Associated Professor Gao Yijing
Children`s Hospital,Fudan University
Diseases of the Blood in Children
血液系统疾病
Diseases of the Blood in Children
? Anemias
Nutritional anemias (Iron deficiency iron)
Hereditary spherocytosis
Glucose-6-phosphate dehydrogenase (G-6-PD)
deficiency
Thalassemia
? Bleeding disorders (Hemorrhagic diseases)
ITP Hemophilia
? Neoplastic diseases
Development of the Hematopoietic System
? Blood formation first can be recognized as early as 3rd
wk after conception
? By 2 mo active hematopoiesis is established in the liver,
which is the main site of blood formation during the
middle portion of fetal life
? After about 6 mo hematopoiesis shifts gradually to the
medullary spaces,and by birth most blood formation
normally takes place in bone marrow
Extramedullary hematopoiesis
Hematologic Values During Infancy and
Childhood
? Normal ranges for peripheral blood
counts vary significantly with age
Red blood cells
Physiologic anemia
? Hemoglobin
? White blood cells
Anemia
A reduction of the red blood cell mass or
hemoglobin concentration below the
range of values occurring in healthy
persons
Lower limit of normal hemoglobin values at various ages
neonate Hb ? 145 g/L ?
1 ~ 4m Hb ? 90 g/L ?
4 ~ 6m Hb ? 100 g/L
6m ~ 6y Hb ? 110 g/L
6y ~ 14y Hb ? 120 g/L
Degree of anemia
Mild Moderate Severe Extremely severe
~90 g/L ~60 g/L ~30 g/L ? 30 g/L
Neonate ~120 g/L ~90 g/L ~60 g/L ? 60 g/L
? Anemia is not a specific entity but an indication of an
underlying pathologic process or disease
? Two useful classification of anemias
Physiologic (erythrokinetic) classification
1,those resulting primarily from decreased production
of red blood cells or hemoglobin
2,those in which increased destruction or loss of red
blood cells
Morphologic classification
the red blood cells being characterized by their mean
corpuscular volume (MCV) as microcytic (MCV < 75fl),
macrocytic (MCV > 100fl),or normocytic (75-100fl)
Classification of the Anemias
? Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
? Hemolytic anemias
? Extrinsic (extracelllular) abnormalities
? Nonimmunologic disorders
Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
Decreased numbers of red blood cell precursors in the
marrow,Pure red blood cell” anemia
Congenital pure red blood cell anemia
Acquired pure red blood cell anemias (e.g,TEC)
Inadequate production despite normal numbers of red
blood cell precursors
Anemia of infection,inflammation,and cancer
Anemia of chronic renal disease
Congenital dyserythropoietic anemias
Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
Deficiency of specific factors
Megaloblastic anemias
Folic acid deficiency or malabsorption
Vitamin B12 deficiency,malabsorption,or transport
Orotic aciduria
Microcytic anemias
Iron deficiency
Pyridoxine-responsive and X-linked hypochromic anemias
Lead poisoning
Copper deficiency
Thalassemia trait
Hemolytic anemias
Intrinsic abnormalities of the red blood cell
“Structural” defects
Hereditary spherocytosis
Hemolytic elliptocytosis
Paroxyknocytosis
Enzymatic defects (nonspherocytic hemolytic
anemias)
Enzymes of glycolytic pathway---pyruvate kinase,
hexokinase,and others
Enzymes of the pentose phosphate pathway and
glutathione complex
Defects in synthesis of hemoglobin
Hb S,C,D,E,etc,alone and in combination Thalassemia
Extrinsic (extracellular) abnormalites
Immunologic disorders
Passively acquired antibodies (hemolytic disease of
the nemborn)
Rh isoimmunzation
A or B isoimmunization
Other blood group families
Active antibody formation
Idiopathic autoimmune hemolytic anemia;
cold agglutinin diseases
Symptomatic---lupus,lymphoma
Drug---induced
Nonimmunologic disorders
Toxic from drugs,chemicals
Infections---malarial,clostridial
155-13 Normal red cell
morphology
155-14 Microcytes in IDA
155-15 Megalocytes in
pernicious anemia
Nutritional Anemias
Iron deficiency anemia ?
Megaloblastic anemia
Iron deficiency anemia
IDA
IDA
?results from lack of sufficient iron for
synthesis of hemoglobin
?Microcytic hypochromic anemia
IDA Epidemiology
? Most common cause of anemia
Globally,~30% of the estimated world population of almost
4.5 billion are anemic,and at least half of these,or 500
million people,are bilieved to have IDA
? Toddlers,adolescent girls,and women of
childbearing age
IDA Etiology
? Insufficient iron stores
? Inadequate iron supply
Diet with insufficient amounts
of bioavailable iron
Impaired absorption of iron
? Increased iron requirements
Blood loss
Growth
Pregnancy and lactation
? Impaired iron transport
IDA Pathogenesis
? Iron depletion,ID
? Iron deficient erythropoiesis,IDE
? Iron deficiency anemia,IDA
Laboratory evaluation of iron status
Serum ferritin,SF ?
Free erythrocyte protoporphyrin,FEP ?
Serum iron,SI ?
Transferrin saturation,TS ?
Total iron binding capacity,TIBC ?
Marrow iron stores ?
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
IDA clinical manifestations
? Pallor is the most important clue
? Few symptoms of anemia are noted in mild to
moderate IDA cases (60~100g/L)
? Irritability and anorexia are prominent when Hb level
falls below 50g/L
? Tachycardia,cardiac dilatation and systolic murmur
are often present
? Palpable spleen in 10 ~15% of patients
? Pica is sometimes prominent
? Changes in neurologic and intellectual function
IDA Laboratory findings
? Peripheral blood
microcytic hypochromic anemia
normal or minimally elevated reticulocyte count
? Bone marrow
hypercellular with iron hyperplasia
? Biochemical indicators
SF? + FEP ? + SI?,TIBC?,TS?
Marrow iron stores 2-3+ 0-Trace ? 0 0
SF (?g/L) 100?60 ? 20 ? 10 ? 10
SI (?g/dl) 115?50 ? 115 ? 60 ? ? 40
TS(%) 35?15 ? 30 ? 15 ? ? 10
Sideroblast(%) 40-60 40-60 ? 10 ? ? 10
TIBC (?g/dl) 330?30 360 390 ? 410
FEP (?g/dl RBC) 30 30 100 ? 200
RBCs Normal Normal Normal
Normal IDAIDEID
Microcytic
hypochromic
Storage iron
Transport iron
Erythron iron
IDA
? Diagnosis
? Differential diagnosis
Thalassemia
Anemia of chronic disease
sideroblastic anemias
IDA treatment
? General Measures
? Oral administration of simple ferrous
salts (sulfate,gluconate,fumarate)
Element iron 4~6mg/kg.d for 2~3mo
? Transfusion
Bleeding disorders
(Hemorrhagic diseases)
ITP
Hemophilia
ITP
Immune thrombocytopenic purpura
Idiopathic thrombocytopenic Purpura
?Most common of the thrombocytopenic purpuras of
childhood
?An immune mechanism is the basis for ITP
?Acute ITP/Chronic ITP
?Excellent prognosis
ITP (acute) Pathogenesis
? Reduced platelet life span in essentially
all patients
? Increased platelet production in most
patients
? Infrequent severe qualitative platelet
defects
ITP clinical manifestation
?Sudden onset
?Most children aged from 2~5 years
?Often follows viral infection
?Petechiae and purpura are common
?Generally no other physical findings
?Isolated thrombocytopenia ?20~30,000/ul
?Higher frequency of spontaneous remission
ITP (acute) laboratory findings
?Peripheral blood
CBC
Blood smear
?(Bone marrow,platelet associated antibody,
PTT and PT)
ITP（ acute）
?an otherwise healthy child
isolated thrombocytopenia
physical examination only for bruising or petechiae
?clinical diagnosis
Diagnosis
鉴别诊断
ITP is a diagnosis of exclusion
ITP (acute) treatment
? General Measures
? Corticosteroids
? Intravenous Immune Globulin (IVIG)
? Anti-D
? Splenectomy
Hemophilia
Hemophilias
Include serious of the congenital coagulation
disorders
incidence 5~10/100000
?HA FVIII
HB FIX
HC FXI
X-linked recessive disease
Autosomal recessive disease
HA
Presentation
Sex male （ 1/5000 male birth）
Onset 1~2 years
Family history with or without
Clinical aspects
excessive bleeding after mild injury
hemarthrosis
HA
Laboratory findings
?PTT （ screening test）
nPT
?FVIII:C ?2% severe
（ diagnostic test） 2%~5% moderate
5%~20% mild
20%~50% subclinical
HA
Diagnosis
clinical presentation
coagulation tests
specific assay
Differential diagnosis
? HB
? von Willebrand disease,vWD
HA
Treatment
Factor replacement therapy
Adjunctive therapeutic measures (DDAVP)
Gene therapy?
Consultation
Leukemia
Epidemiology
Incidence 3~4/100000
Common clinical presentation
Treatment
different from adults
Prognosis
much better than that of adults
Children`s Hospital,Fudan University
Diseases of the Blood in Children
血液系统疾病
Diseases of the Blood in Children
? Anemias
Nutritional anemias (Iron deficiency iron)
Hereditary spherocytosis
Glucose-6-phosphate dehydrogenase (G-6-PD)
deficiency
Thalassemia
? Bleeding disorders (Hemorrhagic diseases)
ITP Hemophilia
? Neoplastic diseases
Development of the Hematopoietic System
? Blood formation first can be recognized as early as 3rd
wk after conception
? By 2 mo active hematopoiesis is established in the liver,
which is the main site of blood formation during the
middle portion of fetal life
? After about 6 mo hematopoiesis shifts gradually to the
medullary spaces,and by birth most blood formation
normally takes place in bone marrow
Extramedullary hematopoiesis
Hematologic Values During Infancy and
Childhood
? Normal ranges for peripheral blood
counts vary significantly with age
Red blood cells
Physiologic anemia
? Hemoglobin
? White blood cells
Anemia
A reduction of the red blood cell mass or
hemoglobin concentration below the
range of values occurring in healthy
persons
Lower limit of normal hemoglobin values at various ages
neonate Hb ? 145 g/L ?
1 ~ 4m Hb ? 90 g/L ?
4 ~ 6m Hb ? 100 g/L
6m ~ 6y Hb ? 110 g/L
6y ~ 14y Hb ? 120 g/L
Degree of anemia
Mild Moderate Severe Extremely severe
~90 g/L ~60 g/L ~30 g/L ? 30 g/L
Neonate ~120 g/L ~90 g/L ~60 g/L ? 60 g/L
? Anemia is not a specific entity but an indication of an
underlying pathologic process or disease
? Two useful classification of anemias
Physiologic (erythrokinetic) classification
1,those resulting primarily from decreased production
of red blood cells or hemoglobin
2,those in which increased destruction or loss of red
blood cells
Morphologic classification
the red blood cells being characterized by their mean
corpuscular volume (MCV) as microcytic (MCV < 75fl),
macrocytic (MCV > 100fl),or normocytic (75-100fl)
Classification of the Anemias
? Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
? Hemolytic anemias
? Extrinsic (extracelllular) abnormalities
? Nonimmunologic disorders
Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
Decreased numbers of red blood cell precursors in the
marrow,Pure red blood cell” anemia
Congenital pure red blood cell anemia
Acquired pure red blood cell anemias (e.g,TEC)
Inadequate production despite normal numbers of red
blood cell precursors
Anemia of infection,inflammation,and cancer
Anemia of chronic renal disease
Congenital dyserythropoietic anemias
Anemias resulting primary from inadequate
production of red blood cells or hemoglobin
Deficiency of specific factors
Megaloblastic anemias
Folic acid deficiency or malabsorption
Vitamin B12 deficiency,malabsorption,or transport
Orotic aciduria
Microcytic anemias
Iron deficiency
Pyridoxine-responsive and X-linked hypochromic anemias
Lead poisoning
Copper deficiency
Thalassemia trait
Hemolytic anemias
Intrinsic abnormalities of the red blood cell
“Structural” defects
Hereditary spherocytosis
Hemolytic elliptocytosis
Paroxyknocytosis
Enzymatic defects (nonspherocytic hemolytic
anemias)
Enzymes of glycolytic pathway---pyruvate kinase,
hexokinase,and others
Enzymes of the pentose phosphate pathway and
glutathione complex
Defects in synthesis of hemoglobin
Hb S,C,D,E,etc,alone and in combination Thalassemia
Extrinsic (extracellular) abnormalites
Immunologic disorders
Passively acquired antibodies (hemolytic disease of
the nemborn)
Rh isoimmunzation
A or B isoimmunization
Other blood group families
Active antibody formation
Idiopathic autoimmune hemolytic anemia;
cold agglutinin diseases
Symptomatic---lupus,lymphoma
Drug---induced
Nonimmunologic disorders
Toxic from drugs,chemicals
Infections---malarial,clostridial
155-13 Normal red cell
morphology
155-14 Microcytes in IDA
155-15 Megalocytes in
pernicious anemia
Nutritional Anemias
Iron deficiency anemia ?
Megaloblastic anemia
Iron deficiency anemia
IDA
IDA
?results from lack of sufficient iron for
synthesis of hemoglobin
?Microcytic hypochromic anemia
IDA Epidemiology
? Most common cause of anemia
Globally,~30% of the estimated world population of almost
4.5 billion are anemic,and at least half of these,or 500
million people,are bilieved to have IDA
? Toddlers,adolescent girls,and women of
childbearing age
IDA Etiology
? Insufficient iron stores
? Inadequate iron supply
Diet with insufficient amounts
of bioavailable iron
Impaired absorption of iron
? Increased iron requirements
Blood loss
Growth
Pregnancy and lactation
? Impaired iron transport
IDA Pathogenesis
? Iron depletion,ID
? Iron deficient erythropoiesis,IDE
? Iron deficiency anemia,IDA
Laboratory evaluation of iron status
Serum ferritin,SF ?
Free erythrocyte protoporphyrin,FEP ?
Serum iron,SI ?
Transferrin saturation,TS ?
Total iron binding capacity,TIBC ?
Marrow iron stores ?
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
GI tract
Hepatocyte
TF
Muscle,other
parenchymal cells
Monocyte/macrophage
system
Circulating
red blood
cells
Erythroid
marrow
IDA clinical manifestations
? Pallor is the most important clue
? Few symptoms of anemia are noted in mild to
moderate IDA cases (60~100g/L)
? Irritability and anorexia are prominent when Hb level
falls below 50g/L
? Tachycardia,cardiac dilatation and systolic murmur
are often present
? Palpable spleen in 10 ~15% of patients
? Pica is sometimes prominent
? Changes in neurologic and intellectual function
IDA Laboratory findings
? Peripheral blood
microcytic hypochromic anemia
normal or minimally elevated reticulocyte count
? Bone marrow
hypercellular with iron hyperplasia
? Biochemical indicators
SF? + FEP ? + SI?,TIBC?,TS?
Marrow iron stores 2-3+ 0-Trace ? 0 0
SF (?g/L) 100?60 ? 20 ? 10 ? 10
SI (?g/dl) 115?50 ? 115 ? 60 ? ? 40
TS(%) 35?15 ? 30 ? 15 ? ? 10
Sideroblast(%) 40-60 40-60 ? 10 ? ? 10
TIBC (?g/dl) 330?30 360 390 ? 410
FEP (?g/dl RBC) 30 30 100 ? 200
RBCs Normal Normal Normal
Normal IDAIDEID
Microcytic
hypochromic
Storage iron
Transport iron
Erythron iron
IDA
? Diagnosis
? Differential diagnosis
Thalassemia
Anemia of chronic disease
sideroblastic anemias
IDA treatment
? General Measures
? Oral administration of simple ferrous
salts (sulfate,gluconate,fumarate)
Element iron 4~6mg/kg.d for 2~3mo
? Transfusion
Bleeding disorders
(Hemorrhagic diseases)
ITP
Hemophilia
ITP
Immune thrombocytopenic purpura
Idiopathic thrombocytopenic Purpura
?Most common of the thrombocytopenic purpuras of
childhood
?An immune mechanism is the basis for ITP
?Acute ITP/Chronic ITP
?Excellent prognosis
ITP (acute) Pathogenesis
? Reduced platelet life span in essentially
all patients
? Increased platelet production in most
patients
? Infrequent severe qualitative platelet
defects
ITP clinical manifestation
?Sudden onset
?Most children aged from 2~5 years
?Often follows viral infection
?Petechiae and purpura are common
?Generally no other physical findings
?Isolated thrombocytopenia ?20~30,000/ul
?Higher frequency of spontaneous remission
ITP (acute) laboratory findings
?Peripheral blood
CBC
Blood smear
?(Bone marrow,platelet associated antibody,
PTT and PT)
ITP（ acute）
?an otherwise healthy child
isolated thrombocytopenia
physical examination only for bruising or petechiae
?clinical diagnosis
Diagnosis
鉴别诊断
ITP is a diagnosis of exclusion
ITP (acute) treatment
? General Measures
? Corticosteroids
? Intravenous Immune Globulin (IVIG)
? Anti-D
? Splenectomy
Hemophilia
Hemophilias
Include serious of the congenital coagulation
disorders
incidence 5~10/100000
?HA FVIII
HB FIX
HC FXI
X-linked recessive disease
Autosomal recessive disease
HA
Presentation
Sex male （ 1/5000 male birth）
Onset 1~2 years
Family history with or without
Clinical aspects
excessive bleeding after mild injury
hemarthrosis
HA
Laboratory findings
?PTT （ screening test）
nPT
?FVIII:C ?2% severe
（ diagnostic test） 2%~5% moderate
5%~20% mild
20%~50% subclinical
HA
Diagnosis
clinical presentation
coagulation tests
specific assay
Differential diagnosis
? HB
? von Willebrand disease,vWD
HA
Treatment
Factor replacement therapy
Adjunctive therapeutic measures (DDAVP)
Gene therapy?
Consultation
Leukemia
Epidemiology
Incidence 3~4/100000
Common clinical presentation
Treatment
different from adults
Prognosis
much better than that of adults
