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

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Enterocyte Erythroid precursor

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Malabsorption Defects in heme synthesis or iron acquisition

• Breastfeeding with inadequate supplementary food • Preterm, low birth weight • Growth spurt • Inadequate calorie intake • Vegetarian diet

• Celiac disease • Helicobacter pylori gastritis • Autoimmune atrophic gastritis • IRIDA (TMPRSS6 mutation) • Chronic inflammation

• Haemoglobinopathies • Sideroblastic anaemia • Erythropoietic porphyria • DMT1 mutations • Ferroportin disease • Hereditary atransferrinaemia • Hereditary aceruloplasminaemia

• Polymenorrhea • Parasitic infestations • Peptic ulcer • Inflammatory bowel disease • Meckel diverticulum

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 - ซด เพลยงาย

– heart failure pedal edema • Special features in IDA:

– Angular cheilitis, atrophic glossitis, – Oesophageal atrophy/web dysphagia, – Koilonychia, brittle nails, gastric atrophy. – Pica =กนสงของทไมใชอาหาร (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 อาย 2 ป มา ER ดวยเรองไข ไอ หอบ 3 วน ตรวจพบซด ไมพบตบหรอมามโต 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

@คลนกโรคเลอด 6 เดอนตอมา CBC : Hct 20.7%, Hb 7.0 g/dl, MCV 41, MCH 13.9, MCHC 33.8

ปญหา ซดมากขน!!! จาก.................? ขอประวตเพม? Feeding – ขาว 3 มอแตกนขาวนอย นม 250 cc x 6 กลอง 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

Utilisation1 Thalassaemia Lead

Intoxication Chronic Disease

Blood smear

Microcytosis, anisocytosis, Poikilocytosis, elliptocytosis, hypochromia

Hypochromia Microcytosis, target cells, helmets, dacryocytes

Coarse basophilic stippling

Microcytosis, hypochromia

Serum iron Normal or

Transferrin saturation

Serum transferrin receptor

Normal

Serum ferritin

Normal

Other diagnostic tools

Bone marrow: ringed sideroblasts

High-performance liquid

chromatography

Blood lead level Erythrocyte sedimentation rate 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.

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.

Effect of IDA in Infancy on Developmental Tests at 5 Years of Age

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 ผปวยวยรนไทย อาย 16 ป U/D APVS S/P Rastelli มาตรวจคลนคโรคหวใจตามนด แพทยพบวาซด 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 • นดเขาคลนกโรคเลอด 1 เดอน @ hematoclinic Hb 8.7 g/dl, Hct 26% ( from 23% เมอ1เดอนกอน) Poor response???

IDA Diagnostic and Treatment Algorithm

Hg/Hct

Low Hg apparently

healthy child

Normal

Reassure family Treat with oral iron and

repeat Hg in 2–4 wk Counsel parents

about diet

An ↑ in Hg ≥1g/dL after 2–4 wk of iron replacement confirms

IDA diagnosis

Failure of response after 2–4 wk of iron replacement

Continue iron replacement for 3–4 mo

Reinforce dietary

counseling

Recheck Hg/Hct at end of

treatment and 6 mo later

Re-evaluate for poor compliance, inadequate iron dose, or other

causes Do additional lab

tests Graphic courtesy of Dr. Adlette C. Inati.

Abbreviations: Hct, haematocrit; Hg, haemoglobin; IDA, iron deficiency anaemia.

Case 3 ทาไมตอบสนองไมด? Poor compliance? – อจจาระสดา เปนกอน Low intake?- กนอาหารเหมอนคนอนๆในบาน กนไดทวไป Concurrent loss? – GU ประจาเดอนมาปกต มามากวนแรกๆ ใช 10+ pads/cycle - GI ปฏเสธรดสดวงทวาร โรคกระเพาะ Absorption? – กนยาหลงอาหาร Mx : fermate 1x3 oral ac + folic +Vit C นด 1 month แต loss F/U (ตดสอบ) 2 mo ตอมา ตามผปวยมาตรวจ 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

All you can TR+EAT

ผกโขม มธาตเหลก 6.5 มลลกรม

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 vegans

Alcoholism Malnutrition

Malabsorption Absence of intrinsic factor Blind loop Pancreatic insufficiency Resection of terminal ileum

Drugs Generalized malabsorption

Increased utilization/loss

Very rare •Pregnancy •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