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HEMATOLOG

Dula D. (B.Pharm; MSc)


Jimma University
School of Pharmacy
Introduction
2

 Hematologic cell types are originate from the


hematopoietic stem cell (bone marrow, lymph
system or blood).

 Each cell line has a defined role and unique


contribution to the overall homeostatic process.

Hematology 04/01/2021
Hematopoietic stem cell lineage

3
Complete Blood Count (CBC)
4

 CBC is one of the most commonly ordered


clinical laboratory tests.
 CBC measures;
o RBCs, Hgb, hematocrit (Hct)
o Mean cell volume (MCV), mean cell Hgb
concentration (MCHC)
o Total WBCs (with differential)
o Platelet . Hematology 04/01/2021
Complete Blood Count (CBC)
5

Hematology 04/01/2021
Red Blood Cells (Erythrocytes)
6

 RBCs are produced in the bone marrow, released


into the peripheral blood;
 circulated for approximately 120 days, and cleared
by the reticuloendothelial system.
 The primary function is to transport oxygen
linked to Hgb from the lungs to tissues.

Hematology 04/01/2021
Red Blood Cells
7

 The concentration of RBCs in the blood can be


measured to detect anemia.
 Hct and Hgb concentrations are generally used
to monitor quantitative changes in RBCs.
 Reference Range:
 Male: 4.3–5.9 × 106/µL

 Female:3.5–5 × 106/µL
Hematology 04/01/2021
Hematocrit (Hct)
8

 Hct (packed cell volume) is the percentage of


RBCs to the total blood volume.
 determined by comparing the height of the settled
RBCs to the height of the column of whole blood.
 A decrease in Hct may result from;
 bleeding
 bone marrow suppressant effects of drugs
 Chronic diseases
 genetic alterations in RBC morphology, or hemolysis
Hematology 04/01/2021
Hematocrit
9

 An increase in Hct may result from;


 Hemoconcentration

 polycythemia vera
 polycythemia secondary to chronic hypoxia
 Reference Range:
 Males: 40.7%–50.3% or 0.4–0.503
 Female: 36%–44.6% or 0.36–0.446
Hematology 04/01/2021
Hemoglobin
10

 Hgb is the major oxygen-carrying compound


contained in RBCs.
 Total Hgb concentration primarily depends on the
number of RBCs in the blood sample.
 Medical conditions that impact the number of RBCs
will also affect Hgb concentration.
 Reference Range:
 Males: 13.8–17.5 g/dL or 138–175 g/L
 Females: 12.1–15.3 g/dL Hematology
or 121–153 g/L
04/01/2021
Red Blood Cell Indices
11

 RBC indices (Wintrobe indices) are useful


in the classification of anemias.
 These indices include;
o the MCV
o the MCH
o the MCHC

Hematology 04/01/2021
Red Blood Cell Indices
12

 These indices are calculated as:


 MCV = Hct (%) x 10 / RBC (mL/µL)

= 80-97.6 (µm3)

 MCH = Hgb (g/dL) x 10 / RBC (mL/µL)

= 27-33 (pg)

 MCHC=Hgb (g/dL) x 100 / Hct (%)

=33-36 (g/dL)

Hematology 04/01/2021
MEAN CELL VOLUME (MCV)
13

 The MCV detects changes in cell size.


 A decreased MCV indicates:
 a microcytic cell, which can result from iron-deficiency
anemia or anemia of chronic inflammation.

 A increased MCV indicates:


 a macrocytic cell, which can be caused by a vitamin B12
or folic acid deficiency.

 The MCV can be normal in a patient with a “mixed”


(microcytic and macrocytic) anemia.
Hematology 04/01/2021
MEAN CELL HEMOGLOBIN (MCH)
14

 The MCHC is a more reliable index of RBC Hgb than MCH.

 MCH measures the weight of Hgb in the RBCs in a sample.

 MCHC measures concentration of the RBCs contained


within a sample.

 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.

Hematology 04/01/2021
MEAN CELL HEMOGLOBIN
15

 Thus, hypochromic refers;


 to a decrease in RBC Hgb

 reflected by reduced MCHC, and may indicate


iron-deficiency anemia.

 Hyperchromic RBCs;

 have an elevated MCHC because of the presence


of greater amounts of Hgb.
 are not commonly encountered.
Hematology 04/01/2021
Reticulocytes
16

 Typically comprise about 1% of the RBCs.


 Measures the percentage of these new cells in the
circulating blood.
 An increase in the number of reticulocytes implies an
increased number of erythrocytes.
 Reticulocyte count is a good indicator of bone
marrow activity because it represents a recent
production.

Hematology 04/01/2021
Reticulocytes
17

 Appropriate treatment of anemias caused by iron,

vitamin B12, or folic acid deficiencies should result

in an increased reticulocyte count.

 Caution must be exercised in the interpretation of

reticulocyte counts.

 Changes in the number of RBCs will result in

proportional changes in the reticulocyte count.


o Adults: RR: 0.5%–1.5% of RBCs
Hematology 04/01/2021
Erythrocyte Sedimentation Rate
(ESR)
18

 The rate at which erythrocytes settle to the bottom of a test

tube through the forces of gravity and in response to fibrinogen

levels in the blood.

 is a nonspecific value and may be increased abnormally in

acute and chronic inflammatory processes.

o acute and chronic infections, neoplasms, infarction, tissue

necrosis, rheumatoid-collagen disease, dysproteinemias,

nephritis, and pregnancy.


 ESR can also be affected by non-inflammation e.g., change in
Hematology
erythrocyte size, shape, or number. 04/01/2021
Erythrocyte Sedimentation Rate
(ESR)
19

 Laboratory technique can also affect the


sedimentation rate substantially.

 Because many factors can enhance the settling rate


of RBCs.

 Moderate to marked elevation of the ESR merely


indicates an inflammatory component to a disease
state.

• RR: 0–30 mm/hour


Hematology 04/01/2021
White Blood Cells
20

 Leukocytes or WBCs comprise five different types of cells.


 Neutrophils, 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 function.

 All WBCs contribute to host defense mechanisms.

 RR: 3.8–9.8 × 103/µL or 3.8–9.8 × 109/L


Hematology 04/01/2021
Neutrophils
21

 RR: 40%–70% of WBC

 Polymorphonuclear neutrophils, and granulocytes are synonymous with

the term neutrophil in clinical practice.

 The number of neutrophils is commonly increased during bacterial or

fungal infections;
o because these cells are essential in killing invading microorganisms.

 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

acute bacterial infection. Hematology 04/01/2021


Neutrophils
22

 Neutrophils are also altered by;

 noninfectious diseases (rheumatoid arthritis, IBD,

asthma, MI, or gout)

 metabolic toxic states (DKA, uremia, and eclampsia)

 physiologic response to stress (physical exercise,

childbirth).

 Drugs (epinephrine and corticosteroids)


o primarily caused by demargination from blood vessel walls.
Hematology 04/01/2021
Agranulocytosis and Absolute
Neutrophil Count (ANC)
23

 Neutropenia is defined as a neutrophil count of <2,000


cells/μL.
 Agranulocytosis refers to severe neutropenia.
o The most common causes are metastatic carcinoma,
lymphoma, and chemotherapeutic agents.

 The degree of neutropenia is often expressed by the ANC.


 The ANC is the total number of granulocytes present in
the circulating pool of WBCs.
 calculated as WBC × (% neutrophils + % bands)/100.
Agranulocytosis and ANC
24

 The risk of infection is low when the ANC exceeds


1,000/μL.

 The risk of infection increases significantly when


the ANC is <500/μL.

 The risk of developing bacteremia is increased


further as the ANC decreases to <100/μL, a
condition commonly referred to as “profound
neutropenia.”
Hematology 04/01/2021
Lymphocytes
25

 RR: 22%–44% of WBC


 These leukocytes respond to foreign antigens by
initiating the immune defense system.
 The lymphocytes circulating in blood represent
<5% of the total amount in the body.
 There are two major types of lymphocytes.
 T-lymphocytes participate in cell-mediated immune
responses.
 B-lymphocytes are responsible for humoral antibody
responses.
Hematology 04/01/2021
Lymphocytes
26

 Diseases affecting lymphocytes primarily manifest


themselves as immune deficiency disorders or as
autoimmune diseases.

 Increased numbers of lymphocytes indicates


lymphoma and viral infections.

Hematology 04/01/2021
Monocytes
27

 RR: 4%–11% of WBC


 are the precursors to macrophages and antigen-presenting
cells (dendritic cells), which are found in the body’s tissues.
 Macrophages and dendritic cells are phagocytic cells that
engulf foreign antigens or dead or dying cells.
 Monocytosis may be observed in,
o subacute bacterial endocarditis
o Malaria
o tuberculosis
o during the recovery phase of some infections 04/01/2021
Hematology
Eosinophils
28

 RR: 0%–8% of WBC

 have surface receptors that bind IgG and IgE

 can modify reactions associated with IgG and IgE-


mediated degranulation of mast cells.

 have phagocytic activity, facilitate killing of


microorganisms, initiate mast cell secretion,
protect against various parasites, and play
some role in host defense.
Hematology 04/01/2021
Eosinophils
29

 probably most commonly associated with;


§ allergic reactions to drugs

§ allergic disorders (hay fever, asthma & eczema)

§ invasive parasitic infections (hookworm,


schistosomiasis, and trichinosis)

§ collagen vascular diseases (RA, eosinophilic


fasciitis, and eosinophilic-myalgia syndrome)

§ malignancies (Hodgkin lymphoma)


Hematology 04/01/2021
Basophils
30

 RR: 0%–3% of WBC


 During infection or inflammation, basophils leave the
blood and mobilize as mast cells to the affected
site and release granules.
 These granules contain histamine, serotonin,
prostaglandins, and leukotrienes.
 Degranulation results in an increased blood flow to
the site and may compound inflammatory processes.
Hematology 04/01/2021
Basophils
31

 An increase in basophils commonly accompanies;


 allergic and anaphylactic responses
 Chronic myeloid leukemia
 Myelofibrosis
 polycythemia vera

 A decrease in the number of basophils is generally


not readily apparent.

Hematology 04/01/2021
Thrombocytes
32

 RR: 150–450 × 103/µL or 150–450 × 109/L

 Thrombocytes (platelets), are tiny fragments of cells that assist

with normal blood clotting.

 Decreased platelet counts (thrombocytopenia) may lead to

petechiae, ecchymosis, and spontaneous hemorrhage.

 Causes include;
 decreased platelet production

 dilution of blood samples secondary to blood transfusion

 sequestration secondary to hypersplenism


Hematology 04/01/2021
 DIC, infection, or systemic lupus erythematosus
Thrombocytes
33

 Elevated platelet counts (thrombocytosis) causes;


 malignancy
 rheumatoid arthritis
 iron-deficiency anemia
 loss from excessive bleeding or trauma
 polycythemia vera
 postsplenectomy syndromes

Hematology 04/01/2021
Coagulation Studies
34

 The control of bleeding depends on the formation of a

platelet plug and the formation of a stable fibrin clot.

 The formation of this clot depends on the complex

interactions of plasma proteins and clotting factors.

 coagulation studies are;


o prothrombin time (PT)

o international normalized ratio (INR)

o activated partial thromboplastin time (aPTT)


 used to monitor effectiveness &Hematology
safety of anticoagulation
04/01/2021 therapy
Activated Partial Thromboplastin
Time
35

 RR: 22–37 seconds

 aPTT measures the time it takes the body to form a clot.

 aPTT depends on;


 the activity of intrinsic pathway (factors VIII, IX, XI, & XII)

 common pathway (factors II, X, & V)

 aPTT is commonly measured to detect;


o bleeding disorders & coagulation deficiencies

o monitor unfractionated heparin therapy


Hematology 04/01/2021
Prothrombin Time
36

 RR: 10–13 seconds

 Prothrombin is converted to thrombin during the blood clotting

process.

 Thrombin formation is the critical event in the hemostatic process,

because thrombin creates fibrin results a clot formation.

 The PT test evaluates the integrity of the extrinsic and common

pathways and directly measures the activity of clotting factors VII

and X, II, and fibrinogen.

 PT is the time required for the blood to clot after a reagent (i.e.,

tissue thromboplastin). Hematology 04/01/2021


International Normalized Ratio [INR]
37

 INR is used as a standard unit to report the result of

PT test, because PT results obtained from one

reagent cannot be reliably with another reagent.

 Used to monitor both the initiation and

maintenance of warfarin.

 INR in normal individuals is 1.

 For patients on anticoagulation therapy, the target

INR is usually between 2 and 3.


Hematology 04/01/2021
International Normalized Ratio [INR]
38

 the higher the INR;


 the higher the likelihood of bleeding because the

blood is taking longer to clot.

 the INR is lower;


 there is an increased risk of developing a clot.

 Many factors including medications, diet, alcohol intake,

and certain medical conditions can influence the INR.

Hematology 04/01/2021
Case study
39

 LH: a 50 year old female, is hospitalized with a sustained


high fever of 39.2°C and severe back pain.
 The results of the CBC are as follows:
 Total WBC count: 21,000/μL
 Neutrophils: 74%
 Bands: 6%
 Lymphocytes: 14.6%
 Monocytes: 8%
 Eosinophils: 1%
 Basophils: 0%
 Imaging and other blood work was ordered.
 LH is diagnosed with an abscess in her lower back and
Staphylococcus aureus bacteremia.
 How is L.H.’s laboratory report consistent with a systemic
bacterial infection? Hematology 04/01/2021
Hematologic Laboratory Values

40 Hematology 04/01/2021
41 Hematology 04/01/2021
42 Hematology 04/01/2021

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