alterations of hematologic function in children chapter 28 mosby items and derived items © 2010,...

Alterations of Hematologic Function Alterations of Hematologic Function in Childrenin Children

Chapter 28Chapter 28

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

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


Hemolytic Disease of the Newborn Hemolytic Disease of the Newborn



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



Postnatal changesPostnatal changes Erythrocytes Erythrocytes LeukocytesLeukocytes PlateletsPlatelets


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



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



Hemolytic disease of the newborn (HDN)Hemolytic disease of the newborn (HDN) ManifestationsManifestations

• AnemiaAnemia

• HyperbilirubinemiaHyperbilirubinemia

• Icterus neonatorumIcterus neonatorum

• KernicterusKernicterus

TreatmentTreatment• Prevention: RhoGAMPrevention: RhoGAM


Hemolytic Disease of the Hemolytic Disease of the NewbornNewborn


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


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)



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


Hereditary SpherocytosisHereditary Spherocytosis



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



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



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


Sickle Cell DiseaseSickle Cell Disease



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



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



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



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


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


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


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


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


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


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


LeukemiaLeukemia


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)

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