Composition of Blood
• Blood is the body’s only fluid tissue
• It is composed of liquid plasma and formed
elements
• Formed elements include:
– Erythrocytes, or red blood cells (RBCs)
– Leukocytes, or white blood cells (WBCs)
– Platelets
• Hematocrit – the percentage of RBCs out of
the total blood volume
Components of Whole Blood
Figure 17.1
Physical Characteristics and Volume
•
•
•
•
•
•
•
•
Color varies from scarlet to dark red
The pH of blood is 7.35–7.45
Temperature is 38C (100.4 F)
Blood accounts for approximately 8% of body
weight
Blood Viscosity 4.5 – 5.5 centipoise per second
Average volume: 5–6 L for males, and 4–5 L
for females
Isotonic with a 0.9% NaCl solution
Osmolarity 276 – 295 milliosmoles per Kg
Formed Elements
• Erythrocytes, leukocytes, and platelets make
up the formed elements
– Only WBCs are complete cells
– RBCs have no nuclei or organelles, and platelets
are just cell fragments
• Most formed elements survive in the
bloodstream for only a few days
• Most blood cells do not divide but are
renewed by cells in bone marrow
Leukocytes (WBCs)
• Leukocytes, the only blood components that
are complete cells:
– Are less numerous than RBCs
– Make up 1% of the total blood volume
– Can leave capillaries via diapedesis
– Move through tissue spaces
• Leukocytosis – WBC count over 11,000 / mm3
– Normal response to bacterial or viral invasion
Groupings of White Blood Cells
• White blood cells are divided into the
Granulocytes and Agranulocytes.
• A granule is a stained vesicle. A vesicle is a
membrane bound organelle in a cell that contains
certain chemicals.
• Cells are translucent so in order to see them
adequately under the microscope a chemical
stained is placed on the cells. The chemical stain
binds chemically to chemicals in the cell – thus
when the slide is rinsed with water the stain
remains – giving a certain color to cellular
components for identification purposes.
Peripheral Smear & Staining (1)
• In order to look at blood under the microscope –
a peripheral smear is made. The term means to
take blood from the peripheral blood vessels
(those not in the bone marrow) and place a drop
of it on a slide and smear it. Since cells are
translucent – a stain must be used to see the
blood cells for the purpose of identification.
• So the first order of business is to do a finger
stick or some other method to get a very small
amount of blood.
Peripheral Smear & Staining (2)
• A droplet of blood is then placed at the corner of
a microscope slide.
• A second microscope slide is then used to push
the blood into a very, very thin smear. Note – you do
not want cells stacked on top of one another because you cannot
see the blood cell underneath for ID purposes.
Peripheral Smear & Staining (3)
• Next a chemical stain is placed on the slide of smeared blood. A
chemical stain is a chemical (in some cases a mixture of chemicals) in
which the chemicals have certain colors (dye) that chemically bond to
certain chemical components of a cell. Since the chemicals bond to
the chemical components of the cell – they will not wash off when
the slide is flooded (rinsed) with water.
• For blood the current staining method uses a stain derived from
Romanovsky in the 19th century. This stain is a combination of
Methylene Blue and Eosin. Modifications of these stains (change in
the percentage of the two chemicals) produced the Wright Stain and
Giemsa stain – which are the two staining chemicals used to stain
blood in most labs – including the one here at Kingwood.
• Methylene blue has a blue color and is a chemical base (pH) thus it
stains acidic components of a cell.
• Eosin is red and is an acid – thus it stains basic components of a cell.
• Some components of a cell color a reddish blue by binding to azures,
substances formed when methylene blue is oxidized.
Peripheral Smear & Staining (4)
• Now the non-stained blood slide is then flooded
with stain. It sits for a few moments – then the
slide is flooded with water to wash off the nonchemically bound stain. As you know nothing is
perfect so some stain may not wash off – and
form artifact on the slide.
All of the white blood cells have vesicles but the
granulocytes have more vesicles than the
agranulocytes. Thus the accepted term
agranulocyte is really misleading. The
agranulocytes have only primary vesicles
(granules) which are the cell’s stained lysosomes.
The granulocytes have the primary granules plus
secondary vesicles (granules). The secondary
granules are special chemicals unique to each of
the granulocytes – thus they are termed “specific
granules” . It is the chemicals in the secondary
vesicles (granules) that determine each
granulocytes function.
• The Granulocytes are the neutrophils,
eosinophils and the basophils
• The Agranulocytes are the lymphocytes and
monocytes
Percentages of Leukocytes
Figure 17.9
Granulocytes
• Granulocytes – neutrophils, eosinophils, and
basophils
– Contain secondary cytoplasmic granules that stain
specifically (acidic, basic, or both) with Wright’s
stain
– Are larger and usually shorter-lived than RBCs
– Have lobed nuclei
Neutrophils
also known as
Polymorphonuclear Leukocytes (PMNs)
Nucleus has 3 – 6 lobes
• Neutrophils have two types of granules that:
– Take up both acidic and basic dyes
– Give the cytoplasm a lilac color
– Contain peroxidases, hydrolytic enzymes, and
defensins (antibiotic-like proteins)
• Neutrophils are our body’s bacteria slayers
Eosinophils
• Eosinophils account for 1–4% of WBCs
– Have red-staining, bilobed nuclei connected via a
broad band of nuclear material
– Have red to crimson (acidophilic) large, coarse,
lysosome-like granules
– Lead the body’s counterattack against parasitic
worms
– Lessen the severity of allergies by phagocytizing
immune complexes and produce an antihistamine
Basophils
• Account for 0.5% of WBCs and:
– Have U- or S-shaped nuclei with two or three
conspicuous constrictions
– Are functionally similar to mast cells
– Have large, purplish-black (basophilic) granules that
contain histamine & heparin
• Histamine – inflammatory chemical that acts as a
vasodilator and attracts other WBCs (antihistamines
counter this effect)
Agranulocytes
• Agranulocytes – lymphocytes and monocytes:
– Lack visible cytoplasmic granules
– Are similar structurally, but are functionally
distinct and unrelated cell types
– Have spherical (lymphocytes) or kidney-shaped
(monocytes) nuclei
Lymphocytes
• Account for 25% or more of WBCs and:
– Have large, dark-purple, circular nuclei with a thin rim of blue
cytoplasm
– Are found mostly enmeshed in lymphoid tissue (some
circulate in the blood)
• There are three types of lymphocytes: T cells, B cells
and natural killer cells (NK cells) – however only the T &
B lymphocytes circulate in the blood
– T cells function in the immune response
– B cells give rise to plasma cells, which produce antibodies
Monocytes
• Monocytes account for 4–8% of leukocytes
– They are the largest leukocytes
– They have abundant pale-blue cytoplasms
– They have purple-staining, U- or kidney-shaped nuclei
– They leave the circulation, enter tissue, and
differentiate into macrophages
Leukocytes
Figure 17.10
Summary of Formed Elements
Table 17.2.1
Summary of Formed Elements
Table 17.2.2
Formation of Leukocytes
• All leukocytes originate from hemocytoblasts
• Hemocytoblasts differentiate into myeloid stem cells and
lymphoid stem cells
• Myeloid stem cells become myeloblasts or monoblasts
• Lymphoid stem cells become lymphoblasts
• Myeloblasts develop into eosinophils, neutrophils, and
basophils
• Monoblasts develop into monocytes
• Lymphoblasts develop into lymphocytes
Stem cells
Hemocytoblast
Myeloid stem cell
Committed
Myeloblast
cells
Myeloblast
Lymphoid stem cell
Myeloblast
DevelopPromyelocyte Promyelocyte Promyelocyte
mental
pathway
Eosinophilic
myelocyte
Basophilic
myelocyte
Neutrophilic
myelocyte
Eosinophilic
band cells
Basophilic
band cells
Neutrophilic
band cells
Eosinophils
Basophils Neutrophils
(a)
(b)
(c)
Lymphoblast
Promonocyte
Prolymphocyte
Monocytes
Lymphocytes
(e)
(d)
Agranular leukocytes
Granular leukocytes
Some become
Macrophages (tissues)
Some
become
Plasma cells
Figure 17.11
Platelets
• Platelets are fragments of megakaryocytes with a bluestaining outer region and a purple granular center
• Their granules contain serotonin, Ca2+, enzymes, ADP,
and platelet-derived growth factor (PDGF)
• Platelets function in the clotting mechanism by forming a
temporary plug that helps seal breaks in blood vessels
• Platelets not involved in clotting are kept inactive by NO
and prostacyclin
Genesis of Platelets

The stem cell for platelets is the hemocytoblast

The sequential developmental pathway is as
shown.
Stem cell
Hemocytoblast
Developmental pathway
Megakaryoblast
Promegakaryocyte
Megakaryocyte
Platelets
Figure 17.12
Complete Blood Cell Count
Samples
A phlebotomist collects the specimen, in this case
blood is drawn in a test tube containing an
anticoagulant (EDTA, sometimes citrate) to stop it from
clotting, and transported to a laboratory.
In the past, counting the cells in a patient's blood was
performed manually, by viewing a slide prepared with a
sample of the patient's blood under a microscope
(a blood film, or peripheral smear). Nowadays, this
process is generally automated by use of an automated
analyzer , with only specific samples being examined
manually.
Automated blood count
Complete blood count performed by an automated analyzer.
The blood is well mixed (though not shaken) and placed on a
rack in the analyzer. This instrument has many different
components to analyze different elements in the blood. The cell
counting component counts the numbers and types of different
cells within the blood. The results are printed out or sent to a
computer for review.
Blood counting machines aspirate a very small amount
of the specimen through narrow tubing. Within this
tubing, there are sensors that count the number of
cells going through it, and can identify the type of cell;
this is flow cytometry. The two main sensors used are
light detectors, and electrical impedance. One way the
instrument can tell what type of blood cell is present is
by size. Other instruments measure different
characteristics of the cells to categorize them.
Because an automated cell counter samples and counts
so many cells, the results are generally very precise.
However, certain abnormal cells in the blood may be
identified incorrectly, and require manual review of the
instrument's results and identify any abnormal cells the
instrument could not categorize.
Lab Tests
Red cells
Total red blood cells - The number of red cells is given as an
absolute number per microliter (4.2 – 5.6 million per
microliter in male and 3.8 – 5.1 in females).
Hemoglobin - The amount of hemoglobin in the blood,
expressed in grams per deciliter. 14 – 18 grams per deciliter in
males and 11 – 16 grams in females)
Hematocrit or packed cell volume (PCV) - This is the fraction
of whole blood volume that consists of red blood cells (39 –
54 in males and 34 – 47 in females).
Note: A microliter occupies the space of a millimeter cubed.
Red blood cell indices
Mean corpuscular volume (MCV) - the average volume of the red
cells, measured in femtoliters ( 78 – 98 fl) . Anemia is classified as
normocytic, microcytic or macrocytic based on whether this value is
normal, above or below the expected normal range.
(RBC too large – macrocytic too small microcytic )
Mean corpuscular hemoglobin (MCH) - the average amount of
hemoglobin per red blood cell, in picograms (27 – 35 pg).
Mean corpuscular hemoglobin concentration (MCHC) - the average
concentration of hemoglobin in the cells (31 – 37%).
Red blood cell distribution width (RDW) - a measure of the
variation of the RBC population RDW = (Standard deviation of MCV
÷ mean MCV) × 100 Normal 11 – 15%
White Blood Cells
A Total white blood cell count is given as the total
number of white blood cells per microliter of blood.
(normal value varies but generally 4 – 11 thousand per
microliter of blood)
The CBC also lists the individual types of white blood
cells as a percentage or as an absolute number or in
cases both. The listing of the individual white blood
cell counts is the termed the “differential count.”
Percentages of Leukocytes
Figure 17.9
Clinical Terms
• Pancytopenia – all blood cells have a low
count – generally caused by a aplastic anemia
• Erythrocytopenia – too few red blood cells
• Erythrocythemia (polycythemia) – too many
red blood cells
• Leukocytosis – too many total white blood
cells
• Leukopenia – too few total white blood cells
• Thrombocytopenia – too few platelets
• Thrombocytosis – too many platelets
•
•
•
•
•
•
•
Neutropenia – too few neutrophils
Neutrophilia – too many neutrophils
Eosinopenia – too few eosinophils
Eosinophilia – too many eosinophils
Basopenia – too few basophils
Basophilia – too many basophils
Lymphopenia (lymphocytopenia) – too few
lymphocytes
• Lymphocytosis – too many lymphocytes
• Monocytopenia – too few monocytes
• Monocytosis – too many monocytes
Erythrocyte/Hemoglobin Disorders
• Anemia – blood has abnormally low oxygencarrying capacity
– It is a symptom rather than a disease itself
– Blood oxygen levels cannot support normal
metabolism
– Signs/symptoms include fatigue, paleness,
shortness of breath, and chills
Anemia can be due to deficient hemoglobin or hemoglobin that
is not functional
• Deficient hemoglobin can be caused by
inadequate production or increased
peripheral destruction
• Thus it said that most anemia is due to either
decreased production or increased peripheral
destruction
• The reticulocyte count is used to determine
which type it is
Production of New RBC's - Erythropoiesis (takes 4 days)
1. Hemocytoblasts - Stem cells in the bone marrow from which all blood
cells form.
2.
Proerythroblasts - are produced by the division and differentiation of
stem cells.
3. Basophilic (early) erythroblasts - During this stage in erythropoiesis
hemoglobin synthesis begins.
4. Intermediate erythroblasts - At this time, we see the accumulation of
hemoglobin due to its continued synthesis.
5. Late erythroblasts - During this stage the nucleus is extruded from the
cell.
6. Reticulocyte - These cells exhibit a net-like appearance or reticulum in
their cytoplasm when stained. A small number of reticulocytes (only 1 to
3% of the circulating red cells) are found in the circulation.
7. Mature erythrocytes - At this final stage of maturation there is a loss of
ribosomes. These cells enter the circulation.
• Examples of increased peripheral destruction
are hemorrhage, splenomegaly and others
• Examples of decreased production iron
deficiency anemia, pernicious anemia, folic
acid deficiency
• Some decreased production anemias can be
microcytic or macrocytic
• Non-functional hemoglobin can be as a result of
problems with the protein globin as in sickle cell
anemia, the thalassemias, and others
• Non-functional hemoglobin can also be a result of
problems with heme like the iron not being in the +2
oxidation state – but rather in the +3 oxidation state –
as a result of being oxidized by a free radical or other
chemical entity. O2 can only be carried on the iron of
hemoglobin if it is in the +2 oxidation state. All of us
have some of our iron in the +3 oxidation state that is it
is said a gram of Hgb. Will carry 1.34 ml. of O2 rather
that its ideal value of 1.39. If a significant amount of
Hgb. In an individual in in the +3 oxidation state such
that it lowers the O2 content of the blood below
normal – the patient has Methemoglobinemia
Polycythemia
• Polycythemia – excess RBCs that increase blood
viscosity
• Three main polycythemias are:
– Polycythemia vera – generally occurs in those over
60 and has no known cause – increase in all the
blood cells as a result of an increased action of the
pluripotential stem cells – but particularly the
RBCs
– Secondary polycythemia – due to an increased
erythropoietin level secondary to high altitudes,
chronic pulmonary disease, CHF, heavy smoking,
abnormal hemoglobins that have high O2 affinity
– Blood doping
– Relative polycythemia
Leukocytosis
• Leukocytosis is very common in acutely ill patients. It
occurs in response to a wide variety of conditions, including
viral, bacterial, fungal, or parasitic infection, cancer,
hemorrhage, and exposure to certain medications or
chemicals including steroids. Leukocytosis can also be the
first indication of neoplastic growth of leukocytes.
• For lung diseases such as pneumonia and tuberculosis,
WBC count is very important for the diagnosis of the
disease, as leukocytosis is usually present.
• The mechanism that causes leukocytosis can be of several
forms: an increased release of leukocytes from bone
marrow storage pools, decreased margination of leukocytes
onto vessel walls, decreased extravasation of leukocytes
from the vessels into tissues, or an increase in number of
precursor cells in the marrow.
Leukopenia
• Low white cell counts are associated with chemotherapy,
radiation therapy, leukemia (as malignant cells overwhelm
the bone marrow), myelofibrosis and aplastic anemia
(failure of white and red cell creation, along with poor
platelet production). In addition, many common
medications can cause leukopenia (eg. minocycline, a
commonly prescribed antibiotic).
• Other causes of low white blood cell count include:
Influenza, systemic lupus erythematosus, Hodgkin's
lymphoma, some types of cancer, typhoid, malaria,
tuberculosis, dengue, Rickettsial infections, enlargement of
the spleen, folate deficiencies, psittacosis and sepsis. Many
other causes exist, such as a deficiency in certain minerals
such as copper and zinc.
Neutrophilia
• Neutrophils are the primary white blood cells that respond to
a bacterial infection, so the most common cause of
neutrophilia is a bacterial infection.
• Neutrophils are also increased in any acute inflammation, so
will be raised with appendicitis and after a heart attack or
other infarct.
• Drugs, such as prednisone, have the same effect as cortisol,
causing marginated neutrophils to enter the blood stream.
Nervousness will very slightly raise the neutrophil count
because of this effect. Exercise also raises the count.
• A neutrophilia might also be the result of a malignancy.
Chronic myelogenous leukemia (CML or chronic myeloid
leukemia) is a disease where the blood cells proliferate out of
control.
"Left shift"
• A "left shift" refers to the presence of increased
proportions of younger, less well differentiated
neutrophils and neutrophil-precursor cells in the
blood. This generally reflects early or premature
release of myeloid cells from the bone marrow,
the site where neutrophils are generated. A
severe neutrophilia with left shift is referred to as
a leukemoid reaction. The leukocyte alkaline
phosphatase (LAP) score, which refers to the
amount of alkaline phosphatase per neutrophil,
will increase. In a severe infection, toxic
granulation changes happen to the neutrophils.
Neutropenia
• Causes can be divided into the following groups:
• Decreased production in the bone marrow:
–
–
–
–
aplastic anemia
cancer, particularly blood cancers
certain medications
hereditary disorders (e.g. congenital neutropenia, cyclic
neutropenia)
– radiation
– Vitamin B12 or folate deficiency.
• Increased destruction:
– autoimmune neutropenia.
– chemotherapy treatments, such as for cancer and
autoimmune diseases
• Margination and sequestration:
– Hemodialysis
Eosinophilia
•
•
•
•
•
•
•
•
•
Hypereosinophilic syndrome
Parasitic infections (intestinal helminthiasis)
Allergic disorders (including eosinophilic esophagitis)
Some drug reactions, e.g. DRESS syndrome
Cholesterol embolization
Churg-Strauss syndrome– autoimmune vasculitis
Some forms of chronic myeloid leukemia
Hodgkin's lymphoma
Gleich's syndrome - episodic angioedema with eosinophilia is a
rare disease in which the body swells up episodically (angioedema),
associated with raised antibodies of the IgM type and increased
numbers of eosinophils
• Addison's disease
• Clonorchis sinensis, a type of flatworm
• Eosinophilia-myalgia syndrome caused by contaminated tryptophan
supplements
Eosinopenia
• Leukocytosis with eosinopenia can be a
predictor of bacterial infection.
• It can be induced by the use of steroids.
Basophilia
• Basophilia as an isolated finding is uncommon.
However it is a common feature of
myeloproliferative disorders and particularly
prominent in chronic granulocytic leukemia.
Basopenia
• One cause is urticaria.
• It has been proposed as an indicator of
ovulation.
Thrombocytosis
• Increase platelet counts can be due to a number of disease
processes:
• Essential (primary) – Not homeostatic
– Essential thrombocytosis (a form of myeloproliferative disease)
– Other myeloproliferative disorders such as chronic myelogenous
leukemia, polycythemia vera, chronic idiopathic myelofibrosis
• Reactive (secondary)
– Inflammation - due to increased production of cytokines
– Surgery (which leads to an inflammatory state)
– Hyposplenism (decreased breakdown and storage of platelets
thus more in the circulation
– Hemorrhage (rebound effect) and/or iron deficiency (cause not
known)
• Over-medication with drugs that treat thrombocytopenia,
such as eltrombopag or romiplostim, may also result in
thrombocytosis.
Essential Thrombocytosis
• Essential thrombocytosis is a rare chronic blood
disorder characterized by the overproduction of
platelets by megakaryocytes in the bone marrow in the
absence of an appropriate homeostatic stimulation.
• The disease usually affects middle aged to elderly
individuals, with an average age at diagnosis of 50-60
years, although it can affect children and young adults
as well. It is seen more commonly in females.
• The pathologic basis for this disease is unknown.
However, essential thrombocytosis resembles
polycythemia vera in that cells of the megakaryocytic
series are more sensitive to growth factors. Platelets
derived from the abnormal megakaryocytes do not
function properly, which contributes to the clinical
features of bleeding and thrombosis.
Primary (Essential) Thrombocytosis
• In 2005, a mutation in the JAK2 kinase (V617F)
was found by multiple research groups to be
associated with essential thrombocytosis in
around 30% of cases.
• Patient has alternation of bleeding and
thrombosis
• The increased bleeding, which is far more
prevalent, is due to acquired Von Willebrand
Disease
Myelofibrosis
• Myelofibrosis, also known as myeloid metaplasia, chronic
idiopathic myelofibrosis, and primary myelofibrosis, is a disorder
of the bone marrow, in which the marrow undergoes fibrosis replacement by fibrous (scar) tissue (collagen.
Pathophysiology
• The bone marrow is replaced by collagen fibrosis, impairing the
patient's ability to generate new blood cells resulting in a
progressive pancytopenia. It is usually reactive following other
myeloproliferative disorders, such as polycythemia rubra vera or
essential thrombocytosis. Extramedullary hamatopoeisis occurs as
the hemopoetic cells migrate away from the bone marrow, to the
liver and spleen. Patients often have hepatosplenomegaly and
poikilocytosis.
• In primary myelofibrosis, a progressive scarring (fibrosis) of the
bone marrow occurs. As a result, blood forms in sites other than
the bone marrow, such as the liver and spleen. This causes an
enlargement of these organs. The cause and risk factors are
unknown. It commonly occurs in the spent phase of Polycythemia
rubra vera, possibly in response to the medication hydroxyurea
poisoning the marrow.
• Genetic associations with JAK2 and MPL have been described.
Thrombocytopenia
• Normal platelet count is 150,000 and 450,000 per mm3
• Thrombocytopenia is generally considered when the
platelet count becomes less than 100,000
• Must rule out pseudothrombocytopenia as a result of the
use of EDTA in the collecting blood test tube. EDTA acts as
an anticoagulant that ties up calcium thus preventing
coagulation. Sometimes this can that can cause IgG and
sometimes IgM to agglutinate the platelets thus making
them appear decreased in number.
General Causes of Thrombocytopenia are:
1. Decreased Production
2. Increased Destruction
3. Medication Induced
Decreased Production
• Vitamin B12 or folic acid deficiency
• Leukemia or myelodysplastic syndrome
• Decreased production of thrombopoietin by
the liver in liver failure.
• Sepsis, systemic viral or bacterial infection
• Dengue fever can cause thrombocytopenia by
direct infection of bone marrow
megakaryocytes as well as immunological
shortened platelet survival
Hereditary syndromes of Decreased Production
– Congenital amegakaryocytic thrombocytopenia (CAMT)
– Thrombocytopenia absent radius syndrome
– Fanconi anemia -FA is characterized by short stature,
skeletal anomalies, increased incidence of solid tumors
and leukemias, bone marrow failure (aplastic anemia), and
cellular sensitivity to DNA damaging agents such as
mitomycin C.
– Bernard-Soulier syndrome, associated with large platelets
– May Hegglin anomaly, the combination of
thrombocytopenia, pale-blue leuckocyte inclusions, and
giant platelets
– Grey platelet syndrome – decrease in the alpha granules
– Alport syndrome – genetic disease with
Glomerulonephritis, end-stage renal disease and hearing
loss
Increased Destruction of Platelets
•
•
•
•
•
•
•
•
•
•
•
Idiopathic thrombocytopenic purpura (ITP)
Thrombotic thrombocytopenic purpura (TTP)
Hemolytic-uremic syndrome (HUS)
Disseminated intravascular coagulation (DIC)
Paroxysmal nocturnal hemoglobinuria (PNH)
Antiphospholipid syndrome
Systemic lupus erythematosus (SLE)
Post transfusion purpura
Neonatal alloimmune thrombocytopenia (NAITP)
Splenic sequestration of platelets due to hypersplenism
Dengue fever has been shown to cause shortened
platelet survival and immunological platelet
destruction
• HIV-associated thrombocytopenia
Medication induced Thrombocytopenia
• Thrombocytopenia-inducing medications include:
• Direct myelosuppression
–
–
–
–
–
–
Valproic acid
Methotrexate
Carboplatin
Interferon
Other chemotherapy drugs
H2 Blockers and Proton Pump Inhibitors have shown increased
Thrombocytopenia symptoms, such as red dots near the bottom of the legs
• Immunological platelet destruction
– Drug binds Fab portion of an antibody. The classic example of this mechanism
is the quinidine group of drugs. The Fc portion of the antibody molecule is not
involved in the binding process.
– Drug binds to Fc, and drug-antibody complex binds and activates platelets.
Heparin induced thrombocytopenia (HIT) is the classic example of this
phenomenon. In HIT, the heparin-antibody-platelet factor 4 (PF4) complex
binds to Fc receptors on the surface of the platelet. Since Fc portion of the
antibody is bound to the platelets, they are not available to the Fc receptors of
the reticulo-endothelial cells, so therefore this system cannot destroy platelets
as usual. This may explain why severe thrombocytopenia is not a common
feature of HIT.
Idiopathic Thrombocytopenia Purpura
• A condition of having a low platelet count
(thrombocytopenia) of no known cause
(idiopathic). As most causes appear to be related
to antibodies against platelets, ITP is also known
as immune thrombocytopenic purpura or
immune-mediated thrombocytopenic purpura.
• Often ITP is asymptomatic, however a very low
platelet count can lead to visible symptoms, such
as purpura (bruises), or more seriously, bleeding
diathesis.
Thrombotic thrombocytopenic purpura
• This is a rare disorder of the blood-coagulation system,
causing extensive microscopic blood clots to form in
the small blood vessels throughout the body
(thrombotic microangiopathy. Most cases of TTP arise
from deficiency or inhibition of the enzyme
ADAMTS13, which is responsible for cleaving large
multimers of von Willebrand factor (vWF.
• Red blood cells passing the microscopic clots are
subjected to shear stress which damages their
membranes, leading to intravascular hemolysis.
Reduced blood flow due to thrombosis and cellular
injury results in end organ damage. Current therapy is
based on support and plasmapheresis to reduce
circulating antibodies against ADAMTS13 and replenish
blood levels of the enzyme.
Leukemia
• A neoplasm of hematopoietic tissue
• Leukemic cells diffusely infiltrate the bone marrow
and lymphoid tissues, spill over into the bloodstream,
and infiltrate throughout the various organs of the
body
• Cells may be mostly mature or they may be extremely
primitive
• The overproduction of white cells may be revealed in
the peripheral blood by a very high white blood count
• The white cells may be confined to the bone marrow,
and the number in the peripheral blood is normal or
decreased; called aleukemic leukemia
Leukemia: Classification
•
Any type of hematopoietic cells can give rise to
leukemia, but the most common types are:
1. Granulocytic
2. Lymphocytic
3. Monocytic
Basis for Classification of Leukemia
1. By Cell type
– Granulocytic, lymphocytic, monocytic
2. By Maturity of Leukemic cells
– Acute, chronic
Clinical Features
Leukemia
Manifestations caused by impairment of bone marrow
function
• Overgrowth of leukemic cells that crowds out
normal cells, causing:
• Anemia: inadequate red cell production
• Thrombocytopenia (low blood platelets): causes
bleeding
• Infections resulting from inadequate number of
normal white cells