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Iron Deficiency Anemia
Iron deficiency
• Neurocognitive effects
– developmental deficits: motoric, mental & cognitive
dysfunctio
– Pica
• Epithelial changes:
– GIT abnormalities, flattened & atrophic lingual
papillae,
– Koilonychia, dry skin
– angular stomatitis, glossitis
• Anemia
Intestinal iron absorption
• non-heme iron
• plants source: beans,
– dark green leafy vegetables
(spinach, kangkung)
– Fortified cereals, rice, enriched
whole-grain
– phytates /tannin, high gastric pH:
 absorption
– Ascorbic acid:  absorption
• heme iron >>
– Animal source: beef,
chicken, fish, cow’s milk
– More readily absorbed
Iron transport
Regulation of iron absorption and exportation by enterocytes.
Both heme and non-heme iron are absorbed by specific pathways, including
divalent metal transporter-1 (DMT-1) and heme carrier protein (HCP1), in
association with the ferrireductase, duodenal cytochrome B (Dcytb).
www.servier.fr/servier-medical-art).
Iron Requirements
• Infants & children
– <6 mo: 0.27 mg/day
– 7 mo - 1 year: 11 mg/day
– 1 - 3 years: 7 mg/day
– 4 - 8 years: 10 mg/day
Food and Nutrition Board at the Institute of Medicine
• Males
– 9 to 13 years: 8 mg/day
– 14 to 18 years: 11 mg/day
• Females
– 9 to 13 years: 8 mg/day
– 4 to 18 years: 15 mg/day
Epidemiology - IDA
SKRT 2001
• Infant 0-6 mo: 61,3%
• Infant 6-12 mo: 64,8%
• Toddler <5 yr: 48,1%.
SKRT 2007
• Toddler: 40-45%
USA, 2000
• Age 1-2 yr: 7 %
• Age 3-4 yr: 5%
Age %
12-59 mo 28,1
5-14 year 26,4
15-24 year 18,4
Riskesdas 2013
Etiology
 Increased demands
o Growth during infancy & childhood
o Treatment with erythropoiesis-stimulating agents
 Limited external supply
o Poor intake
o Inappropriate diet with deficit in bioavailable iron &/or ascorbic acid
o Malabsorption
 Gastric resection
 Helicobacter pylori infection (even without significant bleeding)
 Malabsorption syndromes (Crohn disease and coeliac disease)
o Drug interference (gastric anti-acid agents & antisecretory drugs)
 Increased losses
o Phlebotomy
o Haemorrhage: surgery, trauma, GIT /respiratory tract bleeding
Munoz, M.et al. (2011).. Journal of Clinical Pathology, 64, 287
Etiology
• Blood loss
– GASTROINTESTINAL BLOOD LOSS
• Epistaxis, Gastritis, Ulcer, Meckel’s diverticulum
• Milk-induced enteropathy
• Parasitosis, Varices, Tumor, polyps
• Inflammatory bowel disease
• Arteriovenous malformation
• Colonic diverticula
– VAGINAL BLOOD LOSS
• Increased menstrual flow, Tumor
– URINARY BLOOD LOSS
• Chronic infection, Tumor
– PULMONARY BLOOD LOSS
• Tuberculosis, Bronchiectasis
Anemia (WHO)
• 12-59 month Hb <11,0 g/dL
• 6-12 year Hb <12,0 g/dL
• Male ≥15 year Hb <13,0 g/dL
• Female 15-49 year Hb <12,0 g/dL.
Clinical manifestations
• nonspecific
• symptoms secondary to anemia.
– fatigue, lassitude, pallor, generalized lack of energy
– tachycardia, short breath, poor capillary refilling,
heart failure
• Symptoms secondary to iron deficiency
– Neurological effects
– Mental/psychological: pica,
– Epithelial defects: dry skin, koilonichia, brittle hair
Clinical manifestation
Rare
• Haemodynamic instability
• Syncope • Koilonychia
• Plummer-Vinson syndrome
Very frequent
• Pallor (45–50%)
• Fatigue (44%)
• Dyspnea (40%)
• Headache (63%)
Frequent
• Diffuse & moderate alopecia (30%)
• Atrophic glossitis (27%)
• Restless legs syndrome (24%)
• Dry & rough skin
• Dry & damaged hair
• Cardiac murmur (10%)
• Tachycardia (9%)
• Neurocognitive dysfunction
• Angina pectoris
• Vertigo
Glossitis
Stomatitis
angularis
Diagnosis
Stadium III: iron deficiency anemia
Stadium II
Iron deficiency
Stadium I:
Prelatent iron deficiency
Ferritin 
Serum iron 
TIBC , Sat.
transferrin 
CHr 
+
Hb  Ht 
MCV, MCH 
Labs
• Anemia: Hb , Ht 
• Blood smear
– Microcytic (low MCV)
– Hypochromic (low MCH)
– Pencil cell, target cell
– No hemolysis
https://i2.wp.com/www.stepwards.com/wp-
content/uploads/2016/01/4045_full.jpg
Hb (g/dL) Ht (%) MCV (fL)
Age (yr) Mean
Lower
Limit Mean
Lower
Limit Mean
Lower
Limit
0.5-1.9 12.5 11.0 37 33 77 70
2-4 12.5 11.0 38 34 79 73
5-7 13.0 11.5 39 35 81 75
8-11 13.5 12.0 40 36 83 76
12-14
Female 13.5 12.0 41 36 85 78
Male 14.0 12.5 43 37 84 77
15-17
Female 14.0 12.0 41 36 87 79
Male 15.0 13.0 46 38 86 78
Normal Mean & Lower Limits for Hb, Ht, MCV
Nathan and Oski’s Hematology of Infancy and Childhood 7th ed. 2009
Boy, 5 yr
Hb: 7,2 g/dL
Ht: 21,5 %
Leukosit: 6500/uL
Eritrosit: 2,9 juta/uL
Trombosit 210000/uL
MCV: 74 fL (78-98)
MCH: 22 pg (25-35)
MCHC: 30 g/dL (31-37)
MCV: {Ht/RBC} x 10
MCH: {Hb/RBC} x 10
Labs
• Iron status
– serum iron 
– transferrin saturation
– TIBC 
– Ferritin 
– sTfr 
Low erythropoiesis
• Reticulocyte 
• CHr 
https://courses.washington.edu/conj/bess/iron/ironfig.png
Algorithm diagnosis
(modified from Weiss and Goodnough
(2005)
soluble form of transferrin
receptor (sTfR): total amount of
cell surface transferrin receptors
: IDA
: low erythroid progenitor
Treatment
1. Iron therapy
– Oral
– intravenous
2. Causal treatment
Treatment
Iron therapy
1. Elemental iron 4-6 mg/kg/day
– Empty stomach
– High iron dietary uptake
– Avoid tea, coffee, antacid, H2 antihistamine
blocker, proton pump inhibitor
2. Ascorbic acid supplementation
3. Folic acid supplementation (female teenager)
4. Treat the primary illness
• Iron preparation
– Ferrous sulfate (20% elemental iron)
– Ferrous gluconate (15% elemental iron)
– Elemental iron
• Continue therapy 2 months after anemia
resolved : iron storage
Parenteral iron therapy
Indications:
• oral iron is poorly tolerated;
• rapid replacement of iron stores is needed;
• gastrointestinal iron absorption is
compromised;
• erythropoietin therapy is necessary,
particularly in renal dialysis patients.
Am Fam Physician. 2013 Jan 15;87(2):98-104.
Treatment failure
• Noncompliance
• Insufficient dose / duration of therapy
• Inhibitors of iron absorption/utilization
– Antacids, Histamine H2 blockers, proton pump inhibitors
– Lead, aluminum intoxication (hemodialysis patients)
– Chronic inflammation, Neoplasia
• Primary illness??? Ongoing blood loss
• Incorrect diagnosis
– Thalassemia disorder, anemia of chronic disease
REKOMENDASI IDAI
tentang Suplementasi Besi untuk Bayi dan Anak
Suplementasi besi diberikan kepada semua
anak, dengan prioritas usia balita (0-5 tahun),
terutama usia 0-2 tahun.
REKOMENDASI IDAI
–BBLR (<2500 g): 3 mg/kgBB/hari untuk usia 1
bl-2 th (dosis max 15 mg/hari, dosis tunggal).
–Bayi cukup bulan: 2 mg/kgBB/hari usia 4 bl-2 th
–Usia 2-12 tahun (usia sekolah): 1
mg/kgBB/hari, 2x/minggu selama 3 bl
berturut-turut/thn
–Usia 12-18 th (remaja): 60 mg/hari atau 1
mg/kgBB/hari, 2x/mgg selama 3 bl berturut-
turut/th (remaja perempuan + 400 µg asam
folat).
Take home messages
• Check any risk of iron deficiency
– Diet history, risk factors
– Good clinical exams
• Supplementation (rekomendasi IDAI)

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ADB.pptx

  • 2.
  • 3. Iron deficiency • Neurocognitive effects – developmental deficits: motoric, mental & cognitive dysfunctio – Pica • Epithelial changes: – GIT abnormalities, flattened & atrophic lingual papillae, – Koilonychia, dry skin – angular stomatitis, glossitis • Anemia
  • 4. Intestinal iron absorption • non-heme iron • plants source: beans, – dark green leafy vegetables (spinach, kangkung) – Fortified cereals, rice, enriched whole-grain – phytates /tannin, high gastric pH:  absorption – Ascorbic acid:  absorption • heme iron >> – Animal source: beef, chicken, fish, cow’s milk – More readily absorbed
  • 5. Iron transport Regulation of iron absorption and exportation by enterocytes. Both heme and non-heme iron are absorbed by specific pathways, including divalent metal transporter-1 (DMT-1) and heme carrier protein (HCP1), in association with the ferrireductase, duodenal cytochrome B (Dcytb). www.servier.fr/servier-medical-art).
  • 6. Iron Requirements • Infants & children – <6 mo: 0.27 mg/day – 7 mo - 1 year: 11 mg/day – 1 - 3 years: 7 mg/day – 4 - 8 years: 10 mg/day Food and Nutrition Board at the Institute of Medicine • Males – 9 to 13 years: 8 mg/day – 14 to 18 years: 11 mg/day • Females – 9 to 13 years: 8 mg/day – 4 to 18 years: 15 mg/day
  • 7. Epidemiology - IDA SKRT 2001 • Infant 0-6 mo: 61,3% • Infant 6-12 mo: 64,8% • Toddler <5 yr: 48,1%. SKRT 2007 • Toddler: 40-45% USA, 2000 • Age 1-2 yr: 7 % • Age 3-4 yr: 5% Age % 12-59 mo 28,1 5-14 year 26,4 15-24 year 18,4 Riskesdas 2013
  • 8. Etiology  Increased demands o Growth during infancy & childhood o Treatment with erythropoiesis-stimulating agents  Limited external supply o Poor intake o Inappropriate diet with deficit in bioavailable iron &/or ascorbic acid o Malabsorption  Gastric resection  Helicobacter pylori infection (even without significant bleeding)  Malabsorption syndromes (Crohn disease and coeliac disease) o Drug interference (gastric anti-acid agents & antisecretory drugs)  Increased losses o Phlebotomy o Haemorrhage: surgery, trauma, GIT /respiratory tract bleeding Munoz, M.et al. (2011).. Journal of Clinical Pathology, 64, 287
  • 9. Etiology • Blood loss – GASTROINTESTINAL BLOOD LOSS • Epistaxis, Gastritis, Ulcer, Meckel’s diverticulum • Milk-induced enteropathy • Parasitosis, Varices, Tumor, polyps • Inflammatory bowel disease • Arteriovenous malformation • Colonic diverticula – VAGINAL BLOOD LOSS • Increased menstrual flow, Tumor – URINARY BLOOD LOSS • Chronic infection, Tumor – PULMONARY BLOOD LOSS • Tuberculosis, Bronchiectasis
  • 10. Anemia (WHO) • 12-59 month Hb <11,0 g/dL • 6-12 year Hb <12,0 g/dL • Male ≥15 year Hb <13,0 g/dL • Female 15-49 year Hb <12,0 g/dL.
  • 11. Clinical manifestations • nonspecific • symptoms secondary to anemia. – fatigue, lassitude, pallor, generalized lack of energy – tachycardia, short breath, poor capillary refilling, heart failure • Symptoms secondary to iron deficiency – Neurological effects – Mental/psychological: pica, – Epithelial defects: dry skin, koilonichia, brittle hair
  • 12. Clinical manifestation Rare • Haemodynamic instability • Syncope • Koilonychia • Plummer-Vinson syndrome Very frequent • Pallor (45–50%) • Fatigue (44%) • Dyspnea (40%) • Headache (63%) Frequent • Diffuse & moderate alopecia (30%) • Atrophic glossitis (27%) • Restless legs syndrome (24%) • Dry & rough skin • Dry & damaged hair • Cardiac murmur (10%) • Tachycardia (9%) • Neurocognitive dysfunction • Angina pectoris • Vertigo
  • 14.
  • 15. Diagnosis Stadium III: iron deficiency anemia Stadium II Iron deficiency Stadium I: Prelatent iron deficiency Ferritin  Serum iron  TIBC , Sat. transferrin  CHr  + Hb  Ht  MCV, MCH 
  • 16. Labs • Anemia: Hb , Ht  • Blood smear – Microcytic (low MCV) – Hypochromic (low MCH) – Pencil cell, target cell – No hemolysis https://i2.wp.com/www.stepwards.com/wp- content/uploads/2016/01/4045_full.jpg
  • 17. Hb (g/dL) Ht (%) MCV (fL) Age (yr) Mean Lower Limit Mean Lower Limit Mean Lower Limit 0.5-1.9 12.5 11.0 37 33 77 70 2-4 12.5 11.0 38 34 79 73 5-7 13.0 11.5 39 35 81 75 8-11 13.5 12.0 40 36 83 76 12-14 Female 13.5 12.0 41 36 85 78 Male 14.0 12.5 43 37 84 77 15-17 Female 14.0 12.0 41 36 87 79 Male 15.0 13.0 46 38 86 78 Normal Mean & Lower Limits for Hb, Ht, MCV Nathan and Oski’s Hematology of Infancy and Childhood 7th ed. 2009
  • 18. Boy, 5 yr Hb: 7,2 g/dL Ht: 21,5 % Leukosit: 6500/uL Eritrosit: 2,9 juta/uL Trombosit 210000/uL MCV: 74 fL (78-98) MCH: 22 pg (25-35) MCHC: 30 g/dL (31-37) MCV: {Ht/RBC} x 10 MCH: {Hb/RBC} x 10
  • 19. Labs • Iron status – serum iron  – transferrin saturation – TIBC  – Ferritin  – sTfr  Low erythropoiesis • Reticulocyte  • CHr  https://courses.washington.edu/conj/bess/iron/ironfig.png
  • 20. Algorithm diagnosis (modified from Weiss and Goodnough (2005) soluble form of transferrin receptor (sTfR): total amount of cell surface transferrin receptors : IDA : low erythroid progenitor
  • 21. Treatment 1. Iron therapy – Oral – intravenous 2. Causal treatment
  • 22. Treatment Iron therapy 1. Elemental iron 4-6 mg/kg/day – Empty stomach – High iron dietary uptake – Avoid tea, coffee, antacid, H2 antihistamine blocker, proton pump inhibitor 2. Ascorbic acid supplementation 3. Folic acid supplementation (female teenager) 4. Treat the primary illness
  • 23. • Iron preparation – Ferrous sulfate (20% elemental iron) – Ferrous gluconate (15% elemental iron) – Elemental iron • Continue therapy 2 months after anemia resolved : iron storage
  • 24. Parenteral iron therapy Indications: • oral iron is poorly tolerated; • rapid replacement of iron stores is needed; • gastrointestinal iron absorption is compromised; • erythropoietin therapy is necessary, particularly in renal dialysis patients.
  • 25. Am Fam Physician. 2013 Jan 15;87(2):98-104.
  • 26. Treatment failure • Noncompliance • Insufficient dose / duration of therapy • Inhibitors of iron absorption/utilization – Antacids, Histamine H2 blockers, proton pump inhibitors – Lead, aluminum intoxication (hemodialysis patients) – Chronic inflammation, Neoplasia • Primary illness??? Ongoing blood loss • Incorrect diagnosis – Thalassemia disorder, anemia of chronic disease
  • 27. REKOMENDASI IDAI tentang Suplementasi Besi untuk Bayi dan Anak Suplementasi besi diberikan kepada semua anak, dengan prioritas usia balita (0-5 tahun), terutama usia 0-2 tahun.
  • 28. REKOMENDASI IDAI –BBLR (<2500 g): 3 mg/kgBB/hari untuk usia 1 bl-2 th (dosis max 15 mg/hari, dosis tunggal). –Bayi cukup bulan: 2 mg/kgBB/hari usia 4 bl-2 th –Usia 2-12 tahun (usia sekolah): 1 mg/kgBB/hari, 2x/minggu selama 3 bl berturut-turut/thn –Usia 12-18 th (remaja): 60 mg/hari atau 1 mg/kgBB/hari, 2x/mgg selama 3 bl berturut- turut/th (remaja perempuan + 400 µg asam folat).
  • 29. Take home messages • Check any risk of iron deficiency – Diet history, risk factors – Good clinical exams • Supplementation (rekomendasi IDAI)

Editor's Notes

  1. Regulation of iron absorption and exportation by enterocytes. Both heme and non-heme iron are absorbed by specific pathways, including divalent metal transporter-1 (DMT-1) and heme carrier protein (HCP1), in association with the ferrireductase, duodenal cytochrome B (Dcytb). Within the cell, iron can be stored within the ferritin molecule. The metal is exported by the protein ferroportin (FPN1), and transported into the blood by transferrin. In presence of hepcidin, ferroportin is internalized and degradated. Thus, iron exportation is blocked. Inversely, in the absence of hepcidin, ferroportin is maintained on the cell membrane, and iron transportation is facilitated (illustrations used elements from Servier Medical Art: www.servier.fr/servier-medical-art).