1.
Course
Benign Hematology
Mustafa Selim, MD
Lecturer of Pediatric Oncology, NCI, Cairo University – Consultant of Pediatric Oncology, CCHE - 57357 Egypt
Clinical fellowship program trainer (CCHE-57357/Dana-Farber Cancer Institute pediatric Oncology Fellowship)

2.
Residents in the last day of
Hema/Onc rotation

3.
Death
Problems Negative emotions Failure
Hope Ambitious Success
Birth
The length of hope
‫األن‬ ‫اليه‬ ‫صرت‬ ‫وما‬ ‫كنت‬ ‫ما‬ ‫بين‬ ‫الرحلة‬ ‫أن‬
‫فيه‬ ‫تقع‬ ‫الدي‬ ‫الحيز‬ ‫هي‬
‫الحياة‬ ‫رقصة‬

4.
What is the success?

5.
Tips & Tricks in
CBC reading
What is the most common cause of
Thrombocytopenia?

6.
Q & A

7.
Q & A

8.
Tips & Tricks in
CBC reading
What are the indications for lymph
node biopsy?

9.
Tips & Tricks in
CBC reading
What is the dangerous type of
anemia?

10.
Tips & Tricks in
CBC reading
What is the most common cause of
transient anemia?

11.
Tips & Tricks in
CBC reading
What is the most common cause of
macrocytic anemia in children?

12.
Tips & Tricks in
CBC reading
Why α-thalassemia manifest in the
neonatal period?

13.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

14.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

15.
Thrombocytopenia
in a child
Tips & Tricks in
CBC reading

16.
Thrombocytopenia in a child
Tips & Tricks in
CBC reading
 Labs:
• Thrombocytopenia < 150,000
• Plat clumps = pseudothrombocytopenia (plat aggregate in the syringe before
reaching the anticoagulant)
• Associated anemia or pancytopenia?
 Examination and history:
• Patient is ill appearing?? → do PT, PTT, TT (DIC?)
• Congenital anomalies? (cyanotic heart, Fanconi A, DKC, TAR)
• Organomegaly or lymphadenopathy
• Drugs (sulfa, quinidine, heparin, anticonvulsants, vaccines like measles and varicella)

17.
Plat< 150,000 in a child
No plat clumps
No anemia or pancytopenia
Critical ill
Macrothrombocytes
Not critical ill
No congenital anomalies or drugs
See morphology
No
Macrothrombocytes
PT, PTT, INR
↑ spleen → Malaria, portal HTN, Gaucher disease
↑ liver & lymphadenopathy → lymphoma, leukemia, MDS
Prolonged Normal
Acute febrile illness – chronic ill
Spleen size & liver size & lymph nodes
Acute fever → sepsis, EBV, CMV, HIV, parvovirus
Chronic ill → HIV,
HUS/TTP, autoimmune or
connective tissue disease

18.
Immune thrombocytopenia
Tips & Tricks in
CBC reading

19.
Immune thrombocytopenia
Tips & Tricks in
CBC reading
 Past (idiopathic thrombocytopenic purpura)
 Diagnosis: if the platelet counts are repeatedly below 100 × 109/µL
 The detection of isolated thrombocytopenia in the presence of otherwise normal leukocyte
and erythrocyte parameters is usually sufficient for an initial diagnosis
 A blood smear must always be examined.
 Gender:
o In pediatric boys are more often affected than girls
o In middle age, women are more likely to develop ITP
than men. After age 60 years, men predominate again.
 Pathophysiology

20.
Immune thrombocytopenia
Tips & Tricks in
CBC reading
 Clinical Presentation
o The central clinical symptom of ITP is the increased bleeding tendency.
o Petechiae and mucosal hemorrhages are typical.
o Many ITP patients also complain of exhaustion and fatigue, including
depressive disorders

21.
Immune thrombocytopenia
Tips & Tricks in
CBC reading
 Definition of bleeding manifestations

22.
Immune thrombocytopenia
Tips & Tricks in
CBC reading
 Grading the Severity of Bleeding

23.
Immune thrombocytopenia
Tips & Tricks in
CBC reading
 Prognosis and risk indicators
 Phases of the disease and treatment goals
 Indications for bone marrow biopsy

24.
Tips & Tricks in
CBC reading
Immune thrombocytopenia
 Pre-treatment considered factors

25.
Tips & Tricks in
CBC reading
Immune thrombocytopenia
 First line therapy

26.
Tips & Tricks in
CBC reading
Immune thrombocytopenia
o Early response: plat count ≥ 30 x 109/L and at least doubling baseline at 1 week
o Initial response: plat count ≥ 30 x 109/L and at least doubling baseline at 1 month
o Durable response: plat count ≥ 30 x 109/L and at least doubling baseline at 6 months
o Remission: plat count > 100 x 109/L at 12 months
 Definition of response

27.
Tips & Tricks in
CBC reading
Immune thrombocytopenia
 Pre-treatment considered factors
 First line therapy
o Early response: plat count ≥ 30 x 109/L and at least doubling baseline at 1 week
o Initial response: plat count ≥ 30 x 109/L and at least doubling baseline at 1 month
o Durable response: plat count ≥ 30 x 109/L and at least doubling baseline at 6 months
o Remission: plat count > 100 x 109/L at 12 months
 Definition of response

28.
Tips & Tricks in
CBC reading
Immune thrombocytopenia
 Diagnostic workup for patients with persistent or chronic ITP

29.
Tips & Tricks in
CBC reading
Second-Line Treatment
with TRAs

30.
Thrombocytosis
Tips & Tricks in
CBC reading

31.
Thrombocytosis
Tips & Tricks in
CBC reading
 Thrombocytosis (> 450,000)
 Mild > 500,000 Moderate > 700,000
 Severe > 900,000 Extreme > 1000,000
 Etiology:
 Primary (caused by a process that is intrinsic to megakaryocyte)
 Reactive (caused by a process that is extrinsic to megakaryocyte)
 Thrombocytosis in children is almost always a reactive response, most often
infectious or inflammatory (interleukin-6 & c-reactive protein).
 1/3 of the circulating platelets are normally sequestrated within the spleen.
 Stress like exercise or surgery are commonly cause thrombocytosis.
 Down syndrome, ↑ plat is very common by the 2nd month of life for 1st year.

32.
Thrombocytosis
Tips & Tricks in
CBC reading
 Primary thrombocytosis is very rare:
o Familial: mutation in thrombopoietin gene (TPO) or MPL
o Acquired: Essential thrombocythemia, polycythemia vera, primary
myelofibrosis, chronic myeloid leukemia, MDS
 Essential thrombocytosis is also very rare (diagnosis of exclusion).
 Hematological disorders for reactive thrombocytosis:
o Iron deficiency anemia (at diagnosis or during therapy)
o Megaloblastic anemia
o Hemolysis
o Sickle hemoglobinopathies (functional asplenia→ Howell-jolly bodies)
 Initial labs: cbc, retic, peripheral smear, ESR, hepatic functions, urine analysis, cxr.

33.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

34.
Day
before IT

35.
Day
before IT

36.
The next
morning

37.
Procedure
room

38.
Procedure
room

39.
Always put yourself in the
others shoes. If you feel
that it hurts you,
it probably hurts the
person too.

40.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

41.
Generalized Lymphadenopathy
• Enlarged lymph nodes:
 The neonate: generally, not palpable
 Childhood: cervical & axillary (>1 cm) - inguinal(>1.5cm) – epitrochlear (>5 mm)
 Generalized lymphadenopathy = ≥ non-contiguous lymph node groups
• History: should include
 Travel (TB, histoplasmosis)
 Pets (scratch and toxoplasmosis)
 Allergies
 Sexual (HIV)
 B symptoms (fever, drenching sweats, weight loss >10% in previous 6 months)
 Flu like symptoms without weight loss suggest viral infection

42.
Generalized Lymphadenopathy
• Examination:
 Concomitant splenomegaly suggests a systemic disorder
 Massive splenomegaly & adenopathy suggestive storage disease
 Tenderness, warmth, and erythema are usually due to bacterial infection
 Fluctuance suggests secondary abscess formation
• Labs:
 Initial screening: cbc, blood smear, ESR, LDH, uric acid, hepatic and renal functions.
 CMV screening if cp suggests infection + atypical lymphocytes are noted.
 Mild ↑ AST & ALT suggest viral infection
 ↑ uric acid, BUN, ↓ ca→ tumor lysis syndrome
 Mediastinal widening on cxr → suggest malignancy or (TB – sarcoidosis)
 ↑ WBC, shift to left, ↑ ESR → suggest bacterial infection

43.
Generalized Lymphadenopathy
• Most common infection: EBV, CMV, varicella, rubella, mumps, measles, TB,
syphilis, HIV
• Red flags for malignant nodes:
 Usually are fixed, large, firm or rubbery or matted.
 Painless, progressive ↑ size
 Supraclavicular adenopathy
 Associated pancytopenia, ↑ LDH, ↑ uric acid
• Biopsy should be done if:
 If adenopathy continues to increase over 2 weeks
 If adenopathy fails to resolve over 6 weeks
 If B symptoms present
 If lymph nodes became firm or matted or supraclavicular adenopathy

44.
Localized Lymphadenopathy
• Occipital: scalp infections
• Periauricular: eye infections
• Cervical: tonsilitis, Kawasaki disease
• Submaxillary: teeth and mouth infection
• Supraclavicular: malignancy
• Axillary: cat-scratch disease
• Mediastinal: ALL, NHL, TB, thymoma, sarcoidosis
• Abdominal: NHL, HL
• Ilioinguinal: syphilis

45.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

46.
Who have Fake Smile and why?
A B

47.
Who have Fake Smile and why?
A

48.
Who have Fake Smile and why?
B

49.
Who have Fake Smile and why?
A B

50.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

51.
What ? Why ? How ?
How to read CBC

52.
 Blood is made of two major components:
 plasma + cells.
 CBC = complete blood count→ is a group of
tests that evaluate the cells that circulate in
blood, including RBCs, WBCs, and PLTs.
 Collected in purple tube (EDTA)
 Unit volume: per cubic millimeter (mm3) =
one microliter = µL
WHAT cbc?

53.
Automated
counting
Erythrocytes Leukocytes Thrombocytes
Count 4-5.5 x 106/µL 4-11 x 106/µL 150 - 450 x 109/µL
Size 7 microns 8 – 20 microns 3 – 4 microns
Life span 120 days 7 – 10 days
• Coulter principle: electrical impedance: resistance
or change in current when cell passes between
electrodes in NaCL solution
• Flow cytometry: uses lasers to measure both forward and side scatter
• Forward scatter measures size.
• Side scatter measures granularity

54.
WHY cbc?
 CBC is the 1st most common investigation performed in both in-
patient and out-patient setting.
 CBC is inexpensive maneuver.
 CBC is available everywhere.
 CBC can help in diagnosis
 Blood disorders,
 BM abnormalities,
 Organ dysfunction

55.
Cbc elements?
 RBCs, HB, hematocrit, Retics
 Indices: MCV, MCH, MCHC, RDW
 Differential WBCs count
 Platelets

56.
HOW cbc?
RBCs (4-5.5 x 106/µL) HB (normal 12-16 g/dl) Hematocrit (normal 35-45%)
 Rule of 3
 RBCs x 3 = HB
 HB X 3= hematocrit (% of blood that is made by packed RBCs)
 ↑ Hematocrit
 Polycythemia, diarrhea, dehydration, burn, hear or lung or kidney problems
 ↓ Hematocrit
 Anemia, hemolysis, bleeding, nutritional deficiences

57.
HOW cbc?
 Reticulocytes (normal; 0.5 -1.5%)
 Immature red cells containing residual RNA
 Indicate rate of new RBC production.
 ↓ if the anemia due to BM problem.
 ↑ if the anemia due to problem outside the BM (eg; hemolytic anemia)
Supervital stain

58.
Normal
(0.5 -1.5%)
Newborn
(2 -6%)
• Aplastic anemia
• Anemia of chronic disease
• Nutritional anemias (↓ vit B12 - ↓ folate)
• Myelodysplastic syndrome
• Cirrhotic liver
• Hemolytic anemias
• Hemorrhage
• Response to treatment
• Pregnancy
• Leukemia
Reticulocytes
Indicator of rapid RBCs production
Decreased erythropoiesis

59.
• The reticulocyte count is expressed as a % of the total number of RBCs.
• 1-2% in the setting of a normal hemoglobin.
• In patients with moderate or severe anemia, the reticulocyte count may appear elevated, but
in absolute terms, it may be insufficient for the degree of anemia. Therefore, the reticulocyte
count must be corrected using the following formula:
Corrected reticulocyte count = reticulocyte % × (patient Hct/normal Hct)
• If the corrected reticulocyte count is >2%, then the bone marrow is producing RBCs at an
accelerated pace
Corrected reticulocyte count

60.
• The ratio of immature reticulocytes to the total number of reticulocytes
• IRF in many situations increase before the total reticulocyte count increase
 Post transplant or chemotherapy.
 Monitoring the efficacy of therapy in nutritional anemia.
 Evaluate optimal timing for stem cell collection following mobilization.
Immature reticulocyte fraction (IRF)

61.
• MCV, mean corpuscular volume
• MCH, mean corpuscular hemoglobin
• MCHC, mean corpuscular hemoglobin concentration
• RDW, red cell distribution width
Red Blood Cell Indices

62.
• MCV, mean corpuscular volume
• MCH, mean corpuscular hemoglobin
• MCHC, mean corpuscular hemoglobin concentration
• RDW, red cell distribution width
Red Blood Cell Indices
• = Mean cell volume
• Definition → is a measure of the average volume of a red blood cell
• Calculation→ MCV = Hct/RBCs x 10
 Normal: 80-100 Fl (femtoliters)
 High (macrocytic, >100 FI) – low (microcytic, < 80 FI)
• Some conditions that present with high MCV without megaloblastic cells. ??
• MCV can be normal with low HB?? Hypovolemic or recent hemorrhage
PS, where a normal RBC is about the size of a normal lymphocyte nucleus.

63.
• MCV, mean corpuscular volume
• MCH, mean corpuscular hemoglobin
• MCHC, mean corpuscular hemoglobin concentration
• RDW, red cell distribution width
Red Blood Cell Indices
• Definition → MCH is the average weight of hemoglobin per red cells (give the color of the cell)
• Calculation→ MCH = HB / RBCs x 10
 Normal: 27 - 32 pg (picogram)
 High (with macrocytic anemia) – low (with microcytic anemia)

64.
• MCV, mean corpuscular volume
• MCH, mean corpuscular hemoglobin
• MCHC, mean corpuscular hemoglobin concentration
• RDW, red cell distribution width
Red Blood Cell Indices
• Definition → MCHC is the average concentration of hemoglobin per erythrocyte
• Calculation→ MCHC = = HB / Hct x 100
 Normal: 32 – 36%

65.
• MCV, mean corpuscular volume
• MCH, mean corpuscular hemoglobin
• MCHC, mean corpuscular hemoglobin concentration
• RDW, red cell distribution width
Red Blood Cell Indices
• It is a measure of the range of variation of RBC volume that is reported as part of a standard CBC.
• Normal: 11.5 – 14.5%
• Elevated RDW in 2/3 of deficiencies of Vitamin B12 or folate.
• Elevated RDW is a hallmark of iron deficiency anemia.
• Normal in anemia of chronic disease, hereditary spherocytosis, acute blood loss, aplastic anemia.
• Elevated RDW & normal MCV→ there is a mixture of large and small RBCs.

66.
• MCV, mean corpuscular volume (Hct/RBCs x 10)
• MCH, mean corpuscular hemoglobin (weight> color, HB / RBCs x 10)
• MCHC, mean corpuscular hemoglobin concentration (HB / Hct x 100)
• RDW, red cell distribution width (range of variation of RBC volume)
Red Blood Cell Indices

67.
Tips & Tricks in
CBC reading

68.
If you don’t use it, you lose it
Tips & Tricks in
CBC reading

69.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

70.
C
• Tips & Tricks in CBC
reading
B
D
• Practical approach to
anemia
Agenda
• Plat count
abnormalities
• Lymphadenopathy
A

71.
2
3 Ask about drug or infection history
4 The RBC indices, particularly the MCV + RDW are extremely
helpful in DD.
Do not forget
1/3 of the children with newly diagnosed leukemia will have normal total WBC, but their ANC
mostly reduced
2 The 1st step in evaluating anemia
Is to determine whether other cell lines are also affected??
4
5
1
Peripheral smear should be reviewed to ensure that there are
no errors with the automated counts.
Drugs can cause anemia, neutropenia, and thrombocytopenia like chemotherapy, trimethopri,m/sulfamethoxazole.
Acute viral infections are the most common cause anemia with thrombocytopenia or leukopenia (mild and transient, in chronic
infection like HIV and EBV)

72.
Tips & Tricks in
CBC reading
Persisting abnormalities in the full blood count that remain
unexplained should prompt an opinion from a hematologist.

73.
Tips & Tricks in
CBC reading
Questions
• A male patient, 8 years old,
presented to ER with URTs &
fever.
• Cbc was done as a routine
work up before giving iv 3rd
generation antibiotic

74.
Tips & Tricks in
CBC reading
Questions
1. Do Peripheral smear 2. Consult hematologist 3. Reassure the family 4. Repeat cbc after 48 h
• A male patient, 8 years old,
presented to ER with URTs &
fever.
• Cbc was done as a routine
work up before giving iv 3rd
generation antibiotic

75.
Tips & Tricks in
CBC reading
Questions
1. Do Peripheral smear 2. Consult hematologist 3. Reassure the family 4. Repeat cbc after 48 h
• A male patient, 8 years old,
presented to ER with URTs &
fever.
• Cbc was done as a routine
work up before giving iv 3rd
generation antibiotic
Peripheral smear: no abnormal cells. Numerous Plat clump in the smear. Suggest repeat cbc in blue top tube
Acute viral illness is the most common cause of anemia with thrombocytopenia or leukopenia (mild & transient)

76.
Anemia?

77.
Anemia?

78.
Microcytic hypochromic Anemia
Tips & Tricks in
CBC reading

79.
Microcytic hypochromic Anemia
Tips & Tricks in
CBC reading
1. IDA
2. Thalassemia
3. Chronic illness or infection
4. Pb poisoning
5. Rare disorders (sideroblastic anemia, Protein caloric malnutrition,
metabolic defects of Fe absorption)

80.
Microcytic anemia (↓ MCV)
↓ Fe oral or blood loss
1. History
* No HSM, Hb > 9 g/dl
↓ RBC + ↑ RDW
FH of anemia or thalassemia
Mediterranean/ Asian/ African
Trial oral Fe
↓ serum Fe, ↑𝑻𝑰𝑩𝑪,"↓ TS," ↓ ferritin, ↔ retic, ↔ bilirubin
Rare Causes
IDA
Trait
Chronic infection or inflammation
Hb
Electrophoresis
↑ RBC + ↔↑ RDW
↓ serum Fe, ↓ 𝑻𝑰𝑩𝑪, ↑ ferritin
Pb poisoning
2. Lab
Intermedia/major
* HSM, Hb < 9 g/dl
↔ ↑ serum Fe, ↔ ↑ ferritin, ↑ retic, ↑ bilirubin
Sidroblastic anemia
Metabolic defect Fe absorption & metabolism

81.
Tips & Tricks in
CBC reading
1. IDA:
 Confirmed by trial of oral Fe supplementation.
 Not necessary to do (↓ serum Fe, ↑𝑻𝑰𝑩𝑪,"↓ TS," ↓ ferritin), ↔ bilirubin.
 TTT:
 Fe therapy for at least 3-4 months
 Correct the cause like; change in diet or management of blood loss)
 A dimorphic population (microcytic hypochromic cells + normocytic
normochromic cells)→ early in the disease or with Fe treatment.
 Mentzer index: (MCV/RBC)
 Benefit: to differentiate IDA from thalassemia minor.
 IDA: > 13 - Thalassemia minor: < 13
Microcytic hypochromic Anemia

82.
Tips & Tricks in
CBC reading
 Which is the first stage of iron deficiency?
a. Negative iron balance
b. Decreased iron stores
c. Decrease MCV
d. Decrease in Hemoglobin

83.
Tips & Tricks in
CBC reading
 Which is the first stage of iron deficiency?
a. Negative iron balance
b. Decreased iron stores
c. Decrease MCV
d. Decrease in Hemoglobin

84.
Tips & Tricks in
CBC reading
1. IDA:
 Stages of IDA:
1) Loss of storage Fe: ↓ ferritin, ↓ stainable marrow Fe
2) Loss of circulating Fe: ↓ serum Fe, ↓ transferrin saturation
3) Loss of functional Fe: ↓ Hb, ↓ MCV, ↑ RDW, ↑ TIBC
NB;
• Transferrin saturation: serum iron/TIBC
• Serum iron fluctuates with iron ingestion (if you just ate a steak, it will
be high even u are iron deficient)
Microcytic hypochromic Anemia

85.
Tips & Tricks in
CBC reading
1. IDA:
 IDA which fails to respond to oral Fe:
1) IDA due to blood loss
2) Poor compliance or incorrect Fe dose
3) Concurrent illness (anemia of infection or inflammation)
4) Malabsorptive syndrome (Fe absorption test)
5) Failure to utilizee Fe
6) Hemoglobanthy (β-thalassemia / α-thalassemia/ sickle cell anemia)
7) Pb poisoning
8) Sidroblastic anemia
Microcytic hypochromic Anemia

86.
Tips & Tricks in
CBC reading
2. Thalassemia
 Lab: ↓ HB (microcytic hypochromic), ↔ RDW
 Morphology: target cells
 Other labs; ↑ retic, ↑ bilirubin, ↔ ↑ serum Fe, ↔ ↑ ferritin.
 History: age of manifestations and clinical presentation
 Confirmed by HB electrophoresis
β-thalassemia (major/intermediate) β-thalassemia / (trait) α-thalassemia
HSM present absent
HB < 9 g/dl > 9 g/dl
Normoblastemia Present Absent
Normoblastemia, the presence of nucleated erythrocytes in peripheral blood (prominent in severe forms of β-
thalassemia)
Microcytic hypochromic Anemia

87.
Tips & Tricks in
CBC reading
2. Thalassemia
α-thalassemia (trait) β-thalassemia (trait)
Mild microcytic anemia & not responsive to iron & normal iron panel
• Num of encoding genes 4 2
• Pick up during neonatal period yes No
• HB A2 ↔ ↑
Microcytic hypochromic Anemia

88.
Tips & Tricks in
CBC reading
 Major cause of death in thalassemia major is due to?
a. Endocrinopathies
b. Cardiomyopathies
c. Liver Failure
d. Infection

89.
Tips & Tricks in
CBC reading
 Major cause of death in thalassemia major is due to?
a. Endocrinopathies
b. Cardiomyopathies
c. Liver Failure
d. Infection

90.
Tips & Tricks in
CBC reading
 The co-inheritance of alpha thalassemia with beta thalassemia:
a. Increases the severity of symptoms
b. Decreases the severity of symptoms
c. Does not effect
d. Variable effects

91.
Tips & Tricks in
CBC reading
 The co-inheritance of alpha thalassemia with beta thalassemia:
a. Increases the severity of symptoms
b. Decreases the severity of symptoms
c. Does not effect
d. Variable effects

92.
Tips & Tricks in
CBC reading
3. Many infections and inflammatory disorders cause
leukocytosis and/or thrombocytosis are frequently
accompanying anemia of acute infection
 Toxic granulation, Dohle bodies and vacuolization
3. Anemia of chronic disease:
 Most of cases normocytic normochromic anemia.
 20 – 30% can be microcytic
 (↓ serum Fe, ↓ 𝑻𝑰𝑩𝑪, ↑ ferritin)
4. Pb poisoning:
 Anemia is a late sign of Pb poisoning.
 Anemia usually due to concomitant IDA.
 Basophilic stippling is not consistently present
Sky blue inclusions in
cytoplasm of neutrophils
Microcytic hypochromic Anemia

93.
Tips & Tricks in
CBC reading
5. Rare disorders
• Sideroblastic anemia: anemia, reticulocytpenia, abnormal Fe
deposition in BM erythroblasts.
• Protein caloric malnutrition,
• Metabolic defects of Fe absorption
Microcytic hypochromic Anemia

94.
Tips & Tricks in
CBC reading
 Which of the following is earliest recognizable change in RBC
morphology in case of iron deficiency?
a. Hypochromia
b. Anisocytosis
c. Target cells
d. Poikilocytosis

95.
Tips & Tricks in
CBC reading
 Which of the following is earliest recognizable change in RBC
morphology in case of iron deficiency?
a. Hypochromia
b. Anisocytosis
c. Target cells
d. Poikilocytosis

96.
Normocytic normochromic Anemia
Tips & Tricks in
CBC reading
1. Hemorrhage
2. Hemolysis (immune vs non-immune)
3. Anemia of chronic infection
4. Hypersplenism
5. BM disorders

97.
Normocytic anemia (↔ MCV)
Blood loss
1. History
↔ ↑ retic, ↔ bilirubin
No blood loss
Hemorrhage
Hemolysis
Combs test, LDH,
haptoglopin
↑
2. Lab
Macro-ovalocytosis and/or
hypersegmentation
retic & bilirubin
Blood smear
↓
No Macro-ovalocytosis
and/or hypersegmentation

98.
Tips & Tricks in
CBC reading
 The least severe form of sickle cell disease is:
a. Hb SS
b. Hb Sβ0
c. Hb Sβ+
d. SCD with hereditary persistence of fetal hemoglobin (S/HPFH)

99.
Tips & Tricks in
CBC reading
 The least severe form of sickle cell disease is:
a. Hb SS
b. Hb Sβ0
c. Hb Sβ+
d. SCD with hereditary persistence of fetal hemoglobin (S/HPFH)

100.
Tips & Tricks in
CBC reading
 The most common cause of death in childhood with sickle cell
disease is:
a) Pulmonary hypertension
b) Sudden death of unknown etiology
c) Renal failure
d) Infection
e) Myocardial infarction

101.
Tips & Tricks in
CBC reading
 The most common cause of death in childhood with sickle cell
disease is:
a) Pulmonary hypertension
b) Sudden death of unknown etiology
c) Renal failure
d) Infection
e) Myocardial infarction

102.
Tips & Tricks in
CBC reading
 True regarding sickle cell trait are all, except:
a. Is associated with normal growth and life expectancy
b. The ratio of HbA to HbS is 50:50
c. Impaired urine–concentrating ability and haematuria can occur
d. Splenic infarction is possible at very high altitudes

103.
Tips & Tricks in
CBC reading
 True regarding sickle cell trait are all, except:
a. Is associated with normal growth and life expectancy
b. The ratio of HbA to HbS is 50:50
c. Impaired urine–concentrating ability and haematuria can occur
d. Splenic infarction is possible at very high altitudes

104.
Macrocytic Anemia
Tips & Tricks in
CBC reading
1. ↓ B12 level
2. ↓ folate level
3. Drug induced
4. Reticulocytosis
5. BM failure disorders
6. Liver disease
7. Hypothyroidism
8. Rare, congenital deficiency of transcobalamin II or intrinsic factor

105.
Macrocytic anemia (↑ MCV)
Blood smear
Lab
Macro-ovalocytosis and/or
hypersegmentation
Megaloblastic
anemia
Anemia
↔/↓
Retic count
↑
No macro-ovalocytosis
and/or hypersegmentation
Hb
Normal

106.
Tips & Tricks in
CBC reading
 Macrocytic anemia may be seen with all the following
conditions, except:
a. Liver disease
b. Copper deficiency
c. Thiamine deficiency
d. Orotic aciduria

107.
Tips & Tricks in
CBC reading
 Macrocytic anemia may be seen with all the following
conditions, except:
a. Liver disease
b. Copper deficiency
c. Thiamine deficiency
d. Orotic aciduria

108.
Tips & Tricks in
CBC reading
1. Vitamin B12 deficiency
 Lab: ↓ HB (macrocytic),
 Morphology: macro-ovalocytosis + neutrophil hyper segmentation.
 In the absence of malnutrition megaloblastic anemia is uncommon.
****************************************
 Serum B12 is usually diagnostic
 ↓ B12 commonly due to pernicious anemia
 ↓ B12 can be due to ileal disease, malabsorption, vegan diet.
 Definition of neutrophil hypersegmentation
 Equal or more than 5% of PMNs with 5 nuclear lobes
 Equal or more than 1% of PMNs with 6 lobes
Macrocytic Anemia

109.
Tips & Tricks in
CBC reading
2. Folate deficiency
 Lab: ↓ HB (macrocytic),
 Morphology: macro-ovalocytosis + neutrophil hyper segmentation.
 In the absence of malnutrition megaloblastic anemia is uncommon.
****************************************
 Serum folate reflects recent intake,
 RBC folate reflects longer term intake (more reliable)
 ↓ folate can be due drugs (phenytoin, trimethoprim), malabsorption,
goat milk, ↑ turnover (pregnancy and hemolysis)
 Vitamin B12 deficiency should be excluded before ttt to avoid
irreversible neurological damage.
Macrocytic Anemia

110.
Tips & Tricks in
CBC reading
3. Drug induced
 Lab: ↓ HB (macrocytic),
 Morphology: macro-ovalocytosis + neutrophil hyper segmentation.
 In the absence of malnutrition megaloblastic anemia is uncommon.
****************************************
 Drugs induced macrocytic anemia are the most common cause of
macrocytic anemia in children in industrialized communities.
 Chemotherapy (6-mp – hydroxyurea)
 Anticonvulsant (carbamazepine, valproic acid, phenytoin, phenobarbital)
 Sulfa drugs
Macrocytic Anemia

111.
Tips & Tricks in
CBC reading
 Lab: ↓ HB (macrocytic),
 Morphology: no macro-ovalocytosis & no neutrophil hyper segmentation.
Macrocytic Anemia
4. Reticulocytosis (↑ retic)
 Reticulocytes 20% large normal cbc→ ↑ the overall MCV
5. BM failure syndromes (↔/↓ retic)
 Diamond Blackfan Anemia (congenital anomalies, presents in the first 3 months of life)
 Fanconi anemia (↑ HbF, congenital anomalies, chromosomal breakage test)
 Dyskeratosis congenita
Nb; normal MCV in full term neonate 98 – 118 fl
Down associated with with macrocytosis

112.
Sum up
Macrocytic Anemia
Tips & Tricks in
CBC reading
1. ↓ B12 level (macro-ovalocytosis + neutrophil hyper segmentation)
2. ↓ folate level (macro-ovalocytosis + neutrophil hyper segmentation)
3. Drug induced (sulfa, anticonvulsant, chemotherapy)
4. Reticulocytosis (normocytic RBC, no macro-ovalocytosis & no neutrophil hyper segmentation,↑ retic)
5. BM failure disorders (no macro-ovalocytosis & no neutrophil hyper segmentation, ↔/↓retic)
6. Liver disease
7. Hypothyroidism (excessive membrane lipids)
8. Rare, congenital deficiency of transcobalamin II or intrinsic factor

113.
Neonatal anemia
Tips & Tricks in
CBC reading

114.
Neonatal anemia
Retic count
< 2 % retic
Direct Combs test +ve
↑ Indirect bilirubin
> 5 – 8 % retic
Direct Coombs test & indirect bilirubin
Direct Combs test -ve
↑ Indirect bilirubin
Direct Combs test -ve
↔ Indirect bilirubin
MCV
↑ → Megaloblastic anemia
↓ → Blood loss - α-thalassemia
↔ →
• Blood loss
• Infection
• BM replacement: NB, ALL, LCH, osteopetrosis
• DBA

115.
Neonatal anemia
• Neonatal pallor is a sign of asphyxia, shock, hypothermia, hypoglycemia, and anemia.
• Time:
o At birth: usually hemorrhage or severe alloimmunization.
o < 48 hours: internal or external hemorrhage.
o > 48 hours: usually hemolytic and associated with jaundice
• Capillary samples can average 3.5 g/dl higher than venous samples.
• Reticulocytes reached normal level 0-1% by 7 days of life.
• Anemia without jaundice is usually due to hemorrhage.
• Shock can trigger DIC; DIC can cause hemolytic anemia.
• G6PD screening results are common false negative in mild variants due to reticulocytosis.

116.
Neonatal anemia
• α-thalassemia manifest in neonate because both Hb A and F contains α-chains.
• Critically ill neonates (eg; bronchopulmonary dysplasia) often develop anemia and
reticulopenia.
• Megaloblastic anemia is rare in newborn.
• B 12 deficiency can be seen in:
 Breast fed infants of vegan B12 deficient mothers
 Infants with GI abnormalities (NEC – short gut syndrome)
• Folate deficiency can be seen in:
 Infants receiving goat milk or boiled milk
 Malabsorption

117.
Anemia
in sickle cell disease
Tips & Tricks in
CBC reading

118.
Anemia in sickle cell disease
Hb concentration
Compared to the baseline
> 2 g/dl below baseline
Ill patient (low or normal BP)
Normal spleen
High retic (> 15%)
1-2 g/dl below baseline
Well patient
Spleen size & retic count
Normal spleen
Low retic (< 5%)
Enlarged spleen
↑ retic (> 5%)
Spleen size & liver size & retic count
↑ spleen → Acute splenic sequestration crisis
↑ liver → Acute hepatic sequestration crisis
↑ retic (> 5%) ↓↓ retic (<1%)
Transient aplastic crisis
(Parvo virus B19)
BM necrosis: Rare in pediatric, due to
repeated Vaso occlusive infarction

119.
Anemia in sickle cell disease
• Acute splenic sequestration (ASSC):
 It can be acute, subacute, chronic
 ASSC is less common in HbSc disease.
 Splenomegaly + anemia + thrombocytopenia (↑ retic )
 Death may occur in few hours.
 Immediate TTT→ correct hypovolemia and anemia
 Goal of blood transfusion: to prevent shock (not to restore Hb to normal).
 Mostly will need splenectomy (recurs in 50%)
• Transient aplastic crisis (TAC)
 It is exacerbation of anemia due to infection mostly parvo virus B19
 Severe anemia (↓ retic )
 Goal of blood transfusion: to prevent congestive heart failure and shock
 ↑ risk of stroke is associated with severe anemia