2. Definition
Hematology includes the study of blood cells and
coagulation.
It encompasses;
analyses of the concentration, structure, and function of
cells in blood;
their precursors in the bone marrow;
the chemical constituents of plasma or serum intimately
linked with blood cell structure and function; and
the function of platelets and proteins involved in blood
coagulation.
2
3. • There are several different hematologic cell types that originate
from the hematopoietic stem cell.
• Each cell line has a defined role and unique contribution to the
overall homeostatic process, and may be found in the bone
marrow, lymph system,or blood.
• Each cell line has a defined role and unique contribution to the
overall homeostatic process.
• Typically, routine clinical laboratory testing involves measuring
concentrations of mature myeloid cells found in the blood.
3
5. Hematology
• Stem cells are young cells
• All blood cells start as stem cells
• They get “drafted” as RBCs, WBCs or
platelets depending on the body’s needs
5
7. Case
• You are rounding on an internal medicine with the
ICU team. When preparing for rounds, note that
there was a new admission last night – an
Olympic bicyclist who was struck by a car. Begin
reviewing the patient’s laboratory data in
preparation for rounds.
• On admissision to the hospital last night, patient
X had the following CBC:
7
9. Questions
What do the above abbreviations represent?
Which of the laboratory values are abnormal?
What type of anemia is present?
What is the most likely cause of the anemia in this
patient?
In addition to the CBC, what other laboratory tests
were most likely ordered for this patient upon
admission to the hospital?
9
10. Cont’d
• Several days later the patient begins to spike fever. A CBC, chest x-
ray, UA and blood and urine cultures are done to look for possible
sources of infection. The CBC and UA results are as follows.
– CBC: with differential
– WBC: 17,900
• Segs: 65%
• Bands: 10%
• Lymphocytes: 17%
• Monocytes: 5%
• Eosinophils: 2%
– RBC: 4.2 X 10E6 cells/mm3
– Hgb 14 g/dl
– Hct: 42%
10
12. Questions
• What abnormalities are notes in the CBC?
• What is left shift and what does it indicate?
Is a left shift present?
• What abnormalities are noted on the UA?
• What is the most likely cause of these
abnormalities?
12
13. CBC
A group of tests used for basic screening purposes.
Uses:
• Enumeration of the cellular elements of the blood,
• Measurement of RBC indices, and
• determination of cell morphology
The results can provide valuable information about
overall health of the patient and the patient’s
response to disease and treatment.
CBC can be indicated both for diagnostic and monitoring
13
14. CBC Cont’d
Diagnostic indications, to:
Detect hematologic disorder, neoplasm, leukemia, or
immunologic abnormality,
Determine the presence of hereditary hematologic
abnormality
Evaluate known or suspected anemia and related
treatment
Provide screening as part of a general physical
examination, especially on admission to a health care
facility or before surgery,???
14
15. CBC Cont’d
Monitoring indications, to:
Monitor fluid imbalances or treatment for fluid
imbalances
Monitor hematologic status during pregnancy
Monitor progression of non-hematologic disorders,
such as COPD, malabsorption syndromes, cancer,
and renal disease
Monitor response to chemotherapy and evaluate
undesired reactions to drugs that may cause blood
dyscrasias 15
16. Introduction
• The complete blood count (CBC) is one of the most commonly ordered
clinical laboratory tests.
• Main parameters measured:
• Red blood cell data
– Total red blood cell count (RBC)
– Hemoglobin (Hgb)
– Hematocrit (Hct)
– Red blood cell indices(MCV, MCH, MCHC)
– Erythrocyte Sedimentation Rate(ESR)
• White blood cell data
– Total white blood cell (leukocyte) count (WBC)
– A white blood cell count differential may also be ordered
• Platelet Count (PLT)
16
17. Hemoglobin
• The hemoglobin concentration is a measure of the
amount of Hgb in the peripheral blood, which
reflects the number of red blood cells in the blood
– Hgb constitutes over 90% of the red blood cells
• Decrease in Hgb concentration = anemia
• Increase in Hgb concentration = polycythemia
• Normal range
– Male: 14 – 18 g/dl
– Female 12 – 16 g/dl.
17
18. Hgb
• Hgb is the oxygen-carrying compound found
in the RBCs.
– Hgb level is a direct indicator of the oxygen-
carrying capacity of the blood
• Adaptation to high altitudes, extreme
exercise, and pulmonary conditions may
cause variations in hemoglobin values
18
19. Hgb- Clinical Significance
• Increased hemoglobin:
– Increased in diseases such as chronic obstructive lung
disease, polycythemia vera .
– May also be increased in
• Chronic smokers; athletes (regular vigorous exercise ): high
Landers(live at high altitudes)
• Decreased hemoglobin:
– Decreased in anemia of all types, particularly iron
deficiency anemia.
– Hgb is also reduced in blood loss, hemolysis, pregnancy,
fluid replacement or increased fluid intake
19
20. Hematocrit
• Hematocrit is a measure of the percentage of the
total blood volume that is made up by the red
blood cells
• The hematocrit can be determined directly by
centrifugation (“spun hematocrit”)
– The height of the red blood cell column is measured
and compared to the column of the whole blood
• Normal Range
– Male: 39 – 50%
– Female: 33 – 45% 20
21. Hct
• Hct describes the volume of blood that is occupied by RBCs.
• Expressed as a percentage of total blood volume.
• Rule of thumb
– Hct = 3 x Hgb
– Hgb= 3 x RBC
Useful to detect laboratory error in measuring the Hb,
HCT, and RBC count
NB: Rule of Three applies only for normocytic,
normochromic cells!
21
23. Centrifuged blood (adult male or female)
What is your diagnosis?
23
Plasma
Buffy coat
RBCs
Anemia – there is a low percentage of RBCs
(low hematocrit)
25. Hct- Clinical Significance
• Increase in Hct
– chronic obstructive lung disease and individuals who live at high
altitudes
– Also seen in dehydration
– hemoconcentration,
– polycythemia vera, or polycythemia secondaryto chronic hypoxia.
• Decrease hematocrit
– All types of anemias, blood loss, hemolysis, pregnancy, leukemia
– the bone marrow suppressant effects of drugs,
– chronic diseases,
– genetic alterations in RBC morphology
25
26. RBC count or Erythrocyte count
• Normal range:
– Male: 4.2 – 5.9 x 10e6 cells/mm
– Female: 3.5 – 5.5 x 10e6 cells/mm
• RBCs are produced in the bone marrow.
• Released into systemic circulation to transport oxygen
from the lungs to the body tissues.
• After circulating for a life span of ~120 days, the RBCs
are cleared by the reticuloendothelial system.
• RBC count is the actual amount of RBCs per unit of
blood.
26
27. RBC- Clinical Significance
Increased RBCs (Erythrocytosis)
are associated with high altitudes, strenuous
exercise and with specific disease conditions:
Polycythemia vera
Bone marrow failure
Anxiety or stress
Dehydration with hemoconcentration
Erythremic erythrocytosis
COPD with hypoxia and secondary polycythemia
27
28. RBC- Clinical Significance
Decreased RBCs:
in various types of anemias, lymphomas, leukemia
and other disease states:
Hemorrhage
Chronic inflammatory diseases
Organ failure
Overhydration
Pregnancy (normal dilutional effect)
Subacute endocarditis
Hemoglobinopathy
Hemolytic anemia
After puberty, females have lower RBCs and Hgb due to menstrual
bleeding!
28
30. RBC indices
• RBC indices (also known as Wintrobe indices) are
useful in the classification of anemias.
• These indices include:
the Mean Corpuscular Volume or Mean Cell
Volume(MCV)
The mean cell hemoglobin (MCH), and
the Mean corpuscular Hemoglobin
Concentration(MCHC)
30
32. MCV
• Normal Range: 76 – 100 fL
• MCV provides an estimate of the average volume
of erythrocyte.
• The higher the average size, the larger the
average size of the RBC
• Cells with abnormally large MCV are classified as
macrocytic
• Cells with a low MCV are referred to as
microcytic
32
33. Cont’d
• Cells that have an MCV that falls within the normal range are referred to as
normocytic.
• Increased MCV…..Macrocytic Anemia!
– Associated with folate deficiency, vitamin B12 deficiency, alcoholism, chronic liver
disease, hypothyroidism, anorexia nervosa
– Valproic acid, zidovudine, stavudine
• Decreased MCV….Microcytic Anemia!
– Iron deficiency anemia, hemolytic anemia and lead poisioning
• The MCV can be normal in a patient with a “mixed” (microcytic and
macrocytic) anemia.
• Note that a direct assessment of a blood smear via microscopic
examination is the gold standard for confirming RBC size. 33
34. Mean Corpuscular Hemoglobin
• Normal range: 26 – 34 pg/cell
• Indicates the average weight of hemoglobin in the
RBC.
• Cells with a low MCH are pale in color and are referred to
as hypochromic.
• Cells with an increased MCH are hyperchromic.
• Cells with normal amounts of hemoglobin are
normochromic.
34
35. Cont’d
• Increased MCH
– Folate or vitamin B12 deficiency
– In hyperlipidemia patients, MCH may be
falsely elevated because of specimen
turbidity.
• Decreased MCH
– Associated with iron deficiency anemia
35
36. Mean corpuscular Hemoglobin
Concentration
• Normal Range: 32 – 37 g/dl
• MCHC is a measure of average hemoglobin
concentration in the RBC.
• Increased MCHC
– Associated with hereditary spherocytosis
• Decreased MCHC
– Iron deficiency anemia, hemolytic anemia, lead
poisioning
36
37. Reticulocytes
• Normal Range: 0.1 – 2.5 % RBC
• Reticulocytes are immature RBCs formed in the
bone marrow.
• An increase in reticulocytes usually indicates
– an increase in RBC production
– decrease in the circulating number of mature
erythrocytes.
• Increased (reticulocytosis)
– Hemolytic anemia, hemorrhage 37
38. Cont’d
• Decreased
– Infectious causes, alcoholism, renal disease
(from decreased erythropoietin), drug induced
bone marrow suppression
38
39. REFERENCE RANGE: 4–11 × 103/ΜL OR 4–11 × 109/L
White Blood Cell or Leukocyte Count
39
40. WBC
40
• It comprise five different types of cells.
• Neutrophils are the most abundant of the circulating WBCs, followed in order
of frequency by lymphocytes, monocytes,eosinophils, and basophils.
• The neutrophils, eosinophils, basophils, and monocytes are formed from
stem cells in the bone marrow.
• Lymphocytes are formed primarily in the lymph nodes,thymus, spleen, and,
to a lesser extent, bone marrow.
• Each WBC type has unique functions, and it is best to consider them
independently rather than collectively as “leukocytes.”
• Ultimately, all WBCs contribute to host defense mechanisms.
• A convenient mnemonic for remembering the various types of WBCs is
“Never Let Monkeys Eat
41. WBC
• WBC count represents the total number of WBCs in a given
volume of blood.
• Mature WBCs exist as
– Neutrophils
– Lymphocytes
– Monocytes
– Eosinophils
– Basophils
• WBC count with differential provides a breakdown of the
percentage of each.
41
42. Cont’d
• Increased (leukocytosis)
– Infection, leukemia, trauma
• Decreased WBCs (leukopenia)
– Viral infection, aplastic anemia, bone marrow
suppression caused by cancer chemotherapy
42
43. Neutrophils
• Normal range:
– Seg 36 – 73 %
– Bands 3 – 5 %
• The terms, polys, segs, polymorphonuclear neutrophils, and granulocytes
are synonymous with the term neutrophil in clinical practice.
• Primary function is to fight bacterial and fungal infections by phagocytosis
of foreign particles.
• An increase in bands, left shift, may occur during infection or leukemia.
While the bone marrow increases production of new leukocytes,
there is also an increase in the number of circulating immature
neutrophils (e.g., bands); this phenomenon is commonly referred to
as a “left shift,” which suggests bacterial infection
43
44. Note:
• As the infection progresses, the percentage of band cells may
decrease as a result of an increase in the number of neutrophils
that have a longer half-life.
This decrease in bands does not necessarily indicate
improvement.
• A decrease in the percentage of neutrophils with a decrease in
the total WBC count is characteristic of effective antibiotic
therapy.
44
45. AGRANULOCYTOSIS AND ABSOLUTE NEUTROPHIL COUNT
• The condition involving decreased neutrophils, or neutropenia, is defined as a
neutrophil count <2,000 cells/μL;
• agranulocytosis refers to severe neutropenia.
• The degree of neutropenia is often expressed by the absolute neutrophil count
(ANC).
• The ANC is defined as the total number of granulocytes (polymorphonuclear
leukocytes and band forms) present in the circulating pool of WBCs and can be
calculated as WBC × (% neutrophils + % bands)/100.
• Generally, the risk of infection is low when the ANC exceeds 1,000/μL; however,
the risk of infection increases significantlywhen the ANCis less than 500/μL.
• The risk of developing bacteremia is increased further as the ANC decreases to
less than 100/μL, a condition commonly referred to as “profound neutropenia”
The most commoncauses of neutropenia are metastatic carcinoma, lymphoma, and
chemotherapeutic agents. 45
47. Pools of Neutrophils
1. Bone marrow: many banded forms are
present; neutrophilia with lots of bands
suggest bone marrow was source
2. Circulating Pool: used to deal with day to
day invasion of the body by organisms
3. Marginated Pool: no bands; respond to
physiologic stimulation
47
48. Case
R.L., a 45-year-old man, is hospitalized with a sustained high fever of 39.4◦C, SOB,
and pleurisy. His cough is productive of rusty sputum, and he appears to be in
acute distress. The results of the CBC and leukocyte differential are as follows:
Total WBC count, 18,000/μL
• Neutrophils, 76%
• Bands, 13%
• Lymphocytes, 10%
• Monocytes, 0
• Eosinophils, 1%
• Basophils, 0
• On the basis of this laboratory report and other findings, a diagnosis of
pneumococcal pneumonia is suspected. How is R.L.’s laboratory report
consistent with bacterial infection?
48
49. Lymphocytes
• Normal Range: 20 – 40 %
• Important for immune response to foreign
antigens.
• Increased lymphocytes (lymphocytosis)
– Viral infections and some bacterial infections (e.g.
syphilis)
• Decreased lymphocytes (lymphopenia)
– Acute infections, burns, HIV 49
50. Monocytes
• Normal range: 2 – 8%
• Synthesized in the bone marrow, released
into the circulation and migrate into
– Lymph nodes, spleen, liver, lung and bone
marrow
– Serve as scavengers for foreign substances
• Increased Monocytes
– Recovery phase of some infections, subacute
bacterial endocarditis, tuberculosis 50
52. Eosinophils
• Normal Range: 0 – 4%
• Phagocytic white blood cells, assist in the killing of
bacteria and yeast.
• Reside predominantly in the intestinal mucosa and
lungs.
• Involved in allergic reactions and in immune response
to parasites.
• Eosinophil count must be taken at the same time daily
due to diurnal variation.
52
53. Cont’d
• Increased
– Allergic disorders, allergic drug reactions,
parasitic infections
• Decreased
– Increased adrenal steroid production
53
54. Basophils
• Normal range: < 1%
• Contain heparin, histamin, and
leukotrienes
– Possibly associated with hypersensitivity
reactions
• Increased
– Hypersensitivity reactions to food or
54
55. Platelets
• Normal Range: 150,000 – 450,000/ micro
liter
• Critical element in blood clot formation
• Increased platelets
– Infection, malignancies
• Decrease platelets
– Radiation, chemotherapy
55
56. 56
• Platelets are a critical element in blood clot formation.
Reference interval: 150,000-450,000/μL
(SI 150-450 × 109/L)
• The risk of bleeding is low unless platelets fall below 20,000 to 50,000/μL.
Interpretation
• Increased Platelets
– (Thrombocytosis, Thrombocythemia) may be caused by infection,
malignancies, splenectomy, chronic inflammatory disorders (eg,
rheumatoid arthritis), polycythemia vera, hemorrhage, iron deficiency
anemia, or myeloid metaplasia.
• Decreased Platelets
– Thrombocytopenia may occur in autoimmune disorders such as
idiopathic thrombocytopenic purpura (ITP) and also with aplastic anemia,
radiation, chemotherapy, space-occupying lesion in the bone marrow,
bacterial or viral infections, and use of heparin or valproic acid.
57. Erythrocyte Sedimentation Rate(ESR)
57
Normal Range
Male: 1-15 mm/h (varies with age)
Female: 1-20 mm/h (varies with age)
• The erythrocyte sedimentation rate (ESR) measures the rate of erythrocyte settlement in
anticoagulated blood.
• In the presence of proteins known as acute phase reactants, erythrocytes settle much more
quickly.
• Acute phase reactants are often associated with infectious or inflammatory disorders.
• Thus, the ESR is a nonspecific diagnostic test that may be used to support a diagnosis or
monitor the progress of an inflammatory or infectious process.
• Interpretation:
• The ESR is most valuable in the diagnosis and monitoring of polymyalgia rheumatica and
temporal arteritis.
• The ESR may also be elevated in bacterial infections such as tuberculosis and syphilis,
malignancies, rheumatoid arthritis, SLE, scleroderma, and other collagen vascular diseases.
58. Interpreting the CBC
• If the neutrophils are causing the leukocytosis,
compare the neutrophil % to total WBC.
• The % neutrophils indicates the severity of
the infection
• The total WBC reflects the quality of the
immune system
58
59. Interpreting the CBC - Case
5 yr old male with pneumonia
WBC = 18,000
Neutrophils = 60% (10,800)
N.B: Marked leukocytosis and normal range
for neutrophils indicates moderate infection
but excellent immune system response
Excellent prognosis!!!
59
60. Case
85 yr old female with pneumonia:
Total WBC is: 11,500
Neutrophil % = 80% (9200) bands =
5%
This indicates that a severe infection is
present but the immune system is unable to
respond appropriately.
Prognosis poor!!! 60
61. Case
20 yr old male admitted following MVA
WBC 14,500
75% neutrophils 1% bands
History and low percent of bands suggest
pseudoneutrophilia
Due to liberation of marginated neutrophils
in the intravascular system
61
63. QUIZ!
• A.B., a 35-year-old woman, was treated for
7 days with dicloxacillin for cellulitis of the left leg.
On the eighth day, an allergic urticarial rash
developed.
• The CBC showed a total leukocyte count of
10,000/μL with 6% eosinophils.
• What is the significance of this eosinophil
count?
63
Notes de l'éditeur
Other factors may increase or decrease RBC counts.
• Drugs could potentially result in decreased RBC by
causing anaemia (like Zidovudine), bone-marrow
suppression, and hemolysis. Eg. Dapsone.
• Non-pathologic conditions like dehydration and heavy
exercise could result in false elevations in RBC while
excessive IV fluid intake and pregnancy, in false
decrements.
• Chemotherapy and dietary deficiencies may decrease
The MCHC is a more reliable index of RBC Hgb than MCH.
The former measures the concentration of Hgb, whereas the latter measures the weight of Hgb in the average RBC.
In normochromic anemias, changes in the size of RBCs (MCV) are associated with corresponding changes in the weight of Hgb (MCH), but the concentration of Hgb (MCHC) remains normal.
Changes in the Hgb content of RBCs alter the color of these cells.
Thus, hypochromic refers to a decrease in RBC Hgb, reflected by reduced MCHC, and may indicate iron-deficiency anemia.
Conversely,hyperchromic RBCs have an elevated MCHC because of the presence of greater amounts of Hgb.
Hyperchromic cells are not commonly encountered.
WBCs are the host’s chief defense system, and the neutrophil
is the main component of that system. During bacterial infections,
the leukocyte count and the neutrophils are generally
increased, and a left shift (increase in bands) may be noticeable.
The percentage of other types of WBCs is decreased proportionately
because the number of neutrophils is increased.
As the infection progresses, the percentage of band cells may
decrease as a result of an increase in the number of neutrophils
that have a longer half-life. This decrease in bands does not necessarily
indicate improvement. A decrease in the percentage of
neutrophils with a decrease in the total WBC count is characteristic
of effective antibiotic therapy.
Platelets circulate for 7 to 10 days
The risk of bleeding is inversely proportional to the platelet count. When the platelet count is < 50,000/μL, minor bleeding occurs easily and the risk of major bleeding increases. Counts between 20,000 and 50,000/μL predispose to bleeding with trauma, even minor trauma; with counts < 20,000/μL, spontaneous bleeding may occur; with counts < 5000/μL, severe spontaneous bleeding is more likely. However, patients with counts < 10,000/μL may be asymptomatic for years.