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Anemia Dell Children’s Medical Center April 12, 2014 Virginia Harrod, MD, PhD Pediatric Hematology Oncology 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 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 What is in a CBC? • WBC (white blood cell) – Differential (neutr, lymphs, monos, eos, baso) • Hemoglobin (RBC, Hct, MCV, MCHC) • Platelets (MPV) 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 Definition of Anemia Age (years) Hemoglobin (g/dL) Mean (low limit) Hematocrit (%) Mean (low limit) 0.5-1.9 12.5 (11.0) 37 (33) 2-4 12.5 (11.0) 38 (34) 5-7 13.0 (11.5) 39 (35) 8-11 13.5 (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 Oski’s Hematology of Infancy and Childhood 6th Ed., Ch10, pp409 Hemoglobin • Structure • Synthesis • Function http://themedicalbiochemistrypage.org/hemoglobin-myoglobin.php Hemoglobin • Structure • Synthesis • Function • a2b2 http://sickle.bwh.harvard.edu/hbsynthesis.html 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 en.wikipedia.org American Society of Hematology Image Bank Online Classifications of Anemia • Based on RBC size (MCV) – Microcytic (hypochromic) – Macrocytic – Normocytic (normochromic) • Based on Physiology – Production problem – Maturation problem – Destruction problem Macrocytic Anemias • Megaloblastic marrow changes – Vitamin B12 deficiency – Folic acid deficiency – Hereditary oroticaciduria • Without megaloblastic changes – Liver disease – Hypothyroid – Bone marrow failure • • • • Aplastic anemia Fanconi’s anemia Diamond Blackfan anemia Myelodysplasia 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 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. • 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 OA1, Williamson RS, Zakai NA, Berry RJ, Judd SE, Qi YP, Adedinsewo DA, Oakley GP Jr. Macrocytic Anemias • Megaloblastic marrow changes – Vitamin B12 deficiency – Folic acid deficiency – Hereditary oroticaciduria • Without megaloblastic changes – Liver disease – Hypothyroid – Bone marrow failure • • • • Aplastic anemia Fanconi’s anemia Diamond Blackfan anemia Myelodysplasia Bone Marrow Failure – Fanconi’s anemia Characteristics Smaller than average Usually presents before teen years Developmental defects (60%): thumb/arm Developmental delays GI disturbances – Diamond Blackfan anemia – Aplastic anemia – Myelodysplasia http://radiopaedia.org/articles/fanconi-anaemia Bone Marrow Failure – Fanconi’s anemia – Diamond Blackfan anemia Characteristics Craniofacial malformations Usually presents in infancy Developmental defects (60%): thumb/arm Cardiac, GU malformations Low birth weight, growth delays – Aplastic anemia – Myelodysplasia http://dbafoundation.org/testimonials/ DBA Foundation Support Bone Marrow Failure – Fanconi’s anemia – Diamond Blackfan anemia Characteristics – Aplastic anemia Present similar to leukemia – Myelodysplasia Pancytopenia: fever, bruising, preceding illnesses Normal Marrow MDS Aplastic Anemia ASH Image Bank Online Microcytic Anemias • Usually represents impaired synthesis – Heme • Assembly line is interrupted • Iron • Lead – Globin • Thalassemias Iron Absorption New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004 Iron Absorption New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004 Iron Absorption Calcium ? New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004 Iron Absorption Calcium ? Lead tox New Human Physiology, 2nd Ed., Paulev and Zubieta, 2004 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) Microcytic Anemias • Usually represents impaired synthesis – Heme • Iron • Lead – Globin • Thalassemias ASH Image Bank Online Thalassemia • Alpha – Decreased production of alpha globin chains • Beta – Decreased production of beta globin chains – Beta major (b0), beta intermedia (b+) • Typically autosomal recessive, but some not Microcytic Anemias • Usually represents impaired synthesis – Heme • Iron • Lead – Globin • Thalassemias – Basophilic stippling ASH Image Bank Online Microcytic Anemias • Usually represents impaired synthesis – Heme • Iron • Lead – Globin • Thalassemias ASH Image Bank Online Microcytic Anemia Workup Mentzer Index Not reliable Just measure ferritin http://www.aafp.org/afp/2009/0815/p339.html 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) 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 Membrane Disorders • Spherocytosis – Defect in spectrin – Autosomal Dominant – Often present with “newborn jaundice” (first day of life) – Family history of splenectomies Membrane Disorders ASH Image Bank Online Sickle Cell Anemia • Substitution on 6th 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 Sickle Cell Anemia • Life threatening concerns – Splenic sequestration – Infection (encapsulated organisms, functional asplenia) • Other concerns – Aplastic crisis (parvo) – Vaso-occlusive episodes (acute chest) Sickle Cell Anemia http://en.wikipedia.org/wiki/Sickle-cell_disease ASH online image bank Anemia Workup Algorithm Janus, et al., Evaluation of Anemia in Children, Am Fam Physician 2010 Jun 15; 81(12): 1462-1471 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 Consult Heme? • All “genetic” conditions • Iron deficiency anemia that doesn’t ‘get better’ • Anemia resulting in transfusion or hospitalization • Phone consults are welcome for quick review and ‘next step’ thoughts 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