Iron Deficiency Anemia (IDA)

Iron Deficiency Anemia (IDA)

Tauhid Ahmed Bhuiyan, PharmDPharmacy Practice Resident (PGY-1)

King Faisal Specialist Hospital & Research Center

Objectives

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

Background 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 witho Diminished QOLo Physical and cognitive performance, and o Unfavorable clinical outcomes

http://www.who.int/nutrition/publications/en/ida_assessment_prevention_control.pdf

Morphological Classification

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 loss2. Hemolysis 3. Bone marrow failure4. Anemia of chronic disease

1. Hepatic disease2. Drug-induced

anemia3. Hypothyroidism4. Reticulocytosis

Definition 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 balanceso Progressive loss of iron stores in the form of hemosiderin and ferritin

IDA is defined aso Anemia with biochemical evidence of iron deficiency based on

following laboratory findings• Serum ferritin, total iron binding capacity (TIBC), transferrin saturation, or

transferrin receptor


Epidemiology 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 IDAo 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

Process of RBC Production & Maturation

RBC production


Iron + Hb

Iron Balance 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 allowanceo Adult males/postmenopausal females: 8 mgo Menstruating female: 18 mg

Iron sourceso Heme iron (2-3X more absorbable): meat, fish, and poultryo 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


Pathophysiology

N Iron stores are reduced without reducing serum iron levels and can be assessed with serum ferritin measurementN 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

Etiology IDA results from prolonged negative iron balance

Mainly due to following factors:1. Inadequate iron intake2. Decreased iron absorption 3. Increased iron demand or hematopoiesis4. Increased iron loss

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

Common Cause – Age & Sex

Females in the reproductive period of lifeMenstruationPregnancyPathological blood lossDeficient dietAdult males and postmenopausal femalesPathological blood lossInfants and childrenDeficient dietDiminished iron stores at birth

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

Prognosis 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

Diagnosis

Chief ComplaintsFatigue, lassitude, palpitation, and generalized weakness

HistoryChronic blood loss, deficient diet

Clinical Features1. Palor skin, nailbed, conjunctiva2. 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)

Preliminary Findings

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

Signs & SymptomsSymptoms 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 VertigoShortness of breathChest pain


Laboratory Evaluation 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)

Hematological Parameters in IDA

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

Iron ProfileLab 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 iron3. Levels are decreased by infection and inflammation4. 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 overload3. 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 percentage2. 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

Algorithm for Diagnosis of IDA


Management Management

Therapeutic Goals Short term

o Resolution of symptomso Replenish iron stores

Long termo Improve quality of life (QOL)o Prevention of recurrenceso Better growth and development (children)

Treatment Options

Pharmacological managemento Oral/parenteral iron therapy

Non-pharmacologicalo Blood transfusion

Pharmacological Management

Treatment Approach


Oral Iron Therapy

Recommended dosage requirements o 200 mg elemental iron per day for 3-6 monthso 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, 2011http://www.pharmapacks.com/product_images/g/220/a1174335_2761__43287.jpg

Available Products


Common Side Effects

Gastrointestinal (GI) intoleranceo Nausea, vomiting, heartburn, and diarrhea or constipationo 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


Drug Interactions


Parenteral Iron Therapy Indications for therapy

o Intolerance to oral routeo Malabsorption o Long-term nonadherenceo Patient with significant blood loss who refuse transfusion and are intolerant to oral

therapyo Chronic kidney disease (CKD)

Currently available formulations includeo 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


Comparison of Parenteral Iron Preparations

FormulationAmount 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)

62.5No 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

Calculating Parenteral* Iron Requirement

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 Formularyhttp://online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/289383*Iron sucrose

• 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

Example 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 = 1008o 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

KFSH&RC Reference http://

online.lexi.com/lco/action/doc/retrieve/docid/faisal_f/289383

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



Non-pharmacological Management

Blood Transfusion 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, 2011Szczepiorkowski 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/

http://ig.kfshrc.edu.sa/wps/portal/



Monitoring for Therapeutic Outcome

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

Pharmacist Role 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

Summary 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 intakeo Decreased iron absorption o Increased iron demand or hematopoiesiso 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

Summary 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

Summary 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

Self Assessment Questions Q1: Which of the following is one of the common cause of IDA

in young male?A. Deficient dietB. MenstruationC. Pathological blood lossD. None of the above

Self Assessment Questions Q2: Microcytic hypochromic anemia can be due to the

following factor(s):A. Folic AcidB. Vitamin B12

C. Iron deficiencyD. Hemolysis

Self Assessment Questions Q3: Which of the following statement is false regarding iron in

our body?A. It is best absorb in ferrous (Fe2+) form in the duodenumB. Heme iron is found in meat, fish, and poultryC. Gastric acid/ascorbic acid increases non-heme iron absorptionD. Non-heme iron is 2-3X more absorbable than heme iron

Self Assessment Questions Q4: Identify the following laboratory investigations for

diagnosing IDA as high/low:

HbMCV

Serum ironTIBC

Serum ferritin Transferrin saturation

LowLowLowHighLowLow

Self Assessment Questions Q5: For oral iron products, the following statements are true

except: A. Ferrous sulfate tablet contains 65 mg elemental ironB. Administration of oral iron should be 1 hour before meals or on

empty stomach preferably C. Can cause GI intolerance and discoloration of stoolsD. Percent elemental iron of all oral preparations is roughly the same

Documents

Iron Deficiency Anemia (IDA)