Fe Deficiency

8/6/2019 Fe Deficiency

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Iron DeficiencyIron Deficiency


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Incidence & EtiologyIncidence & Etiology

Iron is one of the most common elementsIron is one of the most common elementsin the earth's crust, yet Fe deficiency isin the earth's crust, yet Fe deficiency isthe most common cause of anemiathe most common cause of anemiaaffecting about 500 million people worldaffecting about 500 million people worldwide.wide.

Why?Why?

The body has a limited ability to absorbThe body has a limited ability to absorbFe.Fe.Excess loss of Fe due to hemorrhage isExcess loss of Fe due to hemorrhage is

frequent.frequent.


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Anemia caused by inadequate dietary Fe isAnemia caused by inadequate dietary Fe isunusual below six months.unusual below six months.

It is mainly due toIt is mainly due to perinatal blood lossperinatal blood loss , in, inpreterm and low birth weight infants withpreterm and low birth weight infants with

depleted iron stores.depleted iron stores.


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BODY IRONDISTRIBUTION ANDBODY IRONDISTRIBUTION AND

TRAN

SPO

RTTRAN

SPO

RT

The transport and storage of iron isThe transport and storage of iron islargely mediated by 3 proteins:largely mediated by 3 proteins:

1.1. TransferrinTransferrin

2.2. Transferrin receptor (TR)Transferrin receptor (TR)3.3. FerritinFerritin


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Transferrin delivers Fe to tissues whichTransferrin delivers Fe to tissues which

have tR especially erythroblast in bonehave tR especially erythroblast in bonemarrow which incorporate Fe into Hbmarrow which incorporate Fe into Hbmolecules .molecules .

Most of Fe on transferrin is provided fromMost of Fe on transferrin is provided fromsenescent RBCs and a small portionsenescent RBCs and a small portioncomes from dietary Fe .comes from dietary Fe .

Fe is stored in RE cells as ferritin on orFe is stored in RE cells as ferritin on orhemosiderin, in a ferric form .hemosiderin, in a ferric form .


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Iron is mobilized after reduction to ferrous formIron is mobilized after reduction to ferrous form(vit. C is involved)(vit. C is involved)

Iron is also present in muscle as myoglobin andIron is also present in muscle as myoglobin and

Fe containing enzymes as:Fe containing enzymes as:

catalase ,cytochrome ,mitochondrialcatalase ,cytochrome ,mitochondrialdehydrogenase.dehydrogenase.

monoamine oxidase, peroxidase, xanthinemonoamine oxidase, peroxidase, xanthineoxidase.oxidase.

--glycerol phosphate dehydrogenase.glycerol phosphate dehydrogenase.


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DIETARY REQUIREMENTSDIETARY REQUIREMENTS

1 mg /kg to a max. of 15 mg /day1 mg /kg to a max. of 15 mg /day

2 mg /kg to a max. of 15 mg /day2 mg /kg to a max. of 15 mg /dayfor the preterm and LBW infants andfor the preterm and LBW infants and

those who have significant perinatalthose who have significant perinatalblood lossblood loss


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Iron deficiency is the most prevalentIron deficiency is the most prevalentsingle deficiency state worldwide.single deficiency state worldwide.

Stores are reduced before deficiency isStores are reduced before deficiency is

diagnosed.diagnosed.

Iron deficiency is not an enoughIron deficiency is not an enough

diagnosisdiagnosis

AA causecause needs to be identified!needs to be identified!


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CAUSES OF IRONDEFICIENCYCAUSES OF IRONDEFICIENCY

Decreased intake .Decreased intake .

Blood loss.Blood loss.

Decreased absorption .Decreased absorption .


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Stages of Iron DeficiencyStages of Iron Deficiency

Iron deficiency is most commonly described asIron deficiency is most commonly described asoccurring inoccurring in three stagesthree stages::

11STST stage:stage: iron depletioniron depletion: a decrease in iron: a decrease in ironstores without any effect on essential body iron.stores without any effect on essential body iron.

22NDND stage:stage: iron deficient erythropoiesisiron deficient erythropoiesis::inadequacy of iron available to bone marrow &inadequacy of iron available to bone marrow &

tissues for normal biochemistry and function.tissues for normal biochemistry and function.

33RDRD last, most severe stage islast, most severe stage is iron deficiencyiron deficiencyanemiaanemia identified by a significant reduction in Hbidentified by a significant reduction in Hblevels and a decrease in MCV.levels and a decrease in MCV.


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Stages of Iron Deficiency and theirStages of Iron Deficiency and their

Detectable Laboratory AbnormalitiesDetectable Laboratory Abnormalities

--Low ferritinLow ferritin--Absent boneAbsent bonemarrow ironmarrow iron

DepletedDepletediron storesiron stores

Stage 1Stage 1

In addition:In addition:

--High TIBCHigh TIBC--Low serum ironLow serum iron--Raised serumRaised serumtransf receptorstransf receptors--Normal HbNormal Hb

Latent ironLatent irondeficiencydeficiency

Stage 2Stage 2

In addition:In addition:

--Low hemoglobinLow hemoglobin

--Low MCVLow MCV

IronIrondeficiencydeficiencyAnemiaAnemia

Stage 3Stage 3


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DiagnosisDiagnosis

Besides the potential gold standard test ofBesides the potential gold standard test ofresponse to iron therapy, and the invasive BMresponse to iron therapy, and the invasive BMexamination, traditional diagnostic tests include:examination, traditional diagnostic tests include:

Peripheral smear, hemoglobin, MCV, and RDW.Peripheral smear, hemoglobin, MCV, and RDW. Serum iron, TIBC, transferrin saturation & serumSerum iron, TIBC, transferrin saturation & serum

ferritin.ferritin. Free erythrocyte zinc protoporphyrin.Free erythrocyte zinc protoporphyrin. GIT assessment & occult blood in stools.GIT assessment & occult blood in stools.

Additionally, there are two newer tests for ironAdditionally, there are two newer tests for irondeficiency:deficiency: soluble transferrin receptor assaysoluble transferrin receptor assayandandreticulocyte hemoglobin content.reticulocyte hemoglobin content.


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Hypochromic Microcytic Anemia, Anisocytosis (variationHypochromic Microcytic Anemia, Anisocytosis (variationin size) & Poikilocytosis (variation in shape).in size) & Poikilocytosis (variation in shape).


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Common Lab tests and cutCommon Lab tests and cut--off values foroff values for

the diagnosis of Fe deficiency in childrenthe diagnosis of Fe deficiency in children

TestTest age (years)age (years) CutCut--off valueoff value

Serum ironSerum iron 11--55 470 ug/dl

> 460 ug/dl> 460 ug/dl

TranferrinTranferrin

SaturationSaturation

11--33

33--55

< 8%< 8%

< 9%< 9%

FE ZincFE ZincProtoporphyrinProtoporphyrin

11--55 > or equal to 90> or equal to 90ug/dl RBCug/dl RBC

Serum ferritinSerum ferritin 11--55


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Common Lab tests and cutCommon Lab tests and cut--off values foroff values for

the diagnosis of Fe deficiency in childrenthe diagnosis of Fe deficiency in children

TestTest age (years)age (years) CutCut--off valueoff value

HematocritHematocrit 11--33

33--55

< 33%< 33%

< 34%< 34%

MCVMCV 11--33

33--55

< 73 fl< 73 fl

< 76 fl< 76 fl

S transf recep.S transf recep. 11--55 >9 mg/l>9 mg/l

MCHCMCHC 11--55 < 32 g/dl< 32 g/dl

Reticulocyte HbReticulocyte Hbcontentcontent

11--55 < 27 pico< 27 pico--gm/cellgm/cell

RDWRDW 11--55 >14.5%>14.5%


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Limitations of Serum IronLimitations of Serum Iron

InterpretationInterpretation1.1. Can not detect the preCan not detect the pre--anemic states ofanemic states offunctional iron deficiency.functional iron deficiency.

2.2. Diurnal variations: Morning levels are generallyDiurnal variations: Morning levels are generallyhigher than afternoon or evening levels.higher than afternoon or evening levels.

3.3. Increased with concomitant acute or chronicIncreased with concomitant acute or chronicinflammation, infection, malignancy, or liverinflammation, infection, malignancy, or liverdisease.disease.

4.4. Varies greatly with lab errors e.g. syringe orVaries greatly with lab errors e.g. syringe or

glass contamination with iron.glass contamination with iron.5.5. Increased with small doses of iron fortifiedIncreased with small doses of iron fortifiedvitamins, or even a single injection of ironvitamins, or even a single injection of irondextran.dextran.


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Serum ferritinSerum ferritin

Good positive but not good negative.Good positive but not good negative. If low, it is a reliable, sensitive, nonIf low, it is a reliable, sensitive, non--invasiveinvasive

parameter for early detection of Fe depletion.parameter for early detection of Fe depletion. In children, the cutIn children, the cut--off value is


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Diagnosis (cont.)Diagnosis (cont.)

IncreasedIncreased (TIBC)(TIBC)> 460 ug/dl is a highly> 460 ug/dl is a highlysensitive and selective for Fe deficiency.sensitive and selective for Fe deficiency.

Transferrin saturationTransferrin saturation < 9 % is diagnostic of< 9 % is diagnostic ofiron deficiency.iron deficiency.

MCVMCV< 76 fl, hypochromic microcytic anemia with< 76 fl, hypochromic microcytic anemia withmarked degree of anisopoikilocytosis, and widemarked degree of anisopoikilocytosis, and wideRDWRDW are highly indicative of Fe deficiency.are highly indicative of Fe deficiency.

Limitation to MCV!Limitation to MCV! CombinedCombined folate deficiencyfolate deficiencyand Fe deficiency canand Fe deficiency can

occur (e.g.occur (e.g. PEMPEM), revealing a population of), revealing a population ofmacrocytes mixed with the hypomacrocytes mixed with the hypo--microcytic cells.microcytic cells. This combination can normalize the MCV. This isThis combination can normalize the MCV. This is

known asknown as Dimorphic blood picture.Dimorphic blood picture.


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Corrected Reticulocyte countCorrected Reticulocyte count

Helps to differentiate between iron def &Helps to differentiate between iron def &thalassemia.thalassemia.

Can be used as a response parameter toCan be used as a response parameter toiron therapy.iron therapy.

To be useful, the reticulocyte count mustTo be useful, the reticulocyte count mustbebe adjustedadjusted for the patient's hematocritfor the patient's hematocritby the following formula:by the following formula:Corrected retic. countCorrected retic. count= Patient retic. x= Patient retic. x

(measured Hct/ Normal Hct)i.e.(pt Hct/45)(measured Hct/ Normal Hct)i.e.(pt Hct/45)

The normal corrected retic is 1The normal corrected retic is 1 -- 2%.2%.


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Red cell distribution width (RDW)Red cell distribution width (RDW)

It is an index of the variation in the size of RBCsIt is an index of the variation in the size of RBCs& can detect subtle degrees of anisocytosis.& can detect subtle degrees of anisocytosis.

Elevated RDW appears to be one of the earliestElevated RDW appears to be one of the earliest

haematological manifestation of iron deficiency.haematological manifestation of iron deficiency. Significance:Significance:

HIGH:HIGH: Fe deficiency.Fe deficiency. NORMAL:NORMAL: Anemia of chronic disease.Anemia of chronic disease.

SLIGHT INCREASE:SLIGHT INCREASE: Thalassemia.Thalassemia. Calculated by the following formula:Calculated by the following formula:

RDW= SD of MCV x 100/MCVRDW= SD of MCV x 100/MCV


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NEW PARAMETERSNEW PARAMETERS


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Serum soluble transferrinSerum soluble transferrin

receptor assayreceptor assay (sTfR)(sTfR)

It detects iron availability at the cellular level &It detects iron availability at the cellular level &increased in iron deficiency.increased in iron deficiency.

High values are present in preHigh values are present in pre--anemic patientsanemic patientswith Fe deficient erythropoiesis or Fe deficiencywith Fe deficient erythropoiesis or Fe deficiencyanemia. Normal range is 3anemia. Normal range is 3--9 mg/l.9 mg/l.

Provides a more stable measurement thanProvides a more stable measurement thantransferrin saturation & affected earlier thantransferrin saturation & affected earlier than

traditional parameters such as MCV or Zntraditional parameters such as MCV or Zn--FEP.FEP.

Unlike serum ferritin,Unlike serum ferritin, (sTfR)(sTfR)remains normal inremains normal inpatients with acute or chronic inflammation orpatients with acute or chronic inflammation orliver disease.liver disease.


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Serum soluble transferrinSerum soluble transferrin

receptor assayreceptor assay (sTfR)(sTfR)

Effective in distinguishing iron deficiencyEffective in distinguishing iron deficiencyanemia from anemia of chronic disease.anemia from anemia of chronic disease.

Limitations:Limitations:

1.1. High cost.High cost.

2.2. Variability with the used lab method.Variability with the used lab method.


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Reticulocyte HemoglobinReticulocyte Hemoglobin

Content (CHr)Content (CHr) (CHr)(CHr) is an early measure of functional ironis an early measure of functional iron

deficiency because the only cells being measureddeficiency because the only cells being measuredare those recently released from the B.M.are those recently released from the B.M.

Very sensitive in detecting recent iron deficiency.Very sensitive in detecting recent iron deficiency.

Can be used to assess therapeutic response toCan be used to assess therapeutic response toiron more quickly than hematocrit measures.iron more quickly than hematocrit measures.

(CHr)(CHr) is a useful, sensitive, earlyis a useful, sensitive, early screeningscreeningtesttest in infants and young children.in infants and young children.

It was determined thatIt was determined that (CHr) < 27 picogm/cell(CHr) < 27 picogm/cellis the optimal cutis the optimal cut--off value to diagnose ironoff value to diagnose irondeficiency.deficiency.


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Differential diagnosis of ironDifferential diagnosis of iron

deficiency anemiadeficiency anemia

First of all, we should investigate for aFirst of all, we should investigate for a possiblepossibleGIT causeGIT cause. (Chronic blood loss, malabsorption,. (Chronic blood loss, malabsorption,or concomitant Hor concomitant H--pylori infection, a recentlypylori infection, a recentlyidentified aggravating factor for Fe deficiency).identified aggravating factor for Fe deficiency).

D.D. includes:D.D. includes:

1.1. -- Thalassemia trait.Thalassemia trait.

2.2. Anemia of chronic disease.Anemia of chronic disease.

3.3. Lead poisoning.Lead poisoning.4.4. Sideroblastic Anemia.Sideroblastic Anemia.

5.5. pyridoxine deficiency.pyridoxine deficiency.


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PROTOPORPHYRINIRON

HAEM GLOBIN+

HAEMOGLOBIN

Fe DEFICIENCY

CHRONIC INF.

MALIGNANCY

SIDEROBLASTIC

ANEMIA

THALASSEMIA

CAUSES OF HYPOCHROMIC MICROCYTIC ANEMIA


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CBC of beta thalassemia trait, low MCV, with less degree of anisocytosis


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Iron DeficiencyIron Deficiency Lead toxicityLead toxicity

Fe def Can lead to Lead poisoning secondary toFe def Can lead to Lead poisoning secondary topicapica:: Iron deficiency enhances uptake of heavy metals.Iron deficiency enhances uptake of heavy metals. Lead is still used in all outside house paint & is highlyLead is still used in all outside house paint & is highly

concentrated in the first few inches of soil (car exhaust)concentrated in the first few inches of soil (car exhaust)Diagnosis of lead poisoning:Diagnosis of lead poisoning: Basophilic stippling of RBCsBasophilic stippling of RBCs

Mild microcytosis.Mild microcytosis.

Markedly high serum free erythrocyte ZnMarkedly high serum free erythrocyte Znprotoporphyrin.protoporphyrin.

Definite diagnosis by measuring serum lead level.Definite diagnosis by measuring serum lead level.Screening is recommended at the age of 1year.Screening is recommended at the age of 1year.


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Basophilic stippling, hypochromic microcyticBasophilic stippling, hypochromic microcyticanemia,anisopoikilocytosis (suggestive of lead poisoning)anemia,anisopoikilocytosis (suggestive of lead poisoning)


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TreatmentTreatment OralOralferrousferrous preparations(Fe sulphate,preparations(Fe sulphate,

gluconate, orfumarate) (6 mg/kg/ day)gluconate, orfumarate) (6 mg/kg/ day)

Oral iron failure ?!Oral iron failure ?!

Incorrect diagnosis (eg, thalassemia trait, or anemiaIncorrect diagnosis (eg, thalassemia trait, or anemia

of chronic disease)of chronic disease) Poor compliance.Poor compliance.

Ongoing blood loss (Ankylostoma, hiatal hernia,Ongoing blood loss (Ankylostoma, hiatal hernia,Meckel's div., Piles, Cow milk allergy etc.)Meckel's div., Piles, Cow milk allergy etc.)

Malabsorption: inflammatory bowel disease, CeliacMalabsorption: inflammatory bowel disease, Celiac

Concomitant nutritional deficiency (e.g.Folic acid)Concomitant nutritional deficiency (e.g.Folic acid)

Concomitant HConcomitant H--pylori infection.pylori infection.


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Concluding RemarksConcluding Remarks

Errors in the diagnosis and treatment ofErrors in the diagnosis and treatment ofironiron--deficiency anemia involve severaldeficiency anemia involve severalareas in history, physical examination &areas in history, physical examination &

laboratory investigations.laboratory investigations. Anemia is a sign, not a disease.Anemia is a sign, not a disease.

Anemia is a dynamic process includingAnemia is a dynamic process includingdifferent stages.different stages.

Most importantlyMost importantly, the diagnosis of iron, the diagnosis of irondeficiency anemia mandatesdeficiency anemia mandates further workfurther work--upup to detect the cause.to detect the cause.


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THANK YOU...THANK YOU...

Fe Deficiency

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