Alterations of Hematologic Function in Children Chapter 28 Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc.

2 Fetal and Neonatal Hematopoiesis The embryo becomes too large for oxygenation by simple diffusion The embryo becomes too large for oxygenation by simple diffusion Erythropoiesis begins within the vessels of the yolk sac Erythropoiesis begins within the vessels of the yolk sac At 8 weeks gestation, erythrocyte production shifts to the liver sinusoids (peaks at 4 months) 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 By 5 months gestation, erythrocyte production begins in the bone marrow At delivery marrow is only significant hematopoiesis site At delivery marrow is only significant hematopoiesis site

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 3 Hemolytic Disease of the Newborn

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 4 Fetal and Neonatal Hematopoiesis Fetal hemoglobin Fetal hemoglobin Two α-chains; two γ-chains Two α-chains; two γ-chains Embryonic hemoglobins Embryonic hemoglobins Gower 1, Gower 2, and Portland Gower 1, Gower 2, and Portland Fetal hemoglobin Fetal hemoglobin Hb F Hb F Greater affinity for oxygen than adult hemoglobin Greater affinity for oxygen than adult hemoglobin

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 5 Fetal and Neonatal Hematopoiesis Postnatal changes Postnatal changes Erythrocytes Erythrocytes Leukocytes Leukocytes Platelets Platelets

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 Acquired Disorders of Erythrocytes Iron deficiency anemia Iron deficiency anemia Most common blood disorder of infancy and childhood Most common blood disorder of infancy and childhood Stored iron: greatest stores are present 4 to 8 weeks after birth Stored iron: greatest stores are present 4 to 8 weeks after birth Dietary iron: needed after weeks of age Dietary iron: needed after weeks of age Lack of iron intake or blood loss Lack of iron intake or blood loss Manifestations Manifestations Irritability, decreased activity tolerance, weakness, and lack of interest in play Irritability, decreased activity tolerance, weakness, and lack of interest in play

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Acquired Disorders of Erythrocytes Acquired congenital hemolytic anemia Acquired congenital hemolytic anemia Hemolytic disease of the newborn (HDN) Hemolytic disease of the newborn (HDN) Alloimmune disease Alloimmune disease Maternal antibody directed against fetal antigens Maternal antibody directed against fetal antigens ABO incompatibility occurs in 20% to 25% of cases ABO 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 fetalis Also termed erythroblastosis fetalis Presence of red cell precursors in the peripheral blood Presence of red cell precursors in the peripheral blood

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 8 Acquired Disorders of Erythrocytes Hemolytic disease of the newborn (HDN) Hemolytic disease of the newborn (HDN) Manifestations Manifestations Anemia Anemia Hyperbilirubinemia Hyperbilirubinemia Icterus neonatorum Icterus neonatorum Kernicterus Kernicterus Treatment Treatment Prevention: RhoGAM Prevention: RhoGAM

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 9 Hemolytic Disease of the Newborn

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Acquired Disorders of Erythrocytes Anemia of infectious disease Anemia of infectious disease Diseases initially acquired by the mother and transmitted to the fetus Diseases initially acquired by the mother and transmitted to the fetus Results in hemolytic anemia Results in hemolytic anemia Likely due to injury to the erythrocyte membranes or erythrocyte precursors Likely due to injury to the erythrocyte membranes or erythrocyte precursors

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 11 Inherited Disorders of Erythrocytes Glucose-6-phosphate dehydrogenase deficiency (G6PD) Glucose-6-phosphate dehydrogenase deficiency (G6PD) Inherited, X-linked, recessive disorder Inherited, X-linked, recessive disorder G6PD: enzyme that helps erythrocytes maintain metabolic processes despite injurious conditions G6PD: enzyme that helps erythrocytes maintain metabolic processes despite injurious conditions Asymptomatic unless stressors present Asymptomatic unless stressors present Without G6PD oxidative stressors damage hemoglobin and the plasma membranes of erythrocytes (Heinz bodies) Without G6PD oxidative stressors damage hemoglobin and the plasma membranes of erythrocytes (Heinz bodies)

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 Inherited Disorders of Erythrocytes Hereditary spherocytosis Hereditary spherocytosis Autosomal dominant trait Autosomal dominant trait Abnormality of proteins or spectrins of the erythrocyte membrane leading to an increased concentration of intracellular sodium Abnormality of proteins or spectrins of the erythrocyte membrane leading to an increased concentration of intracellular sodium Causes splenomegaly and microcytic spherocytes Causes splenomegaly and microcytic spherocytes

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 13 Hereditary Spherocytosis

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 Inherited Disorders of Erythrocytes Sickle cell disease Sickle cell disease Disorders characterized by the presence of an abnormal hemoglobin (Hb S) Disorders characterized by the presence of an abnormal hemoglobin (Hb S) Mutation causes valine to be replaced by glutamic acid 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 Deoxygenation and dehydration cause the red cells to solidify and stretch into an elongated sickle shape

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Inherited Disorders of Erythrocytes Sickle cell disease Sickle cell disease Once sickling begins, continues until Po 2 returns to normal, then it ceases spontaneously Once sickling begins, continues until Po 2 returns to normal, then it ceases spontaneously Extent, severity, and clinical manifestations of sickling depend on the percentage of hemoglobin that is Hb S Extent, severity, and clinical manifestations of sickling depend on the percentage of hemoglobin that is Hb S

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 16 Inherited Disorders of Erythrocytes Sickle cell disease Sickle cell disease Sickle cell trait Sickle cell trait Child inherits Hb S from one parent and Hb A from another Child inherits Hb S from one parent and Hb A from another Can result in: Can result in: Vasoocclusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis Vasoocclusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis Other forms Other forms Sickle cell-thalassemia disease and sickle cell-Hb C disease Sickle cell-thalassemia disease and sickle cell-Hb C disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 17 Sickle Cell Disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 18 Sickle Cell Disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 19 Sickle Cell Disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 20 Sickle Cell Disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Inherited Disorders of Erythrocytes Thalassemias Thalassemias Autosomal recessive disorders Autosomal recessive disorders Synthesis of the globin chains of the hemoglobin molecule is slowed or defective Synthesis of the globin chains of the hemoglobin molecule is slowed or defective Majorhomozygous inheritance Majorhomozygous inheritance Minorheterozygous inheritance Minorheterozygous inheritance

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 Inherited Disorders of Erythrocytes In alpha-thalassemia the α-chains are affected; ß-chains in beta-thalassemia In alpha-thalassemia the α-chains are affected; ß-chains in beta-thalassemia Beta-thalassemia minor Beta-thalassemia minor Beta-thalassemia major Beta-thalassemia major Alpha trait Alpha trait Alpha-thalassemia minor Alpha-thalassemia minor Hemoglobin H disease Hemoglobin H disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 Inherited Disorders of Erythrocytes Beta-thalassemia minor Beta-thalassemia minor Mild to moderate hypochromic-microcytic anemia, mild splenomegaly, bronze coloring of the skin, hyperplasia of bone marrow Mild to moderate hypochromic-microcytic anemia, mild splenomegaly, bronze coloring of the skin, hyperplasia of bone marrow Usually asymptomatic Usually asymptomatic Beta-thalassemia major Beta-thalassemia major May be quite ill May be quite ill Severe anemia results in large cardiovascular burden Severe anemia results in large cardiovascular burden

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 Inherited Disorders of Erythrocytes Alpha-thalassemia minor Alpha-thalassemia minor Clinical manifestations virtually identical to those of beta-thalassemia minor Clinical manifestations virtually identical to those of beta-thalassemia minor Alpha-thalassemia major Alpha-thalassemia major Hydrops fetalis Hydrops fetalis Fulminant intrauterine congestive heart failure Fulminant intrauterine congestive heart failure Fetus has a grossly enlarged heart and liver Fetus has a grossly enlarged heart and liver Diagnosis usually is made post mortem Diagnosis usually is made post mortem

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 Inherited Coagulation and Platelet Disorders Hemophilias Hemophilias Serious bleeding disorders Serious 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 disease von Willebrand disease

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 Inherited Coagulation and Platelet Disorders Congenital hypercoagulability and thrombosis Congenital hypercoagulability and thrombosis Thrombophilia Thrombophilia Protein C deficiency Protein C deficiency Neonatal purpura fulminans Neonatal purpura fulminans Protein S deficiency Protein S deficiency Antithrombin III (AT III) deficiency Antithrombin III (AT III) deficiency

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Antibody-Mediated Hemorrhagic Disease Idiopathic thrombocytopenic purpura Idiopathic thrombocytopenic purpura Autoimmune or primary thrombocytopenic purpura Autoimmune or primary thrombocytopenic purpura Autoimmune neonatal thrombocytopenia Autoimmune neonatal thrombocytopenia Autoimmune neonatal thrombocytopenia purpura Autoimmune neonatal thrombocytopenia purpura Autoimmune vascular purpura Autoimmune vascular purpura

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Leukemia Most common malignancy of childhood Most common malignancy of childhood 80% to 85% are acute lymphoblastic leukemias 80% to 85% are acute lymphoblastic leukemias Cause unclear Cause unclear Genetic susceptibility, environmental factors, viral infections Genetic susceptibility, environmental factors, viral infections

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Leukemia Symptoms Symptoms Pallor, fatigue, petechiae, purpura, bleeding, fever, bone pain Pallor, fatigue, petechiae, purpura, bleeding, fever, bone pain Diagnosis Diagnosis Bone marrow aspiration Bone marrow aspiration Blast cell Blast cell Treatment Treatment Chemotherapy Chemotherapy Radiation Radiation

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Leukemia FAB classification FAB classification Acute lymphoblastic leukemias L1, L2, and L2 Acute lymphoblastic leukemias L1, L2, and L2 Acute non-lymphoblastic leukemias M1-7 Acute non-lymphoblastic leukemias M1-7 Immunoclassification Immunoclassification Surface marker identification Surface marker identification

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Leukemia

Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Lymphoma Non-Hodgkin lymphoma Non-Hodgkin lymphoma Nodular and diffuse Nodular and diffuse Hodgkin lymphoma Hodgkin lymphoma Rare in childhood Rare in childhood Infectious mode of transmission Infectious mode of transmission Many children with Hodgkin lymphoma demonstrate a high antibody titer to Epstein-Barr virus (EBV) Many children with Hodgkin lymphoma demonstrate a high antibody titer to Epstein-Barr virus (EBV)