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

2. 2 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 At delivery marrow is only significant hematopoiesis site

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

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

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

6. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 6 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 Stored iron: greatest stores are present 4 to 8 weeks after birth Dietary iron: needed after 16-20 weeks of age 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 Irritability, decreased activity tolerance, weakness, and lack of interest in play

7. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 7 Acquired Disorders of Erythrocytes  Acquired congenital hemolytic anemia  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

8. 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)  Manifestations Anemia Anemia Hyperbilirubinemia Hyperbilirubinemia Icterus neonatorum Icterus neonatorum Kernicterus Kernicterus  Treatment Prevention: RhoGAM Prevention: RhoGAM

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

10. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 10 Acquired Disorders of Erythrocytes  Anemia of infectious disease  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

11. 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)  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)

12. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 12 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

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

14. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 14 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 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

15. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 15 Inherited Disorders of Erythrocytes  Sickle cell disease  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

16. 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 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: Vasoocclusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis Vasoocclusive crisis (thrombotic crisis), aplastic crisis, sequestration crisis, and hyperhemolytic crisis  Other forms Sickle cell-thalassemia disease and sickle cell-Hb C disease Sickle cell-thalassemia disease and sickle cell-Hb C disease

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

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

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

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

21. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 21 Sickle Cell Disease

22. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 22 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

23. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 23 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

24. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 24 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

25. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 25 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

26. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 26 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

27. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 27 Inherited Coagulation and Platelet Disorders  Congenital hypercoagulability and thrombosis  Thrombophilia  Protein C deficiency  Neonatal purpura fulminans  Protein S deficiency  Antithrombin III (AT III) deficiency

28. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 28 Antibody-Mediated Hemorrhagic Disease  Idiopathic thrombocytopenic purpura  Autoimmune or primary thrombocytopenic purpura  Autoimmune neonatal thrombocytopenia  Autoimmune neonatal thrombocytopenia purpura  Autoimmune vascular purpura

29. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 29 Leukemia  Most common malignancy of childhood  80% to 85% are acute lymphoblastic leukemias  Cause unclear  Genetic susceptibility, environmental factors, viral infections

30. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 30 Leukemia  Symptoms  Pallor, fatigue, petechiae, purpura, bleeding, fever, bone pain  Diagnosis  Bone marrow aspiration Blast cell Blast cell  Treatment  Chemotherapy  Radiation

31. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 31 Leukemia  FAB classification  Acute lymphoblastic leukemias L1, L2, and L2  Acute non-lymphoblastic leukemias M1-7  Immunoclassification  Surface marker identification

32. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 32 Leukemia

33. Mosby items and derived items © 2010, 2006 by Mosby, Inc., an affiliate of Elsevier Inc. 33 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)