth daily, aspirin 81 mg

by mouth daily, atorvastatin

(Lipitor®) 20 mg by mouth at night,

metformin (Glucophage®) 500 mg

by mouth twice daily, ergocalciferol

800 units orally once daily, and

ibandronate (Boniva®) 150 mg

every month.

Social history. The patient denied

any drug and alcohol use or smok-

ing. She retired 4 years ago as a

social worker.

Family history. She has a family

history of CAD, DM, and HTN. Her

mother died at age 55 from CAD.

Her father died of prostate cancer at

age 70. Both her siblings have been

diagnosed with HTN.

Objective Data

Physical Exam and Review of

Systems

The patient is 5 feet 6 inches tall

and weighs 200 pounds.

Vital signs. Heart rate 100 beats

per minute, blood pressure 130/80

mm Hg, respirations 20 breaths per

minute, oxygen saturation 94% on

room air

Head and neck. Patient has a

beefy red tongue and pale conjunc-

tiva.

Cardiac. Auscultation identifies

regular rhythm without any mur-

mur. No peripheral edema is noted.

Respiratory. The patient’s chest

expansion is symmetrical, with no

adventitious breath sounds. She

complains of mild shortness of

breath when walking long dis-

tances.

Gastrointestinal (GI). Patient’s

abdominal wall is soft and non-ten-

der without any masses. Bowel

sounds are active in all four quad-

rants. She denies any nausea,

weight loss or gain, vomiting, or

diarrhea.

Neurologic. The neurological exam

is unremarkable with no decreased

sensation to light touch.

Genitourinary. The patient denies

dysuria, hematuria, urinary inconti-

nence, or polyuria.

Musculoskeletal. The patient denies

joint stiffness, pain, or swelling.

Although she denies any intermit-

tent numbness and tingling in the

legs, they are cool to the touch.

Patient has an unsteady gait and

she uses a cane to walk; she denies

any history of falls.

Diagnostics. Laboratory results

are as follows: hemoglobin (Hgb) 7

g/dl, hematocrit 23%, mean corpus-

cular volume (MCV) 73 fl/red cell,

mean corpuscular hemoglobin

(MCH) 25 pictograms/cell, mean

corpuscular hemoglobin concentra-

tion (MCHC) 30 g/dl, increased

total iron-binding capacity (TIBC)

550 mcg/dl, low serum iron 50

mcg/dl, and low serum ferritin 15

ng/ml.

Discussion

Etiology

IDA may be caused by decreased

production of RBCs, potentially

related to poor diet (e.g., deficient

iron, folate, or vitamin B12 intake).

It also can occur secondary to

increased iron requirements during

infancy, pregnancy, or lactation

(Camaschella, 2015). Blood loss is

another potential cause of iron defi-

ciency anemia, perhaps related to

surgery or heavy menstruation.

Finally, a high rate of RBC destruc-

tion (e.g., hemolytic anemia or tha-

lassemia) may cause IDA. The

patient in this case study was found

to have low serum iron, ferritin,

and MCV, but high TIBC; which are

consistent results for IDA (Api et al.,

2015).

Diagnosis of IDA

Differential diagnoses. The differ-

ential diagnoses formulated for this

patient were as follows (Heeney &

Finberg, 2014; Knollmann-Ritschel

& Markowitz, 2017):

1. Iron deficiency anemia

2. Decreased iron absorption

3. Lead poisoning
4. Thalassemia trait

The diagnosis of IDA is not only

based on results of a complete

blood count, but also on the

patient’s clinical history and pres-

entation. Diagnosis can be made

with measures of RBC size, such as

MCV, MCH, and MCHC (Hennek et

al., 2016; Short & Domagalski,

2013). Other tests for patients with

potential IDA include serum fer-

ritin, iron level, TIBC, and/or trans-

ferrin (American Society of

Hematology, 2018). Expected classic

laboratory findings to confirm IDA

are increased TIBC; decreased Hgb,

serum ferritin, serum transferrin sat-

uration, serum iron concentration;

and presence of microcytic hypo-

chromic red cells (Api et al., 2015;

Camaschella, 2015).

The patient’s shortness of breath,

dizziness, fatigue, cool lower

extremities, and beefy red tongue

are consistent with a diagnosis of

IDA. Abnormal laboratory values

also supported the diagnosis. Serum

ferritin is the most accurate test to

diagnose IDA (Api et al., 2015). This

patient was diagnosed with micro-

cytic hypochromic anemia charac-

terized by production of RBCs that

are smaller than normal. It is associ-

ated with MCV less than 80 fl/red

cell (normal 80-100 fl/red cell).

Hypochromia is characterized by

MCHC less than 32 g/dl (normal

32-36 g/dl), with RBCs having less

color than normal (DeLoughery,

2014). The most common cause of

microcytic hypochromic anemia is

IDA.

Management

The first-line treatment for IDA is

oral iron replacement therapy (e.g.,

ferrous sulfate, ferrous gluconate,

ferrous fumarate) for 3-6 months

for iron stores repletion (Cama-

schella, 2015). A patient can be

given two to four divided doses of

ferrous sulfate by mouth (150-300

mg, or 2-3 mg/kg/day). Other forms

include ferrous gluconate or fuma-

rate 2-3 mg/kg/day orally given in

two to four divided doses.

Although ferrous gluconate and

ferrous fumarate are effective iron

salts replacement therapy, iron sul-

fate is used most frequently for IDA

treatment. Iron sulfate is inexpen-

sive and convenient, and can treat

patients with IDA effectively

(Camaschella, 2015). Also, oral iron

therapy is associated with GI side

effects (e.g., stomach ache, consti-

pation); treatment adherence can

be difficult (Short & Domagalski,

2013). Low doses of iron may

decrease potential GI symptoms

and increase adherence to treat-

ment (DeLoughery, 2014).

Parenteral administration of iron

therapy may be useful for patients

with inadequate response to oral

therapy for IDA. This improves iron

stores more quickly than oral treat-

ment, and carries no concerns

about absorption or GI side effects.

However, the major disadvantage of

intravenous therapy with iron

sucrose (Venofer®) or ferric gluco-

nate (Ferrlecit®) is infusion reaction

(DeLoughery, 2014).

Implications for Practice

Because IDA may affect any

race/ethnicity and age, nurse practi-

tioners need to assess individuals’

risk factors to provide appropriate

care across the lifespan. For in-

stance, women are at higher risk of

developing IDA anemia because of

blood loss during menstruation and

the first 6 months of pregnancy.

Prematurity, feeding of only breast

milk or formula (12-24 months),

and lack of fortified iron intake in

diets by age 6 months put infants at

risk of developing IDA. Likewise,

older adults are at increased risk of

developing IDA because of chronic

diseases (National Institutes of

Health [NIH], n.d.).

Many side effects are associated

with iron replacement therapy. For

instance, common reactions to fer-

rous sulfate and ferrous gluconate

include vomiting, dyspepsia, nau-

sea, and diarrhea (Short & Doma-

galski, 2013). Anaphylaxis or hyper-

sensitivity is an adverse complica-

tion associated with the supple-

ment iron dextran (DexFerrum®)

(DeLoughery, 2014). Patient educa-

tion should include medication

effects, such as constipation and

dark stools, during iron replace-

ment therapy (Short & Domagalski,

2013). If patients are unable to tol-

erate an oral iron replacement, par-

enteral replacement is another

option. Iron dextran is recommend-

ed intravenously to treat IDA

(DeLoughery, 2014). Careful assess-

ment, monitoring, and manage-

ment of iron replacement therapy

are crucial for patients with IDA to

ensure safe administration.

Conclusion

IDA affects patients across the

life span (NIH, n.d.). Nurse practi-

tioners should screen patients for

risk factors for IDA, and also assess

clinical presentation and laboratory

results. They should prioritize

patients’ care to prevent further

complications during iron replace-

ment therapy.

REFERENCES

American Society of Hematology. (2018). Iron-

deficiency anemia. Retrieved from

http://www.hematology.org/patients/

anemia/iron-deficiency.aspx

Api, O., Breyman, C., Çetiner, M., Demir, C., &

Ecder, T. (2015). Diagnosis and treat-

ment of iron deficiency anemia during

pregnancy and the postpartum period:

Iron deficiency anemia working group

consensus report. Journal of Turkish

Society of Obstetrics & Gynecology,

12(3) 173-181. doi:10.4274/tjod.01700

Camaschella, C. (2015). Iron-deficiency ane-

mia. New England Journal of Medicine,

372(19), 1832-1843. doi:10.1056/NEJM

ra1401038
DeLoughery, T.G. (2014). Microcytic anemia.

New England Journal of Medicine,

371(14), 1324-1331. doi:10.1056/NEJM

ra1215361

Hennek, J.W., Kumar, A.A., Wiltschko, A.B.,

Patton, M.R., Lee, S.Y.R., Brugnara, C.,

... Whitesides, G.M. (2016). Diagnosis of

iron deficiency anemia using density-

based fractionation of red blood cells.

Lab on a Chip, 16(20), 3929-3939.

Heeney, M.M., & Finberg, K.E. (2014). Iron-

refractory iron deficiency anemia

(IRIDA). Hematology/Oncology Clinics,

28(4), 637-652. doi:10.1016/j.hoc.2014.

04.009

Knollmann-Ritschel, B.E., & Markowitz, M.

(2017). Educational case: Lead poison-

ing. Academic Pathology, 4, 1-3.

doi:10.1177/2374289517700160

National Institutes of Health (NIH). (n.d.). Iron-

deficiency anemia. Retrieved from

https://www.nhlbi.nih.gov/health/health-
topics/topics/ida/prevention

Shander, A., Goodnough, L.T., Javidroozi, M.,

Auerbach, M., Carson, J., Ershler, W.B.,

... Lew, I. (2014). Iron deficiency anemia

– bridging the knowledge and practice

gap. Transfusion Medicine Reviews,

28(3), 156-166.

Short, M.W., & Domagalski, J.E. (2013). Iron

deficiency anemia: Evaluation and man-

agement. American Family Physician,

87(2), 98-104.

World Health Organization. (2018). Micro-

nutrient deficiencies. Retrieved from

http://www.who.int/nutrition/topics/ida/en

Understanding the management of iron

deficiency anemia
Abstract

Iron deficiency, the most common cause of anaemia, is seemingly easy to manage. However, in
many cases the nutritional

deficiency is complicated by concurrent gastro-intestinal disease and/or inefficient absorption. In

addition, iron absorption and

mobilisation from physiological storage sites is regulated by the peptide hormone hepcidin, which
is upregulated in anaemia

associated with chronic inflammation. Successful patient management requires the continuous
evaluation of iron status as well
as monitoring of haemoglobin levels to measure treatment outcomes. Iron requirements change
with patient physiological

status and this must be taken into consideration when making clinical decisions. Provided that
there is no underlying problem

most patients respond rapidly to oral iron therapy. In non-responsive patients, and patients with
concurrent gastro-intestinal

disease, parenteral therapy must be considered. This brief review provides a summary of some of
the problems that may be

encountered with the management of iron deficiency and iron deficiency anaemia.
Introduction

In the management of anaemic patients, the type and severity

of the anaemia will dictate the appropriate therapeutic

strategy. Globally, iron deficiency is the most common cause

of anaemia.1 Once iron therapy is initiated, regular follow-up

visits are essential to monitor the therapeutic response, and to

manage unpleasant adverse effects which may compromise

patient compliance. Irrespective of the presence or absence

of anaemia, iron deficiency decreases the quality of life and

increases the risk of serious health issues.2

Apart from its well-known function as an oxygen carrier

in haemoglobin and myoglobin, iron is required for the

efficient functioning of numerous other haem and non-haem

enzymes. Cytochromes, essential for the process of oxidative

phosphorylation and generation of ATP in all cells, require

iron to function effectively.3 Therefore, iron deficiency has a

negative impact on cellular respiration and ATP production,

which in turn, decreases DNA synthesis and cell division.4

Who requires iron supplementation?

Patients with an inadequate intake of nutritional iron are

at risk of developing iron deficiency anaemia, which is

characterized by microcytic hypochromic red blood cells.

Patients who present with iron deficiency but without

anaemia show a collection of non-specific symptoms

which include generalised fatigue, weakness, inability to

concentrate, and decreased cognitive performance.3,5 It is

important to determine total body stores of iron in both

anaemic and iron deficient patients.

The physiological demand for nutritional iron is increased in

specific population groups:⁶

• Premature infants, children and adolescents undergoing

growth spurts

• Pregnant and lactating women

• Patients with chronic kidney disease (erythrocyte loss

during haemodialysis)

• Patients receiving erythropoietin

• Patients that suffer from chronic blood loss - menstruating

women, bleeding from the gastro-intestinal tract (GIT).

Diet affects iron status

Unlike haem iron, a vegetarian diet decreases total iron

stores as iron from plant sources is poorly absorbed from the GIT. Meals rich in dairy products
decrease the absorption of

iron. High fibre meals and cereals bind iron and reduce its

absorption from the GIT.⁶

Hepcidin and iron homeostasis

There is no excretory mechanism for iron, which is conserved

in the body by recycling when senescent red blood cells

are engulfed by macrophages. Under normal physiological

conditions, GIT absorption of iron is restricted (1–2 mg daily)

to prevent its accumulation to toxic levels. In iron deficiency

anaemia, absorption of iron from the GIT is increased.⁸ Both

iron recycling from senescent erythrocytes and its absorption

from the GIT are controlled by the hormone hepcidin.⁹

Hepcidin responds to increased plasma and tissue iron

levels by stimulating the degradation of ferroportin, the

protein responsible for the export of iron from cells.10 In iron

deficiency, the synthesis of hepcidin is suppressed and the

absorption of iron from the GIT increases.11

Aetiology of inefficient GIT absorption of iron

Several factors decrease the absorption of iron from the GIT

and complicate the management of iron deficiency anaemia:

• Parasitic hookworm and schistosomiasis infestations

contribute to chronic blood loss and iron deficiency.12

• Helicobacter pylori competes with its human host for

orally ingested iron, decreases vitamin C levels and causes

bleeding from micro-erosions.13

• Iron deficiency is an atypical manifestation of coeliac

disease.14,15

• Patients with chronic inflammatory bowel disease

frequently have concurrent folic acid and vitamin

B12 deficiency, and their anaemia is associated with

chronic inflammation.16 Since oral iron supplementation

aggravates gastric inflammation, parenteral iron is

preferred in these patients.

• Chronic inflammatory states upregulate the synthesis of

hepcidin which decreases the gastrointestinal absorption

of iron.15,17 Use of nonsteroidal anti-inflammatory drugs

(NSAIDS) to counteract inflammation cause GIT bleeding.

• Proton pump inhibitors interfere with iron absorption,

and their widespread use frequently contributes to

unexplained iron deficiency anaemia.18

• Bariatric surgery removes iron absorption sites from the

GIT, and increases gastric pH.19

• Iron refractory iron-deficiency anaemia is defined as

a failure to respond to oral iron therapy after 4 to 6

weeks (an increase of less than 1 g haemoglobin) in the

absence of any other contributing factors. It is caused

by a rare autosomal recessive disorder that increases the

production of hepcidin, preventing iron absorption.20

Therapeutic strategy

Available iron preparations

Oral and parenteral iron preparations are available for

therapeutic use. Parenteral iron must be considered when

there is no therapeutic response after three to four weeks

of oral supplementation. Failure to respond to iron therapy

suggests continuing blood loss, incorrect diagnosis, non-

adherence, and malabsorption. Severe and persistent

gastrointestinal intolerance is another indication for

parenteral iron.

Oral iron therapy

Oral preparations include the ferrous salts; ferrous fumarate,

ferrous sulphate and ferrous gluconate salts as well as ferric

polymaltose complexes. These preparations are equivalent

in terms of therapeutic efficacy and contain various amounts

of elemental iron which should be taken into consideration

when calculating dosages.7

Iron absorption is impaired by calcium, carbonates and

phosphates, common ingredients of multivitamin and

mineral supplements.6,7

In patients with severe iron deficiency and depleted stores,

iron therapy must be continued for a period of three months

after haemoglobin levels are corrected, to replenish iron

stores.6,7 The therapeutic dose of oral iron for adults is

between 100 and 200 mg/day of an iron salt preparation,

given in divided doses. In infants, the dose of elemental

iron is 1–2 mg/kg/day for iron deficiency, and 1mg/kg/day

for prophylaxis. Preterm infants should receive a dose of

2 mg/kg/day after their birthweight has doubled. A dose of

3–6 mg/kg/day is recommended for older children. Further

information on recommended daily dosages can be found in

the South African Medicines Formulary (SAMF), 12th edition.

Iron absorption, transport, storage and

elimination

Absorption

Approximately 25% of orally administered iron is absorbed

from the GIT of anaemic patients and takes place from the
duodenum and the proximal jejunum. Iron in the reduced,

ferrous (Fe2+) state, is absorbed more efficiently than iron in

the ferric (Fe3+) state.21

Iron crosses the luminal membrane of the intestinal mucosal

cell by two mechanisms:

i. Active transport of ferrous iron by the divalent metal

transporter 1 (DMPT1).

ii. Absorption of iron complexed with haem, which is later

split from the haem molecule.

Iron is then transported across the basolateral membrane by

ferroportin and oxidized to the ferric (Fe3+) state.

Transport

In plasma, iron is transported bound to transferrin. This

complex enters maturing erythroid cells by binding to

transferrin receptors followed by receptor mediated

endocytosis. The iron is released, reduced to ferrous iron

and then either used in haemoglobin synthesis or stored as

ferritin.22

Storage

Iron is stored as ferritin in intestinal mucosal cells, spleen

and bone, and in parenchymal liver cells. Its mobilisation is

controlled by hepcidin.
Elimination

There is no mechanism for the elimination of iron. Small

amounts are lost in faeces by exfoliation of intestinal mucosal

cells.23

Adverse effects of oral iron therapy

These are mainly dose related GIT adverse effects which

manifest as heartburn, nausea, abdominal cramps,

constipation, and diarrhoea. The effects can be reduced

by decreasing the dose, or by taking the iron preparations

with meals. Food decreases the absorption efficacy of orally

administered iron by 30–50%. In addition, oral iron therapy causes black stools that obscure the
diagnosis of occult

blood loss. Unless occult blood loss is present, the dark stools

have no clinical significance.6,7

Parenteral iron therapy

Parenteral iron therapy is reserved for patients unable to

tolerate or absorb oral iron or patients with severe chronic

anaemia, caused by advanced chronic renal disease,

gastrectomy or small bowel resection.24 Hypoxia associated

with severe iron deficiency can cause cardiovascular

symptoms like heart failure and angina. These patients

require a blood transfusion to rapidly correct the hypoxia

and improve their iron stores. A unit of packed red blood

cells provides approximately 200 mg of iron.⁵ Parenteral

iron rapidly increases haemoglobin levels and corrects total

iron stores. Both intravenous and intramuscular preparations

are available. When parenteral therapy is started, oral iron

administration must be stopped to prevent iron overload.

Parenteral iron preparations carry the risk of anaphylactic

reactions and also have a high potential for adverse

reactions.25,26 The administration of a small test dose is advised,

since anaphylactic reactions are unpredictable. Iron dextran

solutions are more likely than other preparations to cause

anaphylactic and hypersensitivity reactions.27 Procedures

to manage anaphylaxis and hypersensitivity reactions must

be in place before administration of parenteral iron. Patients

requiring chronic parenteral iron therapy must have total

body iron stores monitored, to prevent iron overload.

Parenteral iron preparations available in SA:

i. iron polymaltose (IM only)

ii. ferric hydroxide sucrose complex (IV only)

iii. iron hydroxide-dextran (IM or IV)

Adverse reactions of parenteral iron therapy

Intramuscular iron injections are painful and cause

staining of the skin. Other adverse effects common with

parenteral iron therapy include; headache, fever, arthralgia,

nausea and vomiting, back pain, flushing, urticaria and

bronchospasm.25,26,27

Iron supplementation during erythropoietin

therapy

Iron status must be determined prior and during

erythropoietin therapy, since the massive haematopoietic

drive will put pressure on available iron stores. Similar

effects on iron stores are seen in the treatment of severe

megaloblastic and pernicious anaemias. It is therefore

important to ensure an adequate supply of iron when

treating patients with these conditions.28,29

Acute iron poisoning

Most cases of acute iron poisoning occur in children and

are potentially fatal. Iron causes the formation of hydroxyl

radicals that cause necrotizing gastroenteritis. Patients

develop haematemesis, GIT perforation, vascular collapse,

metabolic acidosis, cyanosis, hypoglycaemia, pulmonary

oedema, hepatorenal failure and ultimately convulsions

and coma. Despite an apparent improvement after initial

presentation, acidosis develops and patients may die.

Acute iron poisoning must be treated urgently by gastric

lavage or whole bowel irrigation, and deferoxamine which

chelates iron. Patients require intensive supportive therapy

to maintain acid base status.6,7

Summary

• Determine the cause and severity of the iron deficiency /

iron deficiency anaemia.

• Initiate therapy with oral supplementation.

• Monitor patient response and manage adverse effects.

• Patients not responding to oral iron therapy require

further investigations.

• Initiate parenteral therapy if patient is not responding to

oral therapy.

• Continue supplementation until iron stores are

replenished.

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