Alterations of Hematologic Function Alterations of Hematologic Function in Childrenin Children
Chapter 28Chapter 28
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Fetal and Neonatal Fetal and Neonatal HematopoiesisHematopoiesis
The embryo becomes too large for oxygenation The embryo becomes too large for oxygenation by simple diffusion by simple diffusion Erythropoiesis begins within the vessels of the yolk Erythropoiesis begins within the vessels of the yolk
sacsac At 8 weeks’ gestation, erythrocyte production shifts to At 8 weeks’ gestation, erythrocyte production shifts to
the liver sinusoids (peaks at 4 months)the liver sinusoids (peaks at 4 months) By 5 months’ gestation, erythrocyte production begins By 5 months’ gestation, erythrocyte production begins
in the bone marrowin the bone marrow• At delivery marrow is only significant hematopoiesis siteAt delivery marrow is only significant hematopoiesis site
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Hemolytic Disease of the Newborn Hemolytic Disease of the Newborn
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Fetal and Neonatal Fetal and Neonatal HematopoiesisHematopoiesis
Fetal hemoglobinFetal hemoglobin Two Two αα--chains; two chains; two γγ--chainschains Embryonic hemoglobinsEmbryonic hemoglobins
• Gower 1, Gower 2, and PortlandGower 1, Gower 2, and Portland
Fetal hemoglobinFetal hemoglobin• Hb FHb F
Greater affinity for oxygen than adult hemoglobinGreater affinity for oxygen than adult hemoglobin
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Fetal and Neonatal Fetal and Neonatal HematopoiesisHematopoiesis
Postnatal changesPostnatal changes Erythrocytes Erythrocytes LeukocytesLeukocytes PlateletsPlatelets
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Acquired Disorders of Acquired Disorders of ErythrocytesErythrocytes
Iron deficiency anemiaIron deficiency anemia Most common blood disorder of infancy and childhoodMost common blood disorder of infancy and childhood
• Stored iron: greatest stores are present 4 to 8 weeks after Stored iron: greatest stores are present 4 to 8 weeks after birthbirth
• Dietary iron: needed after 16-20 weeks of ageDietary iron: needed after 16-20 weeks of age
Lack of iron intake or blood lossLack of iron intake or blood loss ManifestationsManifestations
• Irritability, decreased activity tolerance, weakness, and lack Irritability, decreased activity tolerance, weakness, and lack of interest in playof interest in play
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Acquired Disorders of Acquired Disorders of ErythrocytesErythrocytes
Acquired congenital hemolytic anemiaAcquired congenital hemolytic anemia Hemolytic disease of the newborn (HDN)Hemolytic disease of the newborn (HDN)
• Alloimmune diseaseAlloimmune disease
• Maternal antibody directed against fetal antigensMaternal antibody directed against fetal antigens
• ABO incompatibility occurs in 20% to 25% of casesABO incompatibility occurs in 20% to 25% of cases
• Rh incompatibility occurs in less than 10%Rh incompatibility occurs in less than 10%
• Also termed erythroblastosis fetalisAlso termed erythroblastosis fetalis Presence of red cell precursors in the peripheral bloodPresence of red cell precursors in the peripheral blood
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Acquired Disorders of Acquired Disorders of ErythrocytesErythrocytes
Hemolytic disease of the newborn (HDN)Hemolytic disease of the newborn (HDN) ManifestationsManifestations
• AnemiaAnemia
• HyperbilirubinemiaHyperbilirubinemia
• Icterus neonatorumIcterus neonatorum
• KernicterusKernicterus
TreatmentTreatment• Prevention: RhoGAMPrevention: RhoGAM
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Hemolytic Disease of the Hemolytic Disease of the NewbornNewborn
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Acquired Disorders of Acquired Disorders of Erythrocytes Erythrocytes
Anemia of infectious diseaseAnemia of infectious disease Diseases initially acquired by the mother and Diseases initially acquired by the mother and
transmitted to the fetustransmitted to the fetus• Results in hemolytic anemiaResults in hemolytic anemia
• Likely due to injury to the erythrocyte membranes or Likely due to injury to the erythrocyte membranes or erythrocyte precursorserythrocyte precursors
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Glucose-6-phosphate dehydrogenase deficiency Glucose-6-phosphate dehydrogenase deficiency (G6PD)(G6PD) Inherited, X-linked, recessive disorderInherited, X-linked, recessive disorder G6PD: enzyme that helps erythrocytes maintain G6PD: enzyme that helps erythrocytes maintain
metabolic processes despite injurious conditions metabolic processes despite injurious conditions Asymptomatic unless stressors presentAsymptomatic unless stressors present Without G6PD oxidative stressors damage Without G6PD oxidative stressors damage
hemoglobin and the plasma membranes of hemoglobin and the plasma membranes of erythrocytes (Heinz bodies)erythrocytes (Heinz bodies)
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Hereditary spherocytosisHereditary spherocytosis Autosomal dominant traitAutosomal dominant trait Abnormality of proteins or spectrins of the Abnormality of proteins or spectrins of the
erythrocyte membrane leading to an increased erythrocyte membrane leading to an increased concentration of intracellular sodiumconcentration of intracellular sodium
Causes splenomegaly and microcytic spherocytes Causes splenomegaly and microcytic spherocytes
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Hereditary SpherocytosisHereditary Spherocytosis
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Sickle cell diseaseSickle cell disease Disorders characterized by the presence of an Disorders characterized by the presence of an
abnormal hemoglobin (Hb S)abnormal hemoglobin (Hb S)• Mutation causes valine to be replaced by glutamic acidMutation causes valine to be replaced by glutamic acid
Deoxygenation and dehydration cause the red Deoxygenation and dehydration cause the red cells to solidify and stretch into an elongated sickle cells to solidify and stretch into an elongated sickle shapeshape
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Sickle cell diseaseSickle cell disease Once sickling begins, continues until PoOnce sickling begins, continues until Po22 returns to returns to
normal, then it ceases spontaneously normal, then it ceases spontaneously Extent, severity, and clinical manifestations of Extent, severity, and clinical manifestations of
sickling depend on the percentage of hemoglobin sickling depend on the percentage of hemoglobin that is Hb Sthat is Hb S
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Sickle cell diseaseSickle cell disease Sickle cell traitSickle cell trait
• Child inherits Hb S from one parent and Hb A from Child inherits Hb S from one parent and Hb A from anotheranother
Can result in: Can result in: • Vasoocclusive crisis (thrombotic crisis), aplastic crisis, Vasoocclusive crisis (thrombotic crisis), aplastic crisis,
sequestration crisis, and hyperhemolytic crisissequestration crisis, and hyperhemolytic crisis Other formsOther forms
• Sickle cell-thalassemia disease and sickle cell-Hb C Sickle cell-thalassemia disease and sickle cell-Hb C diseasedisease
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Sickle Cell DiseaseSickle Cell Disease
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Sickle Cell DiseaseSickle Cell Disease
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Sickle Cell DiseaseSickle Cell Disease
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Sickle Cell DiseaseSickle Cell Disease
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
ThalassemiasThalassemias Autosomal recessive disordersAutosomal recessive disorders Synthesis of the globin chains of the hemoglobin Synthesis of the globin chains of the hemoglobin
molecule is slowed or defectivemolecule is slowed or defective Major—homozygous inheritanceMajor—homozygous inheritance Minor—heterozygous inheritanceMinor—heterozygous inheritance
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
In alpha-thalassemia the In alpha-thalassemia the αα--chains are chains are affected; affected; ß-ß-chains in beta-thalassemiachains in beta-thalassemia Beta-thalassemia minorBeta-thalassemia minor Beta-thalassemia major Beta-thalassemia major Alpha traitAlpha trait Alpha-thalassemia minorAlpha-thalassemia minor Hemoglobin H diseaseHemoglobin H disease
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Beta-thalassemia minor Beta-thalassemia minor Mild to moderate hypochromic-microcytic anemia, Mild to moderate hypochromic-microcytic anemia,
mild splenomegaly, bronze coloring of the skin, mild splenomegaly, bronze coloring of the skin, hyperplasia of bone marrowhyperplasia of bone marrow
Usually asymptomaticUsually asymptomatic Beta-thalassemia major Beta-thalassemia major
May be quite illMay be quite ill Severe anemia results in large cardiovascular burdenSevere anemia results in large cardiovascular burden
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Inherited Disorders of Inherited Disorders of Erythrocytes Erythrocytes
Alpha-thalassemia minor Alpha-thalassemia minor Clinical manifestations virtually identical to those of Clinical manifestations virtually identical to those of
beta-thalassemia minorbeta-thalassemia minor Alpha-thalassemia major Alpha-thalassemia major
Hydrops fetalis Hydrops fetalis Fulminant intrauterine congestive heart failureFulminant intrauterine congestive heart failure Fetus has a grossly enlarged heart and liverFetus has a grossly enlarged heart and liver Diagnosis usually is made post mortemDiagnosis usually is made post mortem
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Inherited Coagulation and Inherited Coagulation and Platelet Disorders Platelet Disorders
HemophiliasHemophilias Serious bleeding disordersSerious bleeding disorders Hemophilia A (classic hemophilia)Hemophilia A (classic hemophilia) Hemophilia B (Christmas disease)Hemophilia B (Christmas disease) Hemophilia C (factor XI deficiency)Hemophilia C (factor XI deficiency) von Willebrand diseasevon Willebrand disease
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Inherited Coagulation and Inherited Coagulation and Platelet Disorders Platelet Disorders
Congenital hypercoagulability and thrombosisCongenital hypercoagulability and thrombosis ThrombophiliaThrombophilia Protein C deficiencyProtein C deficiency Neonatal purpura fulminansNeonatal purpura fulminans Protein S deficiencyProtein S deficiency Antithrombin III (AT III) deficiencyAntithrombin III (AT III) deficiency
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Antibody-Mediated Antibody-Mediated Hemorrhagic Disease Hemorrhagic Disease
Idiopathic thrombocytopenic purpuraIdiopathic thrombocytopenic purpura Autoimmune or primary thrombocytopenic purpuraAutoimmune or primary thrombocytopenic purpura
Autoimmune neonatal thrombocytopeniaAutoimmune neonatal thrombocytopenia Autoimmune neonatal thrombocytopenia Autoimmune neonatal thrombocytopenia
purpurapurpura Autoimmune vascular purpuraAutoimmune vascular purpura
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LeukemiaLeukemia Most common malignancy of childhoodMost common malignancy of childhood 80% to 85% are acute lymphoblastic 80% to 85% are acute lymphoblastic
leukemiasleukemias Cause unclearCause unclear
Genetic susceptibility, environmental factors, viral Genetic susceptibility, environmental factors, viral infectionsinfections
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LeukemiaLeukemia SymptomsSymptoms
Pallor, fatigue, petechiae, purpura, bleeding, fever, Pallor, fatigue, petechiae, purpura, bleeding, fever, bone painbone pain
DiagnosisDiagnosis Bone marrow aspirationBone marrow aspiration
• Blast cellBlast cell
TreatmentTreatment ChemotherapyChemotherapy RadiationRadiation
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LeukemiaLeukemia FAB classificationFAB classification
Acute lymphoblastic leukemias L1, L2, and L2Acute lymphoblastic leukemias L1, L2, and L2 Acute non-lymphoblastic leukemias M1-7Acute non-lymphoblastic leukemias M1-7
ImmunoclassificationImmunoclassification Surface marker identificationSurface marker identification
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LeukemiaLeukemia
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Lymphoma Lymphoma Non-Hodgkin lymphomaNon-Hodgkin lymphoma
Nodular and diffuseNodular and diffuse Hodgkin lymphomaHodgkin lymphoma
Rare in childhoodRare in childhood Infectious mode of transmissionInfectious mode of transmission Many children with Hodgkin lymphoma Many children with Hodgkin lymphoma
demonstrate a high antibody titer to Epstein-Barr demonstrate a high antibody titer to Epstein-Barr virus (EBV)virus (EBV)