HEMATOLOGY -ONCOLOGY Div.

Child Health Depart.- School of Medicine
University of Sumatera Utara

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Anemia
Definition:
reduction in red cell mass or
blood hemoglobin concentration
below 2 standard deviations (SD)

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Table 1.Normal red blood cell values in
children
Age
Birth (cord blood)
1-3 days(capillary)
1 week
2 week
1 month
2 month
3-6 month
0.5-2 years
2-6 years
6-12 years
12-18 years, female
12-18 years, male
18-49 years, female
18-49 years, male

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
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1976): .6 month – <6 year: <11 g/dL .1997) - 6 month – <5 year <11 g/dL >6 year – 14 year <12 g/dL adult (man) <13 g/dL adult (woman) <13 g/dL adult (pregnant woman) <11 g/dL 4 .6 year – 12 year : <12 g/dl (WHO/UNICEF.Anemia (WHO.

IRON DEFICIENCY ANEMIA • Definition : Anemia resulting from lack of sufficient iron for synthesis of hemoglobin.  Prevalence : – The most common cause of anemia worlwide – An estimated 30% of the world’s population : • 4. anemia 5 .5 billion  anemic • 500 – 600 million Iron def.

17 yrs) – Indonesia : 25 – 35% (aged 5 yrs) 6 ..Prevalence – North American (1970) : 30 ..75% of child 1 – 2 years of age – Israelli : 25% females (aged 16 ..

0% 5-14 tahun: 48. 2001 7 .1% 5-14 tahun: 5.Prevalence Prevalence Anemia Anemia Developed countries 0-4 tahun : 20.9% Developing countries 0-4 tahun: 39.1% WHO.

IDA 2% Indonesia (SKRT 2001): Developing countries Adolescent girls 21-35% <5 years 48.1% <1 year 55% 8 .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%.

Etiology of iron deficiency 9 .

g.ETIOLOGY I.premature placental separatio ) • Intraplacental • Fetal blood loss or before birth (e. placenta previa) • Fetofetal bleeding in monochrorionic twins • Placental abnormalities 10 . adolescence. premarurity. Perinatal 1.5 mg iron/L) II. Blood loss : A. Placental • Transplacental bleeding into maternal circulation • Retroplacental (e. Increased demand : • Growth (low birth weight. pregnancy) • Cyanotic Congenital heart disease III.5-1. low-birth-weight twins or multiple births. Deficiency intake : • Dietary (milk 0.g.

g. hookworm /Necator Americanus) .Anatomic gut lesions. vasa previa) and other umbilical cord abnormalities .Gastrointestinal tract .Umbilicus .Postexchange transfusion B.Inadequate cord tying . exudative enteropathy caused by undelying bowel disease .Intestinal parasites( e.Henoch-Scholein Purpura . 11 .Primary iron deficiency anemia resulting in gut alteration with blood loss agravating existing iron deficiency . indomethacin. phenylbutazone . adrenocortical steroids.Hypersensitivity to whole cow’s milk? .g.Gastritis from aspirin.Ruptured umbilical cord (e.2. Postnatal 1.

postgastrectomy. Heart: intracardiac myxomata. Helicobacter pylori infection associated chronic gastritis Lanzkowsky. valvular prostheses or patches 7. Nose: recurrent epistaxis 5. nephrotic syndrome. severe prolonged diarrhea. Imparied absorption Malabsorption syndrome. hematuria. Goodpasture sydrome. defective iron mobilization with IgA deficiency 4.2005 12 . Extracorporeal: hemodialysis. Hepatobililiary system: hematobilia 3. trauma IV.hemosiderinurias-chronic intravascular hemolysis 8. Uterus: menstrual loss 6. Kidney: microangiopathic hemolytic anemia.2. inflammatory bowel disease. Lung: Pulmonary hemosiderosis. celiac disease.

Key Functional of Iron 13 .

Iron Status in Human Body 14 .

Iron cycle 15 .

BLUE OCEAN 16 16 .

BLUE OCEAN 17 17 .

Pathophysiology Stages Iron Deficiency 18 .

2007 19 . 1999 Glader B.Diagnostic Approach • Anamnesis • Physical examination findings • Laboratory examination Korones D.

History taking • • • • • • • • Pallor.dizziness Shortness of breath Arthralgia 20 .floppiness :time of onset Fatigue.lethargy Poor feeding Irritability Abdominal pain Headache .

learning Nathan Oski.jaundice Tachycardia. allertness.postural hypotension Anorexia Angular stomatitis Glossitis Spoon nail Pica (pagophagia) Effect on neurologic and intellectual function: attention span.2003 Lanzkowsky P. 2007 21 .Clinical Manifestation • • • • • • • • Pallor .2005 Glader B.

plump. • Advanced iron deficiency : – Pale. 22 . & petulant . cardiac dilatation & systolic murmurs. tachycardia. ( Hb 6-10 g/dl)  compensatory mechanism (+) • Severe iron deficiency (Hb < 5 g/dl) : – Fatigue. anorexia.…CLINICAL MANIFESTATIONS Consequences of anemia : • Mild – moderate iron def. irritability. listlessness.

…CLINICAL MANIFESTATIONS Nonhematologic consequence : – Pica : • Phagophagia (compulsive eating of ice) • Geophagia : interest in dirt consumption risk for parasitic infestation & lead poisoning) – Ephitelial changes : Koilonychia.Baehner 23 . atrophy of lingual papil – Exercise intolerance – Behavioral changes – Abnormal thermogenesis – Altered host response RL.edisi ke 7 Miller Rd.

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MCHC and MCHC for age .Red cells : hypochromic. microcytic with anisocytosis and poikilocytosis→ Hb concentration ↓ • Reticulocyte count: N/slightly increased • Pleated count : Thrombocytopenia.LABORATORIUM FINDINGS • Hemoglobin(Hb) is below the acceptable level for age • Red cell indices : . thrombocytosis • Free erythrocyte protoporphyrin: > 100 µg/dl 25 .RDW ↑ • Blood smear : .↓/ normal MCV.

Bone marrow iron is insufficient to support heme synthesis .finding • Consentration Ferritin < 12 mg/dl • Serum iron and iron saturation percentage iron metabolism : – Serum iron :  – TIBC :  – Transferrin sat.…Lab.Zinc substituses for iron in protoporphyrin IX 26 . (ratio SI : TIBC) :  • Serum transferrin receptor levels ( STfR ) ↑ • Red blood cell zinc protoporphyrin/ heme ratio .Zinc protoporphrin relative to heme increases .

Do serum lead level (if clinical indicated) 27 .The diagnosis of microcitic anemia using MCV and RDW MCV Low RDW Narrow Hb elektroforesis MCV on Parents Wide FEP* Ferritin Trial of Iron *Also elevated in lead poisonin.

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Poikylocytosis Anisocytosis 29 .

Anemia of chronic diseases 3.Thalassemia trait 2.DIFFERENTIAL DIAGNOSIS 1.Lead poisoning 30 .

1995 31 .Diffrential Diagnosis Hypochrom Microcytic Anemia Lab findings chronic disease MCV ↓ Serum iron ↓ TIBC ↑ Transferrin saturation↓ FEP ↑ Serum ferritin ↓ IDA Thalassemia Minor ↓ N N N N N Anemia N/↓ ↓ ↓ N/↓ ↑ ↑ Lukens.

Serum iron < 50 Ug/dl (N: 80-180 ug/dl) 4.35%) 3. Hb concentration < normal (age dependent) 2. Transferrin sat. Hematocrit < 31% ( N: 32 . < 15 (N: 20-50%) 32 .DIAGNOSIS Criteria of IDA by WHO : 1.

serum ferritin dan FEP) 33 .Diagnostic Criteia of IDA (Cook dan Monsen): • • • • Hypochrom microcytic anemia Transferrin saturation <16% FEP (free erythrocyte portoporphyrin) >100 ug/dL Serum ferritin <12 ug/dL For diagnosis purpose: it is required minimum 2 of 3 criteria (TS.

• This procedure is very practical. Hb level is increased 1-2 g/dL → it is confirmed for IDA.Diagnosis Alternative way to determine IDA: Trial of iron supplementation  Important to know subclinical IDA with monitor hemoglobin respons (increased hemoglobin level). sensitive dan economical especially for children at high risk of IDA • If with iron supplementation 3 mg iron/kgBW/day.. 34 . 3-4 weeks...

MCH. < 16% 5. TIBC  . Serum ferritin :  4. Transferrin sat.Microcytic hypochromic . FEP :  3. Bone marrow : Iron (-) /  35 .…Diagnosis Criteria of IDA by Lanzkowsky : 1.MCV. Response to iron preparation 6. Serum ferritin  . Peripheral smears : .RDW > 17% 2. MCHC :  .

normochromic MCV <80 fL MCV 80-95 fL MCH <27 pg MCH ≥ 27 pg Iron deficiency anemia Hemolytic anemia Thalassemia Anemia chronic disease Anemia chronic disease Anemia due to bleeding 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.Classification of Anemia Screening Hb ↓ CBC: MCV.MCH Microcytic. myelodysplasia Bone marrow failure Aplastic anemia Renal disease 36 . hypochromic Normocytic.

Clinical management • Diagnosis • Assessment of underlying cause: dietary history.endoscopy • Iron therapy 37 . past medical/surgery history • Investigation and treatmentof any underlying cause found : dietary advice . presence of abnormal bleeding . birth history. family history .

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. 17 mg of ferrous glycine sulfate. 9 mg of ferrous succinate. 26 mg of ferrous gluconate. 21 mg of sodium iron edetate 38 . 9 mg of ferrous fumarate.

Persistent or unrecognized blood loss e.inflammatory bowel disease. Coexistent disease (infection . Poor compliance b. Impaired GI absorption 39 .Hematologic response: a.hepatic or renal disease) g. Incorrect diagnosis f. Ineffective iron preparation d.malignant disease. Hb concentration increase Failure to respond to oral iron : The following reasons should be considered: a. Reticulocyte increase within 5-10 days following initiation of iron therapy b. Inadequate iron dose c.

Severe bowel disease(e. hereditary telangiectasia.g.Chronic hemorrhage (e.Acute diarrheal disorder in under privileged populations with iron deficiency anemia 40 .effective .initial Hb x Blood volume(ml)x 3.5 100 It is safe.g. with dose : Normal Hb . menorrhagia) .Parenteral Therapy 1.Noncompliance with oral of iron .well tolerated in infants with acute illness Indications : .4 x 1.Intramuscular Iron dextran ( 50 mg elemental iron/ml) /im .inflammatory bowel disease) .

Iron(III) hydroxyde sucrose comple (Venofer)  Anemia associated with renal failure and hemodialysis  Dose: 1 – 4 mg/Kg/week 41 .2.Sodium ferric gluconate (Ferrlecit) .Intravenous .

Transfusion therapy Packed red cell Severe anemia (Hb < 5 g/dl) requiring correction more rapidly especially when signs of cardiac dysfunction are present 42 .

fish.phosphate .phytates common in vegetarian diets 43 .meat.poultry  Eliminated inhibitors of iron absorption such tea.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).

5-1.4 Meats(strained) Beef. bacon 6.3-0.2 Each Cereal. liver.0 Ounce Pork.2005 44 .1-0.0 Ounce Vegetables(starched) Yellow 0.3 Ounce Green 0.4-2.Iron Content of Infant Foods Food Iron.0-5.6 Ounce Fruits(strained) 0.2-0. lamb.5 Liter Eggs 1.fortified 3. liver 0.mg Unit Milk 0.4 Ounce Lanzkowsky.

tomatoes.2006 45 . Solutes Sugars meat.poultry Hydrochloric acid  Decreased absorption Antacids Pancreatic secretions Hypochlorhydria Phytates Phosphates Blackwell.Factors affecting iron absorption of nonheme iron from the gastrointestinal tract  Increased absorption Vit C: citrus. fish. potatoes.

Delay in the introduction of whole cow’s milk to 1 year of age 4.Prevention 1.Use of iron-fortified infant formula after weaning BF or non-BF 3.Supplemental iron 46 .Encouragement of breast feeding (BF) 2.Use iron fortified infant cereals and ascorbic acid-rich food  solid food are introduced at 6 months 5.

0 kg : 2 mg/kg/day b..5-2.Prevention Iron supplemental: Exclusive breast feeding beyond 6 month : 1 mg/Kg/d Low birth weight infants: a. 1.5 kg : 3 mg/kg/day c. <1 kg : 4 mg/kg/day 47 . 1.….0-1.

MEGALOBLASTIC ANEMIA Definition : Presences of megaloblasts in the bone marrow and macrocytes in the blood Abnormalities of red blood cell (RBC) morphology and maturation • Etiology : – Deficiency of folic acid – Deficiency Vitamin B12 (Cobalamin) – Inborn errors of metabolism (rarely) 48 .

Inhibitor of ribonucleotide reductase (cytosine arabinoside. Refractory megaloblastic anemia C. Pyrimidine analogues 3.Causes of Megaloblastosis I. Lesch-Nyhan syndrome (adenine responsive) B. hydroxyurea) Lanzkwosky. II. Vit B12 (Cobalamin) deficiency Folate deficiency Miscellaneous A. Congenital familial megaloblastic anemia requiring massive dose of vit B12 and folate 4. especially acute myeloid leukemia 4. Acquired defects in DNA synthesis 1. Liver disease 2. 6 mercaptopurine. Aplastic anemia (constitutional/acquired) 5.g. Drug induced megaloblastosis 1. III.2005 49 . Thiamine. Sideroblastic anemias 3. azathioprine and thioguanine) 2. Congenital disorders in DNA synthesis 1. Orotic aciduria(uridine responsive) 2. Purine analogues (e. Associated with congenital dyserythropoietic anemia 5.responsive megaloblastic anemia 3. Leukemia.

Megaloblastic anemia 50 .

Nucleated RBC of megaloblastic anemia Reticulocytes 51 .

52 .free diet.FOLIC ACID DEFICIENCY – Folic acid : adsorbed in the small intestine – Megaloblastic anemia : occurs after 2 – 3 mo on a folate.

Congenital. Tropical sprue 3. Multiple diverticula of small intestine 5.Causes of Folic Acid Deficiency I Inadequate intake A. isolated defect of folate malabsorption B. Aquired 1. Poverty. Malnutrition (marasmus. Defective absorption A. Partial or total gastrectomy 4. Spesial diets for phenylketonuria or maple syrup urine disease F. Prematurity G. Idiopathic steatorrhea 2. kwasiokor) E. ignorance. faddism B. Regional Ileitis 53 . Goat’s milk feeding (6μg folate/ L) D. Method of cooking (sustained boiling loses 40% folate) C. Post bone marrow transplantion II. Jejunal resection 6.

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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IV. Disorders of folic acid metabolism
A. Congenital
1. Methylenetetrahydrofolate reductase
deficiency
2. Glutamate formiminotransferase deficiency
3. Fuctional N5- methyltetrahydrofolate:
homocysteine methyltransferasedeficiency
4. Dihydrofolate reductase deficiency
5. Methenyl-tetrahydrofalate cyclohydrolase
6. Primary methyl-tetrahydrofolate:
homocysteine methyltransferase deficiency

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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
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eggs. poultry.VITAMIN B12 DEFICIENCY ANEMIA  Derived from cobalamin in food (mainly animal sources) secondary to production by microorganism  Obtained primarily from :  Animal proteins (ie. fish. and dairy)  Plants and vegetables lack the vitamin unless they have been contaminated by soil microorganisms 57 . red meat.

B12 58 .Absorption of vit.

Dientary (<2μg/day): foods fads. Congenital intrinsic deficiency a. Juvenile pernicious anemia with IgA deficiency 5. Failure to secrete intrinsic factor 1. veganism. Inadequate vitamins B12 intake A. Quantitative (biologically inert) 2. Juvenile pernicious anemia ( gastric autoantibodies) with autoimune polyendocrinopaathies 4. Gastrectomy ( partial/ total) 59 . poorly controlled PKU diet B. II. Juvenile pernicious anemia (autoimmune)(gastric atrophy) 3. malnutrition. Corrosives b.Cause of vitamins B12 Deficiency I. Quantitative b. Maternal deficiency leading to B12 deficiency in breast milk Defective vit B12 absorption A. Gastric mucosal disease a.

Diplyllobothrium latum. Ingestion of chelating agents 2. Intestinal resection b.B12 malabsorption : a. Intestinal disease causing generalized malabsorption. Competition for vit B12 a. Giardia lamblia. Failure of absorption in small intestine 1. Neonatal necrotizing enterocolitis 3. Celiac disease. HIV infection j. including vit. Other less specific malabsorption syndromes i.B. Defective cobalamin transport by enterocytes c. Strongyloides stercoralis 60 . Small bowel bacterial overgrowth b. Crohn’n disease c. Long standing medication that decreases gastric acidity k. Pancreatic insufficiency f. Plasmodium falcifarum. Abnormal intrinsik factor b. Tunerculosis of terminal ileum d. Lymphosarcoma of teminal ileum e. Zollinger-Ellison syndrome g. Spesific vit B12 malabsorption a. topical sprue h.

III.B12 metabolism A. Adenosylcobalamin Cb1A and Cb1B diseases 2. Combined adenosylcobalamin and methylcobalamin deficiencies B. Conenital 1. Methylcobalamin deficiency Cb1E and Cb1G diseases 4. Congenital TC II deficiency b. Acquired 1. Disorders of vit. Partial deficiency of TC II IV. Defective vit. Drugs associated with impaired absorption and/or utilization of vitB12 Lanzkowsky.B12 transport a.Protein malnutrition 3. Liver diseases 2. Deficiency of methylmalonyl-CoA mutase 3.2005 61 . Transient deficiency of TC II c.

neurologic disorders. unexplained anemias.loss reflexs. fatigability. prematurity. 6.Clinical Features of cobalamin and folate deficiency 1. hypotonia. 4. irritability. 2. or evidance of neurodevelopmental delay. sore red tounge and glossitis. weakness. apathy. loss of developmental milestones. particulary motor achievements. lethargy. fetal loss Inborn errors of metabolism: failure to thrive. 5.paresthesias Neurologic complications are increased risk of vascular thrombosis due to hyperhomocysteinemia Maternal folate deficiency: neural tube defects. Pallor. episodic or continous diarrhea History: similarly affected sibling or a sibling who died. cytopenias 62 . 3. fetal growth retardation. maternal vit B12 deficiency Vit B12 deficiency: developmental delay. and anorexia.

Howell-Jolly bodies 2. neutrophils large and hypersegmentation 3. Hemoglobulin : reduced b. Red cell changes: a. poikilocytosis.Diagnosis 1. MCHC normal c. Urinary excretion of orotic acid to exclude orotic aciduria 8. anisocytosis.000-180. Platelet count: 50. Red cell indices: MCV↑.000/mm3 4. Bone marrow : megaloblastic 5. Deoxyuridine suppression test 63 . White bood cell count: 1500-4000/mm3.B12 level: <80 pg/mL 6. Serum vit. Blood smear: macrocytes and macro ovalocytes. red cell folate levels: 74-640ng/mL 7. Serum levels < 3 ng/mL. RDW: ↑ d.

Investigated : Ileal disease 7. Schilling excretion test 3. History dietary and previous surgery 2. Schilling test is abnormal. Measure serum holo-transcobalamin II 6. Gastric acidity after histamine stimulation 5.Disorders of vitamin B12 metabolism 64 .Vit. 4.B12 deficiency suspected : 1. repeat with commercial intrinsic factor.

gastroenterologic symptoms (malabsorption. Dietary and drugs (antibiotics.anticonvulsants). Enzyme assays 65 .Suspect folic acid deficiency : 1.dietary history) 2. Tests for malabsorption 3. Upper gastrointestinal barium study and follow through 4. Endoscopy and biopsy : upper gut .jejunal 5.diarrhea.

Treatment Folic acid deficiency 1.Transfusion : severe anemia or child is very ill. 6. Folic acid : Initially corrected : 5 mg (100 µg/Kg)daily for 4 months orally or parenteral Diagnostic test: smaller dose 0. Underlying causative disorder 3. Prophylactic folic acid: children with severe hemolytic anemia 5. N-5-formyl tetrahydrofolic acid : Hereditary dihydrofolate reductase deficiency 66 .1 mg/day for a week 2. Improvement of the diet (increase folate intake 4.

Treatment Vitamin B12 deficiency  Prevention Prophylactic vit B12 :total gastrectomy.Low doses of Cobalamin 10 µg/day o 0.Ileal resection  Active treatment .First treated : 6 series im or sc Hydroxocobalamin .Food supplemented with Cobalamin 67 .2 µg/Kg sc for 2 days  reticulocytosis .Maintenance :1000μg Hydroxocobalamin every 3 months .

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