The document discusses the evaluation and diagnosis of pediatric blood disorders. It notes that the history, physical exam, and initial laboratory tests provide clues to diagnose blood diseases. Diagnosis requires knowledge of normal hematological values that vary by age. The initial workup involves tests like hemoglobin, red blood cell indices, blood smear exam. Further tests are used depending on the results to diagnose causes like anemia, hemolytic disorders, and hemoglobinopathies. Specific disorders discussed in more detail include iron deficiency anemia, thalassemias, sickle cell disease, and their typical laboratory findings and treatment approaches.

1. The Anemia
Professor Dr. Salah Al-Zuhairy, MD.

2. INITIAL DIAGNOSTIC
EVALUATION
 The history and physical examination provide important
clues to the diagnosis of blood diseases.
 The basis for the diagnosis of blood disorders is laboratory
testing.
 Diagnosis of pediatric blood disorders requires a detailed
knowledge of normal hematologic values during infancy
and childhood.
 These values vary according to age and, after puberty,
according to sex.

3. INITIAL DIAGNOSTIC
EVALUATION

4.  From the history, physical examination, and screening
laboratory studies, the astute clinician proceeds in an
orderly manner to the diagnosis using specific diagnostic
testing to confirm the diagnosis.
INITIAL DIAGNOSTIC
EVALUATION

5. INITIAL LABORATORY STUDIES
 The initial laboratory evaluation of anemia involves a hemoglobin or
hematocrit test to indicate the severity of the anemia.
 When the diagnosis of anemia has been substantiated: the workup should
include a measurement of red cell indices, platelet count, white blood cell count
and differential, and reticulocyte count; and examination of a peripheral blood
smear.
 Examination of the peripheral blood smear is crucial to assess the number and
morphology of RBCs, WBCs, and platelets.
 After this initial assessment, other useful and simple laboratory procedures
may be used, including, when indicated, measurement of serum ferritin
concentration, supravital staining of erythrocytes, hemoglobin electrophoresis,
a screening test for the presence of unstable hemoglobins, a direct and indirect
Coombs test, a screening test for G6PD deficiency, and examination of bone
marrow.

6. LABORATORY STUDIES
Anemia
 All cell lines should be analyzed to determine whether
anemia is the result of:
A process limited to the erythroid line or
A process that affects other marrow elements
 Using data obtained from the indices and reticulocyte
count, the workup for anemia can be organized on the
basis of whether:
RBC production is adequate or inadequate
 RBCs are microcytic, normocytic, or macrocytic

7. INITIAL LABORATORY STUDIES
Morphologic abnormalities of the red blood cell. A, Normal. B, Macrocytes (folic acid or vitamin
B12deficiency). C, Hypochromic microcytes (iron deficiency). D, Target cells (Hb CC disease).
E, Schizocytes (hemolytic-uremic syndrome).

8. Laboratory Approach in The Diagnosis of
Anemia

9. Usefulness of MCV and RDW in The Diagnosis
of Anemia

10. Hypochromic, Microcytic Anemia with
Inadequate Red Blood Cell Production
Iron Deficiency Anemia (IDA)
Its The most common cause of anemia all over the world
High risk for iron deficiency:
• Low Birth Weight.
• Infants fed large volumes of cow's milk
• Menstruating teenage girls who are not receiving
supplemental iron
• Children ingest little in the way of dietary substances high
in iron, such as meat and green vegetables
• Children with chronic inflammatory diseases
• Blood loss must be considered as a possible cause in every
case of IDA

11. Hypochromic, Microcytic Anemia with
Inadequate Red Blood Cell Production
IDA:
Breast-fed infants are less likely to have iron deficiency than
bottle-fed infants because although there is less iron in breast
milk, this iron is more effectively absorbed.

12. Hypochromic, Microcytic Anemia with
Inadequate Red Blood Cell Production
Clinical Manifestations:
 In addition to the manifestations of anemia
 CNS abnormalities (apathy, irritability, poor concentration)?
(monoamine oxidase & cytochromes enzymes)
 Poor muscle endurance
 Impaired WBC and T cell function have been noted
 Later cognitive deficits and poor school performance

13. Hypochromic, Microcytic Anemia with
Inadequate Red Blood Cell Production
Iron Deficiency Anemia
The laboratory findings vary because the hemoglobin decreases secondary
to iron deficiency anemia
 First, the tissue iron stores represented by bone marrow hemosiderin
disappear
 Low serum ferritin level
 Low MCV,& MCH
 Low serum iron & high TIBC
 The RBCs become deformed and misshapen and present characteristic
microcytosis, hypochromia, poikilocytosis, and increased RDW
 Retic % may be normal or moderately elevated, but absolute
reticulocyte counts indicate an insufficient response to anemia.
 White blood cell counts are normal.
 Thrombocytosis (600,000–1 million/mm3).

14. Hypochromic, Microcytic Anemia with
Inadequate Red Blood Cell Production
Iron Deficiency Anemia
 Therapeutic dose of 4 to 6 mg/day of elemental iron induces an
increase in hemoglobin of 0.25 to 0.4 g/dL/day (a 1% /day increase in
hematocrit)
 The response to oral iron includes rapid subjective improvement(24 hr),
and reticulocytosis (in 48 to 72 hr)
 If the hemoglobin level fails to increase within 2 weeks after the
institution of iron treatment, the clinician should re-evaluate the
patient carefully for:
1. Ongoing blood loss
2. Poor compliance
3. Other causes of microcytic anemia

15. Microcytic Anaemia
DIFFERENTIAL DIAGNOSIS
TEST IDA Thalassemia Minor
Serum Iron Low Normal
Serum Ferritin Low N/H
Marrow iron Low N/H
Hb A2 or F N H= β- thal.
N=α- thal
MCV ÷ RBC >13 < 13
 In Sickle/β- thalassemia → Hb S > Hb A, &↑A2
 Absence of microcytosis in both parents excludes β- thal or
Sickle/β- thalassemia but not α- thalassemia.

16. Normocytic Anemia with Inadequate Red Blood
Cell Production
1- Anemia of Chronic Disease (ACD):
 A major feature of ACD is decreased iron availability.
 Elevated cytokine levels cause iron to be taken up by the RE cells
but not released for erythroid synthesis.
 The anemia may be normocytic or, less often, microcytic
 Absolute reticulocyte counts are normal or low
 The serum iron level is low, without the increase in TIBC
 The serum ferritin level may be elevated
 BM hemosiderin may be increased

17. Normocytic Anemia with Inadequate Red
Blood Cell Production
2. Bone marrow infiltration by malignant cells commonly
leads to a normochromic, normocytic anemia
3. Congenital pure RBC aplasia (Diamond-Blackfan
syndrome), a lifelong disorder, usually presents in the first
few months of life or at birth
 Congenital anomalies are common.
 Many patients (50% to 66%) respond to corticosteroid treatment, but
must receive therapy indefinitely.

18. Macrocytic Anemia
A- Vitamin B12 deficiency :
 Vitamin B12 is abundant in all animal foods, including eggs and dairy
products, and is resistant to cooking and boiling
 Inadequate levels of vitamin B12, or cobalamin, result in a megaloblastic
macrocytic anemia
 Vitamin B12 deficiency can also cause a demyelinating disorder involving the
peripheral nerves and, the spinal cord (demyelination of the posterior and
lateral columns of the spinal cord)
 There are many causes of vitamin B12 deficiency :
(1) Strict vegans
(2) Malabsorption
(3) Pernicious anaemia
(4) Ileal resection
(5) Abnormal intestinal transport

19. Macrocytic Anemia
B- Folate deficiency:
 Megaloblastic anemia secondary to folate deficiency is not
common, but marginal folate stores occur with surprising
frequency even in apparently healthy individuals
 The Four major causes of folate deficiency:
1. Decreased intake: Inadequate diet, Strict goat milk ingestion
2. Increased requirement: puberty, hemolysis, immaturity
3. Increased loss: Hemodialysis
4. Impaired utilization: Folic acid antagonist
C- Other Causes of MacrocyticAnemia:
1. Hypothyroidism
2. Chronic liver disease
3. Marrow failure:AplasticAnemia

20.  The general features of hemolytic anemias characterized by:
1. Increased rate of red cell destruction
2. Compensatory increase in erythropoiesis that results in reticulocytosis
3. The retention by the body of the products of red cell destruction (including
iron) → Iron overload
4. They are almost invariably associated with a marked erythroid hyperplasia
within the marrow and an increased reticulocyte count in peripheral blood
*In severe hemolytic anemias, extramedullary hematopoiesis often develops in the
spleen, liver, and lymph nodes
THE HEMOLYTIC ANEMIAS

21. Hemolytic Anemias
 Hemoglobinopathy: Hb SS, SC, S-B thalassemia.
 Enzymopathy: G6PD deficiency, PK deficiency.
 Membranopathy: Hereditary spherocytosis, elliptocytosis.
 Extrinsic factors: DIC, HUS, Abetalipoproteinemia, Wilsons disease,
Vit E deficiency.
 Immune hemolytic anemia:Autoimmune , Isoimmune , Drug induced.

22. β-Thalassemia Major
Etiology and Epidemiology:
 β-Thalassemia major is a hemoglobinopathy caused by mutations that
impair beta chain synthesis.
 Because of unbalanced synthesis of alpha and beta chains, alpha chains
precipitate within the cells, resulting in RBC destruction either in the
bone marrow or in the spleen when the cell is released.
 β-Thalassemia major is seen most commonly in individuals of
Mediterranean or Asian descent.
 The clinical severity of the illness varies on the basis of the molecular
defect.

23. β-Thalassemia Major
Clinical Manifestations:
 Signs and symptoms of β-thalassemia major result from the
combination of:
1. Chronic hemolytic disease due to
A. Decrease in or absent production of normal hemoglobin A
B. Ineffective erythropoiesis in the marrow.
2. Systemic Iron overload due to:
A. Frequent blood transfusions
B. Increased intestinal iron absorption
 The anemia is severe and leads to growth failure and high output heart
failure
 Ineffective erythropoiesis causes increased expenditure of energy and
expansion of the bone marrow cavities of all bones, leading to
osteopenia, pathologic fractures, extramedullary erythropoiesis, and
an increase in the rate of iron absorption.

24. β-Thalassemia Major
Clinical Manifestations:
 Children with β-thalassemia usually become symptomatic as a result of
progressive hemolytic anemia, with profound weakness and cardiac
decompensation during the 2nd - 6 month of life.
 Patients usually are transfusion dependent before 12 months old.
 Adolescents are subject to complications from transfusion-related iron
overload (hemochromatosis), including:
1. Nonimmune DM
2. Liver cirrhosis
3. Heart failure
4. Bronzing of the skin
5. Multiple endocrine abnormalities (of the thyroid or gonad)

25. β-Thalassemia Major
Investigations:
 Low Hb, few reticulocytes, numerous nucleated red cells, and microcytosis,
with almost no normal-appearing red cells on the smear
 The hemoglobin level falls progressively to <5.0 g/dL unless transfusions are
given.
 The unconjugated serum bilirubin level is usually elevated, but other
chemistry values may be normal at an early stage.
 High serum ferritin level .
 ??? Bone marrow ……. Hyperplasia
 Hb electrophoresis: high Hb F, low Hb A, normal or slight elevated Hb A2

26. β-Thalassemia Major

27. β-Thalassemia Major
Treatment:
 It is based on a hypertransfusion program that corrects the anemia
and suppresses the patient's own ineffective erythropoiesis, limiting the
stimulus for increased iron absorption.

 A transfusion program generally requires monthly transfusions, with the
pretransfusion hemoglobin level >9.5 and <10.5 g/dL
 Chelation therapy with: Deferoxamine, Deferiprone, Exjede.
 Splenectomy: Mechanical discomfort and Secondary hypersplenism
 Hematopoietic stem cell transplantation in childhood, before organ
dysfunction induced by iron overload, has had a high success rate in β-
thalassemia major and is the treatment of choice.

28. Sickle Cell Disease
Etiology and Epidemiology:
 The common sickle cell syndromes are hemoglobin SS disease,
hemoglobin S-C disease, hemoglobin S-β thalassemia, and rare
variants
 The specific hemoglobin phenotype must be identified because the
clinical complications differ in frequency, type, and severity
 As a result of a single amino acid substitution (valine for glutamic acid
at the β6 position), hemoglobin S cells change from a normal biconcave
disc (when oxygenated) to a sickled form, with resultant decreased
deformability in deoxygenated conditions.

29. Sickle Cell Disease
 This sickling phenomenon is
exacerbated by:
1. Hypoxia
2. Acidosis
3. Increased or decreased temperature
4. Dehydration

30. Sickle Cell Disease
Clinical Manifestations and Treatment:
 A child with sickle cell anemia is vulnerable to life-threatening infection by 4
months of age.
 In the absence of normal splenic function, the patient is susceptible to
overwhelming infection by encapsulated organisms, especially S. pneumoniae
and other pathogens
 The hallmark of infection is fever
 A patient with a sickle cell syndrome who has a temperature greater than
38.5°C (>101.5°F) must be evaluated immediately
 Current precautions to prevent infections include:
1. Prophylactic daily oral penicillin begun at diagnosis
2. Vaccinations against pneumococcus, H. influenzae type b, hepatitis B virus,
and influenza virus.

31. Sickle Cell Disease
Clinical Manifestations and Treatment:
 The anemia of SS disease is usually a chronic, moderately severe, compensated
anemia that is not routinely transfusion dependent.
 The severity depends in part on the patient's phenotype.
 Manifestations of chronic anemia include jaundice, pallor.
 Splenic sequestration crisis is a life-threatening, hyperacute decline in the
hemoglobin level (blood volume) secondary to splenic pooling of the patient's
RBCs and sickling within the spleen. The spleen is moderately to markedly
enlarged, and the reticulocyte count is elevated.
 In an aplastic crisis, parvovirus B19 infects RBC precursors in the bone
marrow and induces transient RBC aplasia with reticulocytopenia and a rapid
worsening of anemia.

32. Sickle Cell Disease
Clinical Manifestations and Treatment:
 In the hyperhemolytic crisis, there may be an acute decrease in
hemoglobin, associated with medications or infection. Patients with
these conditions usually have G6PD deficiency.
 For sequestration, aplastic, and hemolytic crises, PRBCs transfusion
therapy is indicated when the anemia is symptomatic

33. Thank You