Iron Deficiency Anemia in Adolescent*

*Definition Hemoglobin concentration is abnormally low age, gender, sea-level altitude

as a result of several situation chronic infection hereditary blood conditions deficiency : folic acid, B12, B6, C, protein, iron, zinc etc.THERE IS NO DOUBT THAT IRON DEFICIENCY IS THE CAUSE OF MOST ANEMIA

*PrevalenceThe Indonesian National Household Health Survey in 2001**: 30 % of adolescent girls (10-19 yrs) were anemic (Hgb level < 120 g/L) smaller studies : 22 44% Infants (9 24 months of age) Adolescent girls 9% toddlers 11% adolescent females < 1% adolescent males} Iron def.* * LookerAC et.al. JAMA. 1997;277:973-976 ** Parmesih dkk. Departemen Kesehatan . 2003 *** Collaboration between Institute for Health Management, Pune & International Center for Research on Women, Washington, 2000-2003 3 % toddlers 3 % adolescent females < 1% adolescent malesIDA*India : 60 70% adolescent females*** USA :

Nutritional and metabolic aspects of iron Iron is one of the most common elements in the Earth crust, yet iron deficiency is the most common cause of anemia, affecting about 500 million people worldwide.This is because the body has a limited ability to absorb iron and excess loss of iron as a result of hemorrhage is frequent.

Nutritional and metabolic aspects of iron

Distribution of body iron (%)

Hb65Ferritin & Hemosiderin30Myoglobin 3,5Heme-enzymes (e.g. cytochromes, catalase, peroxidase,Flavoproteins) 0,5Transferrin-bound iron 0,1

Daily iron cycle

Dietary ironIron is present in food as ferric hydroxides, ferric-protein and heme-protein complexes.Both the iron content and the proportion of iron absorbed differ from food to food; in general, meat-in particular liver-is a better source than vegetables, eggs or diary foods.The average Western diet contains 10 15 mg iron daily from which only 5 - 10% is normally absorbed. The proportion can be increased to 20 30% in iron deficiency or pregnancy but even in these situations most dietary iron remain unabsorbed.

Iron absorption__________________________________________________________________________Factors favouring absorptionFactors reducing absorption__________________________________________________________________Heme ironInorganic ironFerrous form (Fe2+)Ferric form (Fe3+)Acids (HCl, vitamin C)Alkalis-antacids, pancreatic secretionsSolubilizing agents (e.g. sugars, amino acid)Precipitating agents-phytates, phosphatesIron deficiencyIron excessIneffective erythropoiesisDecreased erythropoiesisPregnancyInfectionHereditary hemochromatosisTeaIncreased expression of DMT-1 andDecreased expression of DMT-1 and ferroportin in the duodenal enterocytes ferroportin induodenal enterocytesIncreased hepcidin___________________________________________________________________

A model of the pathways of iron absorption by the entrocyteGut lumenEnterocyteBloodApicalBasolateralHemeHemeHeme oxygenaseFe2+Intracellular iron poolFe2+FerritinFerroportinHephaestinHFETfR1TfR2TransferrinFe-transferrinFe2+Fe3+Fe-transferrinTransferrinEndocytosisFe2+DMT1Fe2+Fe3+Fe2+DMT1DcytbHeme-receptorFe2+The figure shows uptake of ionic iron and heme iron from the gut lumen and transfer of iron to blood. DMT1, divalent metal transporter 1; HFE, hemochromatosis protein, TfR 1, transferrin receptor 1; TfR2, transferrin receptor 2.

Estimated daily iron requirements (mg/day)Adult male0.5 10.5 1Postmenopausal female0.5 1 0.5 1Menstruating female*0.5 10.5 1 1 2Pregnant female*0.5 11 2 1.5 3Children (average)*0.5 0.6 1.1Female (age 1215)*0.5 10.5 1 0.6 1.6 2.6

*These groups are more likely to develop iron deficiency. Therefore these groups are particularly likely to develop iron deficiency if there is additional iron loss or prolonged reduced intake. Puberty: Dietary, Bleeding, Increased demands (i) menstruation; (ii) each 1 kg of weight gain = 80 mL blood and requires 45 mg of iron Urine, MensesPregnancy GrowthTotal sweat, feces

*Diagnosis

*Clinical Aspects The signs & symptoms depend on the degree of deficiency and the rate at which the anemia develops.

Iron deficiency or mild-to-moderate anemia may show few, if any, signs or symptoms.

Iron Deficiency Anemia--- Pallor- Fatigue- Exercise intolerance- Tachycardia- Cardiac dilatation- Systolic murmurs- Splenomegaly- Irritability, anorexia-Even severe anemia may be asymptomatic

-45 % were diagnosed incidentally!

*Consequences systematic condition anemia impaired exercise capacity functional alteration behavior and cognitive performance lower mental and motor developmental test scores cognitive achievement lower standardized math scores} School-aged children* adolescent*(early childhood)* Halterman JS et.al. Pediatrics 2001;107:1381-1386

*Mechanisms Uncertain Several hypothesis: altered neurotransmitter function diminished activity of several enzymes (monoamine oxidase, aldehyde oxidase) reduced activity of dopamine Dd2 receptor myelination may also be affected a brief period of ID during the brain growth spurt causes a lasting deficit in brain iron, which persists into adulthood despite correction of the anemia !!

To describe the degrees of Iron Deficiency Total body iron ferritin

Transport iron transferrin saturation

Serum iron

Hematologic markers

Biochemical markers

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*Normal mean values for hemoglobin (Hb), hematocrit, (Hct) and MCVData from Oski FA, Brugnara C, Nathan DG. A diagnostic approach to the anemic patient. In: Nathan DG, Orkin SE, Ginsburg D, Look AT, editors. Nathan and Oskis hematology of infancy and childhood. Philadelphia: WB Saunders Company; 2003, p. 409

Hematologic markers for identifying iron deficiencyHematologic NormalIronIron deficiencyIron markerdepletionwithout anemiadeficiencyanemiaHemoglobin(g/dL)

MCV (fL)

RDW (%)

CHr (pg)

ReticulocytesMCV: mean corpuscular volume; RDW: red blood cell distribution width; CHr: reticulocyte hemoglobin content; N=normal; I=increased; D=decreasedN : 11

N : 70 100

N : < 15

N : 29

N: 1 5

N : 11

N : 70 100

N : < 15

N : 29

N : 1 5

N : 11

N : 70 100

N : < 15

D : < 29

N : 1 5 D : < 11

D : < 70

I : 15

D : < 29

D : < 1*Values for ages 6 mo to 2 y

*

*Making the Diagnosis : Microcytic

*Making the Diagnosis Gold standard : a direct test-bone marrow biopsy with Prussian blue stainingToo invasive for routine use.

Generally are more readily available and less expensive.

Detect iron deficiency before the onset of anemia. ! CHr may help diagnose iron deficiency before anemia is present Hematologic tests are based on RBC features Biochemical tests are based on iron metabolism

Because many of these tests lack specificity, several tests are often used Differential diagnosis of microcytosis MarkerIron def.Chronic Both Thalassemia Lead poisoningInflammation Combination HbMCVRDWFEPSerum ironTIBCFerritinsTfRsTfR/log ferritin Cytokine CRPHb Electro.RRIIRIRII

NNNR

RRN/INR

IINR

R

R/NN/II

IINRRNNN/INII/NI

NNA

NNNINNNR=reduced; I=increased; N=normal;A=abnormalWeiss G, Goodnough LT, 2005; Hoffbrand AV et.al.,2006; Oski FA, 1993 *

The diagnosis of moderately severe iron-deficiency anemia is easyThe diagnosis of mild forms of iron deficiency anemia may present a greater challenge* the laboratory tests may be less reliable the values of iron-deficient and iron-sufficient persons overlap considerably

In the appropriate clinical setting : The important of iron intake history *

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*Treatment of Iron Deficiency

Determining the cause and correcting the abnormality

Growth spurts, poor dietary patterns, menstrual losses, and benign gastrointestinal bleeding Oral iron supplementation usually replaces stores most efficiently

Iron Supplementation RBC Transfusion

*Oral Supplementation Iron salts: ferrous sulfate inexpensive effective therapy for iron deficiency frequently complain of gastrointestinal discomfort, constipation, bloating, stool discoloration making its use unacceptable to many children: 3 to 6 mg/kg/day three-times-a-day dosing or single-dose daily regimen adolescents : 60 mg/dose (qd or bid) on an empty stomach at night Ascorbic acid enhances iron absorption

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*Reasons for Poor Response to Oral Iron

*Oral iron is not toleratedParenteral ironErythrocyte transfusion should be used only if the anemia is causing severe cardiovascular compromise; hypervolemia and cardiac dilatation may result from rapid correction of the anemia !!

*Parental Iron Replacement iron dextran, iron gluconate, iron sucrose Indication

An anaphylactic reaction

Dose (mL) = 0.0442 x (Desired Hb Observed Hb) x Lean body weight + (0.26 x Lean body weight)Oral iron is poorly tolerated rapid replacement of iron stores is needed gastrointestinal iron absorption is compromised erythropoietin therapy is necessary (in renal dialysis patients)

Regular screening AdolescentsAAP :

CDC : screening all adolescents once between ages 11 and 21 years

screening menstruating females annually

annual screening of adolescent females if their risk is increased; otherwise, anemia should be screened for every 5 to 10 years

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*Iron Replacement in InfantsBreast milk should be provided for at least 5 to 6 months. Iron supplementation of 1 mg/kg/day should be provided to infants who are exclusively fed breast milk beyond 6 months of age. Infants who are not breast-fed should be nourished with an iron-supplemented formula (at least 12 mg/L) until the end of the first year of life. Iron-enriched cereals should should be among the first foods introduced with a solid diet. Cows milk should be avoided during the first year because it contains substances that chelate iron and it sometimes induces occult gastrointestinal hemorrhage in young infants.

The Committee on Nutrition of the American Academy of Pediatrics

The evidence is clear that early diagnosis and adequate treatment of IDA are critical to prevention or reversal of any negative medical or behavioral effects.

*Pediatricians must screen for this common nutritional deficiently actively and accurately.

Thank you andhave a nice day

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