Alterations of Hematologic Function in Children

1. Alterations of Hematologic Function in Children Chapter 28

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 • By the fifth month of gestation, erythrocyte production begins to occur in the bone marrow

3. Hemolytic Disease of the Newborn

4. Fetal and Neonatal Hematopoiesis • Fetal hemoglobin • Two alpha chains; two gamma chains • Embryonic hemoglobins • Gower 1, Gower 2, and Portland • Fetal hemoglobin • Hgb F

5. Fetal and Neonatal Hematopoiesis • Postnatal changes • Erythrocytes • Leukocytes • Platelets

6. Acquired Disorders of Erythrocytes • Iron deficiency anemia • Most common blood disorder of infancy and childhood • Lack of iron intake or blood loss • Manifestations • Irritability, decreased activity tolerance, weakness, and lack of interest in play

7. Acquired Disorders of Erythrocytes • Acquired congenital hemolytic anemia • Hemolytic disease of the newborn (HDN) • Alloimmune disease • Maternal antibody directed against fetal antigens • ABO incompatability occurs in 20% to 25% of cases • Rh incompatibility occurs in less than 10% • Also termed erythroblastosis fetalis • Presence of red cell precursors on the peripheral blood

8. Acquired Disorders of Erythrocytes • Hemolytic disease of the newborn (HDN) • Manifestations • Anemia • Hyperbilirubinemia • Icterus neonatorum • Kernicterus

9. Hemolytic Disease of the Newborn

10. 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

11. Inherited Disorders of Erythrocytes • Glucose-6-phosphate dehydrogenase deficiency (G6PD) • Inherited, X-linked, recessive disorder • G6PD is an enzyme that helps erythrocytes maintain metabolic processes despite injurious conditions • Asymptomatic unless stressors are present

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. Hereditary Spherocytosis

14. Inherited Disorders of Erythrocytes • Sickle cell disease • Disorders characterized by the presence of an abnormal hemoglobin (Hgb 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

15. Inherited Disorders of Erythrocytes • Sickle cell disease • Sickle cell trait • Child inherits Hgb S from one parent and Hgb 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

16. Sickle Cell Disease

17. Sickle Cell Disease

18. Sickle Cell Disease

19. Sickle Cell Disease

20. 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

21. Inherited Disorders of Erythrocytes • In alpha thalassemia, the alpha chains are affected; beta chains in beta thalassemia • Beta-thalassemia minor • Beta-thalassemia major • Alpha trait • Alpha-thalassemia minor • Hemoglobin H disease

22. 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

23. Inherited Coagulation and Platelet Disorders • Congenital hypercoagulability and thrombosis • Thrombophilia • Protein C deficiency • Neonatal purpura fulminans • Protein S deficiency • Antithrombin III (AT III) deficiency

24. Antibody-Mediated Hemorrhagic Disease • Idiopathic thrombocytopenic purpura • Autoimmune or primary thrombocytopenic purpura • Autoimmune neonatal thrombocytopenia • Autoimmune neonatal thrombocytopenia purpura • Autoimmune vascular purpura

25. Leukemia • Most common malignancy of childhood • 80% to 85% are acute lymphoblastic leukemias • FAB classification • Acute lymphoblastic leukemias L1, L2, and L2 • Acute non-lymphoblastic leukemias M1-7 • Immunoclassification • Surface marker identification

26. Leukemia

27. 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)