Iron Deficiency Iron Deficiency AnemiaAnemiaProf.Dr.Teoman SOYSAL Prof.Dr.Teoman SOYSAL

Iron Deficiency AnemiaIron Deficiency Anemia One of the most common medical One of the most common medical

problemsproblems Most common cause of anemiaMost common cause of anemia Iron deficiency anemia is the last step ;Iron deficiency anemia is the last step ;

– Iron depletion: absent or decreased iron storesIron depletion: absent or decreased iron stores– Iron deficiency: depletion of stores + low Iron deficiency: depletion of stores + low

serum iron and ferritinserum iron and ferritin– Iron deficiency anemia: Anemia developing in Iron deficiency anemia: Anemia developing in

an iron deficient patientan iron deficient patient

Total amount of body iron:3-5 Total amount of body iron:3-5 gg

Iron MetabolismIron Metabolism Iron is located at the center of Hem Iron is located at the center of Hem

molecules of molecules of HbHb (amount:1.5-2 gr) (amount:1.5-2 gr) and it is also;and it is also; Part of the Part of the myoglobinmyoglobin Takes place in the Takes place in the tissue enzymestissue enzymes Storage forms are Storage forms are (1gr in men,0.5gr in women):(1gr in men,0.5gr in women):

– FerritinFerritin– HemosiderinHemosiderin– Location: Bone Marrow, Liver, SpleenLocation: Bone Marrow, Liver, Spleen

Transport iron Transport iron is about 7 mg and bound to is about 7 mg and bound to transferrin.transferrin.

Iron MetabolismIron Metabolism

Transferrin picks up iron from ;Transferrin picks up iron from ;1.1. The GI cells to deliver it to Hb forming The GI cells to deliver it to Hb forming

cellscells2.2. Storage parts as a step of iron recycling Storage parts as a step of iron recycling

processprocess Absorbtion + recycling provides the Absorbtion + recycling provides the

constant iron supply of constant iron supply of 20 mg/day 20 mg/day (up to (up to 35 mg)35 mg) necessary for Hb synthesis necessary for Hb synthesis

Daily Iron DemandsDaily Iron Demands

MaleMale 1 mg1 mg

Adolesc. Adolesc. 2-3 2-3 mgmg

Women in repr.age 2-3 Women in repr.age 2-3 mgmg

Pregnant 3-4 Pregnant 3-4 mg mg

Iron MetabolismIron Metabolism Iron absorbtion is restricted to the Iron absorbtion is restricted to the

needs of the bodyneeds of the body 1mg of iron is lost each day1mg of iron is lost each day

– SweatingSweating– Epidermal sheddingEpidermal shedding– Menstruation and Menstruation and

pregnancy/lactation are other major pregnancy/lactation are other major causes of iron loss and incresed causes of iron loss and incresed demand in womendemand in women

Normal diet contains about 15 mg of iron/dayNormal diet contains about 15 mg of iron/day 6mg elemental iron/1000 cal6mg elemental iron/1000 cal 1/10 of ingested iron is absorbed1/10 of ingested iron is absorbed Gastric acid releases iron from foodGastric acid releases iron from food Iron is absorbed in the reduced formIron is absorbed in the reduced form Ascorbate increases absorbtion (by reducing)Ascorbate increases absorbtion (by reducing) Phytates,tannates,antacids decrease Phytates,tannates,antacids decrease

absorbtion by making complexes with ironabsorbtion by making complexes with iron

Iron MetabolismIron Metabolism

Iron MetabolismIron Metabolism Main sites of absorbtion are;Main sites of absorbtion are;

– DuodenumDuodenum– Upper jejunumUpper jejunum

Malabsorbtive states or Malabsorbtive states or gastrojejunostomy prevent gastrojejunostomy prevent absorbtion.absorbtion.

Iron MetabolismIron Metabolism

Transport of ironTransport of iron– Transferrin is the main iron carrier in Transferrin is the main iron carrier in

plasmaplasma– It is produced in liver cells with It is produced in liver cells with

increased synthesis in iron deficiencyincreased synthesis in iron deficiency– Transferrin binds 1-2 ferric iron Transferrin binds 1-2 ferric iron

moleculesmolecules– Transferrin-iron complex is endocytosed Transferrin-iron complex is endocytosed

by Hb producing cells after linking to by Hb producing cells after linking to receptors.receptors.

Iron MetabolismIron Metabolism Total iron binding capacity and ironTotal iron binding capacity and iron

– Transferrin is measured by quantifying Transferrin is measured by quantifying the iron binding sites availablethe iron binding sites available

– This is also called “Total iron binding This is also called “Total iron binding capacity”capacity”

– TIBC is 1/3 saturated under normal TIBC is 1/3 saturated under normal conditionsconditions

– Plasma Transferrin : 300 Plasma Transferrin : 300 μμg/dLg/dL– Plasma Iron: 60-180 Plasma Iron: 60-180 μμg/dLg/dL

Causes of iron Causes of iron deficiencydeficiency Chronic blood lossChronic blood loss Increased demandIncreased demand Malabsorbtion of ironMalabsorbtion of iron Inadequate iron intakeInadequate iron intake Intravascular hemolysis and Intravascular hemolysis and

hemoglobinuria-hemosiderinuriahemoglobinuria-hemosiderinuria CombinationsCombinations

Increased demandsIncreased demandsPregnancy Pregnancy LactationLactationRapid growthRapid growth

Decreased intakeDecreased intake Decreased iron in the dietDecreased iron in the diet

– VegetarianismVegetarianism– Tea-tost type feeding (old age)Tea-tost type feeding (old age)

Decreased absorbtionDecreased absorbtion– Gastric surgeryGastric surgery– AchlorhydriaAchlorhydria– SprueSprue– PicaPica

Increased iron lossIncreased iron loss MenorrhagiaMenorrhagia GIS hemorrhagiaGIS hemorrhagia

•AngiodysplasiaAngiodysplasia•DiverticulosisDiverticulosis•Meckel Meckel diverticuladiverticula•Colitis or imf. Colitis or imf. Bovel diseaseBovel disease•HemorrhoidsHemorrhoids•NSAID useNSAID use•ParasitesParasites

•P.UlcerP.Ulcer•OesophagitiOesophagitiss•VaricesVarices•Hiatal Hiatal herniahernia•MalignancyMalignancy

Increased iron lossIncreased iron loss Bleeding disorderBleeding disorder Pulmonary lesions with bleedingPulmonary lesions with bleeding Hemoglobinuria – hemosiderinuria Hemoglobinuria – hemosiderinuria

(chronic intravascular hemolysis)(chronic intravascular hemolysis) HemodialysisHemodialysis Hematuria (chronic)Hematuria (chronic) Frequent donationFrequent donation

– 250 mg iron /unit-blood250 mg iron /unit-blood

Clinical featuresClinical features General symptoms of anemiaGeneral symptoms of anemia Fatigue may be disproportional to the Fatigue may be disproportional to the

degree of anemia due to deficiency of degree of anemia due to deficiency of tissue enzymes which also need irontissue enzymes which also need iron

ChlorosisChlorosis GlossitisGlossitis Angular stomatitisAngular stomatitis Paterson-Kelly (Plummer Vinson) syndromePaterson-Kelly (Plummer Vinson) syndrome (oesephageal web leading to disphagia)(oesephageal web leading to disphagia)

ClinicalClinical featuresfeatures

Gastric atrophyGastric atrophy Ozena-anosmiaOzena-anosmia Nail changesNail changes

– Brittle/fragilityBrittle/fragility– Koilonchia/spooningKoilonchia/spooning

Hair lossHair loss SplenomegalySplenomegaly

Clinical featuresClinical features Pica:Appetite for bizzare food/substancesPica:Appetite for bizzare food/substances

– Geophagy (earth,clay)Geophagy (earth,clay)– Pagophagia(ice)Pagophagia(ice)– Amylophagia(starch)Amylophagia(starch)

Developmental problemsDevelopmental problems SplenomegalySplenomegaly TayancTayanc-Prasad -Prasad syndromesyndrome (growth retardation, hypogonadism, hepatosplenomegaly, (growth retardation, hypogonadism, hepatosplenomegaly,

zinc and iron deficiency, geophagia)zinc and iron deficiency, geophagia) Immun-deficiencyImmun-deficiency

Lab. FeaturesLab. Features Hb,Htc,RBC:Hb,Htc,RBC:LowLow MCV,MCH,MCHC:MCV,MCH,MCHC:LowLow RDW: RDW: HighHigh Retics: Retics: Normal/LowNormal/Low Plt:Plt:Normal/Low/HighNormal/Low/High WBC:WBC:Normal/LowNormal/Low Smear: Smear:

Hypochromia,anisocytosis,microcytosis, Hypochromia,anisocytosis,microcytosis, poikilocytosispoikilocytosis

Lab.FeaturesLab.Features Serum Serum Iron:Iron: ( (N:N: 60 – 180 60 – 180 μμg/dLg/dL)) TTIIBBC:C: (250 - 430 (250 - 430 μμg/dL)g/dL) Serum Ferritin Serum Ferritin (N:(N:FemaleFemale;10-150 ;10-150 μμg/g/L, L, MaleMale;29-248 ;29-248 μμg/g/L)L)

Males and Males and post menoppost menopauausal sal womenwomen<10 <10 μμg/g/LL

PremenPremenooppauausal sal womenwomen <5 <5 μμg/g/LLIron def+Chr.Disease< 60 Iron def+Chr.Disease< 60 μμg/Lg/L

Lab.FeaturesLab.Features Transferrin saturaTransferrin saturation (Fe/TIBC):tion (Fe/TIBC): (<15%)(<15%)

<<5%:definitely indicates iron deficiency5%:definitely indicates iron deficiency Serum Transferrin ReSerum Transferrin Receptor:ceptor: FFree ree EErythrocyte rythrocyte PProtoporphyrinrotoporphyrin (17 – 27 (17 – 27 μμg/dL)g/dL)

Bone marrowBone marrow : : – ErEryytthhroid hroid hyyperplaperplassiiaa, , – Absence ofAbsence of hhemosiderin emosiderin

Findings Normal Prelatent period

Latent period

Iron def. anemia Early Late

Hb g/dl N N N 8-14 <8

MCV fl N N N N,

S. Ferr. N <12 <12 <12

T. Sat. N N <16 <16 <16

BM iron N - - -

FEP N N

Symptom - - - + + Ept. change - - - - +

Differential diagnosisDifferential diagnosis Microcytic anemiasMicrocytic anemias

– Iron deficiency anemiaIron deficiency anemia– Thalassemia ,HbC,HbE etcThalassemia ,HbC,HbE etc– Sideroblastic anemiaSideroblastic anemia– Lead poisoningLead poisoning– Anemia of chronic diseases Anemia of chronic diseases

(sometimes)(sometimes)

S.Ferritin N N N

TIBC N N N

S.Iron N Variable.

T.Satur. N N

FEP N

Marrow iron - + + + +

Special tests HbA2 RF etc. HbA2 HbF

Ring Siderobl ALA , Pb

Iron deficiency

Chronic disease

Thalasse-mia.

Siderobl.anemia

Lead poisoning

Diff.Diagnostic Tests

aminolaevulinic acidporphobilinogen

Important !!!!!!!Important !!!!!!! The diagnostic procedure is not The diagnostic procedure is not

complete until the underlying complete until the underlying pathology is disclosed.pathology is disclosed.

TreatmentTreatment Replace iron and treat underlying disease.Replace iron and treat underlying disease. Oral route is preferred for replacement.Oral route is preferred for replacement. Response can be followed by retic. Response can be followed by retic.

increase in 1-2 weeks (increase in 1-2 weeks (5-7 days5-7 days)) Hb response to treatmentHb response to treatment

– half normal by a monthhalf normal by a month– returns to normal by 2-4 monthsreturns to normal by 2-4 months

Replacement therapy is prolonged by 6-Replacement therapy is prolonged by 6-12 months to replenish stores of iron.12 months to replenish stores of iron.

Ongoing bleeding may cause indefinite Ongoing bleeding may cause indefinite therapy.therapy.

TreatmentTreatment

Oral iron therapy:Oral iron therapy:dosedose (mg)(mg) elemental elemental iron(mg)iron(mg)

Fe fumaratFe fumaratee 200 65 200 65Fe gluFe glucconatonatee 300 35300 35Fe sulFe sulphphatatee 200 65 200 65

TreatmentTreatmentOral iron therapy:Oral iron therapy:Total daily dose:150-200 mg elemental ironTotal daily dose:150-200 mg elemental ironGive in 3-4 divided doses,Give in 3-4 divided doses,Each one hour before meals.Each one hour before meals.Do not prefer enteric coated forms.Do not prefer enteric coated forms.In case of GIS intolerance;In case of GIS intolerance; Change the route of administration orChange the route of administration or Change the preparation orChange the preparation or Reduce doseReduce dose

TreatmentTreatmentNon responding patientNon responding patient:: possible causespossible causes

– MisdiagnosisMisdiagnosis– Patient does not take the medicinePatient does not take the medicine– Continuing blood lossContinuing blood loss– MalabsorbtionMalabsorbtion

Change the drugChange the drug Change the route of administrationChange the route of administration

– Underlying disease /comorbidity Underlying disease /comorbidity – Combined deficiencyCombined deficiency

TreatmentTreatment Parenteral iron therapy:Parenteral iron therapy:

Routine use is not justified,Routine use is not justified,Response is not faster than oral Response is not faster than oral

replacement.replacement.IndicationsIndications– MalabsorbtionMalabsorbtion– Intolerance to oral replacementIntolerance to oral replacement

Colitis/enteritisColitis/enteritis– Needs in excess of amount that can be Needs in excess of amount that can be

given orallygiven orally– Patient uncooperative/poor compliancePatient uncooperative/poor compliance– Autologous blood donation settingAutologous blood donation setting– HemodialysisHemodialysis

TreatmentTreatmentParenteral iron therapy:Parenteral iron therapy:Total iron dose:Total iron dose: (15-patient Hb) x bw x (15-patient Hb) x bw x

33– Iron Dextran: Iron Dextran: 50 mg/ml (iv/im)50 mg/ml (iv/im)

Max daily dose is 100 mg imMax daily dose is 100 mg im– Ferric gluconate: Ferric gluconate:

A A test dose of 25 mg elemental iron (2 mL) must test dose of 25 mg elemental iron (2 mL) must be given in 50 mL saline over 60 minutesbe given in 50 mL saline over 60 minutes

– Ferric-hydroxy-sucrose Ferric-hydroxy-sucrose (100 mg/5mL)(100 mg/5mL) – 2.5 ml first day2.5 ml first day– 5ml third day5ml third day– 2x5 ml/week2x5 ml/week

Parenteral replacement therapy may Parenteral replacement therapy may causecause

– allergic reactions, allergic reactions, – local pain or induration,local pain or induration,– serum sickness like disease,serum sickness like disease,– lymphadenomegaly,lymphadenomegaly,– arthralgia,arthralgia,– myalgia etc.myalgia etc.

TreatmentTreatment

preventive iron supplementation PregnantsPregnants ( ( at at 20-24 20-24 weeks weeks Hb< 11 Hb< 11

g/dL, Ferritin g/dL, Ferritin ). ). LaLactationctation.. Frequent blood donation.Frequent blood donation. Autologous blood donation settings.Autologous blood donation settings. GaGastrectomised patientsstrectomised patients.. High dose asprin treatmentHigh dose asprin treatment..