Download Chapter 28 Alterations of Hematologic Function in Children

Chapter 28 Alterations of Hematologic Function in Children

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Fetal and Neonatal Hematopoiesis 

The embryo becomes too large for oxygenation by simple diffusion 

Erythropoiesis begins within the vessels of the yolk sac  At 8 weeks’ gestation, erythrocyte production shifts to the liver sinusoids (peaks at 4 months)  By 5 months’ gestation, erythrocyte production begins in the bone marrow • At delivery marrow is only significant hematopoiesis site

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Hemolytic Disease of the Newborn

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Fetal and Neonatal Hematopoiesis 

Fetal hemoglobin    

Two α-chains; two γ-chains Embryonic hemoglobins • Gower 1, Gower 2, and Portland Fetal hemoglobin • Hb F Greater affinity for oxygen than adult hemoglobin

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Fetal and Neonatal Hematopoiesis 

Postnatal changes   

Erythrocytes Leukocytes Platelets

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Acquired Disorders of Erythrocytes 

Iron deficiency anemia 

Most common blood disorder of infancy and childhood • Stored iron: greatest stores are present 4 to 8 weeks after birth • Dietary iron: needed after 16-20 weeks of age

 

Lack of iron intake or blood loss Manifestations • Irritability, decreased activity tolerance, weakness, and lack of interest in play

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Acquired Disorders of Erythrocytes 

Acquired congenital hemolytic anemia 

Hemolytic disease of the newborn (HDN) • Alloimmune disease • Maternal antibody directed against fetal antigens • ABO incompatibility occurs in 20% to 25% of cases • Rh incompatibility occurs in less than 10% • Also termed erythroblastosis fetalis 

Presence of red cell precursors in the peripheral blood

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Acquired Disorders of Erythrocytes 

Hemolytic disease of the newborn (HDN) 



Manifestations • Anemia • Hyperbilirubinemia • Icterus neonatorum • Kernicterus Treatment • Prevention: RhoGAM

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Hemolytic Disease of the Newborn

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Acquired Disorders of Erythrocytes 

Anemia of infectious disease 

Diseases initially acquired by the mother and transmitted to the fetus • Results in hemolytic anemia • Likely due to injury to the erythrocyte membranes or erythrocyte precursors

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Inherited Disorders of Erythrocytes 

Glucose-6-phosphate dehydrogenase deficiency (G6PD)    

Inherited, X-linked, recessive disorder G6PD: enzyme that helps erythrocytes maintain metabolic processes despite injurious conditions Asymptomatic unless stressors present Without G6PD oxidative stressors damage hemoglobin and the plasma membranes of erythrocytes (Heinz bodies)

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Inherited Disorders of Erythrocytes 

Hereditary spherocytosis  



Autosomal dominant trait Abnormality of proteins or spectrins of the erythrocyte membrane leading to an increased concentration of intracellular sodium Causes splenomegaly and microcytic spherocytes

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Hereditary Spherocytosis

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Inherited Disorders of Erythrocytes 

Sickle cell disease 



Disorders characterized by the presence of an abnormal hemoglobin (Hb S) • Mutation causes valine to be replaced by glutamic acid Deoxygenation and dehydration cause the red cells to solidify and stretch into an elongated sickle shape

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Inherited Disorders of Erythrocytes 

Sickle cell disease  

Once sickling begins, continues until Po2 returns to normal, then it ceases spontaneously Extent, severity, and clinical manifestations of sickling depend on the percentage of hemoglobin that is Hb S

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Inherited Disorders of Erythrocytes 

Sickle cell disease 

Sickle cell trait • Child inherits Hb S from one parent and Hb A from another



Can result in: • Vasoocclusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis



Other forms • Sickle cell-thalassemia disease and sickle cell-Hb C disease

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Sickle Cell Disease

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Sickle Cell Disease

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Sickle Cell Disease

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Sickle Cell Disease

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Inherited Disorders of Erythrocytes 

Thalassemias    

Autosomal recessive disorders Synthesis of the globin chains of the hemoglobin molecule is slowed or defective Major—homozygous inheritance Minor—heterozygous inheritance

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Inherited Disorders of Erythrocytes 

In alpha-thalassemia the α-chains are affected; ß-chains in beta-thalassemia 

Beta-thalassemia minor  Beta-thalassemia major  Alpha trait  Alpha-thalassemia minor  Hemoglobin H disease

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Inherited Disorders of Erythrocytes 

Beta-thalassemia minor 

 

Mild to moderate hypochromic-microcytic anemia, mild splenomegaly, bronze coloring of the skin, hyperplasia of bone marrow Usually asymptomatic

Beta-thalassemia major 

May be quite ill  Severe anemia results in large cardiovascular burden

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Inherited Disorders of Erythrocytes 

Alpha-thalassemia minor 



Clinical manifestations virtually identical to those of beta-thalassemia minor

Alpha-thalassemia major    

Hydrops fetalis Fulminant intrauterine congestive heart failure Fetus has a grossly enlarged heart and liver Diagnosis usually is made post mortem

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Inherited Coagulation and Platelet Disorders 

Hemophilias     

Serious bleeding disorders Hemophilia A (classic hemophilia) Hemophilia B (Christmas disease) Hemophilia C (factor XI deficiency) von Willebrand disease

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Inherited Coagulation and Platelet Disorders 

Congenital hypercoagulability and thrombosis     

Thrombophilia Protein C deficiency Neonatal purpura fulminans Protein S deficiency Antithrombin III (AT III) deficiency

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Antibody-Mediated Hemorrhagic Disease 

Idiopathic thrombocytopenic purpura 

 



Autoimmune or primary thrombocytopenic purpura

Autoimmune neonatal thrombocytopenia Autoimmune neonatal thrombocytopenia purpura Autoimmune vascular purpura

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Leukemia  



Most common malignancy of childhood 80% to 85% are acute lymphoblastic leukemias Cause unclear 

Genetic susceptibility, environmental factors, viral infections

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Leukemia 

Symptoms 



Diagnosis 



Pallor, fatigue, petechiae, purpura, bleeding, fever, bone pain Bone marrow aspiration • Blast cell

Treatment  

Chemotherapy Radiation

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Leukemia 

FAB classification  



Acute lymphoblastic leukemias L1, L2, and L2 Acute non-lymphoblastic leukemias M1-7

Immunoclassification 

Surface marker identification

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Leukemia

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Lymphoma 

Non-Hodgkin lymphoma 



Nodular and diffuse

Hodgkin lymphoma   

Rare in childhood Infectious mode of transmission Many children with Hodgkin lymphoma demonstrate a high antibody titer to Epstein-Barr virus (EBV)

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