Transcript Hemolytic anemia

‫بنام خدا‬
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
Pathophysiology of anemia
 Blood loss
 Hemolytic anemia
 Impaired red cell formation
Acute blood loss
 Acute blood loss: (Normal spleen, high
retic count, normal bilirubin, normal urinalysis)
Neonatal problem (fetofetal transfusion,
fetomaternal transfusion,…)
Hemorrhagic disease of newborn
Meckel’s diverticulum, …..
(Spleen, Hb, Retic, Bilirubin, urinalysis )
Hemolytic anemia
Hemolysis
 Shortened lifespan of circulating RBC
 Sites of Hemolysis
– Intravascular– Extravascular-Liver and Spleen
 Hemolytic anemia
1)Corupuscular (enzyme defect, membrane
defect, hemoglobin disorder)
2) Extra corpuscular (immune, non immune)
Hemolytic anemia: Corpuscular
1) Enzyme defect: G6PD deficiency, PK
deficiency
2) Membrane defect: Spherocytosis,
Elliptocytosis
3) Hemoglobin disorder: Normal variant,
Functional disorder, Structural problem,
Thalassemia
Hemolytic anemia:
Corpuscular( Enzyme defect):
G6PD Deficiency
Glucose 6 phosphate dehydrogenase(G6PD)
G6PD DEFICIENCY:
 X-linked disorder
 The most common enzymatic disorder of
red blood cells in humans
 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
Normal wild-type enzymes:
 G6PD B : is found in most Caucasians,
Asians, and a majority of Blacks
 G6PD A+: is found in 20 to 30 percent of
Blacks from Africa
Abnormal wild-type variants:
 G6PD A- variant :is the most common variant associated
with mild to moderate hemolysis (class III). It is found in 10 to 15
percent of African-Americans
 G6PD Mediterranean variant: is the most common
abnormal variant found in Caucasians , its catalytic activity is markedly
reduced and hemolysis can be severe (class II)
 G6PD Canton : a variant enzyme seen in Asians; its
biochemical properties are very similar to those of G6PD
Mediterranean
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
 Patients with G6PD A- usually have
hemolysis that is mild and limited to older
deficient erythrocytes (class III).
 In contrast, red cells of all ages are grossly
deficient in G6PD Mediterranean (class II).
Clinical sign and symptoms:
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Intermittent hemolysis
Chronic non spherocytic hemolytic anemia
Neonatal hyperbilirubinemia
Favism
Increased infection susceptibility(rare)
Hemolytic anemia
Membrane defect:
Spherocytosis
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
non-deformable
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:
Hemoglobin disorder:
Hemolytic anemia: Hemoglobin disorder:
Normal variant,
Functional disorder,
Structural problem,
Thalassemia
Thalassemia minor:
A patient with microcytosis with mild
anemia or actually without anemia
‫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 ‪‬‬
Sickle cell anemia
Extracorpuscular Factors:
 Immune hemolysis : (alloimmune, autoimmune, iso
immune)
 Non immune hemolysis:
Extracorpuscular Factors:
 Non immune hemolysis:
Hypersplenism
Trauma
– malfunctioning prosthetic valves
– DIC
– TTP , HUS
Infection: malaria, clostridium difficile,
snake and insect bites
Impaired red cell formation:
Impaired red cell formation
1)Deficiency (Normal spleen, low retic count,
normal bilirubin, normal urinalysis)
2)Bone marrow failure (Normal spleen, low
retic count, normal bilirubin, normal urinalysis)
3)Bone marrow infiltration (splenomegaly low retic
count, normal bilirubin, normal urinalysis)
1)Deficiency (Normal spleen, low retic
count, normal bilirubin, normal urinalysis):
 Iron deficiency
 Megaloblastic anemia ( vitamin B12
deficiency, folate deficiency)
 Others: vitamin C, vitamin B6, protein
deficiency, Thyroxine deficiency
Iron:
 Iron is an essential nutrient in humans
 most common nutritional deficiency in
children.
 iron balance is achieved by control of
intestinal absorption
‫درصد جذب آهن در موارد ‪‬‬
‫غذایی مختلف‬
‫علل بروز‬
‫فقر آهن‬
‫‪‬‬
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
DIAGNOSIS
 serum ferritin
 serum iron,
 Total iron-binding capacity,
 Transferrin saturation
 serum transferrin receptor, and reticulocyte
hemoglobin content
 Therapeutic trial of iron
 BM Aspiration
2)Bone marrow failure (Normal spleen, low
retic count, normal bilirubin, normal urinalysis):
 Failure of a single cell line(red cell):
1) Congenital pure red cell anemia (Diamond-Blackfan
anemia)
2)Acquired red cell aplasia: a) TEC syndrome b) Aplastic
crisis
 Failure of all cell line:
 1)Constitutional (Fanconi’s anemia)
 2)Acquired(Aplastic anemia)
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
3)Bone marrow infiltration
(splenomegaly, low reticulocyte count, normal
bilirubin, normal urinalysis) :
 Malignant: Leukemia, Bone marrow
involvement in other cancers
 Non malignant: Metabolic disease
(gaucher’s disease, Niemann-pick),
Osteopetrosis