Transcript Anaemia gyermekkorban

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
A vörösvértest
• Élettartam: 120 days – 60-90 days in term & 35-50 days in
preterm babies
• Termelődés
– 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
• Destrukció
– When old or damaged, taken up by spleen
A vörösvértest
• Membrán
• Enzimek
• 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
– Vvt hb koncentrációja a vérben
• Ht (%)
– A vér alakos elemeinek frakcionált volumene a
vérben
• MCV
– A vvt átlagos térfogata
• Microcyter, macrocyter, normocyter
• MCHC
– Kalkulált érték (Hb/Ht)
• Alacsony MCHC hypochromiára utal
Fontosabb terminológia
• RDW (Red Cell Distribution Width)
– Vvt nagyságának variabilitását mutatja; normál értéke
11-15
• Ferritin
– Vas raktározott formája
• 1 ng ferritin: 10 mg raktározott vas
• Transferrin
– Vas transzportját végzi
• Reticulociták
– Fiatal vvt
Anaemia okai
• Csökkent produkció
• Fokozott destrukció
• Vérvesztés
Csökkent vvt termelés
• 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 termelés
• 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 destrukció
• Extracellular
– Antibody mediated
– Microangiopathic; HUS, DIC
– Drugs, toxins
– Hypersplenism
Fokozott pusztulás
• Intracelluláris
– RBC membrán defektusok
• HS (hereditary spherocytosis, stomatocytosis [For as yet
unknown reasons, the cells take on an abnormal shape,
resembling a mouth or 'stoma‘]), HE (hereditary eliptocytosis)
– Enzim defektusok
• PK (pyruvate kinase), G6PD
– Hemglobinopathiák
• Sickle cell, thalassemia
Vérvesztés
• Akut vérzés
• Krónikus vérvesztés
Anaemia
• Definíció
– Hb concentráció > 2 SD a normál populációs
átlag alatt
• Normál értékek korral változnak
Életkori változások
Életkor
Újszülött
2 hetes
3 hónapos
6hó – 6 év
7-12 év
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
• Hb csökkenés 3 hónapos kor környékén
• Háttérben zajló fiziológiás változások
– 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
• Anamnézis
• Fizikális vizsgálat
• Labor és egyéb vizsgálatok
Anamnézis
• Anyai anamnézis
– Anaemia terhesség alatt
– Terhesség és szülés
• Családi anamnézis
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Etnikai hovatartozás
Anaemia
Sárgaság, epekőbetegség, cholecystectomia
Transfusio
Splenomegalia
Anamnézis
• Páciens
– Sárgaság születés utáni időszakban
– Diétás szokások
– Gyógyszerszedés
– Infekciók a közelmúltban
– Krónikus betegségek
– Bőrvérzések, vérzések
– 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
• Vvt nagyság szerint
– Microcyter
– Macrocyter
– Normocyter
Microcyter anaemia
• Low MCV
• Small cells
• Etiologies
– Iron-deficiency
– Thalassemia
– Chronic disease
– Lead poisoning
Macrocyter anaemia
• 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
• Érett újszülött becsült napi vasszükséglete: 1 mg/kg
• A vasraktárak több mint 80%-a az utolsó
trimesterben raktározódik. A koraszülöttek
vasigénye ezért posztnatalisan fokozott.
• Koraszülöttek napi vasigénye:
– 1500 – 2500 gr – 2mg/kg/nap
– < 1500 g – 4 mg/kg/nap
• Koraszülöttek igénye erythropoietin kezelés
esetében - 6 mg/kg/nap
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 hónaposan ha rizikócsoportba tartozik
– Canadian Task force ajánlása
• Magas rizikó
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Kora- vagy sorvadt újsz.
Magas prevalenciájú közösségekben
Alacsony szociális helyzet
Speciális igényű páciensek
• Szűrés megfontolandó
– Kisdedeknél hiányos diétával
– Serdülők
Prevenció
• Anyatejes csecsemő
– > 2 adag vasban gazdagított cerealia 6 hónapos
kortól
• Tápszeres csecsemő
– Vassal szupplementált formula alkalmazása
• Koraszülött anyatejes
– Vas 1 to 2 mg/kg 1-6-12 hónapig
• 12 hónapos korig nincs tehéntej
• Tehéntej fogyasztásának limitálása kisdedeknél
– < 500 ml 1-5 év között
Kezelés
• Diéta módosítás
– Decrease cow’s milk
– Increase iron-rich foods
• Vas terápia
– 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
• Rossz compliance
– 10% GI mellékhatások
– Rossz íz
• Folyamatos vérvesztés
• Rossz diagzózis
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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Neutropaenia és/vagy thrombocytopaenia
Jelentős adenopathia/organomegalia
Haemolysis gyanuja
Hemodynamikai instabilitás és/vagy HCT < 20%
Thalassemia major vagy sarlósejtes anaemia
gyanuja
• Sikertelen vas szubsztitució esetén
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