Anemia in Children - PDF

Anemia in Children Dr. Mostafa Embaby Assistant Professor of Pediatrics Assiut University  Case Scenario An 18-month-old child of Mediterranean origin presents to the physician for routine well-child care. The mother states that the child is a “picky” eate...

Anemia in Children Dr. Mostafa Embaby Assistant Professor of Pediatrics Assiut University  Case Scenario An 18-month-old child of Mediterranean origin presents to the physician for routine well-child care. The mother states that the child is a “picky” eater and prefers milk to solids. In fact, the mother states that the patient, who still drinks from a bottle, consumes 64 ounces of cow milk per day. The child appears pale. Hemoglobin is 6.5 g/dL and hematocrit 20%. Mean corpuscular volume is 65 fL.  OBJECTIVES (ILOs) By the end of this lecture the students will be able to: ▪ Categorize anemias into those caused by inadequate production, acquired production, and congenital anemias ▪ Understand the pathophysiology, diagnosis, and treatment of physiologic anemia of infancy ▪ Describe the pathophysiology, diagnosis, and treatment of iron deficiency anemia, megaloblastic anemia, lead poisoning, anemia of chronic diseases and congenital anemias ANEMIAS OF INADEQUATE PRODUCTION  PHYSIOLOGIC ANEMIA OF INFANCY Intrauterine hypoxia stimulates erythropoietin → ↑ RBCs (Hb, Hct) High FiO2 at birth downregulates erythropoietin Progressive drop in Hb over first 2–3 months until tissue oxygen needs are greater than delivery (typically 8–12 weeks in term infants, to Hb of 9–11 g/dL) Exaggerated in preterm infants and earlier; nadir at 3–6 weeks to Hb of 7–9 g/dL In term infants—no problems, no treatment; preterm infants usually need transfusions depending on degree of illness and gestational age  IRON-DEFICIENCY ANEMIA Contributing factors/pathophysiology Higher bioavailability of iron in breast milk versus cow milk or formula Introducing iron-rich foods is effective in prevention. Infants with decreased dietary iron typically are anemic at 9–24 months of age: caused by consumption of large amounts of cow milk and foods not enriched with iron; also creates abnormalities in mucosa of GI tract → leakage of blood, further decrease in absorption Adolescents also susceptible → high requirements during growth spurt, dietary deficiencies, menstruation Clinical appearances: pallor most common; also irritability, lethargy, pagophagia (an intense craving to chew on ice), tachycardia, systolic murmurs; long-term with neurodevelopmental effects Laboratory findings First decrease in bone marrow hemosiderin (iron tissue stores) Then decrease in serum ferritin Decrease in serum iron and transferrin saturation → increased total iron-binding capacity (TIBC) Increased free erythrocyte protoporhyrin (FEP) Microcytosis, hypochromia, poikilocytosis Decreased MCV, mean corpuscular hemoglobin (MCH), increase RDW, nucleated RBCs, low reticulocytes Bone marrow—no stainable iron Microcytic Hypochromic Anemia Treatment Oral ferrous salts Limit milk, increase dietary iron Within 72–96 hours—peripheral reticulocytosis and increase in Hb over 4–30 days Continue iron for 8 weeks after blood values normalize; repletion of iron in 1–3 months after start of treatment  LEAD POISONING Blood lead level (BLL) up to 5 μg/dL is acceptable. Increased risks Preschool age Low socioeconomic status Older housing (before 1960) Urban dwellers African American Recent immigration from countries that use leaded gas and paint Clinical presentation Behavioral changes (most common: hyperactivity in younger, aggression in older) Cognitive/developmental dysfunction, especially long-term (also impaired growth) Gastrointestinal—anorexia, pain, vomiting, constipation (starting at 20 μg/dL)  Central nervous system—related to increased cerebral edema, intracranial pressure (ICP) [headache, change in mentation, lethargy, seizure, coma → death]) Gingival lead lines Diagnosis Screening—targeted blood lead testing at 12 and 24 months in high-risk Confirmatory venous sample: gold standard blood lead level Indirect assessments: x-rays of long bones (dense lead lines); radiopaque flecks in intestinal tract (recent ingestion) Microcytic, hypochromic anemia Increased FEP Basophilic stippling of RBC Basophilic stippling of RBC Aggregates of ribosomes or fragments of ribosomal RNA precipitated throughout the cytoplasm of circulating erythrocytes Lead Treatment—chelation (μ dL) M Treatment of lead poisoning according to lead level: An 18-month-old child of Mediterranean origin presents to the physician for routine well-child care. The mother states that the child is a “picky” eater and prefers cow milk to solids. The child appears pale. Hemoglobin is 6.5 g/dL. Mean corpuscular volume is 65 fL. Which of the following lab results is mostly expected? a) Increased serum ferretin b) Decreased iron binding capacity c) Decreased free erythrocyte protoporhyrin d) Decreased mean corpuscular hemoglobin (MCH) e) Increased reticulocytic count CONGENITAL ANEMIAS  CONGENITAL PURE RED-CELL ANEMIA (BLACKFAN- DIAMOND) Increased RBC programmed cell death → profound anemia by 2–6 months Congenital anomalies Short stature Craniofacial deformities Defects of upper extremities; triphalangeal thumbs Triphalangeal thumb Labs Macrocytosis Increased HbF Increased RBC adenosine deaminase (ADA) Very low reticulocyte count Increased serum iron Marrow with significant decrease in RBC precursors Treatment Corticosteroids Transfusions and deferoxamine If hypersplenism, splenectomy; mean survival 40 years without stem cell transplant Definitive—stem cell transplant from related histocompatible donor  CONGENITAL PANCYTOPENIA Fanconi anemia Most common is Fanconi anemia—spontaneous chromosomal breaks Age of onset from infancy to adult Physical abnormalities Hyperpigmentation and café-au-lait spots Absent or hypoplastic thumbs Short stature Many other organ defects Short stature with Absent thumb and radius hypoplastic thumbs Labs Decreased RBCs, WBCs, and platelets Increased HbF Bone-marrow hypoplasia Diagnosis—bone-marrow aspiration and cytogenetic studies for chromosome breaks Complications—increased risk of leukemia (AML) and other cancers, organ complications, and bone-marrow failure consequences (infection, bleeding, severe anemia) Treatment Corticosteroids and androgens Bone marrow transplant definitive Which lab finding differentiates Diamond-Blackfan anemia from congenital pancytopenia? (A) Decreased red blood cells (RBCs) (B) Increased RBC adenosine deaminase* (C) Increased HbF (D) Low reticulocytes (E) Low white blood cells and platelets ACQUIRED ANEMIAS TRANSIENT ERYTHROBLASTOPENIA OF CHILDHOOD (TEC) Transient hypoplastic anemia between 6 months–3 years Transient immune suppression of erythropoiesis Often after nonspecific viral infection (not parvovirus B19) Labs—decreased reticulocytes and bone-marrow precursors, normal MCV and HbF Recovery generally within 1–2 months Medication not helpful; may need one transfusion if symptomatic  ANEMIA OF CHRONIC DISEASE AND RENAL DISEASE Mild decrease in RBC lifespan and relative failure of bone marrow to respond adequately Little or no increase in erythropoietin Labs Hb typically 6–9 g/dL, most normochromic and normocytic (but may be mildly microcytic and hypochromic) Reticulocytes normal or slightly decreased for degree of anemia Iron low without increase in TIBC Ferritin may be normal or slightly increased. Marrow with normal cells and normal to decreased RBC precursors Treatment—control underlying problem, may need erythropoietin; rarely need transfusions MEGALOBLASTIC ANEMIAS BACKGROUND RBCs at every stage are larger than normal; there is an asynchrony between nuclear and cytoplasmic maturation. Ineffective erythropoiesis Almost all are folate or vitamin B12 deficiency from malnutrition; uncommon in United States in children; more likely to be seen in adult medicine. Macrocytosis; nucleated RBCs; large, hypersegmented neutrophils (have >5 lobes in a peripheral smear); low serum folate; iron and vitamin B12 normal to decreased; marked increase in lactate dehydrogenase; hypercellular bone marrow with megaloblastic changes FOLIC ACID DEFICIENCY Sources of folic acid—green vegetables, fruits, animal organs Peaks at 4–7 months of age—irritability, failure to thrive, chronic diarrhea Cause—inadequate intake (pregnancy, goat milk feeding, growth in infancy, chronic hemolysis), decreased absorption or congenital defects of folate metabolism Differentiating feature—low serum folate Treatment—daily folate; transfuse only if severe and symptomatic VITAMIN B12 (COBALAMIN) DEFICIENCY Only animal sources; produced by microorganisms (humans cannot synthesize) Sufficient stores in older children and adults for 3–5 years; but in infants born to mothers with deficiency, will see signs in first 4– 5 months Inadequate production (extreme restriction [vegans]), lack of intrinsic factor (congenital pernicious anemia [rare], autosomal recessive; also juvenile pernicious anemia [rare] or gastric surgery), impaired absorption (terminal ileum disease/removal) Vitamin B12 is only of animal source, humans cannot synthesize  Clinical—weakness, fatigue, failure to thrive, irritability, pallor, glossitis, diarrhea, vomiting, jaundice, many neurologic symptoms Labs: normal serum folate and decreased vitamin B12 Treatment: parenteral B12 Note: If autoimmune pernicious anemia is suspected, remember the Schilling test and antiparietal cell antibodies. Comparison of Folic Acid Versus Vitamin B12 Deficiencies