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Anemia
Definition:
reduction in red cell mass or
blood hemoglobin concentration
below 2 standard deviations (SD)
Hemoglobin(g/dl)
Mean
-2SD
16.5
13.5
18.5
14.5
17.5
13.5
16.5
12.5
14.0
10.0
11.5
9.0
11.5
9.5
12.0
10.5
12.5
11.5
13.5
11.5
14.0
12.0
14.5
13.0
14.0
12.0
15.5
13.5
MCV(fl)
Mean
-2SD
108
98
108
95
107
88
105
86
104
85
96
77
91
74
78
70
81
75
86
77
90
78
88
78
90
80
90
80
Caroline Hasting,2002
3
Anemia
(WHO,1976):
- 6 month <6 year: <11 g/dL
- 6 year 12 year : <12 g/dl
(WHO/UNICEF,1997)
-
Prevalence :
The most common cause of anemia worlwide
An estimated 30% of the worlds population :
4.5 billion anemic
500 600 million Iron def. anemia
...Prevalence
Prevalence
Prevalence
Anemia
Anemia
Developed countries
0-4 tahun : 20.1%
5-14 tahun: 5.9%
Developing
countries
0-4 tahun: 39.0%
5-14 tahun: 48.1%
WHO, 2001
7
Prevalence
Prevalence
ofofIDID&&IDA
IDA
UK Infants:
Asian IDA 39%
Afro-Caribbean 20%
White 16%
USA:
1-2 years ID 9%; IDA 3%
adolescent girls ID 9%; IDA 2%
ETIOLOGY
I. Deficiency intake :
Dietary (milk 0,5-1.5 mg iron/L)
II. Increased demand :
Growth (low birth weight, premarurity, low-birth-weight
twins or multiple births, adolescence, pregnancy)
Cyanotic Congenital heart disease
III. Blood loss :
A. Perinatal
1. Placental
Transplacental bleeding into maternal circulation
Retroplacental (e.g,premature placental separatio )
Intraplacental
Fetal blood loss or before birth (e.g, placenta previa)
Fetofetal bleeding in monochrorionic twins
Placental abnormalities
10
2.Umbilicus
- Ruptured umbilical cord (e.g, vasa previa) and
other
umbilical cord abnormalities
- Inadequate cord tying
- Postexchange transfusion
B. Postnatal
1.Gastrointestinal tract
- Primary iron deficiency anemia resulting in gut
alteration
with blood loss agravating existing iron deficiency
- Hypersensitivity to whole cows milk?
- Anatomic gut lesions, exudative enteropathy
caused by undelying bowel disease
- Gastritis from aspirin, adrenocortical steroids,
indomethacin, phenylbutazone
- Intestinal parasites( e.g, hookworm /Necator
Americanus)
- Henoch-Scholein Purpura
.
11
12
13
14
Iron cycle
15
BLUE OCEAN
16
16
BLUE OCEAN
17
17
Pathophysiology
Stages Iron Deficiency
18
Diagnostic Approach
Anamnesis
Physical examination findings
Laboratory examination
Korones D, 1999
Glader B, 2007
19
History taking
Clinical Manifestation
Pallor ,jaundice
Tachycardia,postural hypotension
Anorexia
Angular stomatitis
Glossitis
Spoon nail
Pica (pagophagia)
Effect on neurologic and intellectual function:
attention span, allertness,learning
Nathan Oski,2003
Lanzkowsky P,2005
Glader B, 2007
21
CLINICAL
MANIFESTATIONS
Consequences of anemia :
Mild moderate iron def. ( Hb 6-10 g/dl)
compensatory mechanism (+)
Severe iron deficiency (Hb < 5 g/dl) :
Fatigue, listlessness, irritability, anorexia,
tachycardia, cardiac dilatation & systolic
murmurs.
Advanced iron deficiency :
Pale, plump, & petulant .
22
CLINICAL MANIFESTATIONS
Nonhematologic consequence :
Pica :
Phagophagia (compulsive eating of ice)
Geophagia : interest in dirt consumption risk for
parasitic infestation & lead poisoning)
Ephitelial changes : Koilonychia, atrophy of lingual
papil
Exercise intolerance
Behavioral changes
Abnormal thermogenesis
Altered host response
RL,edisi ke 7
Miller Rd,Baehner
23
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LABORATORIUM FINDINGS
Hemoglobin(Hb) is below the acceptable level for age
Red cell indices :
- / normal MCV,MCHC and MCHC for age
- RDW
Blood smear :
- Red cells : hypochromic, microcytic with
anisocytosis and
poikilocytosis Hb concentration
25
Lab.finding
Consentration Ferritin < 12 mg/dl
Serum iron and iron saturation percentage iron
metabolism :
Serum iron :
TIBC :
Transferrin sat. (ratio SI : TIBC) :
Serum transferrin receptor levels ( STfR )
Red blood cell zinc protoporphyrin/ heme ratio
- Bone marrow iron is insufficient to support
heme synthesis
- Zinc protoporphrin relative to heme increases
- Zinc substituses for iron in protoporphyrin IX
26
Wide
FEP*
Ferritin
Trial of Iron
*Also elevated in lead poisonin. Do serum lead level (if clinical indicated)
27
28
Poikylocytosis
Anisocytosis
29
DIFFERENTIAL DIAGNOSIS
1.Thalassemia trait
2.Anemia of chronic diseases
3.Lead poisoning
30
Serum iron
TIBC
Transferrin saturation
FEP
Serum ferritin
N
N
N
N
N
Anemia
N/
N/
Lukens,1995
31
DIAGNOSIS
32
...Diagnosis
Diagnosis
35
Classification of Anemia
Screening
Hb
CBC:
MCV- MCH
Microcytic,
hypochromic
Normocytic,
normochromic
MCV <80 fL
MCV 80-95 fL
MCH <27 pg
MCH 27 pg
Hemolytic anemia
Thalassemia
Lead poisoning
Sideroblastic anemia
Macrocytic
Peripheral blood
smear
Reticuloyte index
MCV >95 fL
Megaloblastic:
vitamin B12
deficiency or folat
Mixed deficiency
Non-megaloblastic:
alcohol, liver
disease,
myelodysplasia
Aplastic anemia
Renal disease
36
Clinical management
Diagnosis
Assessment of underlying cause: dietary
history, birth history, presence of
abnormal bleeding , family history , past
medical/surgery history
Investigation and treatmentof any
underlying cause found : dietary advice
,endoscopy
Iron therapy
37
Iron therapy
Oral therapy
Dose: 3 mg/kg/day (2 devided doses)max
180mg
Duration: 6-8 weeks after Hb and the red cell
indices return normal
The following preparations provide 3 mg of
elemental iron: 15 mg of ferrous sulfate,
9 mg of ferrous fumarate,
26 mg of ferrous gluconate,
9 mg of ferrous succinate,
17 mg of ferrous glycine sulfate,
21 mg of sodium iron edetate
38
Hematologic response:
a. Reticulocyte increase within 5-10 days following
initiation of iron therapy
b. Hb concentration increase
Failure to respond to oral iron :
The following reasons should be considered:
a. Poor compliance
b. Inadequate iron dose
c. Ineffective iron preparation
d. Persistent or unrecognized blood loss
e. Incorrect diagnosis
f. Coexistent disease (infection ,inflammatory bowel
disease,malignant disease,hepatic or renal disease)
g. Impaired GI absorption
39
Parenteral Therapy
1.Intramuscular
Iron dextran ( 50 mg elemental iron/ml) /im , with dose :
Normal Hb - initial Hb x Blood volume(ml)x 3.4 x 1.5
100
It is safe,effective ,well tolerated in infants with acute illness
Indications :
- Noncompliance with oral of iron
- Severe bowel disease(e.g,inflammatory
bowel disease)
- Chronic hemorrhage (e.g, hereditary
telangiectasia, menorrhagia)
- Acute diarrheal disorder in under privileged
populations with iron deficiency anemia
40
2.Intravenous
.Sodium ferric gluconate (Ferrlecit)
.Iron(III) hydroxyde sucrose comple (Venofer)
Anemia associated with renal failure and hemodialysis
Dose: 1 4 mg/Kg/week
41
Transfusion therapy
Packed red cell
Severe anemia (Hb < 5 g/dl) requiring correction more
rapidly especially when signs of cardiac dysfunction are
present
42
Nutritional Counseling
Maintain breast feeding for at least 6 months
iron fortified (6-12mg/L) infant formulas after
weaning from the breast and in non-breast fed
infants until 1 year of age
Iron-fortified cereal from 6 months to 1 year
Suplemental iron
Facilitator of iron absorption: vitamin C-rich
foods(citrus,tomatoes,potatoes),meat,fish,poultry
Eliminated inhibitors of iron absorption such
tea,phosphate ,phytates common in vegetarian diets
43
Iron,mg
Unit
Milk 0.5-1.5
Liter
Eggs 1.2
Each
Cereal,fortified
3.0-5.0
Ounce
Vegetables(starched)
Yellow
0.1-0.3
Ounce
Green
0.3-0.4
Meats(strained)
Beef, lamb, liver
0.4-2.0
Ounce
Pork, liver, bacon
6.6
Ounce
Fruits(strained)
0.2-0.4
Ounce
Lanzkowsky,2005
44
Increased absorption
Vit C: citrus, tomatoes, potatoes,
Solutes
Sugars
meat, fish,poultry
Hydrochloric acid
Decreased absorption
Antacids
Pancreatic secretions
Hypochlorhydria
Phytates
Phosphates
Blackwell,2006
45
Prevention
1.Encouragement of breast feeding (BF)
2.Use of iron-fortified infant formula after weaning
BF or non-BF
3.Delay in the introduction of whole cows milk to 1
year of age
4.Use iron fortified infant cereals and ascorbic
acid-rich food solid food are introduced at 6
months
5.Supplemental iron
46
..Prevention
Iron supplemental:
Exclusive breast feeding beyond 6 month : 1
mg/Kg/d
Low birth weight infants:
a. 1.5-2.0 kg
: 2 mg/kg/day
b. 1.0-1.5 kg
: 3 mg/kg/day
c. <1 kg
: 4 mg/kg/day
47
MEGALOBLASTIC ANEMIA
Definition :
Presences of megaloblasts in the bone marrow
and macrocytes in the blood
Causes of Megaloblastosis
I.
II.
III.
49
Megaloblastic anemia
50
Reticulocytes
51
FOLIC ACID
DEFICIENCY
52
53
7.
8.
9.
10.
Whipple disease
Intestinal Lymphoma
Broad spectrum antibiotics
Drugs associated with impaired absorption/utilization of folic
acid (e.g, Dilantin, primidone, metformin, ethanol,barbiturates)
11. Post bone marrow transpntation ( total body irradiation, drugs,
intestinal GVH disease)
III. Increased requirements
A. Rapid growth (e.g, prematurity, pegnancy)
B. Cronic hemolytic anemia ( thalassemia major)
C. Dyserythropoietic anemias
D. Malignant disease(e.g, lymphoma, leukemia)
E. Hypermetabolic states (e.g, infection, hyperthyroidism)
D. Extensive skin disease (e.g, Dermatitis herpetiformis,psosiasis)
G. Cirrhosis
H. Post bone marrow transplantation
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55
B. Acquired
1. Impaired utilization of folate
a. Folate antagonis (drugs that are
dihydrofolate reductase inhibitors,e.g,
methotrexate, pyrimethamine,
trimethoprim, pentamidine)
b. Vit B12 deficiency
c. Alcoholism
d. Liver disease (acute and cronic)
e. Other drugs
V. Increased excretion (e.g, chronic dialysis, vit
B12 deficiency, liver disease, heart disease)
Lanzkowsky,2005
56
II.
4.
5.
6.
Diagnosis
1. Red cell changes:
a. Hemoglobulin : reduced
b. Red cell indices: MCV, MCHC normal
c. RDW:
d. Blood smear: macrocytes and macro ovalocytes, anisocytosis,
poikilocytosis, Howell-Jolly bodies
2. White bood cell count: 1500-4000/mm3, neutrophils large and
hypersegmentation
3. Platelet count: 50.000-180.000/mm3
4. Bone marrow : megaloblastic
5. Serum vit.B12 level: <80 pg/mL
6. Serum levels < 3 ng/mL, red cell folate levels: 74-640ng/mL
7. Urinary excretion of orotic acid to exclude orotic aciduria
8. Deoxyuridine suppression test
63
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65
66
Treatment
Vitamin B12 deficiency
Prevention
Prophylactic vit B12 :total gastrectomy,Ileal resection
Active treatment
- First treated : 6 series im or sc Hydroxocobalamin
- Low doses of Cobalamin 10 g/day o 0.2 g/Kg sc for 2
days reticulocytosis
- Maintenance :1000g Hydroxocobalamin every 3 months
- Food supplemented with Cobalamin
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