13.11.2060

1. Appraoch to a child with anaemia Dr. Pushpa Raj Sharma Professor of Child Health Institute of Medicine 13.11.2060

2. Definition of anaemia • The condition of having too few red blood cells. • It is a reduction of the red cell volume or hemoglobin concentration below -2SD for age, race and sex. • Microscopic: normocytic,microcytic,normochromic macrocytic or specific abnormalities (spherocyte,sickle cell,target cell)

3. Case • Nine months old “Rai” female, single child • Recurrent fever • Mass in abdomen with pallor • No history of rash, bleeding, persistent diarrhoea, drug, jaundice, pica, • Had blood transfusion 2 days back • No consanguity of marriage • No family history of gall stones, jaundice. • No loss of weight, exclusive breast feeding

4. Summary of examination finding • 9 Kg. • Mild pallor • No purpuric rash, lymphadenopathy, abnormal facies, • Gross spleenomegaly

5. Diagnostic Approach-History • Age : Iron def rare without blood loss before 6mo in term infants. • Family Hist & Genetics: (1)X-linked: G6PD def (2)Aut dominant: Spherocytosis (3)Aut recessive: Sickle cell,Fanconi anemia (4)Family member with early age of cholecystectomy/splenectomy (5)Ethnicity: Thalassemia; G6PD def

6. Diagnostic Approach-History • Diarrhoea: -Malabsorption of VitB12/E/Fe. Inflammatory bowel disease and anemia of chronic disease with or without blood loss. -Milk protein intolerance induced blood loss -Intestinal resection: Vit B12 def • Infection: - Giardia: iron malabsorption -Intestinal bacterial overgrowth: VitB12def -EBV,CMV,Parvovirus: BM suppression -Mycoplasma,Malaria: hemolysis -Hepatitis: aplastic anaemia -Endocarditis, HIV

7. Diagnostic Approach-History • Nutrition: (1)Cows milk diet:iron def. (2)Strict vegetarian:Vit B12 def. (3)Goats milk: Folate def. (4)Pica: Plumbism,Iron def. (5)Cholestasis,malabsorption:VitE def • Drugs: (1)G6PD:oxidants(sulfa, primaquine, henna) (2)Immune mediated hemolysis (penicillin) (3)Bone marrow suppression (chemotherapy) • (4)Phenytoin increase folate requirement

8. Physical exam reveals presence and potential causes of anaemia • Fever-acute infection,intravascular disease,collagen vascular disease • Jaundice suggests hemolysis • Petechia&Purpura—bleeding tendency • Hypertension&oedema-renal disease • Hepatosplenomegaly and lymphadenopathy—infiltrative disease • Growth failure or poor wt. gain—Anemia of chronic disease or organ failure • Examine stool for blood; urine for hemoglobinuria

9. Physical Findings in Anaemia • Skin:Hyperpigmentation,café au lait spots- Fanconi anemia -Jaundice-hemolysis -Petechia&purpura- BMinfiltration, autoimmune hemolysis&thrombocytopenia -Erythematous rash- Parvovirus,EBvirus -Butterfly rash-SLE; Vitiligo-VitB12def • Head:Frontal bossing-Thalassemia major -Microcephaly-Fanconi anemia

10. Physical Findings in Anaemia • Eyes: Microphthalmia-Fanconi anemia -Retinopathy-Sickle cell disease -Optic atrophy-Osteopetrosis -KF ring-Wilson disease • Ears: Deafness-Osteopetrosis • Mouth: Glossitis-B12 def,iron def - Angular stomatitis-Iron def -Pigmentation-Peutz Jeghers syndrome -Telangiectasia-Osler Weber Rendu syndrome

11. Physical Findings in Anaemia • Chest: Cardiac murmur-Endocarditis,prosthetic valve hemolysis • Abdomen: Hepatomegaly-hemolysis, infiltrative tumour,chronic disease, hemangioma,cholecystitis -Splenomegaly -hemolysis,sickle cell disease,thalassemia,malaria,EBvirus, portal hypertension -Kidney anomaly-pelvic/absent kidney

12. Physical Findings in Anaemia • Extremities:Absent thumb-Fanconi anemia -Spoon nails-Iron deficiency -Dystrophic nails-Dyskeratosis congenita • CNS-Irritable,apathy-Iron def. -Peripheral neuropathy-lead poisoning -Ataxia,post.column signs-Vit B12def - Stroke-Sickle cell anemia • Short stature-Fanconi anemia, Malnutrition

13. COMPLETE BLOOD COUNT • Hb Conc (g/dl) • Hematocrit(PCV) • MCV (fl) • MCH (pg) • MCHC (detects red cell dehydration) • RBC Count (…x10 ) • WbC Count (…x10 ) • Platelet Count (…x10 ) • Reticulocyte Count ( % )

14. Normal values Harriet Lane Handbook, The John Hopkins Hospital,15th edition

15. Reticulocyte Production Index • RPI corrects the retics for the degree of anaemia • RPI indicates whether bone marrow is responding appropriately to anaemia • RPI= Retic x Hb(o) x 0.5 divided by Hb(n) • RPI > 3 increased production (hemolysis or blood loss) • RPI < 2 decreased production or ineffective production for the degree of anaemia • Reticulocytopenia—acute onset of anaemia, antibody mediated destruction, BMdisease

16. AETIOLOGY • (1) Inadequate response RPI < 2 • A. Hypochromic microcyctic • B. Normochromic Normocytic • C. Macrocytic • (2)Adequate response RPI > 3 R/O blood loss---Includes Hemolytic disorders

17. Microcytic Anaemia • TEST Iron def ThalMin • S.Iron - low normal • S.Ferritin - low N/H • Marrow iron - low N/H • Hb A2or F - N H=Bthal • N=Athal • MCV ÷ RBC - >13< 13 • Sickle/B-thal – Hb S > Hb A • Absence of microcytosis in both parents excludes B-thal or Sickle/B-thal but not A-thal

18. Macrocytic anaemia • Vit.B12 def.- (1) pernicious anaemia (2) ileal resection (3) abnomal intestinal transport • Folate def.- (1) malnutrition (2) malabsorption (3) chronic hemolysis (4)drugs - phenytoin, sulfa • Hypothyroidism • Chronic liver disease • Marrow failure-Fanconi anaemia,Aplastic A 13.11.2060

19. Haemolytic anaemia • Hemoglobinopathy– Hb SS,SC,S-B thal • Enzymopathy--G6PD def, PK def • Membranopathy—Hereditary spherocytosis, elliptocytosis • Extrinsic factors—DIC,HUS,Abetalipoproteinemia,Wilsons disease,Vit E def • Immune hemolytic anaemia-Autoimmune,Isoimmune,Drug induced 13.11.2060

20. THALASSEMIA-Lab • Thal trait:Hb 9-10 g/dl • HbH disease:Hb 6-7 g/dl • Thal intermedia:Hb 7-8 g/dl • Thal major:Hb less than 5 g/dl • Peripheral smear:hypochromic,microcytic, anisopoikilocytosis,target cells • Hb electrophoresis: (1)Thal trait-HbF 1-5%, HbA2 3.5-8%,rest HbA (2)Thal major- HbF 20-100%,HbA2 2-7%,HbA 0-60%

21. Pure Red Cell Aplasia:Reticulocytopenia + Absent marrow erythroid precursors.

22. Aplastic anaemia • Severe reduction in platelets and granulocyte series 13.11.2060

23. Anaemia of chronic disease Normal morphology Chronic inflammatory disease—(1)infection (2)collagen vascular disease (3)inflammatory bowel disease Recent blood loss Malignancy/Marrow infiltration Chronic renal failure Transient erythroblastopenia of chidhood Marrow aplasia/hypoplasia HIV infection Hemophagocytic syndrome 13.11.2060

24. Haemolytic anaemia • Polychromasia (Wright-Geimsa). 13.11.2060

25. Leukaemias • Blast cells 13.11.2060

26. Laboratory Evaluation • Hematology:Complete Blood Count, Retic count,Peripheral smear,ESR,G6PD Sickling(+/-inf),Hb electrophoresis,Group,DCT, Osmotic fragility test,BMaspiration • Biochemistry:LFT,UE,RFT,S.Ferrtin, S.Haptoglobin,Iron,VitB12,Folate,Ceruloplasmin • Serology:Heterophil antibody,ANA,Viral t • Urinalysis,microscopy,culture/sensitivity • Stool exam.for ova,parasites,occult blood • Endoscopy: upper and lower bowel • Imaging:US Abdomen,Skeletal radiographs, Tc pertechnetate scan for Meckels diverticulum • Tissue biopsy:skin,lymph node,liver

27. Nine months old female, single child • Recurrent fever • Mass in abdomen with pallor • No rash, bleeding, persistent diarrhoea, drug • Had blood transfusion 2 days back • No consanguity of marriage • No loss of weight, exclusive breast feeding • 9 Kg. • Mild pallor Hb:9.4 g% • No purpuric rash, lymphadenopathy, abnormal facies, • Gross spleenomegaly • Blood report: • TLC: 9,600/ cmm: P: 44%: L: 56%; • Platelets: 30.000/cmm Anisocytosis, hypochromic, reticulocyte 0.8%, occasional NRC.

28. The diagnosis • Reticulocyte production index = Retic x Hb(o) x 0.5 divided by Hb(n) = 0.3 RPI < 2 decreased production or ineffective production for the degree of anaemia • Metabolic • Malignancy • Further work up: • Bone marrow

29. Normal values Cell Type Range %Myeloblasts 0-2 Promyelocytes 2-5 Myelocytes (neutrophilic)9-16 Metamyelocytes 7-23 Band forms 8-15 Neutrophils 4-10 Myelocytes (eosinophilic)0-2 Band 0-2 Mature 0-3 Monocytes/macrophages0-3 Basophils 0-1 Mast cell 0-2 Plasma cells 3-6  This patient Cell Type % Blast 10 Promyelocyte 1.5 Myelocyte 12 Metamyelocyte 18 Neutrophils 31 Bone marrow report

30. Final diagnosis • Malignancy • Juvenile Chronic Myelogenous Leukemia

31. The commonest cause • Iron def. is common in children 9mo-3yr • Iron def. anemia in a child over 3yr should prompt consideration of occult blood loss. • Infants less than 6months generally do not develop iron def.; the exception to this rule is premature infants,who are at risk of iron def.at 4mo, if iron supplementation is not given.

32. Iron deficiency Anemia • Dietary iron def is the usual cause • Manifestations of anemia • CNS abnormalities:apathy,irritability,poor conc,cognitive deficits • Poor muscle endurance • GIT dysfunction • Impaired WBC and T-cell function

33. Iron deficiency: hypochromic anaemia • Iron def.-(1)chronic blood loss (2)poor diet (3)cows milk protein intolerance • Chronic inflammatory disease 13.11.2060

34. Differential Features of Iron Deficiency vs Acute and Chronic Inflammation

35. Iron deficiency Anemia • Treatment:Response to oral iron includes 24-48hr-subjective improvement inCNS 48-72hr-reticulocytosis 4-30days-increase in Hb 1-3 mo-repletion of iron stores • Therapeutic dose:3-6 mg/Kg/day of elemental iron.---Induces an increase in Hb of 0.25-0.4 g/dl per day or 1%/day rise in hematocrit. • Failure of response after 2 weeks of oral iron requires reevaluation for ongoing blood losses,infection,poor compliance or other causes of microcytic anaemia.