In the name of God

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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

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Pathophysiology of anemia

• Blood loss
• Hemolytic anemia
• Impaired red cell formation

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Acute blood loss
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(Spleen, Hb, Retic, Bilirubin, urinalysis )

• Acute blood loss (Normal spleen, high retic
  count, normal bilirubin, normal urinalysis)
• Neonatal problem (fetofetal transfusion,
  fetomaternal transfusion,)
• Hemorrhagic disease of newborn
• Meckels diverticulum, ..

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Hemolytic anemia
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Hemolysis

• Shortened lifespan of circulating RBC
• Sites of Hemolysis
• Intravascular-
• Extravascular-Liver and Spleen

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• Hemolytic anemia
• 1)Corupuscular (enzyme defect, membrane defect,
  hemoglobin disorder)
• 2) Extra corpuscular (immune, non immune)

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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

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Hemolytic anemia Corpuscular( Enzyme defect)

• G6PD Deficiency

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Glucose 6 phosphate dehydrogenase(G6PD)
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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)

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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
         

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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

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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

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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).

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Clinical sign and symptoms

• Intermittent hemolysis
• Chronic non spherocytic hemolytic anemia
• Neonatal hyperbilirubinemia
• Favism
• Increased infection susceptibility(rare)

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Hemolytic anemiaMembrane defect

• Spherocytosis

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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

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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,

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Hemolytic anemiaHemoglobin disorder
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Hemolytic anemia Hemoglobin disorder

• Normal variant,
• Functional disorder,
• Structural problem,
• Thalassemia

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Thalassemia minor

• A patient with microcytosis with mild anemia or
  actually without anemia

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Sickle cell anemia
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Extracorpuscular Factors

• Immune hemolysis (alloimmune, autoimmune, iso
  immune)
• Non immune hemolysis

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Extracorpuscular Factors

• Non immune hemolysis
• Hypersplenism
• Trauma
• malfunctioning prosthetic valves
• DIC
• TTP , HUS
• Infection malaria, clostridium difficile,
• snake and insect bites

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Impaired red cell formation
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• 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)

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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

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Iron

• Iron is an essential nutrient in humans
• most common nutritional deficiency in children.
• iron balance is achieved by control of intestinal
  absorption

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Clinical manifestation of IDAHematological
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

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Clinical manifestation of IDA Non hematological
symptoms

• Neurodevelopmental and Cognitive function
• Immunity
• Exercise capacity
• Pica and pagophagia
• Thrombosis
• Epithelial change dysphagia, esophageal web,
  atrophic glossitis, spoon nails, blue sclerae

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DIAGNOSIS

• serum ferritin
• serum iron,
• Total iron-binding capacity,
• Transferrin saturation
• serum transferrin receptor, and reticulocyte
  hemoglobin content
• Therapeutic trial of iron
• BM Aspiration

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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 (Fanconis anemia)
• 2)Acquired(Aplastic anemia)

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Fanconi AnemiaClinical 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

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3)Bone marrow infiltration (splenomegaly, low
reticulocyte count, normal bilirubin, normal
urinalysis)

• Malignant Leukemia, Bone marrow involvement in
  other cancers
• Non malignant Metabolic disease (gauchers
  disease, Niemann-pick), Osteopetrosis

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