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Approach to a child with anemia.
Viraj.
Overview.
•
•
•
•
•
•

Importance.
Introduction.
Definition.
Physiology.
Approach.
Summary.
Importance.
• Anaemia is a common and often complex
finding throughout childhood.
• May contribute to excess cardiovascula...
• Worldwide, anaemia in adults is responsible for
lost productivity, premature deaths, and perinatal
complications (Center...
RBC-The important players
• Hemoglobin
– Reversibly binds and transports 02 from lungs to
tissues.
– 4 globin chains & iro...
RBC-The important players
• Iron
– Key element in the production of hemoglobin
– Absorption is poor

• Transferrin
– Iron ...
Definition.
• Anaemia refers to red blood cell (RBC) mass,
amount of hemoglobin, and/or volume of
packed RBCs less than no...
• Infants less than 2 months of age have not yet
established steady state values for hemoglobin or
hematocrit, hence refer...
• Anaemia may be mild, moderate, or severe in
nature.
• Mild anaemia: hemoglobin 9.5-11 g/dl, is often
asymptomatic and fr...
Mechanisms of anemia.
• Anaemia conceptually reflects an imbalance
between RBC production and destruction and
may be due t...
Burr cells

Target cells
Spur cells

Spherocytes
Heinz body haemolytic anemia.

Bite cells
Basophilic stippling and tear drop cells

Polychromatophilia
Sickle cell

Schistocytes
Tear drop cell

Howell jolly bodies
DIFFERENCES IN THE EVALUATION OF ANEMIA
BETWEEN PEDIATRIC AND ADULT PATIENTS.
• The normal ranges for red blood cell
param...
• On identification of anemia, the likelihood of
certain diagnostic entities is different in
infants, children, and adults...
APPROACH TO ANAEMIA
• There are 3 different approaches that can be
taken in determining the cause of anaemia in
a particul...
• Pathophysiologic classification
– Is best suited for relating disease processes to
potential treatment.
– In addition, a...
• Morphologic classification
– subdivides anemia into
• Macrocytic anemia,
• Normocytic anemia, and
• Microcytic hypochrom...
Approach.
•
•
•
•
•

History,
Physical examination.
Complete blood cell count,
Reticulocyte count,
Peripheral blood smear.
History.
• Age :
• Newborn: Hemorrhage, Hemolysis, Infections,
Impaired red cell production.
• Infants & children : Iron d...
• Family history : congenital anemias, hemolytic
anemias.
• (1)X-linked: G6PD def.
• (2)Autosomal dominant: Spherocytosis....
• H/o gallstones , recurrent jaundice : Hemolytic
anemias.
• Family history of anemia, requirement for
blood transfusions ...
• H/o tingling sensation , history suggestive of
neuropathy : Vit B 12 deficiency.
Diagnostic Approach-History
• Diarrhea:
– Malabsorption of VitB12/E/Fe.
– Inflammatory bowel disease and anemia of chronic...
Diagnostic Approach-History
• Nutrition:
–
–
–
–
–

(1)Cows milk diet : iron def.
(2)Strict vegetarian : Vit B12 def.
(3)G...
Physical examination.
• Fever - acute infection, intravascular disease, collagen
vascular disease.
• Jaundice suggests Hem...
Physical Findings in Anemia
• Skin:
• Hyper pigmentation, café au lait spots - Fanconi
anemia
• Jaundice - Hemolysis
• Pet...
Physical Findings in Anemia
– Eyes:
•
•
•
•

Microphthalmia - Fanconi anemia
Retinopathy - Sickle cell disease
Optic atrop...
Physical Findings in Anemia
• Chest:
• Cardiac murmur-Endocarditis, prosthetic valve
Hemolysis.
• Abdomen:
• Hepatomegaly ...
Physical Findings in Anemia
• Extremities :
• Absent thumb-Fanconi anemia
• Spoon nails-Iron deficiency
• Dystrophic nails...
• Pallor : nail beds, oral mucous membranes
and conjunctivae.
• Observing skin pallor and palmar creases is
insufficient i...
Mean Corpuscular Volume
• The average volume of the red blood cells is a
useful red cell index that is used in
classificat...
Red Cell Distribution Width.
• The RDW is a red cell measurement that
quantitates red cell volume heterogeneity that is
pr...
• RDW is particularly useful when characterizing
microcytic anemias, particularly distinguishing
between iron deficiency a...
• RDW is useful as a method for initial
characterization of anemia, particularly
microcytic anemias, although other tests ...
Automated Reticulocyte Counts.
• Determination of the numbers of reticulocytes or
immature, nonnucleated red blood cells t...
• Normal values for reticulocytes in adults are 0.5
to 1.5%, although they may be 2.5 to 6.5% in
newborns (falling to adul...
Reticulocyte Production Index.
• RPI corrects the retics for the degree of anemia
• RPI indicates whether bone marrow is
r...
AETIOLOGY
• (1) Inadequate response RPI < 2
– A. Hypochromic microcyctic
– B. Normochromic Normocytic
– C. Macrocytic

• (...
Corrected reticulocyte count.
• Corrected reticulocyte count = patient reticulocyte
count
patient hematocrit / normal hema...
Pathophysiological approach.
• Based on pathophysiology, anemias are
divided into
– Anemia due to acute hemorrhage,

– Ane...
APPROACH TO HYPOPROLIFERATIVE ANEMIA IN THE CHILD.
APPROACH TO HEMOLYTIC ANEMIA IN THE CHILD.
Approach to a child with anemia(scenario approach)
Anemia (Hb less than normal level)
- No lymph nodes
- No hepatosplenome...
Anemia (Hb less than normal level)
- No lymph nodes
- No hepatosplenomegaly
- With petechiae and ecchymosis
----- Aplastic...
Anemia (Hb less than normal level)
With hepatosplenomegaly
----- Thalassemia
----- Liver disorders
Anemia (Hb less than normal level)
With petechiae, lymphadenopathy and
hepatosplenomegaly
--- Leukamia
--- Infections
--- ...
Morphological approach.
• Anemias may be morphologically categorized
on the basis of RBC size (mean corpuscular
volume [MC...
Microcytes

Macrocytes

Normocytes
Approach to Microcytic anemia
Reticulocyte count

Increased

Normal or reduced

Low serum iron
Low ferritin
Increased TIBC...
Approach to Normocytic anemia
Reticulocyte count
Increased

Normal or reduced
Screen for
renal,hepatic,endocrine
disease

...
Approach to Macrocytic anemia
Peripheral smear shows hyper segmented neutrophils and macro- ovalocytes.

Yes

Likely megal...
What to do?
• Brief clinical history.
• Physical findings.
• 1st line : Hemoglobin, hematocrit, MCV,
retic.count, peripher...
Summary.
• Anaemia is a common and often complex
finding throughout childhood.
• Iron is a Key element in the production o...
• The determination of whether anemia is
present or not must be made in an ageappropriate context.

• Morphologic classifi...
References
•
•
•
•
•

Nelson’s textbook. 17th edition.
Hoffman’s hematology.
William’s hematology. 7th edition.
Wintrobe’s...
Than
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
a child with anaemia - an approach
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Transcript of "a child with anaemia - an approach"

  1. 1. Approach to a child with anemia. Viraj.
  2. 2. Overview. • • • • • • Importance. Introduction. Definition. Physiology. Approach. Summary.
  3. 3. Importance. • Anaemia is a common and often complex finding throughout childhood. • May contribute to excess cardiovascular or respiratory work (Cohen, 1996). • About 42% of pregnant women and 47% of children <5 yr of age in developing countries are anemic. (nelson)
  4. 4. • Worldwide, anaemia in adults is responsible for lost productivity, premature deaths, and perinatal complications (Centers for Disease Control, 2002) and poor growth, developmental delays, and increased susceptibility to infection in children (Lesperance et al., 2002). • Timely screening coupled with appropriate diagnostic testing will afford the most optimal identification and management of childhood anaemia.
  5. 5. RBC-The important players • Hemoglobin – Reversibly binds and transports 02 from lungs to tissues. – 4 globin chains & iron.
  6. 6. RBC-The important players • Iron – Key element in the production of hemoglobin – Absorption is poor • Transferrin – Iron transporter • Ferritin – Iron binder, measure of iron stores, *also acute phase reactant.*
  7. 7. Definition. • Anaemia refers to red blood cell (RBC) mass, amount of hemoglobin, and/or volume of packed RBCs less than normal, determined either as a hematocrit or hemoglobin concentration > 2 standard deviations below the normal mean for age (Abshire, 2001; Cohen, 1996; Korones & Cohen, 1997; Walters & Abelson, 1996).
  8. 8. • Infants less than 2 months of age have not yet established steady state values for hemoglobin or hematocrit, hence reference ranges for normal are extensive. • Children with chronic pulmonary or cardiac disease experience symptoms traditionally suggestive of anaemia at hemoglobin and hematocrit levels above reference cut-offs (Segel, Hirsh, & Feig, 2002a).
  9. 9. • Anaemia may be mild, moderate, or severe in nature. • Mild anaemia: hemoglobin 9.5-11 g/dl, is often asymptomatic and frequently escapes detection. • Moderate anaemia: hemoglobin 8-9.5 g/dl, may present with other symptoms and warrants timely management to prevent long-term complications. • Severe anaemia: hemoglobin < 8 g/dl, will warrant investigation and prompt management.
  10. 10. Mechanisms of anemia. • Anaemia conceptually reflects an imbalance between RBC production and destruction and may be due to one of three mechanisms. – Excess RBC loss, as occurs with hemorrhage, may create anaemia as RBCs are depleted in addition to loss of intravascular volume. – Excess or premature RBC destruction, such as from hemolysis, may create anaemia as RBCs are lost from circulation prior to their normal turnover. – A third mechanism, insufficient RBC production, may create anaemia either from lack of stimulation of production or lack of RBC precursor availability (Cohen, 1996; Hermiston & Mentzer, 2002; Ioli, 2002).
  11. 11. Burr cells Target cells
  12. 12. Spur cells Spherocytes
  13. 13. Heinz body haemolytic anemia. Bite cells
  14. 14. Basophilic stippling and tear drop cells Polychromatophilia
  15. 15. Sickle cell Schistocytes
  16. 16. Tear drop cell Howell jolly bodies
  17. 17. DIFFERENCES IN THE EVALUATION OF ANEMIA BETWEEN PEDIATRIC AND ADULT PATIENTS. • The normal ranges for red blood cell parameters are significantly different in infants and children and do not reach adult levels until adolescence. • Thus, the determination of whether anemia is present or not must be made in an ageappropriate context.
  18. 18. • On identification of anemia, the likelihood of certain diagnostic entities is different in infants, children, and adults. • In infants and children, anemia often represents a nutritional deficiency or a primary hematologic process, whereas in adults anemia more commonly is an indicator of systemic disease or malignancy.
  19. 19. APPROACH TO ANAEMIA • There are 3 different approaches that can be taken in determining the cause of anaemia in a particular child: • 1. Pathophysiological approach. • 2. “Scenario approach.” • 3. Approach based on “Morphologic classification.”
  20. 20. • Pathophysiologic classification – Is best suited for relating disease processes to potential treatment. – In addition, anemia resulting from deficiency states occurs in a significant proportion of patients with normal indices.
  21. 21. • Morphologic classification – subdivides anemia into • Macrocytic anemia, • Normocytic anemia, and • Microcytic hypochromic anemia. – The main advantages of this classification are that the classification is simple, is based on readily available red cell indices (MCV and MCHC), and forces the physician to consider the most important types of curable anemia: vitamin B12 , folic acid, and irondeficiency anemias. – Such practical considerations have led to wide acceptance of this classification.
  22. 22. Approach. • • • • • History, Physical examination. Complete blood cell count, Reticulocyte count, Peripheral blood smear.
  23. 23. History. • Age : • Newborn: Hemorrhage, Hemolysis, Infections, Impaired red cell production. • Infants & children : Iron deficiency anemia, Vit.B12 deficiency, hemolytic anemias. • Adolescent, menstruating & pregnant teens : Iron deficiency. • Sex : Male : G-6 PD deficiency. • Race : • Tribes : Sickle cell anemia, • Sindhi,punjabi,gujarati : Thalassemia.
  24. 24. • Family history : congenital anemias, hemolytic anemias. • (1)X-linked: G6PD def. • (2)Autosomal dominant: Spherocytosis. • (3)Autosomal recessive: Sickle cell anemia , Fanconi anemia. • (4)Family member with early age of cholecystectomy/ splenectomy. • (5)Ethnicity: Thalassemia; G6PD def.
  25. 25. • H/o gallstones , recurrent jaundice : Hemolytic anemias. • Family history of anemia, requirement for blood transfusions and demise of children: Thalassemia major. • H/o Pica, chronic diarrhea, prior surgery, acute and prolonged infections, liver and renal diseases.
  26. 26. • H/o tingling sensation , history suggestive of neuropathy : Vit B 12 deficiency.
  27. 27. Diagnostic Approach-History • Diarrhea: – 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: Vit.B12 def EBV, CMV, Parvovirus : BM suppression Mycoplasma, Malaria : Hemolysis Hepatitis : aplastic anemia Endocarditis, HIV
  28. 28. 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 : Vit.E def • Drugs: – – – – (1)G6PD:oxidants(sulfa, primaquine, henna) (2)Immune mediated Hemolysis (penicillin) (3)Bone marrow suppression (chemotherapy) (4) Phenytoin increase folate requirement
  29. 29. Physical examination. • Fever - acute infection, intravascular disease, collagen vascular disease. • Jaundice suggests Hemolysis. • Petechia & Purpura—bleeding tendency. • Hypertension & edema - 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.
  30. 30. Physical Findings in Anemia • Skin: • Hyper pigmentation, café au lait spots - Fanconi anemia • Jaundice - Hemolysis • Petechia & Purpura - BMinfiltration, autoimmune Hemolysis & thrombocytopenia • Erythematous rash- Parvovirus , E.B.Virus • Butterfly rash - SLE; • Vitiligo – Vit B12 def. • Head : • Frontal bossing - Thalassemia major • Microcephaly - Fanconi anemia
  31. 31. Physical Findings in Anemia – 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
  32. 32. Physical Findings in Anemia • Chest: • Cardiac murmur-Endocarditis, prosthetic valve Hemolysis. • Abdomen: • Hepatomegaly - Hemolysis, infiltrative tumor, chronic disease, hemangioma, cholecystitis. • Splenomegaly - Hemolysis, sickle cell disease, Thalassemia, malaria, EBvirus, portal hypertension. • Kidney anomaly - pelvic/absent kidney.
  33. 33. Physical Findings in Anemia • 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.
  34. 34. • Pallor : nail beds, oral mucous membranes and conjunctivae. • Observing skin pallor and palmar creases is insufficient in children as the skin creases do not show pigmentation. (O.P.GHAI)
  35. 35. Mean Corpuscular Volume • The average volume of the red blood cells is a useful red cell index that is used in classification of anemias and may provide insights into Pathophysiology of red cell disorders. • Usually measured directly with automated instruments but may also be calculated from the erythrocyte count and the Hct by means of the following formula.
  36. 36. Red Cell Distribution Width. • The RDW is a red cell measurement that quantitates red cell volume heterogeneity that is provided by the more modern automated hematology analyzers and reflects the range of red cell sizes measured within a sample. • RDW has been proposed to be useful in early classification of anemias because it becomes abnormal earlier in nutritional deficiency anemias than any of the other red cell parameters, especially in cases of iron deficiency anemia.
  37. 37. • RDW is particularly useful when characterizing microcytic anemias, particularly distinguishing between iron deficiency anemia (high RDW, normal to low MCV) and uncomplicated heterozygous Thalassemia (normal RDW, low MCV).
  38. 38. • RDW is useful as a method for initial characterization of anemia, particularly microcytic anemias, although other tests are usually required to confirm the diagnosis. • RDW is also useful in identifying red cell fragmentation, agglutination, or dimorphic cell populations (including patients who have had transfusions or have been recently treated for a nutritional deficiency)
  39. 39. Automated Reticulocyte Counts. • Determination of the numbers of reticulocytes or immature, nonnucleated red blood cells that contain RNA provides useful information about the bone marrow's capacity to synthesize and release red cells in response to a physiologic challenge, such as anemia. • In the past, reticulocyte counts were performed manually using supravital staining with methylene blue. • Reticulocytes will stain precipitated RNA that appears as a dark blue meshwork or granules (at least two per cell) allowing reticulocytes to be identified and enumerated by manual counting methods
  40. 40. • Normal values for reticulocytes in adults are 0.5 to 1.5%, although they may be 2.5 to 6.5% in newborns (falling to adult levels by the second week of life). • Because there are relatively low numbers of reticulocytes, the CV for reticulocyte counting is relatively large (10 to 20%). • To increase accuracy of reticulocyte counting, alternative methods using flow cytometry and staining with acridine orange or thioflavin allow for many more cells to be analyzed, thereby increasing accuracy and precision of counts.
  41. 41. Reticulocyte Production Index. • RPI corrects the retics for the degree of anemia • RPI indicates whether bone marrow is responding appropriately to anemia • 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 anemia • Reticulocytopenia—acute onset of anemia, antibody mediated destruction, BMdisease.
  42. 42. 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
  43. 43. Corrected reticulocyte count. • Corrected reticulocyte count = patient reticulocyte count patient hematocrit / normal hematocrit. • High reticulocyte count : – – – – – Hemolysis, Hemorrhage, Splenic sequestration, Sepsis, Recovery from vitamin or iron deficiency. • Low reticulocyte count : – – – – – Congenital or acquired, Aplastic/hypoplastic anemia. Transient erythroblstopenia of childhood, Pure red cell aplasia, BM infiltration
  44. 44. Pathophysiological approach. • Based on pathophysiology, anemias are divided into – Anemia due to acute hemorrhage, – Anemia due to hypo proliferation, – Anemia due to Hemolysis.
  45. 45. APPROACH TO HYPOPROLIFERATIVE ANEMIA IN THE CHILD.
  46. 46. APPROACH TO HEMOLYTIC ANEMIA IN THE CHILD.
  47. 47. Approach to a child with anemia(scenario approach) Anemia (Hb less than normal level) - No lymph nodes - No hepatosplenomegaly - No petechiae or ecchymosis ----- Nutritional iron deficiency or megaloblastic ----- Pure red cell aplasia ----- Thalassemia trait ----- Lead poisoning ----- Renal disease
  48. 48. Anemia (Hb less than normal level) - No lymph nodes - No hepatosplenomegaly - With petechiae and ecchymosis ----- Aplastic anemia ----- Bleeding disorder ----- Coagulation disorder ----- ITP ----- DIC
  49. 49. Anemia (Hb less than normal level) With hepatosplenomegaly ----- Thalassemia ----- Liver disorders
  50. 50. Anemia (Hb less than normal level) With petechiae, lymphadenopathy and hepatosplenomegaly --- Leukamia --- Infections --- DIC
  51. 51. Morphological approach. • Anemias may be morphologically categorized on the basis of RBC size (mean corpuscular volume [MCV]), and microscopic appearance. • They can be classified as microcytic, normocytic, or macrocytic based on whether the MCV is low, normal, or high, respectively. • RBC size also changes with age, and normal developmental changes in MCV should be recognized before a designation is made.
  52. 52. Microcytes Macrocytes Normocytes
  53. 53. Approach to Microcytic anemia Reticulocyte count Increased Normal or reduced Low serum iron Low ferritin Increased TIBC Normal serum iron Normal TIBC Normal ferritin Hemoglobin electrophoresis Peripheral smear for RBC morphology, Tests for hemolysis (bilirubin,LDH,haptoglobin) Hemoglobin electrophoresis Iron deficiency Low serum iron Normal or high ferritin Normal or low TIBC Raised ESR,CRP Inflammatory disease Hemoglobinopathies Anemia of chronic disease Increased serum iron Low TIBC Increased ferritin Sideroblastic anemia
  54. 54. Approach to Normocytic anemia Reticulocyte count Increased Normal or reduced Screen for renal,hepatic,endocrine disease Serum iron Low Normal or high BM biopsy negative Positive Anemia of renal, hepatic, endocrine disease Anemia of chronic disease Early iron deficiency Infiltrative disease (leukemia, metastasis, myelofibrosis) Aplastic anemia, pure red cell aplasia, Myelodysplastic syndrome Positive tests for Hemolysis Yes No Hemolytic anemia Hemorrhage Recovery from nutritional deficiency, sepsis.
  55. 55. Approach to Macrocytic anemia Peripheral smear shows hyper segmented neutrophils and macro- ovalocytes. Yes Likely megaloblastic anemia Likely non megaloblastic anemia No Reticulocyte count BM Examination to confirm megaloblastic anemia and vit B12/folic acid levels or response to vit B12 /folic acid therapy Megaloblastic marrow and anemia improves Continue vit B12/folate Treat underlying cause Decreased Increased Non megaloblastic Hypothyroidism, marrow or no Liver disease Hemolysis, improvement hemorrhage Investigate for Drug induced, e.g. phenytoin, If negative do BM for Cyanotic heart disease, Aplastic anemia, Down syndrome, Red cell aplasia, Hypothyroidism MDS, Sideroblastic anemia
  56. 56. What to do? • Brief clinical history. • Physical findings. • 1st line : Hemoglobin, hematocrit, MCV, retic.count, peripheral smear. • 2nd line : Iron studies, evidence of Hemolysis, electrophoresis. • 3rd line : bone marrow.
  57. 57. Summary. • Anaemia is a common and often complex finding throughout childhood. • Iron is a Key element in the production of hemoglobin with poor absorption. • Infants less than 2 months of age have not yet established steady state values.
  58. 58. • The determination of whether anemia is present or not must be made in an ageappropriate context. • Morphologic classification is widely accepted. • A systematic approach is the key to diagnosis.
  59. 59. References • • • • • Nelson’s textbook. 17th edition. Hoffman’s hematology. William’s hematology. 7th edition. Wintrobe’s hematology. O.P.Ghai.
  60. 60. Than
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