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Anemia Dell Childrens Medical Center April 12, 2014 Virginia Harrod, MD, PhD Pediatric Hematology Oncology Slide 2 Overview Definition of anemia Review of CBC values Review of Hemoglobin Types of Anemia Microcytic, macrocytic, normocytic Diagnostic Evaluations and Workup When to consult or refer to Hematology Slide 3 Definition of Anemia a condition in which the blood is deficient in red blood cells, in hemoglobin, or in total volume http://www.merriam-webster.com/dictionary/anemia Slide 4 What is in a CBC? WBC (white blood cell) Differential (neutr, lymphs, monos, eos, baso) Hemoglobin (RBC, Hct, MCV, MCHC) Platelets (MPV) Slide 5 What is missing from a CBC? Reticulocyte count Gives an indication if the body knows something is wrong and if it can respond appropriately Peripheral smear Gives us insight into processes Slide 6 Definition of Anemia Age (years)Hemoglobin (g/dL) Mean (low limit) Hematocrit (%) Mean (low limit) 0.5-1.912.5 (11.0)37 (33) 2-412.5 (11.0)38 (34) 5-713.0 (11.5)39 (35) 8-1113.5 (12)40 (36) 12-14 Female Male 13.5 (12.0) 14.0 (12.5) 41 (36) 43 (37) 15-17 Female Male 14.0 (12.0) 15.0 (13.0) 41 (36) 46 (38) 18-49 Female Male 14.0 (12.0) 16.0 (14.0) 42 (37) 47 (40) Nathan and Oskis Hematology of Infancy and Childhood 6 th Ed., Ch10, pp409 Slide 7 Hemoglobin Structure Synthesis Function Structure of Hemoglobin http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.php Slide 8 Hemoglobin Structure Synthesis Function Structure of Hemoglobin http://sickle.bwh.harvard.edu/hbsynthesis.html Slide 9 Hemoglobin Structure Synthesis Function Carry oxygen from lungs to body and carry CO2 from body to lungs Found in Red Blood Cells 97% of the RBC is hemoglobin Structure of Hemoglobin en.wikipedia.org American Society of Hematology Image Bank Online Slide 10 Classifications of Anemia Based on RBC size (MCV) Microcytic (hypochromic) Macrocytic Normocytic (normochromic) Based on Physiology Production problem Maturation problem Destruction problem Slide 11 Macrocytic Anemias Megaloblastic marrow changes Vitamin B12 deficiency Folic acid deficiency Hereditary oroticaciduria Without megaloblastic changes Liver disease Hypothyroid Bone marrow failure Aplastic anemia Fanconis anemia Diamond Blackfan anemia Myelodysplasia Slide 12 Macrocytic Anemias Megaloblastic marrow changes Vitamin B12 deficiency Usually associated with pernicious anemia Loss of gastric parietal cells/intrinsic factor required for absorption of vit B12 in ileum. Otherwise rare except some at risk groups: Lower socioeconomic group, infants, elderly Folic acid deficiency Hereditary oroticaciduria Slide 13 Macrocytic Anemias Megaloblastic marrow changes Vitamin B12 deficiency Folic acid deficiency Natural food sources Dark green leafy veggies, fruit, nuts, beans, dairy, liver 01/1998 US Government (FDA) requiring supplementation Breads, cereals, pastas, rice, grains Uncommon (poor diet, alcoholism, malabsorptive d/o) Am J Clin Nutr. 2013 Oct;98(4):1042-7. doi: 10.3945/ajcn.113.059683. Epub 2013 Aug 14. Am J Clin Nutr. Near-elimination of folate-deficiency anemia by mandatory folic acid fortification in older US adults: Reasons for Geographic and Racial Differences in Stroke study 2003-2007. Odewole OA 1, Williamson RS, Zakai NA, Berry RJ, Judd SE, Qi YP, Adedinsewo DA, Oakley GP Jr. Odewole OAWilliamson RSZakai NABerry RJJudd SEQi YPAdedinsewo DAOakley GP Jr Slide 14 Macrocytic Anemias Megaloblastic marrow changes Vitamin B12 deficiency Folic acid deficiency Hereditary oroticaciduria Without megaloblastic changes Liver disease Hypothyroid Bone marrow failure Aplastic anemia Fanconis anemia Diamond Blackfan anemia Myelodysplasia Slide 15 Bone Marrow Failure Fanconis anemia Diamond Blackfan anemia Aplastic anemia Myelodysplasia Characteristics Smaller than average Usually presents before teen years Developmental defects (60%): thumb/arm Developmental delays GI disturbances http://radiopaedia.org/articles/fanconi-anaemia Slide 16 Bone Marrow Failure Fanconis anemia Diamond Blackfan anemia Aplastic anemia Myelodysplasia Characteristics Craniofacial malformations Usually presents in infancy Developmental defects (60%): thumb/arm Cardiac, GU malformations Low birth weight, growth delays http://dbafoundation.org/testimonials/ DBA Foundation Support Slide 17 Bone Marrow Failure Fanconis anemia Diamond Blackfan anemia Aplastic anemia Myelodysplasia Characteristics Present similar to leukemia Pancytopenia: fever, bruising, preceding illnesses Normal Marrow Aplastic Anemia MDS ASH Image Bank Online Slide 18 Microcytic Anemias Usually represents impaired synthesis Heme Assembly line is interrupted Iron Lead Globin Thalassemias Slide 19 Iron Absorption New Human Physiology, 2 nd Ed., Paulev and Zubieta, 2004 Slide 20 Iron Absorption New Human Physiology, 2 nd Ed., Paulev and Zubieta, 2004 Slide 21 Iron Absorption New Human Physiology, 2 nd Ed., Paulev and Zubieta, 2004 Calcium ? Slide 22 Iron Absorption New Human Physiology, 2 nd Ed., Paulev and Zubieta, 2004 Calcium ? Lead tox Slide 23 Iron Deficiency Anemia Low MCV Low Retic Low ferritin Common clinical scenarios: Pale child, high milk intake, picky eater, clinically appears well (not fatigued, no fevers, etc) Slide 24 Microcytic Anemias Usually represents impaired synthesis Heme Iron Lead Globin Thalassemias ASH Image Bank Online Slide 25 Thalassemia Alpha Decreased production of alpha globin chains Beta Decreased production of beta globin chains Beta major ( beta intermedia Typically autosomal recessive, but some not Slide 26 Microcytic Anemias Usually represents impaired synthesis Heme Iron Lead Globin Thalassemias Basophilic stippling ASH Image Bank Online Slide 27 Microcytic Anemias Usually represents impaired synthesis Heme Iron Lead Globin Thalassemias ASH Image Bank Online Slide 28 Microcytic Anemia Workup http://www.aafp.org/afp/2009/0815/p339.html Mentzer Index Not reliable Just measure ferritin Slide 29 Normocytic anemias Hemolysis (destruction) External factor mediated Antibodiy mediated, microangiomathic, toxins, infectious, hypersplenism Membrane disorders of RBC Spherocytosis, elipotocytosis, PNH (paroxysmal nocturnal hemoglobinuria) Hemoglobinopathies (sickle cell disease) Hb S, Hb C Enzyme disorders G6PD, PK def Hemorrhage Some production disorders: Red cell aplasia, TEC, marrow replacement (leukemia) Slide 30 Antibody Mediated Auto-immune hemolytic anemia (AIHA) Idiopathic or possibly infection, drugs, etc Warm and Cold antibodies Diagnostic indicators: Direct coombs Reticulocyte counts Microangiopathic/infectious Slide 31 Membrane Disorders Spherocytosis Defect in spectrin Autosomal Dominant Often present with newborn jaundice (first day of life) Family history of splenectomies Slide 32 Membrane Disorders ASH Image Bank Online Slide 33 Sickle Cell Anemia Substitution on 6 th position beta chain (val for glutamic acid) Hemoglobin forms long polymers under deoxygenated (hypoxic) states Shortened RBC life span Microvascular obstruction/ischemia/infarction 10% African Americans carry trait, other populations too Slide 34 Sickle Cell Anemia Life threatening concerns Splenic sequestration Infection (encapsulated organisms, functional asplenia) Other concerns Aplastic crisis (parvo) Vaso-occlusive episodes (acute chest) Slide 35 Sickle Cell Anemia http://en.wikipedia.org/wiki/Sickle-cell_disease ASH online image bank Slide 36 Anemia Workup Algorithm Janus, et al., Evaluation of Anemia in Children, Am Fam Physician 2010 Jun 15; 81(12): 1462-1471 Slide 37 Treatments All anemias Fix the problem Deficiencies give iron, vitamin, etc Sickle cell/thal Control symptoms Hydroxyurea Transfusions Destruction issues Splenectomy, treat infection Marrow failure/leukemia Immune suppression, chemotherapy, marrow transplant Slide 38 Consult Heme? All genetic conditions Iron deficiency anemia that doesnt get better Anemia resulting in transfusion or hospitalization Phone consults are welcome for quick review and next step thoughts Slide 39 In Review Definition of anemia Review of CBC values Review of Hemoglobin Types of Anemia Microcytic, macrocytic, normocytic Diagnostic Evaluations and Workup When to consult or refer to Hematology