Anemia – edited......................pptx

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1. Approach to the child with anemia Presenters: Girma A. (C-I), and Daniel A. (C-I) Moderator: Dr. Selamawit A. (Ass/Professor O f Paediatrics)

2. Outline Introduction Definition Normal RBC characteristics Causes of anemia Age characteristics in anemia History, physical examination, laboratory evaluation Management of anaemia in children

3. Objective To discuss on the possible causes of childhood anemia To know how to approach a child with anemia To know the common laboratory tests for anaemia

4. Introduction Anemia is the most common hematologic abnormality identified in infants and children. Approximately a quarter of the world’s population suffers from anemia, with 50% of children <5 years of age affected. Highest prevalence in pre-school children in African; Anemia is not a specific disease entity per se but represents a heterogeneous group of pathologic conditions.

5. Introduction … There are many causes of anemia, both inherited and acquired, and these causes vary widely in populations across the world. It is associated with increased morbidity and mortality in children, particularly children of preschool age. The WHO has recognized iron deficiency anemia as the most common nutritional deficiency in the world, with 30% of the population being affected.

6. Definition of anemia Anemia is defined as reduced blood hemoglobin (HGB) concentration or red blood cell (RBC) mass. The threshold for defining anemia is HGB or HCT at or below the 2.5 th  percentile for age and sex based on the reference ranges of healthy individuals.  HGB and HCT reference ranges vary with age and sex. MCV helps classify anemia in conjunction with HGB, HCT, and reticulocyte count.

7. Normal Red Cells No nucleus, enzyme packets. Biconcave discs. Center 1/3 pallor. Pink cytoplasm. 100-120 days of life span. Size 7-8 mic.

8. Normal RBC characteristics RBC life span across different age groups: Preterm RBC 35 – 50 days Neonatal RBC 60 – 90 days Adult RBC 110 – 120 days

9. What Happens in Anemia? Increased O2 carrying capacity of the blood . Few physiological disturbances occur until Hb <7- 8g/ dL Pallor more evident when Hb <8g/ dL . Pallor less obvious in dark skin . Younger children less symptoms and signs . Gradual drop in Hgb cause less symptoms and signs.

10. Compensatory Mechanisms for low Hgb level Increase CO and PR to improve blood oxygenation. Increase erythropoiesis because of increased EPO production by the kidneys. Blood shunted to O2 sensitive organs (Heart, CNS ). Increase in amount of 2,3 bi-phosphoglycerate .

11. Causes of anemia Causes of anemia: Decreased or ineffective red cell production , Increased red cell destruction (hemolysis), and Blood loss,

12. Causes of anemia Depending on the marrow response of generating the reticulocytes, anemia can be : Hypoproliferative (microcytic/macrocytic based on MCV)   Hyperproliferative Normal MCV: For 0-1 month = 99-115 fL For 1-23 months = 72-88 fL For 2-9 years = 76-90 

13. Type of anemia Causes Hypoproliferative Iron deficiency anemia Anemia of chronic disease (AOCD) Sideroblastic anemia  Thalassemia Lead poisoning  Hyperproliferative anemia Infections (Malaria, Babesiosis ) Transfusion reactions Hemoglobinopathies (sickle cell, thalassemias ) Enzyemopathies (G6PD deficiency) Membrane defects (hereditary spherocytosis) Drug-induced Autoimmune hemolytic anemia (AIHA) DIC

14. Causes of anemia … Macrocytic anemia can be due to hypoproliferative disorder, hemolysis, or both. Thus , it is important to calculate the corrected reticulocyte count when evaluating a patient with macrocytic anemia. Normal fraction of reticulocytes: 2.5-6.5% for newborn; 0.5-3.1% for infant; 0.5-2% for adult/elderly/child

15. Age characteristics and anemia Birth to 03 months: The most common cause of anemia in young infants is "physiologic anemia," which occurs after the first month of life. HGB levels are high (>14 g/ dL ) at birth in healthy term infants Then, rapidly decline and reach a nadir of approximately 10 to 11 g/ dL at 6 – 12 weeks of age, which is called "physiologic anemia of infancy" (also called the "physiologic nadir“).

16. Age characteristics and anemia Birth to 03 months … Pathologic anemia in newborns and young infants is distinguished from physiologic anemia by any of the following: Anemia (HGB <13.5 g/ dL ) within the first month of life Anemia with lower HGB level than is typically seen with physiologic anemia (<9 g/ dL ) Signs of hemolysis (jaundice, scleral icterus, or dark urine) or symptoms of anemia (irritability or poor feeding)

17. Age characteristics and anemia Birth to 03 months … Common causes of pathologic anemia in newborns: include blood loss, immune hemolytic disease (Rh or ABO incompatibility), congenital infection, twin-twin transfusion, and congenital hemolytic anemia

18. Age characteristics and anemia Birth to 03 months … Compared with term infants, preterm infants are born with lower HCT and HGB, have shorter red blood cell (RBC) life span, and have impaired erythropoietin production due to immature liver function. Hence, the decline in RBC production occurs earlier after birth and is more severe than the anemia seen in term infants. This is referred to as "Anemia of prematurity (AOP )".

19. Age characteristics and anemia Infants 3 – 6 months: Anemia detected at 3 – 6 months of age suggests a hemoglobinopathy . Nutritional iron deficiency is an unlikely cause of anemia before the age of six months in term infants.

20. Age characteristics and anemia Toddlers , older children, and adolescents: Acquired causes of anemia are more likely in these age groups, particularly iron deficiency anemia. Children who are exclusively breastfed or breastfed without sufficient iron supplementation are at highest risk for iron deficiency. In contrast, infants who primarily receive iron-fortified formula during the first year of life are at risk for iron deficiency after transition to cow milk.

21. Age characteristics and anemia Toddlers , older children, and adolescents … Screening for iron deficiency anemia is recommended in all children at 9 to 12 months of age. Additional laboratory screening should be considered in children with additional risk factors (excessive cow milk intake in toddlers 12 to 36 months of age, onset of menarche in adolescent females).

22. Family History X-linked : G6PD deficiency.    Autosomal dominant : Spherocytosis.                     Autosomal recessive : Sickle cell, Fanconi’s anemia.  Ethnicity : Thalassemia; G6PD deficiency.

23. Approach to the child with anemia History – the degree of symptoms, past medical history, family history, dietary history, and developmental history may provide important clues to the cause of anemia. Symptoms attributable to anemia: Common symptoms – lethargy, tachycardia, and pallor. Infants may present with irritability & poor oral intake. Because of the body's compensatory abilities, patients with chronic anemia may have few or no symptoms compared with those with acute anemia at comparable hemoglobin (HGB) levels.

24. Clinical Assessment WHO Grading of Anemia: Clinical grading: Mild : Conjunctival pallor/mucous membrane Moderate : Obvious skin pallor Severe : Palmar crease pallor

25. Approach to the child with anemia … History … Symptoms of hemolysis: Changes in urine color, scleral icterus, or jaundice may indicate the presence of a hemolytic disorder. Hemolytic episodes that occur only in male family members may indicate a sex-linked disorder, such as glucose-6-phosphate dehydrogenase (G6PD) deficiency.

26. Approach to the child with anemia … History … Bleeding symptoms: Bleeding from the gastrointestinal tract, including changes in stool color, identification of blood in stools, and history of bowel symptoms, Whether there is a personal or family history of inflammatory bowel disease, celiac disease, intestinal polyps, colorectal cancer, hereditary hemorrhagic telangiectasia, von Willebrand disease, platelet disorders, or hemophilia. 

27. Approach to the child with anemia … History … Bleeding symptoms … Severe or recurrent epistaxis also may result in anemia from blood loss and iron deficiency. In adolescent girls, menstrual history should be obtained, including duration and amount of bleeding. Severe epistaxis and/or heavy menstrual bleeding should raise suspicion for an underlying bleeding disorder.

28. Approach to the child with anemia … History … Pica: The presence of pica, the intense craving for nonfood items, should be assessed given its strong association with iron deficiency. In young children, pica may manifest as craving dirt, rocks, and paper. Particularly, pagophagia (compulsive ice chewing) is common in adolescents, and may suggest lead poisoning and/or iron deficiency.

29. Approach to the child with anemia … History … Past medical history: Birth and neonatal history – anemia in newborn period and/or jaundice (including onset and need for phototherapy). Results of newborn screening (such as screening for sickle cell disease). History of prior episodes of anemia (including etiology, therapy, and resolution) Chronic medical conditions (infectious/inflammatory)

30. Approach to the child with anemia … History … Drug and toxin exposure history: Current and past medications with particular attention to oxidant drugs that can cause hemolysis Particularly, drugs that can cause hemolysis in patients with G6PD deficiency (fluoroquinolones, dapsone , nitrofurantoin, and sulfonylureas; foods such as fava beans; and others).

31. Approach to the child with anemia … History … Family history: Family history of anemia should be reviewed in depth. Family members with jaundice, gallstones, or splenomegaly should be identified. Family history of cholecystectomy or splenectomy may aid in the identification of additional individuals with inherited hemolytic anemias.

32. Approach to the child with anemia … History … Dietary history : Focused on assessing iron intake and, to a lesser degree, folate and vitamin B12 content. For infants and toddlers, the type of diet, type of formula (if iron fortified), and age of infant at the time of discontinuation of formula or breast milk should be documented. In addition, the amount and type of milk the patient is drinking should be determined.

33. Approach to the child with anemia … History … Dietary history : Those exclusively fed goat milk can develop anemia due to folate deficiency. Those didn't receive sufficient supplementation of iron may be anemic at the time of initial screening at age 9 to 12 months, But those received iron-fortified formula until age 12 months are unlikely to be anemic at this time, though they are at risk of iron deficiency during the second year of life after transitioning to cow's milk.

34. Approach to the child with anemia … Physical examination : Particular focus should be directed to examination of skin, eyes, mouth, facies , chest, hands & abdomen. Pallor is assessed by examining sites where capillary beds are visible (conjunctiva, palm, and nail beds). However, the sensitivity of clinical assessment of pallor in these locations in detecting severe anemia (HGB <7 g/ dL ) is only approximately 50 – 60%.

35. Approach to the child with anemia … Physical examination … Hemolytic processes resulting in anemia may present with jaundice, and hepatosplenomegaly resulting from increased red cell destruction. However, as with clinical detection of anemia through pallor, clinical detection of jaundice is often poor. As an example, in an emergency department setting, the clinical detection of jaundice was found to have sensitivity and specificity of only approximately 70%.

36. Cont’d… Vital sign - Fever = Acute infection, Collagen vascular disease - HTN = Renal origin - Tachycardia/ Tachypenea = Degree of anemia A/M - Stunted = Fanconi, Malnutrition - Microcephally = Fanconi anemia, Diamond blackfan Growth failure or poor weight gain = Anemia of chronic disease

37. Cont’d… HEENT - Head - Frontal bossing, prominence malar = Thalassemia, Congenital hemolytic anemia

38. Cont’d… - Eyes : Microphthalmia : Fanconi anemia - Cataracts: G6PD deficiency, galactosemia with hemolytic anemia - Blue sclera: IDA, collagen vascular disease - Jaundice: hemolysis, hepatitis - Edema of eyelids: infectious mononucleosis, renal failure

39. Cont’d… -Mouth -Glossitis = Vitamin B12, IDA -Angular stomatitis = IDA -Cleft lip and palate = DBA

40. Cont’d… LGS -LAP-infiltrative diseases Chest -Wide spread nipples -- DBA CVS - Murmur - Endocarditis, prosthetic valve hemolysis Abdomen -HSM— infiltrative, tumor , hemolysis, chronic disease

41. Cont’d…               Skin: - Hyperpigmentation, café au lait spots - Fanconi anemia - Petechiae , Purpura - BM infiltration, autoimmune hemolysis & thrombocytopenia                              - Jaundice ---- Hemolysis, Hepatitis - Erythematous rash – Parvovirus, EBV                   - Malar rash – SLE                  - Spoon nails—IDA - Vitiligo – Vitamin B12 deficiency

42. Cont’d… MSS - A bsent thumb = Fanconi anemia - Triphalangeal thumb, Thenar eminence hypoplesia =DBF - Edema– Renal failure, protein loosing enteropathy. CNS -Irritability, apathy = IDA       -Ataxia, posterior column sign = Vitamin B12 deficiency -Peripheral neuropathy = lead poisoning -Stroke = Sickle cell anemia, paroxysmal nocturnal hemoglobinuria.

43. Laboratory evaluation CBC with red blood cell (RBC) indices, Peripheral blood smear, Reticulocyte count, Direct antiglobulin test (DAT ), Serum bilirubin determination. Red cell distribution width (RDW) – is a quantitative measure of the variability of RBC sizes in the sample ( anisocytosis ). Reference values for RDW vary a little with age and are generally between 12 and 14%.

44. Laboratory evaluation … Peripheral smear : Peripheral smear is an essential part of any anemia evaluation. Even if the patient's RBC indices are within reference range, review of the blood smear may reveal abnormal cells that can help identify the cause of anemia.

45. Laboratory evaluation … Peripheral smear … Appearance of leukocytes should also be noted: Increased neutrophils , especially increased numbers of band forms, or the presence of atypical lymphocytes suggest the possibility of infectious or inflammatory conditions. Hypersegmented neutrophils suggest  vitamin B12 or folate deficiency The presence of early WBC forms (blasts) along with anemia should raise the suspicion of leukemia or lymphoma.

46. Diagnostic approach Abnormalities in other cell lines … Pancytopenia  – Causes of pancytopenia in children include infection, myelosuppressive medications, leukemia, aplastic anemia, and hypersplenism .  Anemia with thrombocytopenia  – Causes of anemia associated with low platelet count include hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, and Evans syndrome. Rarely, children with severe iron deficiency anemia may also have thrombocytopenia.

47. Diagnostic approach Abnormalities in other cell lines Anemia with thrombocytosis  – Iron deficiency anemia is commonly associated with thrombocytosis but can also be rarely associated with thrombocytopenia. Other causes of anemia associated with elevated platelet count include post-splenectomy anemia and infection or inflammation.  Anemia with leukocytosis  – Causes of anemia associated with elevated WBC count include leukemia and infection.

48. Other Laboratory Tests Bilirubin level Direct antiglobulin test or Coombs test   Red cell enzyme studies-enzymopathy Osmotic fragility (spherocytosis) Iron, TIBC, ferritin Hemoglobin electrophoresis

49. Folate, vitamin B12 (macrocytic) Bone marrow aspiration and biopsy Viral titers (e.g. Epstein-Barr virus, cytomegalovirus) BUN/ creatinine TFT, LDH Other Laboratory Tests …

50. Microcytic anemia — A nemia with a low MCV (≤2.5 th percentile for age and sex reference) Normocytic anemia— MCV within reference range (between the 2.5 th and 97.5 th percentile for age and sex reference) Macrocytic anemia— Macrocytic anemia is defined as anemia with a high MCV (≥ 97.5 th  percentile for age and sex reference).   Classification of anemia based on RBC size …

51. The reticulocyte count is especially helpful in evaluating children with normocytic anemia. Hyperproliferative (in response to increased loss, or destruction with a resultant shortened RBC survival ). High reticulocyte count (>3 percent) Reflects an increased erythropoietic response. Hypoproliferative (low or normal reticulocyte count) Relative or absolute bone marrow failure Deficient or reduced production of RBCs, or a reduced marrow response to the anemia. Anemia based on reticulocyte count

52. Use of the mean corpuscular volume (MCV) and reticulocyte count in the diagnosis of anemia

53. Prevention of pediatric anemia Some types of anemia are inherited and can’t be prevented. Iron deficiency anemia the most common form of anemia, and can be prevented by the diet rich in iron. Infants will get enough iron from breastmilk until about 4 months of age – iron supplementation after 4 month. Cow’s milk doesn't have enough iron, and also prevents absorption of iron – should not be given before 1 year. After 1 year, include iron-enriched grains and cereals, egg yolks, red meats, etc.

54. Management of pediatric anemia Management of anemia depends on the causes. Sometimes, it may require changing the child's diet Stopping drugs that presumed to cause anemia Administering vitamins and minerals, Blood transfusions Stem cell  transplants Surgery to remove the spleen

55. Management of pediatric anemia Iron deficiency anemia: The therapeutic dose should be calculated in terms of elemental iron. A daily total dose of 3-6 mg/kg of elemental iron in 1 or 2 doses is adequate , with the higher dose used in more severe cases. Maximum dose is 150-200 mg of elemental iron daily. Ferrous sulfate is 20% elemental iron by weight and is ideally given between meals with vitamin C–containing juice, although this timing is usually not critical with a therapeutic dose.

56. Management of pediatric anemia Iron deficiency anemia … Parenteral iron preparations are considered when malabsorption is present or when compliance is poor, because oral therapy is otherwise as effective, much less expensive and less toxic. When necessary, intravenous low-molecular-weight iron dextran, parenteral iron sucrose, ferric carboxymaltose , and ferric gluconate complex are available .

57. Management of pediatric anemia Iron deficiency anemia … Iron-refractory iron-deficiency anemia (IRIDA ) is a rare, autosomal recessive disorder of systemic iron balance characterized by defects in both the absorption and the utilization of iron. Patients with IRIDA exhibit iron-deficiency anemia that is refractory to oral iron therapy and only partially responsive to parenteral iron administration.

58. Management of pediatric anemia Folate deficiency anemia: If the specific diagnosis is in doubt, smaller doses of folate (0.1 mg/day) may be used for 1 week as a diagnostic test because a hematologic response can be expected within 72 hours. The trial to distinguish different causes of megaloblastic anemia is rarely necessary in developed countries for vit-B12 and folate blood levels are readily measured. If the diagnosis is fixed, folic acid orally or parenterally at 0.5-1.0 mg/day.

59. Management of pediatric anemia Folate deficiency anemia Doses of folate >0.1 mg can correct the anemia of vitamin B12 deficiency but might aggravate any associated neurologic abnormalities. Folic acid therapy should continue for 3-4 weeks until a definite hematologic response is achieved. Maintenance therapy with a multivitamin (containing 0.2 mg of folate) is adequate. Parenteral or high doses of specific folate formulations are required in the setting of hereditary folate malabsorption (HFM).

60. Management of pediatric anemia … The indications for blood transfusion in pediatric anemia vary based on the age and condition of the child. Acute anemia usually warrants immediate medical attention. Treatment depends on the severity and underlying cause of the anemia. Initial treatment begins with careful assessment of the signs and symptoms of the anemia that indicate therapy.

61. Management of pediatric anemia … Indications for blood transfusion: Transfusion is typically recommended f or neonates, and for infants < 4 months with: Acute blood loss of >10% blood volume Hgb levels less than 8.0 g/ dL in a stable newborn with symptoms of anemia (apnea, bradycardia, tachycardia, decreased vigor, poor weight gain) Hgb levels < 12.0 g/ dL in an infant with respiratory distress syndrome or congenital heart disease .

62. Management of pediatric anemia Indications for blood transfusion … For infants > 4 months, the guidelines are similar to those for adults, with transfusions recommended for: Acute blood loss >15% total blood volume Hgb levels < 7.0 g/ dL with symptoms of anemia Significant preoperative anemia if other corrective therapy is not available Hemoglobin levels < 13.0 g/ dL if on extracorporeal membrane oxygenation.

63. END!

64. References Nelson’s text book of paediatrics, 21 st edition Illustrated Textbook of Pediatrics, 4 th edition Guideline on haemoglobin cutoffs to define anaemia in individuals and populations (WHO, 2024). National library of medicine