Pimlak Charoenkwan, M.D. Division of Hematology and Oncology, Department of Pediatrics

Chiang Mai University, Chiang Mai, Thailand

APPROACH TO ANEMIA

การประชุมโลหติวทิยาสัญจร ครัง้ที ่ 15 โรงพยาบาลน่าน 20 กนัยายน 2562

Scope

• RBC production and catabolism • Criteria for diagnosis of anemia • Approach to anemia • Hemolytic anemia • Case discussion by blood smear

Erythroid differentiation

1. Pronormoblast 2. Basophilic normoblast 3. Polychromatophilic normoblast 4. Orthochromatic normoblast 5. Polychromasia 6. Mature RBC

Hoffman Hematology 5th edition

RBC catabolism

Noronha SA. Pediatr Rev 2016;37:235-46.

Hoffman Hematology 5th edition

Criteria for diagnosis of anemia

Hemoglobin level

WHO CDC

Infant 0.5-4.9 y - < 11 g/dL

Children 5.0-11.9 y - < 11.5 g/dL

Menstruating women < 12 g/dL -

Pregnant women in first or third trimester

< 11 g/dL < 11 g/dL

Pregnant women in second trimester

< 11 g/dL < 10.5 g/dL

Men < 13 g/dL -

Killip S, Bennett JM, Chambers MD. Iron deficiency anemia. Am Fam Physician 2007;75:671-8.

Approach to anemia

Hoffman Hematology 5th edition

Origin Disorder Mechanism of destruction

Acquired

Hemolytic disease of newborn Warm AIHA

Mechanical valve HA Hemolytic ureic syndrome

Cold agglutinin disease Malaria

Extravascular Extravascular Intravascular Intravascular Intravascular

Intra/Extravascular

Congenital Thalassemia

Hereditary spherocytosis G6PD deficiency

Extravascular Extravascular

Intra/extravascular

Classification of common hemolytic anemia

Adapted from: Noronha SA. Pediatr Rev 2016;37:235-46.

1. Anemia

2. Anemia

3. Neonatal jaundice

4. Anemia and jaundice

5. Neonatal anemia and jaundice

6. Anemia and jaundice

7.1 Anemia

7.2 Anemia

8. Anemia and thrombocytopenia

9. Neonatal anemia

10. Newborn with sepsis

Summary

1. Anemia Iron deficiency anemia

Iron deficiency anemia

• Microcytic, hypochromic anemia (low MCV, MCH) • Alters red cell size unevenly (high RDW) • Poikilocytic changes, seen particularly with severe iron

deficiency • Thrombocytosis with platelet counts in the range of

500,000 to 700,000 cells/fL occurs frequently

2. Anemia Hypersegmented neutrophil

Hypersegmented neutrophils

• Presence of one or more six-lobed neutrophils or • Five or more neutrophils with five well-separated

lobes

among 100 segmented neutrophils

Nathan and Oski’s Hematology of Infancy and Childhood. 9th ed. 2015.

Megaloblastic anemia

• Mostly from vitamin B12 or folate deficiency • Macrocytic anemia, usually accompanied by

leukopenia and thrombocytopenia • Maturation of the nucleus and cytoplasm is

asynchronous, with the nucleus appearing less mature than the cytoplasm.

Nathan and Oski’s Hematology of Infancy and Childhood. 9th ed. 2015.

3. Neonatal jaundice Hereditary elliptocytosis

4. Anemia and jaundice Hereditary spherocytosis

Microspherocyte

Mushroom-shaped RBC or “pincered” RBC

5. Neonatal anemia and jaundice Southeast Asian Ovalocytosis

θ

Theta cell

Red blood cell membranes

• Membrane: protein-lipid bilayer • Deformable, tolerant against mechanical stress

and various pH and salt concentrations • Cytoskeleton

• spectrin (fibrous polypeptide) • ankyrin (fix spectrin to membrane) • protein band 3 (transmembrane protein)

Nathan and Oski’s Hematology of Infancy and Childhood. 9th ed. 2015.

Southeast Asian Ovalocytosis (SAO)

SAO/G701D

SAO (27 bp deletion)

G701D

6. Anemia and jaundice G-6-PD deficiency with acute hemolysis

Enzyme metabolic activities

• Glycolytic pathway (Embden-Meyerhof): produce ATP

• Oxidative pathway (Hexose monophosphate shunt): produce NADPH

Hoffman R. Hematology: basic principles and practices 2005

Prevalence of G6PD deficiency

Region Male Female Reference

Northern 14.8-15.7 - Flatz G, et al. Lancet 1963;2:1248-50.

Northern* 16.6 13.4 (I), 1.8 (C) Charoenkwan P, et al. SEA J Trop Med Public Health 2014;45:187-93.

Siriraj hospital 12.08 - Tanphaichitr VS. SEA J Trop Med Public Health 1995;26 Suppl 1:137-41.

Chula hospital* 11.1 5.8 Nuchprayoon I, et al. Hum Mutat 2002;19:185.

*G6PD Mahidol, G6PD Kaiping, G6PD Canton, G6PD Viangchan, G6PD Union, G6PD Chinese 5 **G6PD Viangchan (class II), G6PD Canton, G6PD Mahidol (class III), G6PD Union, G6PD Kaiping

7.1 Anemia Thalassemia disease

7.2 Anemia Basophilic stippling

Basophilic stippling

• Represents aggregated ribosomes • May be observed in

• Thalassemia diseases • Iron deficiency • Ineffective erythropoiesis

• Unstable hemoglobinopathies • Lead poisoning

• Pyrimidine 5′-nucleotidase deficiency

8. Anemia and thrombocytopenia Autoimmune hemolytic anemia

9. Neonatal anemia Acid elution test: F cell

Acid elution test

• Kleihauer-Betke technique of acid elution • Resistance of fetal Hb to acid elution • Interpret with caution in

• Maternal thalassemia minor • Hereditary persistent of fetal hemoglobin • Pregnancy-induced increase in Hb F production

10. Newborn with sepsis Toxic changes in neutrophils

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