Iron deficiency anaemia

1.  
Tauhid Ahmed Bhuiyan, PharmD
Pharmacy Practice Resident (PGY-1)
King Faisal Specialist Hospital & Research Center

2.  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

3.  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

4. DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
Anemia
Macrocytic Normocytic Microcytic
Megaloblastic Non-megaloblastic IDA Genetic
Anomaly
1. Vitamin B12
deficiency
2. Folic acid
deficiency
1. Sickle cell
2. Thalassemia
1. Recent blood loss
2. Hemolysis
3. Bone marrow failure
4. Anemia of chronic disease
1. Hepatic disease
2. Drug-induced
anemia
3. Hypothyroidism
4. Reticulocytosis

5.  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

6.  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

7. RBC production
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
Iron + Hb

8.  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

9. ̶ Iron stores are reduced without reducing serum iron levels and can be
assessed with serum ferritin measurement
̶ Iron stores can be depleted without causing anemia
Iron deficiency occurs; Hb falls just above the lower limit normal
Considered as IDA and occurs because of Hb falls to less than normal values
Initial
Stage
Second
Stage
Third
Stage
Once iron stores are depleted, there still is adequate iron from daily RBC turnover
for Hb synthesis

10.  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

11. 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
Firkin F. Hypochromic anemia. In: de Gruchy’s Clinical Hematology in Medical Practice, 1989
Etiology

12.  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

13.  

14. 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

15. Symptoms Signs
Decreased exercise tolerance Tachycardia
Fatigue
Pale appearance (most prominent in
conjunctiva)
Dizziness Decreased mental acuity
Irritability
Increased intensity of some cardiac valvular
murmurs
Weakness
Palpitations
Vertigo
Shortness of breath
Chest pain
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011

16.  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)

17. 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

18. Lab Exams Comments In IDA
Serum Fe
(50-100 mcg/dL)
1. It is the concentration bound to transferrin
2. Approximately one-third transferrin bound to iron
3. Levels are decreased by infection and inflammation
4. Best interpreted in conjunction with TIBC
Low
Serum ferritin
(>10-20 mcg/L)
1. Ferritin (storage iron) is proportional to total iron
stores
2. Best indicator of iron deficiency or overload
3. Infection or inflammation can increase the
concentration, independent of iron status
Low
Total iron binding capacity (TIBC)
(250-410 mcg/dL)
1. Indirect measurement of the iron-binding capacity of
serum transferrin (protein)
2. Levels don’t fluctuate over hours or days unlike serum
iron
High
% Saturation of transferrin (>20%)
1. Ratio of serum iron level to TIBC in percentage
2. Reflects the extent to which iron-binding sites are
occupied on transferrin and indicates the availability
of iron for erythropoiesis
3. Less sensitive and specific for IDA than ferritin
Low
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011c

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

20.  

21.  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)

22.  Pharmacological management
o Oral/parenteral iron therapy
 Non-pharmacological
o Blood transfusion

23.  

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

25.  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

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

27.  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

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

29.  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

30. Formulation
Amount of
elemental
iron
(mg/mL)
Warning Treatment Common adverse effects
Iron Dextran
(INFeD)
50
Black Box
Warning (BBW):
anaphylactic type
reactions
10 doses x 100 mg
= 1,000 mg
Pain and brown staining
at injection site, flushing,
hypotension, fever, chills,
myalgia, anaphylaxis
Sodium Ferric
Gluconate
(Ferrlecit)
62.5
No BBW:
Hypersensitivity
reaction
8 doses x 125 mg =
1,000 mg
Cramps, nausea and
vomiting, flushing,
hypotension, rash, pruritis
Iron Sucrose*
(Ferosac®) 20
BBW:
anaphylactic type
reactions
Up to 10 doses x
100 mg = 1,000 mg
Leg cramps, hypotension
Ferumoxytol
(Feraheme)
30
No BBW:
Hypersensitivity
reaction
2 doses x 510 mg =
1,020 mg
Diarrhea, constipation,
dizziness, hypotension,
peripheral edema
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
*KFSH&RC Formulary

31. 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
Total iron deficiency in mg =
Hb-iron deficiency + depot iron
KFSH&RC Formulary
http://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/289383
*Iron sucrose

32. • Total vials of iron requirement for SA:
• 1508 mg elemental iron / (20 mg/mL)
• Total iron sucrose = 75 mL
• Iron sucrose (5 mL / ampule)
• (75 mL / 5) = 15 ampules
 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
o Step 2: depot iron
• 500 mg (since SA >34 kg)
o Step 3: total iron deficiency
• Step 1 + Step 2 = 1008 + 500 = 1508 mg elemental iron

33.  http://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/
289383

34.  

35.  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
Szczepiorkowski Z. et al. ASH Education Book 2013;1:638-644 or
http://asheducationbook.hematologylibrary.org/content/2013/1/638.full
KFSH&RC Transfusion Guideline: http://ig.kfshrc.edu.sa/wps/portal/

36.  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

37.  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

38.  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

39.  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

40.  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

42.  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

43.  Q2: Microcytic hypochromic anemia can be due to the
following factor(s):
A. Folic Acid
B. Vitamin B12
C. Iron deficiency
D. Hemolysis

44.  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

45.  Q4: Identify the following laboratory investigations for
diagnosing IDA as high/low:
Hb
MCV
Serum iron
TIBC
Serum ferritin
Transferrin saturation
Low
Low
Low
High
Low
Low

46.  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