Pediatric Hematology 6.3 Lecture

• Hematopoietic sites do not change during intrauterine and extrauterine development.
• Erythropoietin can increase site production up to eight times normal.
• Democratic marrow replaces yellow marrow when red blood cell production begins.
• Extramedullary hematopoiesis is more likely in children than adults, causing enlargement of the spleen and liver.
• Fetal hemoglobin has a greater affinity for oxygen than adult hemoglobin due to less interaction with 2,3-DPG.
• Blood cell counts tend to be higher than adult levels at birth and gradually decline throughout childhood.
• Lymphocyte count is high at birth and continues to rise for the first year of life.
• Neutrophil count peaks 6 to 12 hours after birth and then declines over the next few days.
• Eosinophil count is elevated in the first year of life.
• Platelet counts are comparable to adult values throughout infancy and childhood.
• Anemia is the most common blood disorder in children.
• Childhood anemias are caused by ineffective erythropoiesis or premature destruction of erythrocytes.
• Iron deficiency is the most common cause of anemia in children.
• Iron deficiency may result from inefficient intake or chronic blood loss.
• Iron deficiency anemia is the most common nutritional disorder worldwide, with the highest incidence between 6 months and 2 years.
• In the US, iron deficiency anemia prevalence is highest in toddlers, adolescent girls, and women of childbearing age.
• Clinical manifestations of iron deficiency anemia are related to inadequate hemoglobin synthesis.
• Chronic iron deficiency anemia can cause koilonychia, widened skull fractures, decreased physical growth, developmental delays, and pica.
• Hemolytic disease of the fetus and newborn is due to antigens on fetal erythrocytes differing from antigens on maternal erythrocytes.
• Erythrocytes could be A, B, or O blood type, and then may or may not include RH antigen D.
• Individuals with the D antigen are RH positive; those without are RH negative.
• Most cases of hemolytic disease of the fetus and newborn are caused by ABO incompatibility.
• The first RH incompatible pregnancy usually presents no difficulties, but subsequent pregnancies can be affected.
• Infections acquired by the mother and transmitted to the fetus may result in clinical manifestations similar to hemolytic diseases.
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzyme deficiency leading to damaged red blood cells that can rupture prematurely.
• G6PD deficiency is an X-linked recessive disorder.
• G6PD enables erythrocytes to maintain normal metabolic processes despite injury from oxidative stress.
• G6PD deficiency is often asymptomatic unless there is a stressor.
• G6PD deficiency occurs more often in tropical and subtropical regions of the Eastern Hemisphere.
• Hereditary spherocytosis is an inherited disorder caused by defects in the membrane skeleton of red blood cells.
• The decrease in deformability of red blood cells in hereditary spherocytosis leads to splenic sequestration and destruction.
• Clinical manifestations of hereditary spherocytosis are anemia, jaundice, and splenomegaly.
• Sickle cell disease involves a mutation in the hemoglobin gene for beta-globin that distorts erythrocytes into a sickle shape.
• Intracellular dehydration and decreased pH can increase sickling, but deoxygenation is the most important variable.
• Sickling red blood cells can damage the vascular wall, causing inflammation and promoting clotting.
• Treatment for sickle cell disease consists of supportive care aimed at preventing sickling episodes and their consequences.
• Genetic studies have identified more than 100 different causative mutations for thalassemia.
• Beta thalassemia minor causes mild to moderate microcytic hypochromic hemolytic anemia.
• Beta thalassemia major causes impaired physical growth and development with severe anemia, and results in early death from cardiac failure.
• Alpha thalassemia trait is symptom-free.
• Alpha thalassemia minor causes traits similar to beta minor.
• Alpha thalassemia major causes intrauterine congestive heart failure as well as enlarged liver, and most affected babies are stillborn or die shortly after birth.
• Treatment for thalassemia depends on severity but may involve regular transfusions and chelation therapy.
• Severe hemophilia is caused by mutations that eliminate factor VIII or coagulation factor IX.
• Factor VIII is a cofactor for factor IX in the clotting cascade.
• More than 2000 unique mutations have been identified for hemophilia A, and a thousand mutations for hemophilia B.
• Many children are diagnosed with hemophilia around the time they become mobile because they are easily injured.
• Hemophilia A or B will have prolonged PTT times.
• Prophylaxis for severe hemophilia consists of regular infusions of factor VIII or IX.
• Von Willebrand factor binds factor VIII and platelets to the blood vessel wall as part of the clotting process.
• Von Willebrand disease results from a deficiency or dysfunction of von Willebrand factor.
• Primary immune thrombocytopenia is a disorder of platelet consumption in which antiplatelet antibodies bind the platelets, causing sequestration and destruction.
• Leukemia is the most common malignancy of children and adolescents.
• Chronic leukemias are rare in children, accounting for fewer than 5% of cases.
• The cause of most childhood cancer is unknown, with about 5% caused by inherited mutations.
• Down syndrome predisposes a child to AML.
• Ionizing radiation can lead to a higher risk of leukemia.
• Leukemic clusters have raised speculation that factors include prenatal exposure to pesticides or benzene could be a problem.
• Considerable success has been achieved with chemotherapy treatment for leukemia.
• Hodgkin's and non-Hodgkin's lymphomas are rare in children under the age of five.
• Risk factors for non-Hodgkin's lymphoma include Epstein-Barr virus and immunodeficiency.
• Hodgkin's lymphoma is characterized by the presence of Reed-Sternberg cells.
• Risk factors for Hodgkin's lymphoma include having Epstein-Barr virus, HIV, mononucleosis, or a family history of Hodgkin's lymphoma.

Pediatric hematology overview including hematopoietic sites during development. Fetal hemoglobin has higher affinity for oxygen than adult hemoglobin. Blood cell counts decline throughout childhood. Anemia is the most common blood disorder in children.