Studi Kasus

• B, seorang bayi perempuan 10 bulan, dibawa ke poliklinik karena

panas dan batuk pilek.
• Bayi tampak pucat dan kurang aktif.
• Riwayat bayi mendapat ASI eksklusif.
• Saat ini bayi mendapat MPASI dan ASI.
• Selama ini bayi sulit makan.

Anemia Defisiensi Besi - dr Lucia, SpA 2

ANEMIA DEFISIENSI BESI
dr. Lucia Pudyastuti Retnaningtyas, SpA
BLOK HEMATO-IMUNOLOGI
Fakultas Kedokteran Universitas Surabaya
Referensi
• Buku Ajar Hematologi-Onkologi Anak, IDAI 2012
• Nelson textbook of pediatric
• Harrison textbook of medicine 18th ed

Anemia Defisiensi Besi - dr Lucia, SpA 4

Anemia Hemolitik- dr Lucia, SpA 5
CAPAIAN PEMBELAJARAN
• Mahasiswa mampu menjelaskan dan menganalisis:
• Definisi
• Epidemiologi
• Etiologi
• Patofisiologi
• Gejala dan Tanda
• Diagnosis banding
• Diagnosis
• Terapi
• Prognosis
dari Anemia Defisiensi Besi

Anemia Defisiensi Besi - dr Lucia, SpA 6

NUTRIEN ESENSIAL
Besi
Asam folat
Vit B 12
Protein
eritrosit
Perkembangan optimal
Eritropoetik

Anemia Defisiensi7Besi - dr Lucia, SpA

ANEMIA
• a condition in which hemoglobin (Hb) concentration and/or red blood
cell (RBC) numbers are lower than normal and insufficient to meet an
individual’s physiological need
• WHO criteria (2011) :
1. Anemia is still the most common
problems in the world
2. 50% of anemia is caused by IDA
3. IDA affects child's growth and
development
4. Long-term side effects are
irreversible
Anemia Defisiensi Besi - dr Lucia, SpA 8
ANEMIA DEFISIENSI BESI
• Definisi: Anemia yg disebabkan oleh kurangnya besi yg diperlukan utk
sintesis hemoglobin
• Paling sering ditemukan di dunia ➔ negara sedang berkembang
• Kemampuan ekonomi terbatas
• Masukan protein hewani terbatas
• Infestasi parasite → mslh endemik
• 30% penduduk dunia menderita anemia, > 1/2nya mrpk ADB
• Di Indonesia, ADB mrpk slh 1 masalah gizi utama (selain kekurangan
kalori-protein, vit A & yodium)

Anemia Defisiensi Besi - dr Lucia, SpA 9

High risk population for iron deficiency

Anemia Defisiensi Besi - dr Lucia, SpA 10

Epidemiologi
• Negara maju : 20%
• Negara berkembang / miskin : 30-80%
( terutama BALITA )

WHO ( INDONESIA )
• 2/3 ibu hamil : Hb rendah
• Kejadian BBLR : 20%

50% Bayi lahir berisiko

Anemia Defisiensi Besi - dr Lucia, SpA 11

 The prevalence of anemia In Indonesia

• The 2013 National Health Survey in Indonesia showed that the prevalence
of anemia in children aged 1–4 years, 5–14 years, and 15–24 years were
28.1%, 26.4%, and 18.4%.
• Iron deficiency (ID) is the most common micronutrient deficiency in the
world and the most common cause of anemia
• A study in 50 school-aged Indonesian children (6–12 years) found the
prevalence of IDA to be 32%
Anemia Defisiensi Besi - dr Lucia, SpA 12
Pentingnya Besi

• Elemen (unsur) yang penting:

• Komponen fungsional utama pada transportasi O2 & molekul
tersimpan (Hb, Mb)
• Berbagai enzym red-oks (cytochromes)
• Produksi berbagai metabolit
• Untuk pertahanan (NADPH oxidase)
• Fungsi kognitif

Anemia Defisiensi Besi - dr Lucia, SpA 13

• Besi sebagai mikronutrien berperan esensial pada berbagai proses
biokimia penting.
• Kebutuhan besi seperti nutrien lain meningkat selama masa
pertumbuhan cepat dan diferensiasi khususnya pada masa janin akhir
dan neonatus.
• Semua besi, yang jumlahnya sekitar 1 gram pada saat lahir, berasal
dari ibu yang ditransfer melalui plasenta.
• Transfer besi yang tidak cukup membuat homeostasis besi pada masa
ini buruk sehingga mengakibatkan perkembangan terganggu.

Anemia Defisiensi Besi - dr Lucia, SpA 14

METABOLISME BESI
Zat besi
Fe+++
Dalam makanan

HCL
Fe+++
lambung
Ferritin
Vit C
usus Fe++ Hemosiderin
Myoglobin
Transferin enzim
Sintesa Hb
( sumsum tulang )
Anemia Defisiensi15
Besi - dr Lucia, SpA
 Keseimbangan besi
(Iron Balance)
Diatur secara ketat (strictly regulated)
• Kehilangan minimal 1 – 2 mg/hari
• Jumlah besi dalam tubuh sekitar 3 – 4 gram
• Kebutuhan besi untuk eritropoiesis hanya 20
mg/hari
• Absorpsinya bergantung pada besi dalam
makanan
• Mekanisme homeostasis besi penting untuk
mencegah absorpsi yang berlebihan dalam
duodenum dan mengatur pengeluaran besi dari
RES
• Besi toksik untuk sel manusia; dibutuhkan oleh
mikroorganisme patogen

Anemia Defisiensi Besi - dr Lucia, SpA 16

Apa yang kita ketahui tentang keseimbangan besi?
• Absorpsi besi dalam usus meningkat pada:
• Cadangan besi menurun
• Aktivitas eritropoiesis meningkat
• Anemia
• Hipoksia
• Absorpsi besi dalam usus menurun pada peradangan (inflamasi)
• Pada haemochromatosis herediter ada peningkatan absorpsi besi
relatif terhadap cadangan besi dalam tubuh

Anemia Defisiensi Besi - dr Lucia, SpA 17

KEBUTUHAN TERHADAP BESI

• 5 – 10 mg / hari
• Meningkat pada :
• Bayi
• Prasekolah Pertumbuhan
• Remaja / pubertas meningkat
• Penyakit infeksi

Sangat sedikit
Pengeluaran besi Deskuamasi: sel-sel kulit, sal cerna
Keringat, urine & empedu
Anemia Defisiensi18
Besi - dr Lucia, SpA
FAKTOR PENYEBAB

INTAKE KURANG
Gizi buruk
Makanan tambahan

ABSORBSI KURANG
Diare KEBUTUHAN MENINGKAT
Sindr malabsorbsi Pertumbuhan
Gizi buruk Infeksi kronis / berulang

SINTESIS BERKURANG PENGELUARAN MENINGKAT

Perdarahan: Infestasi cacing
Kongenital hipo-
amubiasis
transferinemia

Anemia Defisiensi19
Besi - dr Lucia, SpA
Patofisiologi
• Gangguan sintesis Hb akibat defisiensi Fe
• Penurunan survival precursor eritroid & eritrosit
• ADB ➔ hasil akhir keseimbangan negatif besi yg berlangsung lama
• Bl menetap → cadangan besi trs berkurang

Anemia Defisiensi Besi - dr Lucia, SpA 20

 Derajat Defisiensi Besi

PRELATEN LATEN LANJUT

=Iron deficient erythro- ( ANEMIA)
= Iron depletion
poietin
= Storage iron deficiency
=Iron limited erythro- =Iron deficiency
Cadangan besi kurang
poiesis anemia
Besi serum masih normal
Cadangan tdk ada Cadangan tdk ada
Feritin kurang
Besi serum kurang Besi serum rendah
Belum anemia (Hb msh
Feritin kurang Feritin sangat
normal)
SI ↓, Transferin ↓ kurang
TIBC ↑, FEP ↑ Timbul gejala (Hb ↓)
Belum anemia
21

Anemia Defisiensi Besi - dr Lucia, SpA

Anemia Defisiensi Besi - dr Lucia, SpA 22
Anemia Defisiensi Besi - dr Lucia, SpA 23
MANIFESTASI KLINIS
• Pucat Kelainan non hematologi akibat
• Anoreksia kekrgan besi:
• Iritabel • Perubahan epitel: Koilonikia,
atrofi papilla lidah, perubahan
• Takikardi mukosa lambung & usus halus
• Dilatasi jantung • Intoleransi thd latihan
• Murmur sistolik • Termogenesis tdk normal
• Daya tahan tbh thd infeksi ↓
• Splenomegali

Anemia Defisiensi Besi - dr Lucia, SpA 24

PEMERIKSAAN LABORATORIUM
• Darah rutin (Hb, PCV, leukosit, trombosit)
• Indeks eritrosit
• Retikulosit
• Morfologi darah tepi
• Status besi (Fe serum, TIBC, saturasi transferrin, FEP, ferritin)
• Apus sumsum tulang

Anemia Defisiensi Besi - dr Lucia, SpA 25

• Hb & PCV ↓
• Indeks eri MCV, MCH, MCHC turun sejajar dg pe ↓ Hb
• Pd infestasi cacing → eosinophilia
• Trombosit meningkat

Anemia Defisiensi Besi - dr Lucia, SpA 26

MDT: hipokromik, mikrositik, anisositosis, poikilositosis
(sel pensil, sel target, ovalosit, mikrosit, sel fragmen)

Anemia Defisiensi Besi - dr Lucia, SpA 27

• Status besi: Fe serum ↓, TIBC ↑
• Fe serum: utk menentukan jumlah besi yg terikat pd
transferrin
• TIBC: utk mengetahui jumlah transferin yg berada dlm
sirkulasi drh
• Saturasi transferrin= perbandingan Fe serum dg TIBC x 100%
• ➔ menggambarkan suplai besi ke eritroid sutul & sbg penilaian
terbaik utk menget pertukaran besi antr plasma & cadangan besi
dlm tbh
• ST < 16% : suplai besi tdk adekuat
• ST 7-16%: ADB (+) bl + MCV yg rendah
• ST < 7%: Dx ADB dpt ditegakkan

Anemia Defisiensi Besi - dr Lucia, SpA 28

• Kecukupan penyediaan besi ke eritroid sutul: FEP (Free Erythrocyte
Protoporphyrin)
• >100ug/dl: ADB (+) → Deteksi ADB lbh dini
• FEP ↑ & ST ↓ ➔ tanda ADB progresif
• Kadar ferritin serum: mengetahui cadangan besi tubuh (<10-12ug/dl
→ penurunan cad besi)
• Apus sutul: hyperplasia sistem eritropoitik, berkrgnya hemosiderin
➔ pewarnaan Prussian blue

Anemia Defisiensi Besi - dr Lucia, SpA 29

Effect on Iron Deficiency
• Poor growth
• Anemia
• Decreased cell-mediated immune response
• Impaired neurodevelopment

Anemia Defisiensi Besi - dr Lucia, SpA 30

Anemia Defisiensi Besi - dr Lucia, SpA 31
Anemia Defisiensi Besi - dr Lucia, SpA 32
Anemia Defisiensi Besi - dr Lucia, SpA 33
Laboratory parameter for iron status

Anemia Defisiensi Besi - dr Lucia, SpA 34

ID investigation with current laboratory parameter

Anemia Defisiensi Besi - dr Lucia, SpA 35

AAP recommendation to diagnose ID & IDA

Anemia Defisiensi Besi - dr Lucia, SpA 36

RET-He
• reflects the amount of iron available for Hb production in the bone
marrow

Anemia Defisiensi Besi - dr Lucia, SpA 37

Practical approach to diagnosis(1)

Anemia Defisiensi Besi - dr Lucia, SpA 38

Practical approach to diagnosis (2)

Anemia Defisiensi Besi - dr Lucia, SpA 39

DIAGNOSIS
• Hasil temuan anamnesis, pemeriksaan fisik & lab
• Bbrp kriteria dx ADB
• WHO:
1. Kadar Hb kurang dr normal sesuai usia
2. Konsentrasi Hb eritrosit rata2 (MCHC) < 31 g/dL (N: 32-35 g/dL)
3. Kadar Fe serum < 50ug/dL (N: 80-180ug/dL)
4. Saturasi transferrin < 15% (N: 20-50%)

Anemia Defisiensi Besi - dr Lucia, SpA 40

Cara lain:
• Trial pemberian preparat besi selama 3-4 minggu
• Bl Hb naik 1-2g/dL ➔ ADB (+)

Anemia Defisiensi Besi - dr Lucia, SpA 41

DIAGNOSIS BANDING
• Semua keadaan yg memberi gambaran anemia hipokrom mikrositik
➔ talasemia minor & anemia penyakit kronis (APK), Lead poisoning &
anemia sideroblastic
➔ anamnesis, DP, lab

1. Talasemia minor & ADB ➔ lihat jumlah eritrosit

• Talasemia → meningkat meskp sdh anemia
• ADB→ turun sejajar dg HB & MCV
➔ Cara mudah: MCV : jumlah eritrosit (<13: talasemia) ➔ Mentzer Index

Anemia Defisiensi Besi - dr Lucia, SpA 42

2. Anemia karena Penyakit Kronis (APK): normokrom normositer
• Terganggunya mobilisasi besi & makrofag oleh transferrin

3. Lead poisoning → basophyllic stippling, FEP meningkat

Anemia Defisiensi Besi - dr Lucia, SpA 43

 Anemia

MCV?

Microcytic (<78) Normal (78-100) Macrocytic (>100)

Reticulocyte Reticulocyte Reticulocyte

count? count? count?

Low or N High Low or N High Low or N High

Anemia of Bilirubine, LDH,

Thallasemia Follat/B12 Hemolytic
Iron chronic disease Haptoglobin?
Aplastic anemia deficiency anemia
deficiency
Sickle cell disease
Abnormal
↑Bilirubine,
Normal
Leukemia ↑LDH,
Aplastic anemia ↓Haptoglobin
Renal Failure
Drug Toxicity
Hemolytic anemia
Acute blood Hemolytic Uremic
loss
Systematic Approach of ANEMIA dr Lucia Syndrome
SpA 44
Sickle Cell Disease
Systematic Approach of ANEMIA dr Lucia SpA 45
Anemia Defisiensi Besi - dr Lucia, SpA 46
Systematic Approach of ANEMIA dr Lucia SpA 47
Anemia Defisiensi Besi - dr Lucia, SpA 48
PENATALAKSANAAN
• Pengobatan kausal
• Pemberian preparat besi :
• Ferro sulfat, fosfat, fumarat
• Suplementasi besi
• Fortifikasi besi
• Transfusi darah

Anemia Defisiensi Besi - dr Lucia, SpA 49

Oral Iron Treatment

• Oral Fe binds to plasma transferrin after its

release from the basolateral membrane of
intestinal cells Well tolerated
• Chemical compounds for each oral Fe Cheap Safe and
preparation are different: Effective
• Divalent (Fe2+ or ferrous)
• Trivalent (Fe3+ or ferric)
• Formed in iron salt or iron polysaccharide
complexes ➔ ferrous gluconate, ferrous
fumarate, ferrous sulfate
Anemia Defisiensi Besi - dr Lucia, SpA 50
 Treatment of Oral Iron

Doses
• Common Dosage: 3-6 mg/kg
• Maximal Dose: 150 mg/daily
Adminitration
• Single Daily dose versus a 3-times-daily
dose of ferrous sulfate drops over 2
months resulted in a similar rate of
successful treatment of anemia, without
side effects
• It is thought that iron consumed one day
before disrupts the absorption of iron
consumed next day, makes mucosal
inhibition. Therefore, every other day or
weekly treatments is also being
discussed, but limited study conducted in
childhood daily vs alternate day
administration or weekly

Anemia Defisiensi Besi - dr Lucia, SpA 51

• Preparat besi parenteral • Transfusi darah
• Intravena, nyeri, mahal • Tidak sering dilakukan
• Tdk lbh baik dari oral • Indikasi khusus :
• Parenteral is a safe and effective • Keadaan umum yang buruk
means to treat iron deficiency in • Infeksi berat ( Bronkopneumonia )
children who cannot receive/do not • Gagal jantung
response to oral iron due to • Pemberian transfusi: sedikit dan
intolerance, poor adherence or iron berulang
malabsorption
• Severe anemia
• Iron dextran/iron sucrose
• Evalutaion valuation of treatment is
usually performed at 4– 12 weeks
after the initial infusion

Anemia Defisiensi Besi - dr Lucia, SpA 52

 PENCEGAHAN
Pd awal masa kehidupan: Upaya umum:
• ASI eksklusif • Tingkatkan konsumsi Fe (+ vit C & A)
• Tunda PASI smp 1 tahun (krn risiko • Fortifikasi bahan makanan
perdrhan sal cerna tersamar) • Suplementasi
• MPASI mengandung besi + kaya
askorbat
• Ibu hamil ***
• Suplementasi zat besi pd bayi
kurang bulan (mulai 2 minggu) dan
cukup bulan (mulai 4 bulan)
• Pemakaian PASI yg mengandung
besi

Anemia Defisiensi Besi - dr Lucia, SpA 53

IRON SUPPLEMENTATION
• Three categories in which iron supplementation are indicated:
1. Low birth weight or preterm baby
2. Pregnant mother
3. Reproductive women
• Hemoglobin content is low in normal infant around 4-6 months as
consequence of:
• decrease or diminish iron pool in the infant (especially in breastfed infants)
• the change of globin chains in which the reducing γ chain is replacing by
increasing β Chain

Anemia Defisiensi Besi - dr Lucia, SpA 54

Pencegahan

Anemia Defisiensi Besi - dr Lucia, SpA 55

Anemia Defisiensi Besi - dr Lucia, SpA 56
Anemia Defisiensi Besi - dr Lucia, SpA 57
Parents Education
• Nutritional education eg. restrict cow’s milk consumption maximum
16-20 oz daily
• Possibility of Side Effect (upset stomach, nausea, diarrhea, faintness,
vomiting, dark stool, constipation)
• Importance of Compliance
• Iron supplement should be given between meals and preferably with
juice because absorption of ferrous sulfate is increased when it is
given with juice rather than with milk or other fluids
• For maximum absorption of iron, administration 30–45 minutes
before meal or 2 hours after meal is highly recommended.

Anemia Defisiensi Besi - dr Lucia, SpA 58

Monitoring Oral Iron Treatment Response
Clinically Definition of refractoriness to oral iron
therapy - less than 1 g/dl Hb increase after 4
• Signs observed in patients including weeks of oral iron therapy, provided patient
restlessness, loss of appetite and compliance is adequate and acquired forms of
GI disorders have been ruled out
fatigue rapidly disappear with
initiation of treatment.
Increase in reticulocytes was evident at 3
days, while Hb increase appeared at 2
weeks (doubtfull diagnosis/severe anemia)
Laboratory Peak Reticulocyte Count: 7-10 day
Increase hemoglobin : 14-21 day
• Increase of reticulocyte Normal Hb and Hct: 2months
Normal iron store: 4-5 month
• Increase hemoglobin

Anemia Defisiensi Besi - dr Lucia, SpA 59

PROGNOSIS
• Baik, bl penyebabnya hanya kekurangan zat besi
• Gejala & manifestasi klinis lainnya akan membaik dg pemberian
preparat besi
• Jika gagal:
• Dx salah
• Dosis obat tdk adekuat
• Preparat Fe tdk tepat & kadaluarsa
• Perdrhan yg tdk teratasi
• Perdrhan tdk tampak, berlangsung menetap
• Disertai penyakit yg mempengrauhi absorpsi & pemakaian besi (Infeksi,
keganasan, penyakit hati, ginjal, tiroid, def vit B12, asam folat)
• Ggn absorpsi sal cerna (missal pemberian antasida berlebihan pd ulkus
peptikum → pengikatan besi)
Anemia Defisiensi Besi - dr Lucia, SpA 60
Anemia Defisiensi Besi - dr Lucia, SpA 61