Nutritional Anemia Kanjanapongkul S., MD 20-9-19 Criteria for Diagnosis Anemia Hb.( g/dl) Hct (%) Children 11.0 33 Pregnant women 11.0 33 Female ( 15-50 ) 12.0 36 Male 13.0 40 Anemia • Classification base on rbc size 1. Microcytic anemia : thalassemia, iron deficiency, lead poisoning 2. Normochromic anemia : aplastic anemia, PRCA, acute blood loss, G6PD def, AIHA 3. Macrocytic anemia : retic , B12 def, folate def Normochromic-normocytic Hypochromic-microcytic Megaloblastic and hypersegmented neutrophils Case1-pallor • Hx : A 14 mo. male infant was seen because of pallor of 1 month duration. He was taken care by grandma. Dietary history revealed that the infant consumed about 40 0z of milk dialy with very little solids in his diet. No family Hx of anemia. Case 1 • PE :Well developed with moderate pale 14 mo infant with wt. 10 kg. and no organomegaly • Lab : Hb 7.8 g/dl, Hct 23, retic 2.1% MCV 58, MCH 16, MCHC 27 Q: What is most likely cause of anemia in this child? A. G6PD def. B. Iron def. anemia C. Thalassemia minor D. AIHA Ans : B Diagnostic Tree Causes of Hypochromic Microcytic Anaemias Erythroid Enterocyte intake precursor losses Malabsorption Defects in heme synthesis Blood or iron acquisition Inadequate • Breastfeeding with inadequate • Celiac disease • Haemoglobinopathies • Polymenorrhea supplementary food • Helicobacter pylori gastritis • Sideroblastic anaemia • Parasitic infestations • Preterm, low birth weight • Autoimmune atrophic gastritis • Erythropoietic porphyria • Peptic ulcer • Growth spurt • IRIDA (TMPRSS6 mutation) • DMT1 mutations • Inflammatory bowel • Inadequate calorie intake • Chronic inflammation • Ferroportin disease disease • Vegetarian diet • Hereditary atransferrinaemia • Meckel diverticulum • Hereditary aceruloplasminaemia Graphic courtesy of Dr. Mariane de Montalembert. Iron Deficiency Anemia (IDA) • Most abundant metal but most common deficiency..! • Common in developing world • Most common in infants and children (Toddlers and adolescent girls) ( poor Fe intake, often cow’s milk intake > 1 L/day) Iron deficiency anemia • Blood loss should be considerd , but more likely in older children. • Parasitic Worm infestation + Malnutrition What are some of clinical features? • อาการแสดง - ซีด เพลียง่าย – heart failure pedal edema • Special features in IDA: – Angular cheilitis, atrophic glossitis, – Oesophageal atrophy/web dysphagia, – Koilonychia, brittle nails, gastric atrophy. – Pica =กินสิ่งของที่ไม่ใช่อาหาร (compulsive comsumption of non-nutritive substance : soil, clay) Laboratory findings: •Red cell indices: Low Hb conc MCV, MCH, MCHC* ↓ •Blood film: Hypochromic microcytic Occasional Target cells Pencil shaped poikilocytes Normal reticulocyte count •Bone marrow iron: Normal to hypercellular RBC precursors are increased in number Iron stain negative •Chemical testing on serum: Serum iron Decreased Transferrin/TIBC Normal to High Serum ferritin Decreased (Very low) IDA Laboratory tests: • Iron study - serum ferritin (<10ng/dl) : sensitve, but also increase in inflammation - serum iron (SI) and Total Iron Binding Capacity (TIBC) transferrin saturation (%) = SI x 100 TIBC (%sat <12-16 ) *measurements are not usually necessary Cut-Off Values for Iron Status by Age and Gender NHANES Survey in the United States • Transferrin saturation (%) – 1–2 y: 9 – 3–5 y: 13 – 6–15 y: 14 • Serum ferritin (μg/L) – 1–5 y: 10 – 6–15 y: 12 Dallman PR. In: Iron Nutrition in Health and Disease. John Libbey & Company; 1996:65-71. Looker AC, et al. JAMA. 1997;277:973-976. Cogswell ME, et al. Am J Clin Nutr. 2009;89:1334-1342. Slide courtesy of Dr. Mariane de Montalembert Case 2 ดช.ไทย อายุ 2 ปี มา ER ด้วยเรื่องไข้ ไอ หอบ 3 วัน ตรวจพบซีด ไม่พบตับหรือม้ามโต CBC : Hct 27%, Hb 9.5 g/dL, WBC 12,290 (N70, L24, M6%) platelets 533,000/cu.mm. MCV 43.4, MCH 14,MCHC 32.3 Hb typing : E87.6, F6.8% Dx – Homozygous E Case 2 @คลินิกโรคเลือด 6 เดือนต่อมา CBC : Hct 20.7%, Hb 7.0 g/dl, MCV 41, MCH 13.9, MCHC 33.8 ปัญหา ซีดมากขึ้น!!! จาก.................? ขอประวัติเพิ่ม? Feeding – ข้าว 3 มือแต่กินข้าวน้อย้ นม 250 cc x 6 กล่อง Serum ferritin 7.13 ng/ml IDA vs ThalaTrait Test Iron Deficiency β-Thalassaemia Trait MCV/RBC >13 <13 RDW Increased Normal Fe/TIBC Decreased Normal Ferritin Decreased Normal FEP Increased Normal HbA2 Decreased Increased HbF Normal Increased RBC morphology Pencil forms Fine basophilic stippling, target cells Abbreviations: FEP, free erythrocyte porphyrin; HbA2, haemoglobin A2; HbF, haemoglobin F; MCV, mean corpuscular volume; RBC, red blood cells; RDW, red blood cell distribution width; TIBC, total iron binding capacity. Hypochromic Microcytic Anaemias in Children Iron Deficiency Defects in Iron Thalassaemia Lead Chronic Disease Utilisation1 Intoxication Blood Microcytosis, anisocytosis, Hypochromia Microcytosis, target Coarse basophilic Microcytosis, Poikilocytosis, cells, helmets, stippling hypochromia smear elliptocytosis, dacryocytes hypochromia Serum iron Normal or Transferrin saturation Serum Normal transferrin receptor Serum Normal ferritin Other Bone marrow: ringed High-performance Blood lead level Erythrocyte sideroblasts diagnostic liquid sedimentation rate tools chromatography C-reactive protein Iolascon A, et al. Haematologica. 2009;94:935-948. Benefits of Correcting IDA in Early Childhood • Increase in haemoglobin concentration, related to Baseline status Exposure to anaemia risk factors in addition to iron deficiency (ie, malaria…) • Decrease in the number of upper respiratory tract infections in a controlled study in children age 5–10 years in Sri Lanka • Controversial results on development; effect, if present, is modest • In most studies, no significant growth effect or limited to anaemic children Martin S, et al. Cochrane Data Base of Systematic Reviews. 2001;2. Iannotti LL, et al. Am J Clin Nutr. 2006;84:1261-1276. Domellof M. Nestle Nutr Workshop Ser Ped Program. 2010;65:153-162. de Silva A, et al. Am J Clin Nutr. 2003;77:234-241. Effect of IDA in Infancy on Developmental Tests at 5 Years of Age Difference in results of developmental tests at 5 years of age between children with moderate iron deficiency anaemia in infancy and control group adjusted for a comprehensive set of background factors Lozoff B, et al. N Engl J Med. 1991;325:687-694. Treatment of Iron Deficiency and Iron Deficiency Anaemia Treatment of IDA Iron Replacement Therapy • When indicated, treatment with a cost-effective oral iron preparation with minimal side effects will suffice. • The cheapest preparation iron sulfate liquid/tablets • Iron dose: 3–6 mg/kg/d for infants and children 60–120 mg/d for school-age children / adolescents → increase in haemoglobin of 0.25–0.4 g/dL/d or 1%/d rise in haematocrit • Duration: 3–4 months after reversal of anaemia to replenish body iron stores *Dx of IDA is usually established by Hx and a successful trial of oral Fe therapy. Response to Iron • 4–7 days: reticulocytosis • 1–4 week: increase in Hb level • 1–4 months: repletion of iron stores Failure of response after 2 wks of oral iron requires re- evaluation for • Poor compliance with oral iron • Other acquired causes associated with gastrointestinal blood loss, such as celiac disease, autoimmune atrophic gastritis, H. pylori, inflammatory bowel disease • Genetic anaemias Treatment of IDA Blood Transfusion • Rarely necessary even for severe IDA with Hb 4–5 g/dL • Should be reserved for patients in cardiorespiratory distress, lethargy, and very poor nutritional intake • Needs to be given slowly to avoid heart failure Case 3 ผู้ป่วยวัยรุ่นไทย อายุ 16 ปี U/D APVS S/P Rastelli มา ตรวจคลินิคโรคหัวใจตามนัด แพทย์พบว่าซีด Hb 6.6 g/dl, Hct 23.3% MCV 61.9 fl, MCH 17.6 pg, MCHC 28.3 g/dl Hb typing A2A (A2 2.1, A 89, F 0.2%) Serum ferritin 2.18 Case 3 Diagnosis : IDA • Treatment : Fermate 1x2 • นัดเข้าคลินิกโรคเลือด 1 เดือน @ hematoclinic Hb 8.7 g/dl, Hct 26% ( from 23% เมื่อ1 เดือนก่อน) Poor response??? IDA Diagnostic and Treatment Algorithm Hg/Hct Low Hg Normal apparently healthy child Reassure Treat with oral iron and Counsel parents family repeat Hg in 2–4 wk about diet An ↑ in Hg ≥1g/dL after 2–4 wk Failure of response of iron replacement confirms after 2–4 wk of IDA diagnosis iron replacement Re-evaluate for Continue iron Reinforce Recheck Hg/Hct poor compliance, replacement dietary at end of inadequate iron for 3–4 mo counseling treatment and dose, or other 6 mo later causes Abbreviations: Hct, haematocrit; Hg, haemoglobin; Do additional lab IDA, iron deficiency anaemia. tests Graphic courtesy of Dr. Adlette C. Inati. Case 3 ทําไมตอบสนองไม่ดี? Poor compliance? – อุจจาระสีดํา เป็นก้อน Low intake?- กินอาหารเหมือนคนอื่นๆในบ้าน กินได้ทัวไป่ Concurrent loss? – GU ประจําเดือนมาปกติ มามากวัน แรกๆ ใช้ 10+ pads/cycle - GI ปฏิเสธริดสีดวงทวาร โรคกระเพาะ Absorption? – กินยาหลังอาหาร Mx : fermate 1x3 oral ac + folic +Vit C นัด 1 month แต่ loss F/U (ติดสอบ) 2 mo ต่อมา ตามผู้ป่วยมาตรวจ Hb 12.6 g/dl Hct 37.6% MCV 93.1 Treatment of IDA: Dietary Measures Iron-containing dietary sources – Heme: fish, poultry, meat – Non-heme: grains, fruits, vegetables, cereals, bread • Iron from heme sources has a higher bioavailability (3x more) than that from non-heme sources but comprises a small portion of dietary iron in most diets • Ascorbic acid, meat, orange juice, and fish enhance iron absorption of non-heme sources • Calcium, phytates, cereals, milk, bran foods rich in phosphates, and tannates (teas) in food impair iron absorption to a variable degree ผักโขม มีธาตุเหล็ก 6.5 มิลลิกรัม All you can TR+EAT Case 4 Case 5 Megaloblastic anemia Cause 1.Vitamin B 12 deficiency 2.Folate B-12 AND FOLATE DEFICIENCY Cause B-12 Folate Decreased intake Strict vegetarians and Alcoholism vegans Malnutrition Malabsorption Absence of intrinsic Drugs factor Generalized Blind loop malabsorption Pancreatic insufficiency Resection of terminal ileum Increased Very rare •Pregnancy utilization/loss •Hemolysis Drug inhibition Nitrous oxide Methotrexate Genetic defects Transcobalmin II (rare) Even rarer Clinical features Diagnosis Macro-ovalocyte and hypersegmented neutrophils Diagnosis Vit. B12 deficiency diagnosis Pernicious anemia diagnosis Treatment : Pernicious anemia Folic acid deficiency diagnosis Treatment : Folic acid deficiency .