Transcript Anemia in childhood

Anaemia gyermekkorban
Molnár Dénes
Gyermekklinika
Cél
• Anaemia okainak áttekintése
• Anaemia diagnózisának felállításának
megközelítése
• Vashiányos anaemia diagnosisa és
kezelése
• Rövid tárgyalása a gyermekkori anaemiák
egyéb okainak
The Red Blood Cell
• Life span: 120 days – 60-90 days in term & 35-50 days in
preterm babies
• Production
– Regulated by epo (other hemopoietic factors. Colony- stimulating
factors, interleukins, thrombopoietin are not mentioned here)
• Produced by kidneys in response to low O2
– Epo stimulates marrow to make RBC precursors
– Needs iron, B12, folate, and amino acid
• Destruction
– When old or damaged, taken up by spleen
The RBC
• Membrane
• Enzymes
• Hemoglobin
– Heme (4 heme groups per Hb molecule)
• Mediates binding of O2 by Hb
– Globin
• Protein that surrounds and protects heme
molecule
• 2 alpha and 2 beta genes (adult Hb)
Fontosabb terminológia
• Hb
– Concentration of RBC Hb in whole blood
• Ht (%)
– Fractional volume of whole blood occupied by RBC
• MCV
– Mean value of volume of individual RBC
• Microcytic, macrocytic, normocytic
• MCHC
– Calculated value (Hb/Ht)
• Low MCHC indicates hypochromia
Fontosabb terminológia
• RDW (Red Cell Distribution Width)
– Variability of RBC sizes; normal range 11-15
• Ferritin
– Storage form of iron
• 1 ng of ferritin: 10 mg of iron stores
• Transferrin
– Transports iron through plasma
• Reticulocytes
– Young RBC
Anaemia okai
• Decreased production
• Increased destruction
• Blood loss
Csökkent vvt productio
• Defective heme synthesis
– Iron deficiency, anemia of chronic disease, lead
poisoning
• Defective globin synthesis
– Alpha and beta thalassemia
• Defective DNA synthesis
– Nutrient deficiencies (B12, folate)
• Impaired epo production
– Renal disease
Csökkent vvt productio
• Marrow failure
– Aplastic anemia
• congenital Fanconi anemia is an autosomal recessive
disorder affecting all bone marrow elements and associated
with cardiac, renal, and limb malformations as well as dermal
pigmentary changes.(congenital)
• acquired
– Red cell aplasia
• Congenital (Diamond-Blackfan)
• Acquired (Transient erythroblastopenia of childhood)
• Marrow replacement
– Malignancy, myelofibrosis
Fokozódó destructio
• Extracellular
– Antibody mediated
– Microangiopathic; HUS, DIC
– Drugs, toxins
– Hypersplenism
Fokozódó destructio
• Intracellular
– RBC membrane defects
• HS (hereditary spherocytosis, stomatocytosis [For as yet
unknown reasons, the cells take on an abnormal shape,
resembling a mouth or 'stoma‘]), HE (hereditary eliptocytosis)
– Enzyme defects
• PK (pyruvate kinase), G6PD
– Hemglobinopathies
• Sickle cell, thalassemia
Vérvesztés
• Acute hemorrhage
• Chronic blood loss
Anaemia
• Definition
– Hb concentration > 2 SD below mean for
population
• Normal values vary with age
Életkori változások
Age
Newborn
2 wks
3 months
6m – 6 yrs
7-12 yrs
Hb (g/l)
168
(137-210)
165
(130-200)
120
(95-145)
120
(105-140)
130
(110-160)
Hct (%)
55 (45-65)
50 (42-66)
36 (31-41)
37 (33-42)
38 (34-40)
MCV (fl)
lowest
110
70-74
76-80
Reticuloc
ytes (%)
5
1
1
1
1
Physiologiás anaemia
• Drop in Hb around 3 months of age
• Pathophysiology
– At birth, O2 sat rises sharply
• 65% in utero, nearly 100% when comes out
– Decrease in epo production
– Fetal RBC have shorter survival time (60
days)
Anaemia diagnózisa
• History
• Physical exam
• Investigations
Anamnézis
• Maternal history
– Anemia during pregnancy
– Pregnancy and delivery
• Family history
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Ethnicity
Anemia
Jaundice, gallstones, cholecystectomy
Transfusion history
Splenomegaly
Anamnézis
• Patient’s history
– Jaundice at birth
– Diet history
– Medications
– Recent infection
– Chronic disease
– Bruising, bleeding
– Pica
Fizikális vizsgálat
General appearance
– Pallor, jaundice, bruising
• Head and neck
– Pale mucous membranes and conjunctiva
– Angular stomatitis
– Adenopathy
• Cardiac
– Tachycardia, heart failure if severe
– Heart murmur
• Abdomen
– Organomegaly
Laborvizsgálatok
• Most often incidental finding
• CBC and smear
– Hb, WBC, plt
– MCV
• Reticulocyte count
• Depending on suspected process
– Ferritin and iron studies, folate and B12, LDH, bili,
Coombs, osmotic fragility, sickle screen,
electrophoresis, bone marrow aspiration, renal
function, liver function, etc
Morphológiai osztályozás
• Cell volume
– Microcytic
– Macrocytic
– Normocytic
Microcyter anaemia
• Low MCV
• Small cells
• Etiologies
– Iron-deficiency
– Thalassemia
– Chronic disease
– Lead poisoning
Macrocytic anemia
• High MCV
• Big cells
• Etiologies
– Folic acid and B12
deficiency
– Hypothyroidism
– Chronic liver disease
– Aplastic anemias
Normocyter Anaemia
• Normal MCV
• Production, destruction or loss
• Must look at reticulocyte count
– Young RBC
– Determines
adequacy of
bone marrow
response
Normocyter anaemia
• High retic count
– Blood loss
– Hemolysis
• Low retic or normal count
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Aplastic anemia
Leukemia
Chronic disease
TEC
Congenital hypoplastic syndromes
Vashiányos anaemia
• Epidemiology
– Most common heme abnormality of childhood
– Most common nutritional deficiency worldwide
– 500 million to 2 billion people are irondeficient according to WHO
• 80% of world’s population
Vas metabolismus
• Body iron content: 2 to 6 g (2 g in adult female, 6 g in adult
male)
– 1.5-2 g in Hb
– 0.5-1 g bound to enzymes, transferrin (protein that carries iron), in
storage form (hemosiderin and ferritin)
– The rest in myoglobin
– At birth, most term infants have 75 mg of elemental iron per
kilogram of body weight, found primarily as hemoglobin (75%), but
also as storage (15%) and tissue protein iron (10%).
• Most iron is recycled
• Gut absorption depends on:
– Epo production
– Body iron stores
– Bioavailability of dietary iron
Vas források
• Bioavailability factors
– Fish, poultry, meat
• Iron 30% bioavailable
– Vegetables
• Iron 10% bioavailable
• Absorbtion factors
– Vitamin C increases absorbtion
– Phytates (bran, oats, rye, fiber) and tea decrease
absorbtion
Vasszükséglet
• The estimated iron requirement of the term infant is
1 mg/kg per day.
• Because more than 80% of the iron is accreted
during the third trimester of gestation, infants born
before term must accrete more iron postnatally.
Thus, the requirements for preterm infants range
from 2 mg/kg per day (bwt. 1500 and 2500 g) to
4 mg/kg per day (bwt. < 1500 g).
• Preterm infants who receive erythropoietin appear
to need at least 6 mg/kg per day of iron.
Vas felszívódás
• Generally 10% of dietrary iron is absobed
• Greater than 50% of iron from human milk
is absorbed compared with typically less
than 12% of iron from cow milk-derived
formula
Rizikócsoportok
• Babies
– Newborn body contains 75mg/kg
– Infants triple blood volume in 1st year
– Each kg gain requires increase of 35 to 45 mg
body iron
– Term babies usually iron replete for 5-6
months, then need iron-fortified foods
• Iron recycled in first 2 to 3 months
– Pre term at greater risk
Rizikócsoportok
• Toddlers
– Too much cow’s milk!!!
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Maximum 16 oz/day
Interferes with absorption from other food
Colitis
Decreased appetite for food
• Teenagers
– Increased requirement due to growth spurt
– Menstrual loss
Vashiány okai
• Newborn factors
– LBW, perinatal hemorrhage, prematurity
• Dietary deficiencies
– Insufficient intake, poor iron bioavailability
• Early cow’s milk exposure
– Excessive cow’s milk intake
• Blood loss
• Iron deficiency itself!
– Blunting of intestinal villi leads to increased blood loss
Lab eltérések
• Bone marrow hemosiderin first disappears
– Most reliable indicator of tissue stores
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 RDW earliest sign on blood work
 Ferritin
 Iron,  TIBC
 Hb
Smear
– microcytosis and hypochromia
• Retic normal or moderately increased
– Insufficient response
Vashiány hosszútávú
következményei
• Has been linked to ADHD and breath-holding
spells
– Although not well substantiated
• Exercise intolerance
– Study done in teenagers
• Neurological impairment
– More school difficulties, especially math and memory
skills
• Increases lead absorption
– Leading to more cognitive abnormalities
Szűrés
• 9 mos of age if high risk
– Recommanded by Canadian Task force
• High risk
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Pre-term / LBW baby
High prevalence in community
Low SES
Special health needs
• Consider screening
– Toddlers with poor diets
– Teenagers
Prevenció
• Breast fed infant
– > 2 servings of iron-fortified cereals at 6 months
• Formula-fed infant
– Iron-fortified formula
• Pre-term breast fed infant
– Iron 1 to 2 mg/kg at 1-2 mos, until 6-12 mos
• No cow’s milk until 12 months
• Limit cow’s milk intake in toddlers
– < 500 cc from 1 to 5 yrs
Kezelés
• Diet modification
– Decrease cow’s milk
– Increase iron-rich foods
• Iron therapy
– 4 to 6 mg/kg of elemental iron
• Increased absorption with Vit C
Kezelés
• Parenteral iron
– 2-3% anaphylaxis
– No advantage
• PRBC transfusion
– RARELY necessary
– Only if hemodynamically unstable
– 3 to 5 cc/kg at a time, watch for CHF
Kezelésre adott válasz
• 12-24 hours
– Intracellular replaced
– Subjective improvement
– Increased appetite
• 36-48 hours
– Bone marrow response
– Erythroid hyperplasia
• 48 to 72 hours
– Retics increased, peak at around 5 to 7 days
Kezelésre adott válasz
• 4 to 30 days
– Increased Hemoglobin
• 1 to 3 months
– Repletion of iron stores
• Treat for a total of at least 3 months
Sikertelen kezelés
• Poor compliance
– 10% GI side effects
– Poor taste
• Ongoing blood loss
• Wrong diagnosis
Különböző anaemiák jellemzői
Parameterek, Apl.
Folate, B12 Fe def.
indexek
Anaemia def.
MCV
Hgb conc
RBC Hgb
conc
Rets
Se Bil
Hemolysis
Vérvesztés
Mikor forduljunk gyermek
hematológushoz?
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•
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Neutropenia and /or thrombocytopenia
Significant adenopathy/organomegaly
Suspected hemolysis
Hemodynamic compromise and/or HCT < 20%
Suspected thalassemia major or sickle cell dis
Failure to respond to therapeutic iron trial
Hereditary spherocytosis
• Prevalence: 1/5000
• Etiology: Autosomal dominant, 25% have
no previous family history
• Most common molecular defects: spectrin,
ankyrin
Clinical manifestations
• Hyperbilirubinemia in the neonate
• Some children stay symptomeless until
adulthood, others have recurrent hemolytic
crisis
• After infancy the spleen is enlarged
• Gallstone
• Icterus
Treatment
• Transfusion
• Splenectomy
Diamond-Blackfan anemia
• Diamond-Blackfan anemia (DBA), also known as
Blackfan–Diamond anemia and Inherited
erythroblastopenia, is a congenital erythroid aplasia
that usually presents in infancy. DBA patients have low
red blood cell counts (anemia). The rest of their blood
cells (the platelets and the white blood cells) are normal.
This is in contrast to Schwachman-Diamond
syndrome, in which the bone marrow defect results
primarily in neutropenia, and Fanconi anemia, where all
cell lines are affected resulting in pancytopenia.
Clinical picture
• Diamond-Blackfan anemia is characterized by anemia
(low red blood cell counts) with decreased erythroid in
the bone marrow. This usually develops during the
neonatal period. About 47% of affected individuals also
have a variety of congenital abnormalities, including
craniofacial malformations, thumb or upper limb
abnormalities, cardiac defects, urogenital malformations,
and cleft palate. Low birth weight and generalized growth
delay are sometimes observed. DBA patients have a
modest risk of developing leukemia and other
malignancies
Diagnosis
• Typically, a diagnosis of DBA is made through a simple blood count
and a bone marrow biopsy.
• A diagnosis of DBA is made on the basis of anemia, low reticulocyte
(immature red blood cells) counts, and diminished erythroid
precursors in bone marrow. Features that support a diagnosis of
DBA include the presence of congenital abnormalities,
macrocytosis, elevated fetal hemoglobin, and elevated adenosine
deaminase levels in red blood cells.
• Most patients are diagnosed in the first two years of life. However,
some mildly affected individuals only receive attention after a more
severely affected family member is identified.
• About 20-25% of DBA patients may be identified with a genetic test
for mutations in the RPS19 gene.(19q13.2)
Treatment
• Corticosteroid
• Transfusion
• Bown marrow transplantation
Transient erythroblastopenia of
childhood (TEC)
• Acquired erythroid bone marrow failure
– Unknown etiology
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18 mos to 2 yrs
Often follows viral illness
Child otherwise healthy
Resolves spontaneously
– Weeks to months
TEC
• Lab findings
– Normocytic anemia (Hb 50-70, sometimes as low as
20)
– Low retic count
– No evidence of hemolysis
– Other cell lines unaffected
• Treatment
– Supportive
– Transfusion if symptomatic
Hemoglobinopathies
• Thalassemia
– Decreased or absence of production of one or
more globin chains
• Alpha, beta, and variants
• Sickle cell disease
– Structural defect of beta-globin chain
Thalassemia
• Epidemiology
– Prevalent in certain populations
• Africa, Middle East, Asia, and Mediterranean population
• Pathogenesis
– Decreased or absent synthesis of one or more globin
chains
• Imbalance in number of chains
– Precipitation of unstable Hb
• Hemolysis occurs
Alpha-Thalassemia
• Common in Asian and black populations
• Phenotype depends on number of deletions
– 1-gene deletion
• Silent carrier, no anemia
– 2-gene deletion (trait)
• Mild hypochromic, microcytic anemia
– 3-gene deletion (Hemoglobin H)
• Severe anemia
• Hb Bart (gamma globin tetramers)
– 4-gene deletion
• Incompatible with life
• Hb Bart
Beta-thalassemia
• Mediterranean or Southeast Asian origin
• Phenotype depends on number and type of
mutations
– Minor
• Microcytic anemia
– Intermedia
• Moderate to severe anemia
– Major
• Severe anemia, transfusion dependant
Diagnosis
• Family history, ethnic origin
• CBC
– Microcytic anemia
• Normal or increased ferritin
• Hb electrophoresis
– Decreased HbA, increased HbF
– Abnormal Hemoglobins
• Gene studies
Treatment
• Alpha trait
– None
– Counseling
• Severe anemia
– Transfusion
– Watch for iron overload
– Chelation therapy
– Splenectomy
Sickle Cell Disease
• Defect of beta-globin chain
– Amino acid substitution (valine for glutamine)
• Prevalent in certain populations
– African, Caribbean, Middle Eastern, Indian,
Mediterranean populations
Hb susceptible to deoxygenation, acidosis,
temperature, dehydration
– RBC distorted into sickle shape
– Results in tissue ischemia and infarction
– Shortened RBC survival
Sickle Cell Disease
• Manifestations (only in disease, not if trait)
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Bony crisis
Chest crisis
Strokes
Splenic sequestration
Aplastic anemia
• Susceptibility to infections; autosplenectomize
– Encapsulated organisms
• Need penicillin prophylaxis
Treatment
• Pain control
– NSAIDs, opiates
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Hydration
Antibiotics if febrile
Transfusions
Exchange transfusions
Hydroxyurea