Tauhid Ahmed Bhuiyan, PharmD

 Resident
Pharmacy Practice  (PGY-1)
King Faisal Specialist Hospital & Research Center
 Explain background, definition, epidemiology, and etiology of
iron deficiency anemia (IDA)

 Outline diagnostic algorithm of IDA

 Identify key laboratory findings to diagnose IDA

 Discuss available therapeutic management of IDA

 Anemia is a group of disease characterized by a decrease in either
hemoglobin (Hb) or circulating red blood cells (RBCs)
o Results in reduced oxygen-carrying capacity of the blood

 According to World Health Organization (WHO)

o ̴1.6 billion people (1/4 of world’s population ) are anemic

 Not an innocent bystander; affects both length and quality of life

(QOL)

 IDA occurs across all populations and is associated with

o Diminished QOL
o Physical and cognitive performance, and
o Unfavorable clinical outcomes
http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
 Anemia

Macrocytic Normocytic Microcytic

Megaloblastic Non-megaloblastic IDA Genetic

Anomaly
1. Hepatic disease
1. Vitamin B12 2. Drug-induced
deficiency 1. Recent blood loss 1. Sickle cell
anemia
2. Hemolysis 2. Thalassemia
2. Folic acid 3. Hypothyroidism
deficiency 3. Bone marrow failure
4. Reticulocytosis
4. Anemia of chronic disease

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

 According to WHO
o Anemia is defined as Hb <130 g/L in men or <120 g/L in female

 IDA is the result of long-term negative iron balances

o Progressive loss of iron stores in the form of hemosiderin and ferritin

 IDA is defined as
o Anemia with biochemical evidence of iron deficiency based on
following laboratory findings
• Serum ferritin, total iron binding capacity (TIBC), transferrin saturation, or
transferrin receptor

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

  IDA is the most common nutritional deficiency in developing and
developed countries

 IDA is considered to be the leading cause of anemia worldwide,

accounting for as many as 50% of cases

 Prevalence of IDA greatly varies according to age, gender,

physiological, pathological, environmental, and socioeconomic
conditions

 Data from NHANES*, prevalence of IDA

o Young children 1.2%
o Women of childbearing age 4.5%

*National Health and Nutrition Examination Survey http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf

RBC production

Iron + Hb

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

 Normal iron content of the body
o ̴3-4 g (Hb, myoglobin, and cytochromes)

 Iron is best absorb as ferrous (Fe2+) form in the duodenum, and to a smaller
extent in jejunum

 Daily recommended allowance

o Adult males/postmenopausal females: 8 mg
o Menstruating female: 18 mg

 Iron sources
o Heme iron (2-3X more absorbable): meat, fish, and poultry
o Non-heme iron: vegetables, fruits, dried beans, nuts, grain products, and dietary
supplements

 Gastric acid/ascorbic acid increases non-heme iron absorption whereas

phytates (in bran), tannins/polyphenols (in tea), and calcium (in dairy product)
form insoluble complexes
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 ̶ Iron stores are reduced without reducing serum iron levels and can be
Initial
assessed with serum ferritin measurement
Stage
̶ Iron stores can be depleted without causing anemia
Once iron stores are depleted, there still is adequate iron from daily RBC turnover
for Hb synthesis
Second
Iron deficiency occurs; Hb falls just above the lower limit normal
Stage

Third Considered as IDA and occurs because of Hb falls to less than normal values
Stage
 IDA results from prolonged negative iron balance

 Mainly due to following factors:

1. Inadequate iron intake
2. Decreased iron absorption
3. Increased iron demand or hematopoiesis
4. Increased iron loss

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104

Females in the reproductive period of life
Menstruation
Pregnancy
Pathological blood loss
Deficient diet
Adult males and postmenopausal females
Pathological blood loss
Infants and children
Deficient diet
Diminished iron stores at birth

Etiology Firkin F. Hypochromic anemia. In: de Gruchy’s Clinical Hematology in Medical Practice, 1989
 IDA adversely effects
o Cognitive performance, behavior, and physical growth of infants,
preschool, and school-aged children

o The immune status and morbidity from infections of all age groups

o The use of energy sources by muscle and thus the physical capacity
and work performance of adolescents and adults of all age groups

o Increase perinatal risks for mothers and neonates and overall infant
mortality during pregnancy

http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf
 
Chief Complaints
Fatigue, lassitude, palpitation, and generalized weakness
History
Chronic blood loss, deficient diet
Clinical Features
1. Palor skin, nailbed, conjunctiva
2. Koilonychia (brittle, spoon shaped nails)
3. Atrophic glossitis (atrophy of tongue papilla; making the tongue
smooth and shiny)
4. Pica (compulsive eating of nonfood items) or pagophagia
(compulsive eating of ice)
Firkin F. Hypochromic anemia. In: de Gruchy’s Clinical Hematology in Medical Practice, 1989
 Symptoms Signs
Decreased exercise tolerance Tachycardia
Pale appearance (most prominent in
Fatigue
conjunctiva)
Dizziness Decreased mental acuity
Increased intensity of some cardiac valvular
Irritability
murmurs
Weakness
Palpitations
Vertigo
Shortness of breath
Chest pain
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Complete blood count (CBC), erythrocyte sedimentation rate
(ESR), and peripheral blood film (PBF)

 Serum Iron profile

 Bone marrow study (if needed)

 Investigations to determine other causes of IDA (e.g. fecal

occult blood test, colonoscopy, urine examination)
 Hematologic Indices Normal Range IDA
Hb 70—160 g/L Low
Hematocrit (Hct) 0.320—0.47 L/L Low
Mean corpuscular volume (MCV) 75—95 fL Low
Mean corpuscular hemoglobin (MCH) 24—30 pg Low
Mean corpuscular hemoglobin
concentration (MCHC) 290—370 g/L Low

Red cell distribution width (RDW) 11—15% High (early)

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011c

 Lab Exams Comments In IDA
1. It is the concentration bound to transferrin
Serum Fe 2. Approximately one-third transferrin bound to iron
3. Levels are decreased by infection and inflammation
Low
(50-100 mcg/dL)
4. Best interpreted in conjunction with TIBC
1. Ferritin (storage iron) is proportional to total iron
stores
Serum ferritin
2. Best indicator of iron deficiency or overload Low
(>10-20 mcg/L) 3. Infection or inflammation can increase the
concentration, independent of iron status
1. Indirect measurement of the iron-binding capacity of
Total iron binding capacity (TIBC) serum transferrin (protein)
2. Levels don’t fluctuate over hours or days unlike serum
High
(250-410 mcg/dL)
iron
1. Ratio of serum iron level to TIBC in percentage
2. Reflects the extent to which iron-binding sites are
% Saturation of transferrin (>20%) occupied on transferrin and indicates the availability Low
of iron for erythropoiesis
3. Less sensitive and specific for IDA than ferritin

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011c

Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
 
 Short term
o Resolution of symptoms
o Replenish iron stores

 Long term
o Improve quality of life (QOL)
o Prevention of recurrences
o Better growth and development (children)
 Pharmacological management
o Oral/parenteral iron therapy

 Non-pharmacological
o Blood transfusion
 
Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
 Recommended dosage requirements
o 200 mg elemental iron per day for 3-6 months
o 2-3 divided doses to maximize tolerability
o Administration should be 1 hour before meals or on empty
stomach

 Absorption of all oral preparations are similar

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

http://www.pharmapacks.com/product_images/g/220/a1174335_2761__43287.jpg
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Gastrointestinal (GI) intolerance
o Nausea, vomiting, heartburn, and diarrhea or constipation
o Slow release or sustained release preparations may be used
o Combination products, e.g. Ferro-DDS (ferrous fumarate/docusate),
may be advantageous for certain patient population

 Cause discoloration of stool

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Indications for therapy
o Intolerance to oral route
o Malabsorption
o Long-term nonadherence
o Patient with significant blood loss who refuse transfusion and are
intolerant to oral therapy
o Chronic kidney disease (CKD)

 Currently available formulations include

o Dextran, sodium ferric gluconate, iron sucrose, and ferumoxytol

 Formulations differ in their molecular size, degradation kinetics,

bioavailability, and side effects profile

 All preparations carry a risk for anaphylactic reactions but likely

to a lesser extent than iron dextran
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Amount of
elemental
Formulation Warning Treatment Common adverse effects
iron
(mg/mL)
Black Box Pain and brown staining
Iron Dextran Warning (BBW): 10 doses x 100 mg at injection site, flushing,
50
(INFeD) anaphylactic type = 1,000 mg hypotension, fever, chills,
reactions myalgia, anaphylaxis
Sodium Ferric No BBW: Cramps, nausea and
8 doses x 125 mg =
Gluconate 62.5 Hypersensitivity vomiting, flushing,
1,000 mg
(Ferrlecit) reaction hypotension, rash, pruritis
BBW: Leg cramps, hypotension
Iron Sucrose*
anaphylactic type Up to 10 doses x
(Ferosac®) 20
reactions 100 mg = 1,000 mg

No BBW: Diarrhea, constipation,

Ferumoxytol Hypersensitivity 2 doses x 510 mg = dizziness, hypotension,
30
(Feraheme) reaction 1,020 mg peripheral edema
*KFSH&RC Formulary DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
 Total iron deficiency in mg =
Hb-iron deficiency + depot iron

Hb-iron deficiency (in mg) = body weight (kg) x (normal Hb - actual Hb in g/L) x 0.24 §

Above calculation is based on:

 A normal Hb 150 g/L for body weights >35 kg and 130 g/L ≤34 kg body weight
respectively
 The iron-content of hemoglobin (0.34%)
 The blood volume (∼7% of the body weight) and the requirements of depot iron
(∼15 mg/kg up to a weight of about 34 kg, total of 500 mg >34 kg)
 §Factor 0.24 = 0.0034 x 0.07 x 1000

KFSH&RC Formulary
*Iron sucrose
http://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/289383
 SA, 60 kg woman with a hemoglobin concentration of 80 g/L due to
iron deficiency needs parenteral iron replacement, which will be
given intravenously in the form of iron sucrose (20 mg iron/mL).
Calculate total iron deficiency and amount of iron sucrose
(ampules) for SA? [Injection: 5 mL/ampule]

 Solution:
o Step 1: calculating elemental iron deficiency in Hb of SA
• 60 kg X (150 g/L – 80 g/L) X 0.24 = 1008
• Total vials of iron requirement for SA:
o Step 2: depot iron • 1508 mg elemental iron / (20 mg/mL)
• 500 mg (since SA >34 kg) • Total iron sucrose = 75 mL
o Step 3: total iron deficiency • Iron sucrose (5 mL / ampule)
• (75 mL / 5) = 15 ampules
• Step 1 + Step 2 = 1008 + 500 = 1508 mg elemental iron
 http://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/
289383
 
 Decision to manage anemia is based on the evaluation of risk and
benefit

 Transfusion is generally not indicated if Hb >100 g/L whereas

transfusion of RBCs should be considered when Hb is <70 to 80 g/L
in hospitalized, stable patient

 Transfusion of allogeneic blood is indicated in acute situations (e.g.

severe blood loss)

 Transfusions may also be necessary for patient with cardiac

instability
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
KFSH&RC Transfusion Guideline: http://ig.kfshrc.edu.sa/wps/portal/
Szczepiorkowski Z. et al. ASH Education Book 2013;1:638-644 or
http://asheducationbook.hematologylibrary.org/content/2013/1/638.full
 Positive response in reticulocytosis is seen in few days of oral
therapy

 Hb should reach to normal level after 2 months

 A Hb response of <20 g/L over a 3-week period warrants therapy

evaluation

 Iron profile should be measure in the first week for oral therapy and
2 weeks after large intravenous doses

 Hb and Hct should be measured weekly, and serum iron and ferritin
levels should be measured monthly
 Provide education on healthy lifestyle

 Identify high risk population for necessary preventative measures

 Select appropriate medication therapy based on patient and drug

related factors

 Provide medication counseling and adherence

 Monitor therapeutic outcome and minimize adverse drug reactions

 IDA is the most common form of anemia and is usually the result of
prolonged negative iron balance in the body

 Four main factors contributing to IDA include

o Inadequate iron intake
o Decreased iron absorption
o Increased iron demand or hematopoiesis
o Increased iron loss

 Clinical diagnosis of IDA should include complete patient history

and physical exams, followed by laboratory investigations

 Abnormal laboratory investigations generally include low MCV,

serum iron, and ferritin; and high TIBC
 Treatment of IDA usually consists of dietary supplementation and
administration of oral iron preparations

 General recommendation for oral iron replacement is ̴200 mg

elemental iron/day, divided into 2-3 doses to maximize tolerability

 Parenteral therapy is usually not indicated unless patient is

intolerant to oral therapy, having malabsorption, or in the case of
CKD

 Anaphylactic reaction should be considered for all parenteral

formulation along with strictly monitoring adverse drug reaction
 Decision to manage anemia with blood transfusion is based
on the evaluation of the risk and benefit and is only
considered when Hb is <70 to 80 g/L

 Complete therapeutic response requires iron

supplementation for up to 2-6 months, however, symptoms
may improve within few days after oral therapy
 Q1: Which of the following is one of the common cause of IDA
in young male?
A. Deficient diet
B. Menstruation
C. Pathological blood loss
D. None of the above
 Q2: Microcytic hypochromic anemia can be due to the
following factor(s):
A. Folic Acid
B. Vitamin B12
C. Iron deficiency
D. Hemolysis
 Q3: Which of the following statement is false regarding iron in
our body?
A. It is best absorb in ferrous (Fe2+) form in the duodenum
B. Heme iron is found in meat, fish, and poultry
C. Gastric acid/ascorbic acid increases non-heme iron absorption
D. Non-heme iron is 2-3X more absorbable than heme iron
 Q4: Identify the following laboratory investigations for
diagnosing IDA as high/low:

Hb Low
MCV Low
Serum iron Low
TIBC High
Serum ferritin Low
Transferrin saturation Low
 Q5: For oral iron products, the following statements are true
except:
A. Ferrous sulfate tablet contains 65 mg elemental iron
B. Administration of oral iron should be 1 hour before meals or on
empty stomach preferably
C. Can cause GI intolerance and discoloration of stools
D. Percent elemental iron of all oral preparations is roughly the same