Anemia definition classification hx and physical examination and investigation

1. SEMINAR ON APPROACH TO ANEMIA
PREPARED BY:
Mesay Abera (C1)
and
Mihret Abush (C1)
Moderator:
Dr. Fikretsion(MD,Pediatrician)
13thDecember 2023

2. OUTLINES
Introduction
 Definition
 Epidemiology
 Causes of anemia
 Physiologic adjustments in
anemia
 Classification
Approach to Anemic Child

3. INTRODUCTION
OVERVIEW OF ERYHROPOISESIS
• Fetal erythropoiesis begins with primitive megaloblastic erthropoiesis
in yolk sac at approximately 4-5 weeks of gestation.
• A transition is made to normoblastic erythropoiesis at approximately 6
weeks of gestation .At this time ,blood formation begnis in the liver.
• Liver is the primary organ of hematopoiesis from 3rd to 6th month of
gestation.
• At approxmatilly 3rd month of gestation ,hematopoiesis begins in the
spleen, thymus and lymph nodes .

4. Con.
• The liver and spleen continue to produce blood cells in the first week
of postnatal life.
• Bone marrow hematopoiesis begins around the 4th month of gestation
and increase throughout intrauterine development.
• After birth, further marrow volume expantion occurs.

5. DEFINITION OF ANEMIA
• Anemia is defined as a reduction of the hemoglobin concentration or
red blood cell (RBC) volume below the range of values occurring in
healthy persons.
• In practice, anemia most commonly is defined by reductions in one or
both of the following:
• Hematocrit (HCT)
• Hemoglobin (HGB)

6. Con.
• “Normal” hemoglobin and hematocrit vary substantially with age and
sex.

7. EPIDEMIOLOGY
• Anemia is a significant global health problem affecting children and
reproductive-age women .
• Children from low socioeconomic status are at increased risk for iron
deficiency because of poor dietary intake.

8. Con.

9. CAUSES OF ANEMIA
Nutrition Problems
• Iron deficiency
• Folic acid deficiency
• Vitamin B12 deficiency
• Vitamin A deficiency
• Protein energy malnutrition

10. Con.
Genetic hemoglobin Disorders
• Thalassemias
• Hemoglobin variants
• Glucose-6-phosphate
• Dehdrogenase deficiency

11. Con.
Infectious disease
• Soil-transmitted helminths
• Malaria
• Schistosomiasis
• Tuberculosis
• AIDS

12. Physiologic Anemia
• At birth, normal full- term infants have higher hemoglobin level and
larger red blood cells than do older children and adults.
• however, after birth the oxygen saturation is 95%, EPO is
undetectable.
• So, within the 1st week of life, a progressive decline in hemoglobin
level begins and persists for 6-8 weeks, the resulting anemia is known
as the physiologic anemia of infancy.

13. Con.
• Pathologic anemia in newborns and young infants is distinguished
from physiologic anemia by:
Anemia with lower HGB level than is typically seen with
physiologic anemia (e.g., <9 g/dL)
Signs of hemolysis (e.g., jaundice, scleral icterus) or symptoms
of anemia (e.g., irritability or poor feeding)

14. Physiologic Adjustments In Anemia
Increased cardiac output
Increased oxygen extraction (increased arteriovenous
oxygen difference)
Shunting of blood flow toward vital organs and tissues.
Concentration of (2,3-DPG) increases within the RBC
Increased EPO production (to increase RBC number)

15. CLASSIFICATIONS OF ANEMIA
1) Morphologic classification-based on RBC size and microscopic
appearance.
by MCV ,MCH and MCHC
2) Pathophysiologic classification-based on underlying etiology
-decreased production
-increased destruction or RBC loss(bleeding)

16. 1, Morphologic classification

17. CON.

18. CON.

19. 2, PATHOPHYSIOLOGIC CLASSIFICATION
I. Impaired red cell formation
A. Deficiency
• Decreased absorption
Specific: intrinsic factor lack  vitamin B12
Generalized: malabsorption syndromes
• Decreased dietary intake
excessive cows’milk  iron-deficiency anemia
vegan vitamin B12 deficiency
Vitamin C deficiency
• Increased demand,
rapid growth (iron)

20. Con.
B. Bone marrow failure
a. Aplastic anemia
characterized by pancytopenia
b. Pure red cell aplasia
 Congenital: Diamond–Blackfan Syndrome
Acquired: Transient erythroblastopenia of childhood

21. con
C. Impaired erythropoietin production
Anemia of chronic disease in renal failure
Chronic inflammatory diseases
Severe protein malnutrition

22. • II. Increased destruction
membrane defects
Hereditary spherocytosis
Hereditary elliptocytosis
enzyme defects (G6PD def…, PK def…)
hemoglobin defects (SCD, thalassemia)
PNH : Complement mediated lysis

23. Con.
Mechanical injury
Hemolytic uremic syndrome
Disseminated intravascular coagulation
Infections (malaria)
Thermal injury to RBCs (with severe burns)

24. Con.
III. Blood loss
it can be:-
Acute: massive hemorrhage
Chronic: GI tract loss : can be
- leech infestation and bleeding disorders
- seen in different causes of upper GI or lower GI bleeding.

25. • A detailed history and thorough physical exam are essential when
evaluating an anemic child.
• Clinical findings generally do not become apparent until the
hemoglobin level falls to <7-8 g/dL.
APPROACH TO ANEMIC
CHILD

26. General Clinical Features
• Sleepiness, Irritability
• Decreased exercise tolerance and
Easy fatigability
• Shortness of breath on exertion
• Pallor, can involve the tongue,
nail beds, conjunctiva, palms, or
palmar creases.
• Tachypnea,Tachycardia
• Flow murmur

27. • HISTORY
• Age
In Newborns, hemolytic anemia is common(e.g HDN)
Nutritional iron deficiency is common cause of anemia after six month
in term infants.
In older children, acquired causes are more likely particularly
IDA,Megaloblastic anemia.
• Sex
Some hereditary X-linked disorders like G6PD deficency associated
hemolytic anemia is observed mainly in males.

28. • Birth History: Prematurity, low birth weight,hemorrhagic obistetrical
or perinatal complications and any possible twin-twin transfusion.
• Dietary History: it is critical to obtain a dietary history with attention
to excessive complications of cow’s millk or exclusive breast
feeding, both of which may cause iron deficiency anemia.
Strict vegetarian : Vit B12 deficiency
Pica (dirty) -IDA

29. • Bleeding History: Ask about overt bleeding from any site:
• Including the gastrointestinal tract (melena, hematochezia),
genitourinary tract( hematuria, menorrhagia) and other mucocutanous
sites(epistaxis,oral bleeding).
• Race, Ancestry, Family history: African discent, or family history of
splenectomy or cholecystectomy may suggest inherited hemolytic
anemia.
• Travel history
Travel to malaria or tuberculosis endemic area

30. • Medications: can cause either decreased red cell production or
hemolysis.
• Inquire about:
• fever, bone pain,weight loss,bruising,jaundice,fatigue,rash and cough
that may suggest other systemic causes of anemia.
• Review of system: poor weight gain could indicate systemic disease or
malabsorption.
• A history of recurrent acute or chronic inflamation, such as: RA,IBD
may suggest anemia of chronic disease.

31. • PHYSICAL EXAMINATION
• A careful examination can reveal the presence and severity of anemia by
the degree of pallor( skin,conjunctivae, mucosae) and loss of palmar
crease pigmentation.
• The examiner should seek clues of specific causes of anemia.
• General Appearance
Acutely sick looking - infectious causes like malaria ,sepsis.
Chronically sick looking as in anemia of chronic illness.

32. VITALS
Patients with acute and severe anemia appear in distress with
tachycardia, tachypnea, and hypovolemia.
 Patients with chronic anemia are typically well compensated and only
have tachycardia.
 Fever - acute infection

34. Laboratory investigation
Initial laboratory testing should include:
CBC
Reticulocyte count
 Examination of the peripheral blood smear.

35. Laboratory investigation of anemia
I. Complete blood count
• CBC is a test that measures the cells that make up our blood cells such as:
Red blood cell
Hematocrit
Hemoglobin
white blood cell and
Platelets
NB. RBC indices should also be calculated

36. a. Red blood cell count
• is the total number of red cells in a Litre of whole blood
• Significance of RBC count
• is used to diagnose anemia
• to know the number of RBCs in a pathological conditions
• to Know RBC numbers during physiological alterations (E.g,
Pregnancy)

37. Cont.…
• RBC count is increased in:
• Polycythemia vera
• Polycythemia secondary to other causes such as dehydration and excessive
erythropoietin production like in high altitude.
• RBC counts decreased in:
• Decreased erythropoiesis(e.g, bone marrow suppression)
• Increased loss( E.g, Bleeding)
• Increased distruction

38. B. Packed cell volume(PCV) or Hematocrit
It is the measure of volume contrbution of erythrocytes to that of
the whole blood.
It is expressed as percentage or decimal.
It can be used to :
Screen anemia
Estimate hemoglobin (Hct%= 3x Hgb)
Calculate red cell indices

39. C.Hemoglobin
• A conjugated protein that serves as a vehicle to transport oxygen and
carbon dioxide.
Hgb determination is used to:
1. Determine the severity of anemia (Hgb<7 severe anemia in well
naurished child and Hgb<5 severe anemia for SAM ).
2. Follow the response to treatment of anemia.
3. To diagnose polycythemia.
4. To determine the Hgb level of blood donors.

40. Normal hematologic values by age

41. D.White blood cell count and Platelet count
• Anemia can be isolated finding or associated with other
abnormalities.
• High WBC and anemia as in infectious causes of anemia
• Pancytopenia(supression of every cell linage) is seen in - BMF,
Leukemia

42. • Are absolute values calculated from:-
Measured hemoglobin
Hematocrit or packed cell volume
RBC count
• Useful in identifying the type of anemia through morphological
characterization.
• The red cell indices include:-
MCV
MCH
MCHC
RDW

43. A. Mean Cell Volume(MCV)
• The average volume of a red cell expressed in fl
• Obtained by dividing the hematocrit by red cell number.
MCV(fl) = PCV/No. of RBC/L.
• It is increased in Macrocytic anemia
• Decreased in Microcytic anemias
• Infants have increased MCV compared to older children.
• MCV value increases with decreasing gestational age.

44. MCV variations with Age
Age MCV(fl)
Birth 98 to 118
1 to 3 days 95 to 121
2 weeks 86 to 124
2 months 77 to 115
3 to 6 months 74 to 108
0.5 to 2 years 70 to 86
2 to 6 years 75 to 87
6 to 12 years 77 to 95
12 to 18 years, females 78 to 102
12 to 18 years, males 78 to 98

45. B.Mean Cell Hemoglobin (MCH)
• It is a measure of the average weight of Hgb in a red blood cell.
• Can be calculated from Hgb and RBC count.
• Expressed in picogram
MCH=Hgb(g/l)/RBC count/l
• It increased in macrocytic anemia.
• Is decreased in microcytic anemia.

46. C. Mean Cell Hemoglobin Concentration(MCHC)
• Is the average hemoglobin per unit volume of red cell.
• It is expressed in g/l, and calculated from Hgb and Hct.
• It is increased in some form of hereditary sperocytosis.
• It is decreased in iron deficiency anemia.

47. D.Red Cell Distribution Width(RDW)
• Is specifically designed to reflect the variability of red cell size.
• larger values of RDW indicate grater variability
• An elevated RDW may be an early sign of iron-deficiancy anemia.
• Proposed as an aid in distinguishing iron deficiency from other causes
of microcytic anemia, such as thalassemia.

48. II. Reticulocyte Count
• Reticulocytes are juvenile or immatured red cells.
• Clinical significance
it is an index of bone marrow red cell
production.
it measures erythropoietic activity.

49. • In the presence of anemia the reticulocyte percentage does not
accurately reflect reticulocyte production
• We use reticulocyte production index(RPI)
• calculated as

50. • RPI > 3 indicate increased production
• it seen in the following conditions:-
• Hemolytic anemia
• Hemorrhage
• After treatment of anemias
• Physiological increase in pregnancy &in infants
• RPI < 2 indicate decreased production or ineffective production for
the degree of anemia.

51.  Decreased level means that Bone Marrow is not producing enough
erythrocytes.
 Conditions associated with decreased BM production are
• Iron deficiency anemia
• Aplastic anemia
• Radiation therapy
• Untreated pernicious anemia
• Tumor in the marrow

52. III. Peripheral Smear
• It is particularly important when assessing cytopenic states (e.g.
anemia, leukopenia, thrombocytopenia).
• Important in assessing membrane defect as a cause of anemia
• Peripheral smear is especially important in.
• Hemolytic anemia
• Thrombocytopenia
• White cell disorders

53. General Management Of Anemia
 Vitamin and mineral supplementation ( iron tablets, folate and vitamin
B12)
 Dietary modifications
Precautions in drug prescription
Treatment of the underlying disorder
Spleenectomy(for the risk of spleenic rupture in certain hemolytic
disorders)

54. Cont…
 Blood transfusions, if necessary (to replace significant loss).
N.B: Blood transfusions in those without symptoms is not
recommended until the hemoglobin is below 6 to 8 g/dl.
 Antibiotics ( if infection is the cause)
Stem cell transplant (for bone marrow failure)
Erythropoiesis-Stimulating agents- for decreased erythropoiesis

55. • IDA is the most common nutritional deficiency in children
• Prevalence is higher in developing countries
• The development & the rapidity of IDA is dependent upon the body’s
iron store
• Iron store in turn depends on : age, sex, rate of growth and balance b/n
loss & absorption
• Peak prevalence occurs during late infancy and early childhood

56. Iron Metabolism
• Iron is available in the body as
• Functional iron - Hgb, myoglobin and cytochromes
• Transport iron – transferrin
• Storage iron –ferritin and hemosiderin
• Dietary requirement of iron is about 8-10 g/dl/day of which only 10% will
be absorbed.
• Dietary iron absorption occurs through out the intestine, but especialy in
duodenum and proximal jejunum.
• Intestinal iron absorption is a function of three principal factors
• Body iron stores (transferrin and ferritin)
• Rate of Erythropoiesis
• Bioavailability of dietary iron

57. • Iron absorption is;
• Facilitated by - citrates and ascorbic acid
• Inhibited by - phytates, tannates, oxalates, phosphates, sulphates
and antacids.
• Dietary iron exists in two states:
• Heme (10%) – found in animal proteins
• Nonheme(90%) – vegetarians, found in the form of ferric state

58. Causes of IDA
•

59. Clinical Manifestations

60. Cont…
• Pallor
• Blue sclera
• Angular cheilities
• Atrophic glossitis
• Koilonychias (spooning of nails)
• Tachycardia
• Systolic murmurs are often present
• Plummer – Vinson syndrome:
characterized by the combination of
IDA, glossitis, cheilosis and
esophageal web

61. IDA pathogenesis
• The progression to iron deficiency can be divided into 3 stages:
• negative iron balance
• iron-deficient erythropoiesis
• iron deficiency anemia
• Negative iron balance
• demands for (or losses of) iron exceed the body’s ability to
absorb iron from the diet.
• Under these circumstances, the iron deficit must be made up by
mobilization of iron from storage sites.

62. Cont…
• Iron-deficient erythropoiesis
• Once the transferrin saturation falls to 15–20%, Hgb synthesis
becomes impaired.
• Careful evaluation of the peripheral blood smear reveals the first
appearance of microcytic cells.
• Gradually, the hemoglobin and hematocrit begin to fall, reflecting iron
deficiency anemia

63. Hgb – decreased
RBC count – decreased
Peripheral smear, RBCs are Small (microcytic ),Pale
(hypochromic),Poikilocytosis in the form of small elongated red
cells (pencil cells).
Red cell distribution width (RDW)– increased
Free erythrocyte protoporphyrin – elevated
LABORATORY
STUDIES

64. Iron studies
• Serum iron – decrease
• Total iron binding capacity – increased
• Serum ferritin – decreased
• Iron saturation – decreased
• Bone marrow iron stain (Prussian blue stain)
• The disappearance of stainable iron from mononuclear phagocytic
cells is a diagnostic finding.

65. • Management Principle
Oral supplement
4-6 mg/kg elemental iron daily in three divided doses
for 6–8 weeks after Hgb level and the RBC indices
return to normal
For at least 3 months
Parenteral iron therapy ; indications
-Unable to tolerate oral iron
-Who need iron on an ongoing basis, usually due to
persistent GI blood
Blood transfusion

66. Cont…
• Nutritional Counseling
• Maintain breastfeeding for at least
6 months, if possible.
• Use an iron-fortified (6–12 mg/L)
infant formula until 1 year of age.
• Avoid cow’s milk until after the
first year of age.
• Use iron-fortified cereal from 6
months - 1 year

67. Cont…
• Evaporated milk or soy-based formula should be used when iron-
deficiency is due to hypersensitivity to cow’s milk.
• Provide supplemental iron for LBW infants:
• Infants 1.5–2.0 kg: 2 mg/kg/day supplemental iron
• Infants 1.0–1.5 kg: 3 mg/kg/day supplemental iron
• Infants < 1 kg: 4 mg/kg/day supplemental iron

68. Prevention
Appropriate nutrition
Health education
Supplementation for those with increased demand
Fortification of formulas, cereals…
Diagnose and treat underlying conditions
Quality antenatal and neonatal care
In term infants, Exclusive Breast Feeding for the first 6
month
In breast fed preterm or low birth weight infants,
elemental iron supplementation starting at one month of
age and is continued until 12 months of age

69. REFERENCES
• Nelson,21st Ed.
• Upto date 21.6
• Blueprint Pediatrics