iron deficiency anemia (ida)
TRANSCRIPT
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
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
Matthew W. et al. Am Fam Physician. 2013;87(2):98-104
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
Drug Interactions
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
DiPiro J. Anemia. In: Pharmacotherapy: A Pathophysiological Approach, 2011
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
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/
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