Transcript In the name of God - Isfahan University of Medical Sciences

‫بنام خدا‬
‫آنمی های شایع در کودکان‬
DEFINITION OF ANEMIA :
 Anemia may be defined as a reduction in
red blood cell mass or blood hemoglobin
concentration.
 It is particularly important to use age and
sex adjusted norms when evaluating a
pediatric patient for anemia
Normal limit of Hb in children:
CLASSIFICATIONS OF ANEMIA :
 Physiologic classification
 Morphologic classification
 Mean corpuscular volume
 Blood loss (acute) Normal spleen,
high retic count, normal bilirubin, normal
urinalysis
 Hemolytic anemia Splenomegaly,
Anemia
Retic, bilirubin,
spleen, U/A,
increased reticulocyte count, high bilirubin
(indirect), urobilinogen or hemoglobinuria
 Impaired red cell formation
Normal spleen, low retic count, normal
bilirubin, normal urinalysis
Approch to anemia : blood loss(Acute):
(Normal spleen, high retic count, normal bilirubin,
normal urinalysis)
 Neonatal problem (fetofetal transfusion,
fetomaternal transfusion,…)
 Hemorrhagic disease of newborn
 Meckel’s diverticulum, …..
 Blood loss (acute)
Anemia
 Hemolytic anemia Splenomegaly,
increased reticulocyte count, high bilirubin
(indirect), urobilinogen or hemoglobinuria
 Impaired red cell formation
Approch to anemia: Hemolytic anemia
(Splenomegaly, increased reticulocyte count, high bilirubin (indirect),
urobilinogen or hemoglobinuria):
1) Corupuscular :
 Enzyme defect,
 Membrane defect,
 Hemoglobin disorder
2) Extra corpuscular  immune,
 non immune
Hemolytic anemia: Corpuscular
1) Enzyme defect:
 G6PD deficiency
 PK deficiency
Glucose 6 phosphate dehydrogenase(G6PD)
G6PD DEFICIENCY:
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X-linked disorder
Affecting 200 to 400 million people
Contains 515 amino acids
Over 400 variant enzymes have been
reported (90 according to specific mutations)
Classification of G6PD variants:

Class I variants: are rare, have severe enzyme deficiency (less than 10
percent of normal) and have chronic hemolytic anemia(44 variants)
 Class II variants : have severe enzyme deficiency, but there is usually only
intermittent hemolysis (28 variants)

Class III variants: have moderate enzyme deficiency (10 to 60 percent of
normal) with intermittent hemolysis usually associated with infection or drugs
(16 variants)
 Class IV variants: have no enzyme deficiency or hemolysis
(2 variants)
 Class V variants: have increased enzyme activity
PATHOPHYSIOLOGY OF G6PD DEFICIENCY:
 The in vivo half-life of enzyme: normal
enzyme (G6PD B): 62 days, G6PD A- :13 days, G6PD
Mediterranean: in hours
 G6PD A- : Patients usually have hemolysis that is mild
and limited to older deficient erythrocytes (class III).
 G6PD B+(Mediterranean): red cells of all ages
are grossly deficient (class II).
DIAGNOSIS :
 Clinical presentation (should be considered in the
differential diagnosis of any nonimmune hemolytic anemia)
 Laboratory findings: Hemolysis (Hb, Retic count,
bilirubin, hemoglobinemia, hemoglobinuria), PBS
(polychromatophlia,Heinz bodies, bite cells ),Rate of
NADPH generation
Hemolytic anemia: Corpuscular
1) Enzyme defect:
 G6PD deficiency
 PK deficiency
Pyruvate kinase deficiency :
 Clinical presentation :
a broad spectrum of clinical and hematologic
findings occurs, ranging from a mild, completely
compensated hemolytic state to severe anemia.
Anemia and hyperbilirubinemia may occur in
the neonatal period.
In the older patient, pallor, scleral icterus,
and splenomegaly are usual findings.
Pyruvate kinase deficiency :
 Laboratory findings :
 Elevated reticulocyte count.
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A few small spiculated erythrocytes
No increased number of spherocytes
Osmotic fragility is normal.
Hemolytic anemia: Corpuscular
1) Enzyme defect
2) Membrane defect: Spherocytosis,
 Elliptocytosis
Membrane defect :Spherocytosis
 Pathophysiology : A deficiency or
abnormality of the erythrocyte membrane
structural protein: spectrin , ankyrin, band 3,
and protein 4.2.
 The spherocyte is relatively rigid and nondeformable
Membrane defect :Spherocytosis
 Clinical presentation: anemia,
hyperbilirubinemia, splenomegaly Expansion of
the marrow cavities .
 Laboratory findings reticulocytosis, anemia,
hyperbilirubinemia, spherocyte in PBS, Erythroid
hyperplasiain BMA, osmotic fragility test,
Autohemolysis,
Hemolytic anemia: Corpuscular
1)Enzyme defect
2) Membrane defect
3) Hemoglobin disorder
Normal variant,
Functional disorder,
 Structural problem,
Thalassemia
Hemolytic anemia: Hemoglobin disorder:
Normal variant,
Functional disorder,
Structural problem,
Thalassemia
‫عوارض کم خونی‬
‫تغییرات استخوانی ‪‬‬
‫بزرگی طحال ‪‬‬
‫خون سازی خارج مغز ‪‬‬
‫استخوان‬
‫شکستگی پاتولوژ یک ‪‬‬
‫افت سطح هوشی ‪‬‬
‫زخم اندام تحتانی ‪‬‬
‫توقف رشد ‪‬‬
‫عوارض سیستم انعقادی ‪‬‬
Hemolytic anemia: Extracorpuscular
 Immune:
 Nonimmune:
 Alloimmune,
 isoimmune,
 Autoimmune
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HUS syndrome,
TTP,
DIC,
Infection,
Burn,
Hypersplenism, ……..
Typical Hemolytic Uremic Syndrome:
 In the majority of cases, Stx HUS is associated with
strains of Escherichia coli that produce a Shiga toxin
 D+ HUS associated with Shigella dysenteriae
serotype 1 will be included in the discussion of Stx
HUS
 Cases of HUS in children due to Shiga toxinproducing E. coli infections other than colitis (e.g.
UTI) can occur .
 Blood loss (acute)
Anemia  Hemolytic anemia
 Impaired red cell formation
Normal spleen, low retic count, normal
bilirubin, normal urinalysis
Approch to anemia : Impaired red cell formation
(Normal spleen, low retic count, normal bilirubin, normal
urinalysis)
1)Deficiency
Iron deficiency
Megaloblastic anemia
vitamins,
Thyroxine deficiency
2)Bone marrow failure
Failure of a single cell line
Failure of all cell line:
3)Bone marrow infiltration
Malignant:
Non malignant:
Approch to anemia : Impaired red cell formation
(Normal spleen, low retic count, normal bilirubin, normal
urinalysis)
1)Deficiency
Iron deficiency
Megaloblastic anemia
vitamins
Thyroxine deficiency
2)Bone marrow failure
3)Bone marrow infiltration
Clinical manifestation of IDA;
Hematological symptoms
 The most common
presentation of IDA is
an otherwise
asymptomatic, well
nourished infant or
child who has a mild
to moderate
microcytic,
hypochromic anemia
Clinical manifestation of IDA;
Non hematological symptoms
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Neurodevelopmental and Cognitive function
Immunity
Exercise capacity
Pica and pagophagia
Thrombosis
Epithelial change: dysphagia, esophageal web,
atrophic glossitis, spoon nails, blue sclerae
Approch to anemia : Impaired red cell formation
(Normal spleen, low retic count, normal bilirubin, normal
urinalysis)
1)Deficiency
2)Bone marrow failure
Failure of a single cell line : CPRA, TEC, A.crisis
Failure of all cell line: Aplastic anemia
3)Bone marrow infiltration
Fanconi Anemia:
Clinical features
 Incidence is 3/1,000,000
– Heterozygote frequency ~1/300 in U.S. and Europe
 Median age at diagnosis is 5-7
 Median survival is 20-30 yrs.
 Phenotypic variability occurs even within families
Frequency of abnormalities in FA
Abnormality
Frequency
(%)
Skeletal (radial ray, hip, vertebral scoliosis, rib)
71
Skin pigmentation (café au lait, hyper- and hypopigmentation)
64
Short stature (median height 5th %ile)
63
Eyes (microphthalmia)
38
Renal and urinary tract
34
Male genitalia
20
Mental retardation
16
Gastrointestinal (eg, anorectal, duodenal atresia)
14
Cardiac abnormalities
13
Hearing
11
Central nervous system (eg, hydrocephalus, septum
pellucidum)
8
No abnormalities
30
Approch to anemia : Impaired red cell formation
(Normal spleen, low retic count, normal bilirubin, normal
urinalysis)
1)Deficiency
2)Bone marrow failure
3)Bone marrow infiltration
Malignant: Leukemia…
Non malignant: Metabolic disease Osteopetrosis
Fast Cases
A 15 yo girl with a history of systemic lupus
erythematosus comes to the clinic for
evaluation of fatigue and pallor.
Hgb is 7.2, MCV 85, Retic 10%, WBC 3.5 (50%
polys, 40% lymphs, 10% atypicals), and plts
of 125.
The smear shows microspherocytes and
rouleaux formation. She does not have a
history of blood loss.
What does she have?
Autoimmune hemolytic anemia
 17 mounts age infant with an unexplained
persistent anemia
 History of neonatal jaundice
 Requirement of pRBC transfusion * 2 early
infancy
 Hb stable 7-9 gr/dl from age 3-17 months
 spleen 5 cm below costal margin
 Retic 20%, with indirect hyperbilirubinemia
 What does she have?
 Pyruvate kinase deficiency
A 3 yo girl has had diarrhea, sometimes
bloody, for several days. Now, she has
fever, edema, petechiae & hypertension.
The CBC shows: Hgb 7.5, MCV 79, Retic
15%, Plts 35, and WBC 13.5 with a
normal differential. The smear shows
several helmet cells and polychromasia
and confirms the thrombocytopenia
What does she have?
Hemolytic uremic syndrome
A 3 month old boy is brought to the ED lethargic
and with a fever of 40° C. While attending to
the airway, correcting hypotension and initiating
antibiotics, the nurse informs you of the CBC
results: Hgb 5.8, MCV 81, Retic 16%, WBC
23.5 (56% polys, 24% bands, 10% lymphs, &
10% atypical lymphs) and plts of 350.
He has blood on dipstick analysis of his urine with
no RBC’s on microscopic analysis.
The blood shows polychromasia, and several bite
cells.
What does he have?
G6PD deficiency
A 9 month old boy comes the Dr.’s office
for evaluation of a cold. Further hx
reveals introduction of whole cow’s milk
at 5 months and no well baby visits.
He appears quite pale and has the
following findings: Hgb 5.3, MCV 48,
plts 780, WBC 12.5 and retic 1.7%
What does he have?
Iron Deficiency anemia
An 18 month old girl was in good health until
she developed a cold 10 days ago.
Now she is pale but without visible jaundice.
The CBC shows a Hgb of 6.8, MCV of 78
and retic of 0.1%, WBC & Plts are normal
as is the peripheral blood smear.
What does she have?
Transient Erythroblastopenia
Childhood
of
The CBC of an 8 yo girl reveals the
following: Hgb 10, MCV 102, Retic
0.4%, WBC normal, Plts 125.
She is slightly short, has several large
café-au-lait spots, is performing below
average in school and has short
thumbs.
What does she have?
Fanconi’s Anemia
You are asked to assist in the care of political
refugees from Afghan. On the screening
entrance exam you note that one of them, a 2 yo
girl, is very pale and lethargic. Her spleen is
down to the level of the umbilicus.
The labs reveal: Hgb 6.3, Retic 6%, MCV 55, with
normal WBC & plts.
The smear shows many target cells, polychromasia,
basophilic stippling, red cell fragment,
anisocytosis and hypochromia.
What does she have?
 thalassemia major
People may doubt what you say
but they will believe what you