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ANEMIA IN PEDIATRICS 2019
1. 11--ANEMIA INANEMIA IN
PEDIATRICSPEDIATRICS
for clinical pharmacyfor clinical pharmacy
Prof Dr Hussein AbdeldayemProf Dr Hussein Abdeldayem
Professor of Pediatrics,Professor of Pediatrics,
Alex UniversityAlex University
3. Regulation ofRegulation of
ErythropoiesisErythropoiesis
While the kidney produces most of theWhile the kidney produces most of the
erythropoietin, the liver and othererythropoietin, the liver and other
tissues also produce some.tissues also produce some.
In fetal life, the liver produced all of theIn fetal life, the liver produced all of the
erythropoietinerythropoietin –– as the final kidneyas the final kidney ––
the metanephros - had not yetthe metanephros - had not yet
completed development.completed development.
4. Regulation ofRegulation of
ErythropoiesisErythropoiesis
How many are produced:How many are produced:
– 25 billion /24 hours.25 billion /24 hours.
– The entering cells are reticulocytes whichThe entering cells are reticulocytes which
should be 1% of the total population ofshould be 1% of the total population of
circulating erythrocytes.circulating erythrocytes.
– Erythrocytes last 120 days and areErythrocytes last 120 days and are
destroyed by the spleen.destroyed by the spleen.
– Red cell production should equal red cellRed cell production should equal red cell
destruction.destruction.
5. Uses of erythropoietinUses of erythropoietin
epoetin alfaepoetin alfa
Indication:
Anemia of chronic renal failure.
Cancer and AIDS chemotherapy
Transplant patients
Chronic inflammatrory illness as SLE
Prematurity .
Anemia in surgical or extracorporeal proceduresAnemia in surgical or extracorporeal procedures
because the pumps may have destroyed many redbecause the pumps may have destroyed many red
blood cells.blood cells.
6. Uses of epoetin alfaUses of epoetin alfa
Recommended starting dose is 80 – 120 U/kg -
sc three times a week. Average maintenance
dose - 75 U/kg, three times a week in most
patients.
The most common side effect - aggravation of
hypertension
11. What is AnemiaWhat is Anemia??
Anemia is a decrease in HbAnemia is a decrease in Hb
concentration or the number of redconcentration or the number of red
blood cells (RBC) as measuredblood cells (RBC) as measured
– 1. gm per cu mm or1. gm per cu mm or
– 2. by volume of packed RBC per 100 ml2. by volume of packed RBC per 100 ml
of blood. This is clinically obtained byof blood. This is clinically obtained by
doing a hematocrit (HCT)doing a hematocrit (HCT)
Below average of normal values for ageBelow average of normal values for age
and sexand sex
12. ANEMIAS
CLASSIFICATION OF ANEMIAS
1. Anemia from inadequate erythropoiesis.
2. Anemia of blood loss (post-hemorrhagic).
3. Anemia due to ↑ destruction (hemolytic).
13. ANEMIAS
Diagnosis:
Type, Severity, Etiology
CLINICAL EVALUATION:
1. Common manifestations: Pallor, exercise
intolerance, dyspnoea, palpitations, headache, lack of
conc., irritability, syncope, hemic murmurs.
2. Less commonly: anorexia, nausea, flatulence,
constipation, mild proteinuria, fever
3. Severe cases: ↑ C.O, CHF
18. Reticulocyte CountReticulocyte Count
Is required in the evaluationIs required in the evaluation
of all patients with anemia asof all patients with anemia as
it is a simple measure ofit is a simple measure of
productionproduction
Young RBC that still containsYoung RBC that still contains
a small amount of RNAa small amount of RNA
Normally take 1 day forNormally take 1 day for
reticulocyte to mature.reticulocyte to mature.
1/1201/120thth
of RBC normallyof RBC normally
19. Classification according to MCV
Microcytic
Iron deficiency
Thalassemia
Lead poisoning
Chronic disease
Normocytic
↓ Production
Macrocytic
Vit. B12
Folic acid
20. 2. Biochemical Investigations
A. Iron status
Serum iron (N 60-150 µg/dl)
TIBC (N 100-400 µg/dl)
Serum ferritin (N 10-150 ng/dl)
B. Megaloblastic anemia
Serum vit. B12, folate
Laboratory Investigations
21. Commonest Causes of Anemia
Nutritional Deficiency : Iron Deficiency
Acute Hemolytic: G6PDD
Chronic Hemolytic: β-Thalassemia
24. ANEMIAS DUE TO DEFICIENCYANEMIAS DUE TO DEFICIENCY
OF SPECIFIC NUTRIENTSOF SPECIFIC NUTRIENTS
IRON DEFICIENCY ANEMIAIRON DEFICIENCY ANEMIA
Most commonMost common nutritional deficiency innutritional deficiency in
children and is worldwide.children and is worldwide.
Highest :Highest : ●● 6 - 246 - 24 monthsmonths
●● artificially fed infants.artificially fed infants.
●● low socioeconomic status.low socioeconomic status.
25. Iron-deficiency anemia remains the mostIron-deficiency anemia remains the most
common nutritional problem from a globalcommon nutritional problem from a global
perspective, it is estimated that roughly 2-5%perspective, it is estimated that roughly 2-5%
of the world population are anaemic.of the world population are anaemic.
Prevalence of Iron Deficiency AnemiaPrevalence of Iron Deficiency Anemia
26. Normal Daily IronNormal Daily Iron
RequirementsRequirements
FT baby: with store enough for 4 moFT baby: with store enough for 4 mo
PMT baby: with store enough for 2 moPMT baby: with store enough for 2 mo
1mg/kg/day elemental iron for infants and1mg/kg/day elemental iron for infants and
children (max 15 mg/day)children (max 15 mg/day)
2 mg/kg/day elemental iron for low birth2 mg/kg/day elemental iron for low birth
weight and newborns with very low initial Hbweight and newborns with very low initial Hb
valuesvalues
6 mg/kg/day elemental iron is needed for tt6 mg/kg/day elemental iron is needed for tt
for 3 mofor 3 mo
27. Dietary ironDietary iron
I:Heme iron compoundsI:Heme iron compounds (hemoglobin and(hemoglobin and
myoglobin) :myoglobin) : foods of animal origin:foods of animal origin: 1.5 - 6 mg1.5 - 6 mg
iron /100 giron /100 g meat, liver, poultry, fish, etc.meat, liver, poultry, fish, etc.
Easily digested and readily absorbed.Easily digested and readily absorbed.
Absorption is not affected by diet.Absorption is not affected by diet.
II:Non-heme ironII:Non-heme iron ( ferric iron salts ) :( ferric iron salts ) :
egg yolk, green vegetables, whole grains, legumes,egg yolk, green vegetables, whole grains, legumes,
nutsnuts (( ++ 1.5 mg/100 g)1.5 mg/100 g). ferric. ferric →→ ferrous beforeferrous before
absorption.absorption.
Absorption (50% : breast milk , 10% of cowAbsorption (50% : breast milk , 10% of cow ’’s milks milk
iron .iron .
AbsorptionAbsorption ↑↑ : Vitamin C, sugar, amino acids (meat,: Vitamin C, sugar, amino acids (meat,
poultry, fish) & HCl.poultry, fish) & HCl.
AbsorptionAbsorption ↓↓ : Fibers (bran), tannate (tea),: Fibers (bran), tannate (tea),
28. Iron is used inIron is used in::
Hemoglobin: transfer O2 to tissuesHemoglobin: transfer O2 to tissues
Heme enzymes, e.g., cytochromes, catalase,Heme enzymes, e.g., cytochromes, catalase,
peroxidaseperoxidase
Myoglobin:transfer O2 to muscle cellsMyoglobin:transfer O2 to muscle cells
Metalloflavoprotein enzymes such as xanthineMetalloflavoprotein enzymes such as xanthine
oxidaseoxidase
The mitochondrial enzyme alpha-The mitochondrial enzyme alpha-
glycerophosphate oxidase and otherglycerophosphate oxidase and other
mitochondrial enzymes.mitochondrial enzymes.
Other enzymes and processesOther enzymes and processes
29. Most commonMost common nutritional deficiency innutritional deficiency in
children and is worldwide.children and is worldwide.
More common at:More common at:
●● 6 - 246 - 24 monthsmonths
●● artificially fed infants.artificially fed infants.
●● low socioeconomic statuslow socioeconomic status
IRON DEFICIENCYIRON DEFICIENCY
ANEMIAANEMIA
30. STAGESSTAGES
Iron stores S.IronIron stores S.Iron
AnemiaAnemia
(s. ferritin)(s. ferritin)
Stage of IRONStage of IRON Low Normal NoneLow Normal None
DEPLETIONDEPLETION
Stage of IRONStage of IRON Absent Low NoneAbsent Low None
DEFICIENCYDEFICIENCY
Stage of IRONStage of IRON Absent Low PresentAbsent Low Present
DEF. ANEMIADEF. ANEMIA
31. ↓↓ iron stores.iron stores.
↓↓ iron‑storage protein (ferritin)iron‑storage protein (ferritin)
↓↓ serum ironserum iron
↑↑iron binding capacity TIBC.iron binding capacity TIBC.
Anemia: hypochromia,microcytosis.Anemia: hypochromia,microcytosis.
↓↓ activity of iron‑containing intraactivity of iron‑containing intra
cellular enzymes (e.g. CNS -MAO).cellular enzymes (e.g. CNS -MAO).
PathogenesisPathogenesis
32. Clinical manifestationsClinical manifestations
- Particular CP due to effect of iron def. on- Particular CP due to effect of iron def. on
systems:systems:
GIT:GIT: Anorexia, glossitis, Pica (ingestion of wallAnorexia, glossitis, Pica (ingestion of wall
plaster, clay), Geophagia (earth), Pagophagiaplaster, clay), Geophagia (earth), Pagophagia
(ice,(ice,
CNS:CNS: Short attention span, irritability, breathShort attention span, irritability, breath
holding,holding,
↓↓ alertness, ↓ learning ability and schoolalertness, ↓ learning ability and school
performance.performance.
33. IRON replacement TREATMENT (oral,IRON replacement TREATMENT (oral,
IM, IV)IM, IV)
TREAT THE CAUSETREAT THE CAUSE
TREATMENTTREATMENT
34. TreatmentTreatment
Oral Iron saltsOral Iron salts::
6 mg/kg/day elemental for 3 mo6 mg/kg/day elemental for 3 mo
Ferrous sulfate drops for infants ( 20%Ferrous sulfate drops for infants ( 20%
elemental iron).elemental iron).
Ferrous gluconate drops ( 12 % elementalFerrous gluconate drops ( 12 % elemental
iron).iron).
ferrous fumarate (30% elemental iron) tabletsferrous fumarate (30% elemental iron) tablets
or syrup for older children.or syrup for older children.
Iron better between meals. fibers (e.g. wholeIron better between meals. fibers (e.g. whole
bread and cereals), tannate (like tea),bread and cereals), tannate (like tea),
phosphates (in bread, cow's milk and eggphosphates (in bread, cow's milk and egg
yolk) and phytic acid ↓ absorption of iron.yolk) and phytic acid ↓ absorption of iron.
absorption ↑ by vitamin C (e.g. citrous fruits),absorption ↑ by vitamin C (e.g. citrous fruits),
sugar and amino acids (meat, poultry, fish).sugar and amino acids (meat, poultry, fish).
35. TreatmentTreatment
Parenteral iron therapyParenteral iron therapy :: Iron dextranIron dextran
mixture (mixture (ImferonImferon))®®
50 mg elemental iron / ml50 mg elemental iron / ml
only in intolerance or malabsorptiononly in intolerance or malabsorption
Packed RBC transfusionPacked RBC transfusion :: SeverelySeverely
anemic children with Hb < 4 g/dlanemic children with Hb < 4 g/dl
Treatment of etiologyTreatment of etiology correct diet , ttcorrect diet , tt
parasiteparasite
36. These preparation are mostlyThese preparation are mostly
available as ferrous(Fe+2) and someavailable as ferrous(Fe+2) and some
in ferric(Fe+3)formin ferric(Fe+3)form
Ferrous salt are better absorbedFerrous salt are better absorbed
than ferric saltsthan ferric salts
ORAL IRON THERAPYORAL IRON THERAPY
37. Iron is poorly absorbed in the form ofIron is poorly absorbed in the form of
carbonate, citrate and pyrophosphate,carbonate, citrate and pyrophosphate,
colloidal iron and iron carbohydratecolloidal iron and iron carbohydrate
complexcomplex
FORMS :FORMS :
Tablets, capsulesTablets, capsules
Sugar coated & uncoated tablets •Sugar coated & uncoated tablets •
Slow release tabsSlow release tabs
chewable tabs •chewable tabs •
Drops &syrups—used by children'sDrops &syrups—used by children's
38. 1. Ferrous sulphate: 20 – 32% iron1. Ferrous sulphate: 20 – 32% iron
2. Ferrous fumarate: 33% elemental2. Ferrous fumarate: 33% elemental
ironiron
3. Ferrous gluconate : 12% elemental3. Ferrous gluconate : 12% elemental
ironiron
4. Colloidal ferric hydroxide:50%4. Colloidal ferric hydroxide:50%
elemental iron •elemental iron •
Other oral preparations are ferrousOther oral preparations are ferrous
choline citrate , ferric ammoniumcholine citrate , ferric ammonium
citrate , iron calcium complex, ironcitrate , iron calcium complex, iron
hydroxy polymatose.hydroxy polymatose.
FERRIC
HYDROCHLORIDE
POLYMALTOSE
39. It is rapidly absorbed, with a high rate of ironIt is rapidly absorbed, with a high rate of iron
utilization and produces an effective increase inutilization and produces an effective increase in
Haemoglobin. Due to its favourable nonionicHaemoglobin. Due to its favourable nonionic
nature it has the following properties unlikenature it has the following properties unlike
ionised iron salt preparations: · Ferose does notionised iron salt preparations: · Ferose does not
give rise to irritation of the intestinal mucosa andgive rise to irritation of the intestinal mucosa and
does not stain the teeth. · Ferose has palatable,does not stain the teeth. · Ferose has palatable,
non metallic taste (Ferose chewable tablets havenon metallic taste (Ferose chewable tablets have
chocolate flavour and are acceptable even by thechocolate flavour and are acceptable even by the
most resistant patients of all ages). · Ferose hasmost resistant patients of all ages). · Ferose has
excellent tolerance.excellent tolerance.
Ferrous form of oral ironFerrous form of oral iron
FEROSEFEROSE
40. •• Important points to remember ;ElementalImportant points to remember ;Elemental
iron content and not quantity of ironiron content and not quantity of iron
compound per unit dose to be consideredcompound per unit dose to be considered
Sustained released preparations expensiveSustained released preparations expensive
and irrationaland irrational
Liquid formulations: should be put on backLiquid formulations: should be put on back
of tongue and swallowedof tongue and swallowed
41. Iron saltsIron salts
Ferrous sulfateFerrous sulfate ––least expensiveleast expensive –– treatment oftreatment of
choicechoice
Ferrous salts (sulfate, fumarate, gluconate,Ferrous salts (sulfate, fumarate, gluconate,
succinate) are absorbed about three times assuccinate) are absorbed about three times as
well as ferric salts.well as ferric salts.
Vitamin C increases absorption - AscorbicVitamin C increases absorption - Ascorbic
acid, 200 mg or more, increases absorption byacid, 200 mg or more, increases absorption by
at least 30% (with increased incidence of sideat least 30% (with increased incidence of side
effects too)effects too)
Carbonyl iron: microspheres of pure ironCarbonyl iron: microspheres of pure iron –– lessless
gastrointestinal toxicity than iron saltsgastrointestinal toxicity than iron salts
42. •• Constipation (BLACK) is commonConstipation (BLACK) is common
than diarrheathan diarrhea
•• Epigastric painEpigastric pain
•• VomitingVomiting
•• Heart burnHeart burn
•• Metallic tasteMetallic taste
•• NauseaNausea
•• Staining of teeth.Staining of teeth.
Adverse reactions to oralAdverse reactions to oral
ironiron
43. •• Oral iron is not toleratedOral iron is not tolerated
•• Failure to absorb oral ironFailure to absorb oral iron
•• Non compliance to oral ironNon compliance to oral iron
•• In presence of severe deficiency withIn presence of severe deficiency with
chronic bleedingchronic bleeding
Indications of parenteralIndications of parenteral
therapytherapy
44. •• Parenteral iron therapy needsParenteral iron therapy needs
calculation of total iron requirement ofcalculation of total iron requirement of
the patient –the patient –
Iron requirement (mg) = 4.4 X Body wtIron requirement (mg) = 4.4 X Body wt
(Kg) X Hb deficit g/dL(Kg) X Hb deficit g/dL
Calculation for parenteralCalculation for parenteral
ironiron
45. 1. Iron dextran (Imferon): I.V/ I.M1. Iron dextran (Imferon): I.V/ I.M
2. Iron sorbitol citric acid complex:2. Iron sorbitol citric acid complex:
Only I.M 3. Iron carbohydrate complexOnly I.M 3. Iron carbohydrate complex
: I.M: I.M
4. Sodium ferric gluconate: Recently4. Sodium ferric gluconate: Recently
approved preparation for I.V use hasapproved preparation for I.V use has
much lower risk of anaphylacticmuch lower risk of anaphylactic
reaction than iron dextranreaction than iron dextran
Parenteral ironParenteral iron
preparationspreparations
46. •• Iron dextran and iron sorbitol bothIron dextran and iron sorbitol both
contain 50 mg/mL recommended dosecontain 50 mg/mL recommended dose
is 100 mg daily 2 mL on alternate daysis 100 mg daily 2 mL on alternate days
until total required dose isuntil total required dose is
administered or maximum 2 g .administered or maximum 2 g .
To prevent staining to skin given deepTo prevent staining to skin given deep
I.M in buttock using z track techniqueI.M in buttock using z track technique
I.M therapyI.M therapy
Elemental iron 100 mg (As Ferric
hydroxide polymaltose complex)
47. •• Intramuscular: – Local pain at site ,Intramuscular: – Local pain at site ,
pigmentation of skin , sterile abcesspigmentation of skin , sterile abcess
–– Systemic: headache, fever,Systemic: headache, fever,
arthralgia, backache, tachycardia,arthralgia, backache, tachycardia,
flushing hemolysis and collapse theseflushing hemolysis and collapse these
effects are probably due to excessiveeffects are probably due to excessive
amount of free iron in plasmaamount of free iron in plasma
–– Iron sorbitol may causeIron sorbitol may cause
disorientation and temporary loss ofdisorientation and temporary loss of
taste, urine turns black on standingtaste, urine turns black on standing
Adverse effectsAdverse effects
48. •• Iron dextran after test dose 0.5 mLIron dextran after test dose 0.5 mL
iron dextran injected I.V over 5 to 10iron dextran injected I.V over 5 to 10
minmin
•• Total dose required diluted in 500 mLTotal dose required diluted in 500 mL
NS & infused slowly over 6 to 8 hoursNS & infused slowly over 6 to 8 hours
under supervisionunder supervision
•• If required amount greater than 50If required amount greater than 50
mL given on two consecutive daysmL given on two consecutive days
I.V TherapyI.V Therapy
50. Acute iron intoxicationAcute iron intoxication
Accidental ingestion of large doses of iron:Accidental ingestion of large doses of iron:
mortality rate 50%.mortality rate 50%.
Early symptomsEarly symptoms :: Vomiting, diarrhea,Vomiting, diarrhea,
dehydration, corrosive iron ondehydration, corrosive iron on
stomach,intestines.stomach,intestines.
LaterLater :: Severe irreversible CV collapse, shock,Severe irreversible CV collapse, shock,
coma.coma.
markedmarked ↑↑in plasma iron.in plasma iron.
51. 1. Stomach wash with 1% NaHCO3 to render it insoluble and1. Stomach wash with 1% NaHCO3 to render it insoluble and
remove undissolved iron tabletsremove undissolved iron tablets
2. IV Desferrioxamine 5 to 10 g in 100 mL isotonic saline or2. IV Desferrioxamine 5 to 10 g in 100 mL isotonic saline or
calcium sodium edetate 35 to 40 mg/Kg to retard the absorptioncalcium sodium edetate 35 to 40 mg/Kg to retard the absorption
from GITfrom GIT
3. Early replacement of fluids and electrolytes, correction of3. Early replacement of fluids and electrolytes, correction of
metabolic acidosis and hypotension by vasopressorsmetabolic acidosis and hypotension by vasopressors
4 Diazepam and other anticonvulsa-nts if epileptic4 Diazepam and other anticonvulsa-nts if epileptic
Treatment of Acute iron poisoningTreatment of Acute iron poisoning
52. •• Potent specific chelator of iron binds ferric iron to formPotent specific chelator of iron binds ferric iron to form
ferrioxamine a stable water soluble chelateferrioxamine a stable water soluble chelate
•• Ferrioxamine is excreted 2/3 in urine and 1/3 in bile colorsFerrioxamine is excreted 2/3 in urine and 1/3 in bile colors
urine reddish brownurine reddish brown
•• Removes iron from hemosiderin except that in bone marrowRemoves iron from hemosiderin except that in bone marrow
•• Well tolerated rapid I.V may causeWell tolerated rapid I.V may cause
hypotension, anaphylactic reactions andhypotension, anaphylactic reactions and
tachycardiatachycardia
•• Allergic reactions and cataract known with chronicAllergic reactions and cataract known with chronic
administrationadministration
•• Contraindicated in renal disease anuriaContraindicated in renal disease anuria
Desferrioxamine MesylateDesferrioxamine Mesylate
53.
54. MEGALOBLASTICMEGALOBLASTIC
ANEMIASANEMIAS
Megaloblasts in B.MMegaloblasts in B.M
↑↑ MCV,MCV,
Hypersegmented neutrophils in peripheralHypersegmented neutrophils in peripheral
blood.blood.
Causes:Causes:
Deficiency of :Deficiency of :
folic acid (megaloblastic anemia of infancy)folic acid (megaloblastic anemia of infancy)
vit.B12 (juvenile pernicious anemia).vit.B12 (juvenile pernicious anemia).
55. Megaloblastic anemia ofMegaloblastic anemia of
infancyinfancy
Folic acid :Folic acid :
Normal daily requirements :Normal daily requirements : 30 - 6030 - 60 µµgg
per dayper day (10 times that of adult).(10 times that of adult).
Folic deficiency in pregnant :Folic deficiency in pregnant :
Fetal neural tube defectsFetal neural tube defects
Preterm labour (2 folds)Preterm labour (2 folds)
LBWLBW
So folicSo folic should beshould be supplemented to pregnantsupplemented to pregnant
mothermother
58. TreatmentTreatment
Folic acid, 2-5 mg/day P/O or inj. 3-4Folic acid, 2-5 mg/day P/O or inj. 3-4
wks.wks.
Ascorbic acid if scurvy.Ascorbic acid if scurvy.
Packed RBCs transfusion:Packed RBCs transfusion: ONLYONLY inin
severe cases.severe cases.
Folinic acid in defects d.t methotrexateFolinic acid in defects d.t methotrexate
59. A 6 months infant has had intermittentA 6 months infant has had intermittent
diarrhoea for 1 month, after multiplediarrhoea for 1 month, after multiple
formula changes, he was receivingformula changes, he was receiving
goat milk. At 12 months of age hegoat milk. At 12 months of age he
presented with pallor, decreasedpresented with pallor, decreased
activity. Blood film was macrocytic.activity. Blood film was macrocytic.
Most likely diagnosis isMost likely diagnosis is ::
ThalassemiaThalassemia
GiardiasisGiardiasis
IDAIDA
Folate deficiencyFolate deficiency
G6PD deficiencyG6PD deficiency folicfolic
60. A 18 month old girl likes to eat dirt andA 18 month old girl likes to eat dirt and
ice and her diet is cow milk with littleice and her diet is cow milk with little
amount of solid foods. On exam, sheamount of solid foods. On exam, she
was found to be pale with nowas found to be pale with no
hepatosplenomegaly.hepatosplenomegaly.
diagnosisdiagnosis
Iron deficiency anemiaIron deficiency anemia
Megaloblastic anemiaMegaloblastic anemia
Acute hemolytic anemiaAcute hemolytic anemia
Chronic hemolytic anemiaChronic hemolytic anemia
61. Concerning the previous girl, if Hb andConcerning the previous girl, if Hb and
Hct returned to normal, when to stopHct returned to normal, when to stop
iron therapy?iron therapy?
Stop it as soon Hb becomes normalStop it as soon Hb becomes normal
Continue for 1-2 weeksContinue for 1-2 weeks
Continue for 4-8 weeksContinue for 4-8 weeks
Continue for 4-6 weeksContinue for 4-6 weeks
4-84-8