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LOM Hematology Notes

CHAPTER 10 -HEMATOLOGY

INTRODUCTION

The primary function of blood is to maintain a constant environment for the other living
tissues of the body. Blood transports nutrients, gases, and wastes to and from the cells of
the body. Nutrients from food, digested in the stomach and small intestine, pass into the
bloodstream through the lining cells of the small intestine. Blood then carries these
nutrients to all body cells. Oxygen enters the body through the air sacs of the lungs. Red
blood cells then transport the oxygen to cells throughout the body. Blood also helps
remove the waste products released by cells. It carries gaseous waste (such as carbon
dioxide) to the lungs to be exhaled. It carries chemical waste, such as urea, to the kidneys
to be excreted in the urine.
Blood transports chemical messengers called hormones from their sites of secretion in
glands, such as the thyroid or pituitary, to distant sites where they regulate growth,
reproduction, and energy production. These hormones are discussed later in the endocrine
chapter.Finally, blood contains proteins, white blood cells and antibodies that fight
infection, and platelets (thrombocytes) and other proteins that help the blood to clot.

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COMPOSITION AND FORMATION OF BLOOD

Blood is composed of cells, or formed elements, suspended in a clear, straw-colored


liquid called plasma. The cells normally constitute 45% of the blood volume and
include erythrocytes (red blood cells), leukocytes (white blood cells), and platelets
or thrombocytes (clotting cells). The remaining 55% of blood is plasma, a solution of
water, proteins, sugar, salts, hormones, lipids, and vitamins.

CELLS

Beginning at birth, all blood cells originate in the marrow cavity of bones. Both the red
blood cells that carry oxygen and the white blood cells that fight infection arise from the
same blood-forming or hematopoietic stem cells. Under the influence of proteins in the
blood and bone marrow, stem cells change their size and shape to become specialized, or
differentiated. In this process, the cells change in size from large (immature cells) to
small (mature forms), and the cell nucleus shrinks (in red cells, the nucleus actually
disappears).

ERYTHROCYTES

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As a red blood cell matures (from erythroblast to erythrocyte), it loses its


nucleus and assumes the shape of a biconcave disk. This shape (a depressed or hollow
surface on each side of the cell, resembling a cough drop with a thin central portion) allows
for a large surface area so that absorption and release of gases (oxygen and carbon
dioxide) can take place. Red cells contain the unique protein hemoglobin, composed of heme
(iron-containing pigment) and globin (protein). Hemoglobin enables the erythrocyte to
carry oxygen. The combination of oxygen and hemoglobin (oxyhemoglobin) produces the
bright red color of blood.

Erythrocytes originate in the bone marrow. The hormone called


erythropoietin (secreted by the kidneys) stimulates their production (-poiesis means
formation). Erythrocytes live and fulfill their role of transporting gases for about 120
days in the bloodstream. After this time, macrophages (in the spleen, liver, and bone
marrow) destroy the worn-out erythrocytes. This process is called hemolysis. From 2 to 10
million red cells are destroyed each second, but because they are constantly replaced, the
number of circulating cells remains constant (4 to 6 million per μL of blood). Macrophages
break down erythrocytes and hemoglobin into heme and globin (protein) portions. The heme
releases iron and decomposes into a yellow-orange pigment called bilirubin. The iron in
hemoglobin is used again to form new red cells or is stored in the spleen, liver, or bone
marrow. Bilirubin is excreted into bile by the liver, and from bile it enters the small
intestine via the common bile duct. Finally it is excreted in the stool, where its color
changes to brown.

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LEUKOCYTES

White blood cells (7000 to 9000 cells per μL of blood) are less numerous than
erythrocytes, but there are five different types of mature leukocytes.
These are three polymorphonuclear granulocytic leukocytes (neutrophil, eosinophil, and
basophil) and two mononuclear agranulocytic leukocytes (lymphocyte and monocyte). The
granulocytes, or polymorphonuclear leukocytes (PMNs), are the most numerous (about
60%). Basophils contain granules that stain dark blue with a basic (alkaline) dye. These
granules contain heparin (an anticlotting substance) and histamine (a chemical released in
allergic responses). Eosinophils contain granules that stain with eosin, a red acidic dye.
These granules increase in allergic responses and engulf substances that trigger the
allergies. Neutrophils contain granules that are neutral; they do not stain intensely and
show only a pale color. Neutrophils are phagocytes (phag/o means to eat or swallow) that
accumulate at sites of infection, where they ingest and destroy bacteria. Specific
proteins called colony-stimulating factors (CSFs) promote the growth of granulocytes in
bone marrow. G-CSF (granulocyte CSF) and GM-CSF (granulocyte-macrophage CSF) are
given to restore granulocyte production in cancer patients. Erythropoietin, like CSFs, can
be produced by recombinant DNA techniques. It stimulates red blood cell production
erythropoiesis).

Although all granulocytes are polymorphonuclear (they have multilobed nuclei), the term
polymorphonuclear granulocytes (“polys”) often describe the neutrophil, which is the most
numerous of the granulocytes.

Mononuclear (containing one large nucleus) leukocytes do not have large numbers of
granules in their cytoplasm, but they may have a few granules. These are lymphocytes and
monocytes. Lymphocytes are made in bone marrow and lymph nodes and circulate both in
the bloodstream and in the parallel circulating system, the lymphatic system.

Lymphocytes play an important role in the immune response that protects the body against
infection. They can directly attack foreign matter and, in addition, make antibodies that
neutralize and can lead to the destruction of foreign antigens (bacteria and viruses).
Monocytes are phagocytic cells that also fight disease. As macrophages, they move from
the bloodstream into tissues and dispose of dead and dying cells and other tissue debris
by phagocytosis.

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PLATELETS (THROMBOCYTES)

Platelets, actually blood cell fragments, are formed in bone marrow from giant cells with
multilobed nuclei called megakaryocytes. Tiny fragments of a megakaryocyte break off to
form platelets. The main function of platelets is to help blood to clot. Specific terms
related to blood clotting are discussed later in this chapter.

PLASMA

Plasma, the liquid part of the blood, consists of water, dissolved proteins, sugar, wastes,
salts, hormones, and other substances. The four major plasma proteins are albumin,
globulins, fibrinogen, and prothrombin (the last two are clotting proteins).
Albumin maintains the proper proportion (and concentration) of water in the blood.
Because albumin cannot pass easily through capillary walls, it remains in the blood and
carries smaller molecules bound to its surface. It attracts water from the tissues back
into the bloodstream and thus opposes the water’s tendency to leave the blood and leak
out into tissue spaces. Edema (swelling) results when too much fluid from blood “leaks” out

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into tissues. This happens in a mild form when a person ingests too much salt (water is
retained in the blood and seeps out into tissues) and in a severe form when a person is
burned in a fire. In this situation, albumin escapes from capillaries as a result of the burn
injury. Then water cannot be held in the blood; it escapes through the skin, and blood
volume drops.

Globulins are another component of blood and one of the plasma proteins. There are alpha,
beta, and gamma globulins. The gamma globulins are immunoglobulins, which are antibodies
that bind to and sometimes destroy antigens (foreign substances). Examples of
immunoglobulin antibodies are IgG (found in high concentration in plasma) and IgA (found
in breast milk, saliva, tears, and respiratory mucus). Other immunoglobulins are IgM, IgD,
and IgE. Immunoglobulins are separated from other plasma proteins by electrophoresis.
In this process, an electrical current passes through a solution of plasma. The different
proteins in plasma separate as they migrate at different speeds to the source of the
electricity.
Plasmapheresis (-apheresis means to remove) is the process of separating plasma from
cells and then removing the plasma from the patient. In plasmapheresis, the entire blood
sample is spun in a centrifuge machine, and the plasma, being lighter in weight than the
cells, moves to the top of the sample.

The composition of blood

BLOOD TYPES

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Transfusions of whole blood (cells and plasma) are used to replace blood lost after injury,
during surgery, or in severe shock. A patient who is severely anemic and needs only red
blood cells will receive a transfusion of packed red cells (whole blood with most of the
plasma removed). Human blood falls into four main types: A, B, AB, and O. These types are
based on the antigens on red blood cells and antibodies found in each person’s serum .

There are harmful effects of transfusing blood from a donor of one blood type into a
recipient who has blood of another blood type. Therefore, before blood is transfused,
both the blood donor and the blood recipient are tested, to make sure that the transfused
blood will be compatible with the recipient’s blood type. During transfusion, if blood is not
compatible, then hemolysis (breakdown of red blood cells) occurs. This may be followed by
excessive clotting in blood vessels (disseminated intravascular coagulation, or DIC), which
is a life-threatening condition.

Besides A and B antigens, many other antigens are located on the surface of red blood
cells. One of these is called the Rh factor (named because it was first found in the blood
of a rhesus monkey). The term Rh positive (Rh+) refers to a person who is born with the
Rh antigen on his or her red blood cells. An Rh negative (Rh−) person does not have the Rh
antigen. In clinical practice, blood types are named to indicate both Rh and ABO antigen
status. If a woman has an A+ (A positive) blood type, for example, this means that she was
born with both A antigen and Rh antigen on her red blood cells. If a man has a B− (B
negative) blood type, this means he was born with the B antigen on his red blood cells but
not Rh antigen.

BLOOD CLOTTING

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Blood clotting, or coagulation, is a complicated process involving many different substances


and chemical reactions. The final result (usually taking less than 15 minutes) is the
formation of a fibrin clot from the plasma protein fibrinogen. The suffix -gen means giving
rise to. Platelets are important in beginning the process following injury to tissues or blood
vessels. The platelets become sticky and collect, or aggregate, at the site of injury. Then,
in combination with tissue and clotting factors, plus calcium, prothrombin, and thrombin,
fibrinogen is converted to fibrin to form a clot. One of the important clotting factors is
factor VIII. It is missing in some people who are born with hemophilia. Other hemophiliacs
are missing factor IX.

The fibrin threads form the clot by trapping red blood cells. Then the clot retracts into a
tight ball, leaving behind a clear fluid called serum. Normally, clots (thrombi) do not form in
blood vessels unless the vessel is damaged or the flow of blood is impeded. Anticoagulant
substances in the blood inhibit blood clotting, so clots do not form. Heparin, produced by
tissue cells (especially in the liver), is an example of an anticoagulant. Other drugs such as
warfarin (Coumadin) are given to patients with thromboembolic diseases to prevent the
formation of clots.

The following are the blood clotting factors:

Factor I, fibrinogen: A protein present in blood plasma; converts to fibrin when blood
clots.

Factor II, prothrombin: A protein in blood plasma that is the inactive precursor of
thrombin.

Factor III, thrombokinase, thromboplastin: An enzyme liberated from blood platelets


that converts prothrombin into thrombin as blood starts to clot.

Factor IV, calcium ion: Ion of calcium; a factor in the clotting of blood

Factor V, prothrombin accelerator, proaccelerin:A coagulation factor.

Factor VII, cothromboplastin, proconvertin, stable factor: A coagulation factor formed


in the kidney under the influence of vitamin K.

Factor VIII, Hemophil, antihemophilic globulin: A coagulation factor (trade name


Hemofil) whose absence is associated with hemophilia A.

Factor IX, Christmas factor: Coagulation factor whose absence is associated with
hemophilia B

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Factor X, prothrombinase: coagulation factor that is converted to an enzyme that


converts prothrombin to thrombin in a reaction that depends on calcium ions and other
coagulation factors.

Factor XI, plasma thromboplastin antecedent: Coagulation factor whose deficiency results
in a hemorrhagic tendency

Factor XII, Hageman factor: Coagulation factor whose deficiency results in prolongation
of clotting time of venous blood.

Factor XIII, fibrinase: In the clotting of blood thrombin catalyzes factor XIII into its
active form (fibrinase) which causes fibrin to form a stable clot.

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VOCABULARY

Agglutination Clumping of recipient's blood cells when incompatible bloods


are mixed.
Albumin Protein found in blood; maintains the proper amount of water
in the blood. Also called serum albumin.
Antibodies Protein substances whose formation by lymphocytes is
stimulated
by the presence of antigens in the body. An antibody then
helps neutralize or inactive the antigen that stimulated its
formation.
Antigens Foreign materials that cause the production of an antibody.
Naturally occurring antigens are the blood type factors A and
B that are present at birth in some individuals.
Basophil White blood cell with large, dark-staining granules that has an
affinity for basic dyes.
Bilirubin Dark green pigment produced from hemoglobin when red blood
cells are destroyed. Bilirubin is concentrated in bile by the
liver and excreted in the feces.
Coagulation The process of blood clotting.
Corpuscle Little body, refers to a blood cell.
Differentiation Change in structure and function of a cell as it matures,
specialization.
Electrophoresis Method of separating substances (such as proteins) by
electrical charge.
Eosinophil White blood cell with dense, reddish granules, having an
affinity for the red acid dye eosin; associated with allergic
reactions.
Erythrocytes A red blood cell. There are about 5 million in a speck of blood
the size of a pinhead.
Erythropoietin A hormone secreted by the kidney to stimulate bone marrow
to make red blood cells.
Ferritin This is the plasma protein that carries iron in bound form
Fibrin Protein threads that form the basis of a blood clot.
Fibrinogen Plasma protein that is converted to fibrin in the clotting
process.
Globin The protein part of hemoglobin.
Globulin Plasma protein; separates into alpha, beta and gamma types by
electrophoresis.
Granulocytes White blood cells with granules; eosinophils, neutrophils and
basophils.

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Heme Iron-containing nonprotein portion of the hemoglobin molecule.


Hemoglobin Blood protein found in red blood cells; enables the red blood
cell to carry oxygen.
Globulin Plasma protein; separates into alpha, beta and gamma types by
electrophoresis.
Granulocytes White blood cells with granules; eosinophils, neutrophils and
basophils.
Heme Iron-containing nonprotein portion of the hemoglobin molecule.
Hemoglobin Blood protein found in red blood cells; enables the red blood
cell to carry oxygen.
Heparin An anticoagulant produced by liver cells and found in blood and
tissues.
Immune reaction Reaction between an antigen and an antibody in which the
antigen is neutralized or inactivated by the antibody.
Immunoglobulin A protein (globulin) with antibody activity.
Leukocyte A white blood cell
Lymphocyte White blood cell (agranulocyte) found in lymph tissue;
produces antibodies.
Macrophages large phagocytes that destroy worn-out red blood cells and
engulf foreign material in body tissues. They are monocytes
that have left the blood and entered tissue spaces.
Megakaryocyte Platelet precursor (forerunner) formed in the bone marrow.
Monocyte White blood cell (agranulocyte) formed in lymph tissue;
phagocyte. Monocytes become macrophages as they leave the
blood and enter body tissues.
Myeloid Derived from bone marrow cells.
Neutrophils White blood cells formed in bone marrow; a phagocyte with
neutral-staining granules; also called a polymorphonuclear
leukocyte.
Plasma: Liquid portion of blood; contains water, proteins,
salts, nutrients, hormones and vitamins.
Plasmapheresis Process of using a centrifuge to separate or remove the
formed elements from the blood plasma. Formed elements are
retransfused into the donor and fresh frozen plasma is used
to replace withdrawn plasma. The procedure may be done to
collect plasma for analysis or therapy.
Platelet Smallest formed element in the blood; a thrombocyte.
Prothrombin Plasma protein; converted to thrombin in the clotting process.
Reticulocyte Developing red blood cell with a network of granules in its
cytoplasm.
Rh factor An antigen normally found on red blood cells of Rh-positive

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individuals.
Serum Plasma minus clotting proteins and cells.
Stem cell A cell in bone marrow that gives rise to different types of
blood cells.
Thrombin An enzyme that helps to convert fibrinogen to fibrin during
coagulation.
Thrombocyte Platelet.
Thromboplastin A clotting factor that, in combination with calcium, promotes
the formation of the fibrin clot.

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SYMPTOMS

1. Fatigue
2. Poor exercise tolerance
3. Palpitations.
4. Shortness of breath
5. Chronic blood loss
6. Brittle nails
7. Pallor: Paleness of skin.
8. Jaundice
9. Lethargy
10. Splenomegaly
11. Weakness
12. Night sweats
13. Bone pain.
14. Dizziness and vertigo.
15. Irregular menstrual cycles.
16. Ecchymosis - bruising
17. Petechiae - tiny red dots on skin or mucous membranes.
18. Hemorrhage.
19. Granulocytosis - It is a condition that results when there is an abundance of
granulocytes in the blood
20. purpura - Hemorrhage (bleeding) into the surface of the skin. The area of skin with
purpura is greater than 3 millimeters in diameter. The appearance of an individual area of
purpura varies with the duration of the lesions. Early purpura is red and becomes darker,
then purple, and brown-yellow as it fades.

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PATHOLOGY

Any abnormal or pathologic condition of the blood generally is referred to as a blood


dyscrasia (disease). The blood dyscrasias discussed in this section are organized in the
following manner: diseases of red blood cells, disorders of blood clotting, diseases of white
blood cells, and disease of the bone marrow.

DISEASES OF RED BLOOD CELLS

Topic Description
Disease Anemia
Definition The condition of having a lower-than-normal number of red
blood cells or quantity of hemoglobin. Anemia diminishes the
capacity of the blood to carry oxygen.
Cause  Anemia occurs when your blood doesn't have enough red
blood cells.
 This can happen if:
 the body doesn't make enough red blood cells
 Bleeding causes to lose red blood cells more quickly than
they can be replaced
 the body destroys red blood cells
o Iron deficiency anemia - A common form of
nutritional disorder, iron deficiency results
in anemia as iron is necessary to
make hemoglobin, key molecule in red blood cells
responsible for the transport of oxygen
o Aplastic anemia - Failure of blood cell production
in the bone marrow.
o Hemolytic anemia - Reduction in red cells due to
excessive destruction.
o Pernicious anemia - Lack of mature erythrocytes
caused by inability to absorb vitamin B12 into the
bloodstream.
o Sickle cell anemia - Hereditary disorder of
abnormal hemoglobin producing sickle-shaped
erythrocytes and hemolysis.
o Thalassemia -Inherited defect in ability to
produce hemoglobin, leading to hypochromia.
Risk factor  A diet lacking in certain vitamins and minerals. A diet
consistently low in iron, vitamin B-12 and folate
increases your risk of anemia.

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 Intestinal disorders - Having an intestinal disorder that


affects the absorption of nutrients in your small
intestine — such as Crohn's disease and celiac disease —
puts you at risk of anemia.
 Menstruation - In general, women who haven't had
menopause have a greater risk of iron deficiency anemia
than do men and postmenopausal women. Menstruation
causes the loss of red blood cells.
 Pregnancy - If pregnant and aren't taking a
multivitamin with folic acid and iron, there is an
increased risk of anemia.
 Chronic conditions.- If patient have cancer, kidney
failure, diabetes or another chronic condition, you could
be at risk of anemia of chronic disease. These conditions
can lead to a shortage of red blood cells.
 Slow, chronic blood loss from an ulcer or other source
within your body can deplete your body's store of iron,
leading to iron deficiency anemia.
 Family history. If your family has a history of an
inherited anemia, such as sickle cell anemia, you also
might be at increased risk of the condition.
 Other factors. A history of certain infections, blood
diseases and autoimmune disorders increases your risk
of anemia. Alcoholism, exposure to toxic chemicals, and
the use of some medications can affect red blood cell
production and lead to anemia.
 Age. People over age 65 are at increased risk of anemia.
Types 1. Iron deficiency anemia
2. Aplastic anemia
3. Hemolytic anemia
4. Pernicious anemia
5. Sickle cell anemia
6. Thalassemia
Signs and symptoms  Dizziness, lightheadness, or feeling like you are about to
pass out
 Fast or unusual heartbeat
 Headache
 Pain, including in your bones, chest, belly, and joints
 Problems with growth, for children and teens
 Shortness of breath
 Skin that’s pale or yellow
 Cold hands and feet

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 Tiredness or weakness
Diagnosis/ Investigation  History collection
 Physical Exam
 Blood test
Treatment  Iron deficiency anemia
o iron supplements
o Diet Change.
o If the cause of iron deficiency is loss of blood —
other than from menstruation — the source of
the bleeding must be located and the bleeding
stopped. This might involve surgery.
 Vitamin deficiency anemias - Treatment for folic acid
and vitamin C deficiency involves dietary supplements
and increasing these nutrients in your diet.
 If your digestive system has trouble absorbing vitamin
B-12 from the food you eat, you might need vitamin B-12
shots. At first, you might have the shots every other
day. Eventually, you'll need shots just once a month,
possibly for life, depending on your situation.
 Anemia of chronic disease
 Focus on treating the underlying disease.
 If symptoms become severe, a blood transfusion or
injections of a synthetic hormone normally produced by
your kidneys (erythropoietin) might help stimulate red
blood cell production and ease fatigue.
 Aplastic anemia
o blood transfusions
o bone marrow transplant
 Hemolytic anemias -Managing hemolytic anemias
includes avoiding suspect medications, treating
infections and taking drugs that suppress your immune
system, which could be attacking your red blood cells.
 Depending on the cause or your hemolytic anemia, you
might be referred to a heart or vascular specialist.
 Sickle cell anemia -
o Oxygen
o pain relievers
o oral and intravenous fluids to reduce pain and
prevent complications
o blood transfusions
o folic acid supplements
o Antibiotics.

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o A cancer drug called hydroxyurea (Droxia,


Hydrea, Siklos) also is used to treat sickle cell
anemia.
 Thalassemia
o Most forms of thalassemia are mild and require
no treatment
o More severe forms of thalassemia generally
require
 blood transfusions
 folic acid supplements
 Removal of the spleen, or a blood and bone
marrow stem cell transplant.
Complication  Severe fatigue - Severe anemia can make you so tired
that you can't complete everyday tasks.
 Pregnancy complications - Pregnant women with folate
deficiency anemia may be more likely to have
complications, such as premature birth.
 Heart problems.- Anemia can lead to a rapid or irregular
heartbeat (arrhythmia). When you're anemic your heart
must pump more blood to make up for the lack of oxygen
in the blood. This can lead to an enlarged heart or heart
failure.
 Death - Some inherited anemias, such as sickle cell
anemia, can lead to life-threatening complications.
Losing a lot of blood quickly results in acute, severe
anemia and can be fatal.

Topic Description
Disease Polycythemia vera
Definition Overproduction (proliferation) of red blood cells due to bone
marrow disease (myeloproferative disorder).
Cause  It occurs when a mutation in a gene causes a problem
with blood cell production. The mutation that causes
polycythemia vera is thought to affect a protein switch
that tells the cells to grow. Specifically, it's a mutation
in the protein Janus kinase 2 (JAK2).
Risk factor  Polycythemia vera can occur at any age, but it's more

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common in adults older than 60.


Signs and symptoms  Many people with polycythemia vera don't have signs or
symptoms. Others might have:
o Itchiness, especially following a warm bath or
shower
o Headache
o Dizziness
o Bleeding or bruising, usually minor
o Weakness
o Fatigue
o Blurred vision
o Excessive sweating
o Painful swelling of one joint, often the big toe
o Shortness of breath
o Numbness, tingling, burning or weakness in your
hands, feet, arms or legs
o A feeling of fullness or bloating in your left
upper abdomen due to an enlarged spleen
o Fevers
o Unexplained weight loss
Diagnosis/ Investigation  Blood tests - If you have polycythemia vera, blood tests
might reveal:
o An increase in the number of red blood
cells and, in some cases, an increase in platelets
or white blood cells
o Increased percentage of red blood cells that
make up total blood volume (hematocrit
measurement)
o Elevated levels of the iron-rich protein in red
blood cells that carries oxygen (hemoglobin).
o Very low levels of a hormone that stimulates
bone marrow to produce new red blood cells
(erythropoietin)
 Bone marrow aspiration or biopsy
Treatment  Phlebotomy
 Low-dose aspirin
 hydroxyurea (Droxia, Hydrea), a pill that lowers red
blood count and eases symptoms.
 interferon alfa (Intron A), helps the immune system cut
back on making blood cells.
 ruxolitinib (Jakafi) is approved for use in people who
aren’t helped by hydroxyurea or can’t handle its side

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effects.
Complication  Blood clots. Increased blood thickness and decreased
blood flow, as well as abnormalities in your platelets,
increase your risk of blood clots.
 Enlarged spleen (splenomegaly).
 Problems due to high levels of red blood cells.

Topic Description
Disease Hemochromatosis
Definition An inherited disorder characterized by abnormally high
absorption of iron by the intestinal tract, resulting in excessive
storage of iron, particularly in the liver, skin, pancreas, heart,
joints, and testes.
Cause  It can be caused by disorders such as thalassemia (an
inherited blood disorder), anemia, chronic alcoholism,
and other conditions.
Risk factor  alcoholism.
 a family history of diabetes, heart disease, or
liver disease.
Signs and symptoms  Pain in your joints, especially your knuckles
 Feeling tired
 Unexplained weight loss
 Skin that has a bronze or gray color
 Pain in your belly
 Loss of sex drive
 Loss of body hair
 Heart flutter
 Foggy memory
Diagnosis/ Investigation  History Collection
 Physical exam
 Liverbiopsy
 MRI
 Blood test
o Transferrin saturation. This shows how much iron
is stuck to transferrin, a protein that carries
iron in blood.
o Serum ferritin. This test measures the amount
of ferritin, a protein that stores iron, in blood.
Treatment  Phlebotomy is the removal of blood from body. Patient
may need phlebotomy on a regular basis to remove

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excess iron.
Complication  Liver cirrhosis.
 Hepatocellular carcinoma.
 Congestive heart failure.
 Cardiac arrhythmias.
 Diabetes mellitus.
 Hypogonadism.
 Impotence.

DISORDERS OF BLOOD CLOTTING

Topic Description
Disease Hemophilia
Definition Hemophilia is one of a group of inherited bleeding
disorders that cause abnormal or exaggerated bleeding and
poor blood clotting.
Cause  Hemophilia is a bleeding disorder usually caused by
defects (mutations) in the genes that code for the
blood-clotting factors VIII, IX or XI.
Risk factor  Family history
 Male sex
 Risk Factors for Acquired Hemophilia[5][6][7][8]
 Malignancy
 Pregnancy
 Autoimmune disorders (SLE, rheumatoid arthritis)
 Infections (Hepatitis C, AIDS)
 Drugs (Interferon-alpha)
Types  Hemophilia A is caused by a deficiency of clotting
Factor VIII
 Hemophilia B (also called Christmas disease) results
from a deficiency of Factor IX.
Signs and symptoms  Blood in the urine.
 Blood in the stool.
 Deep bruises.
 Large, unexplained bruises.
 Excessive bleeding.
 Bleeding gums.
 Frequent nosebleeds.
 Pain in the joints.
Diagnosis/ Investigation  Family History

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 Blood Test
Treatment  coagulation factor replacement therapy
Complication  Deep internal bleeding.
 Bleeding that occurs in deep muscle can cause your limbs
to swell. The swelling may press on nerves and lead to
numbness or pain.

DISEASES OF WHITE BLOOD CELLS

Topic Description
Disease Leukemia
Definition It is the general term used to describe a group of malignant
disorders affecting the blood and blood forming tissues of the
bone marrow , lymph system and spleen
Cause  The exact cause of leukemia is not known, but it is
thought to involve a combination of genetic and
environmental factors.
Risk factor  Exposure to cancer-causing agents
 Smoking
 History of radiation therapy or chemotherapy.
 Myelodysplastic syndromes.
 Rare genetic syndromes.
 Family history.
Types  Acute lymphocytic leukemia (ALL). This is the most
common form of childhood leukemia. It can spread to
your lymph nodes and central nervous system.
 Acute myelogenous leukemia (AML). This is the second
most common form of childhood leukemia and one of the
most common forms for adults.
 Chronic lymphocytic leukemia (CLL). This is the other
most common form of adult leukemia. Some kinds of CLL
will be stable for years and won’t need treatment. But
with others, your body isn’t able to create normal blood
cells, and you’ll need treatment.
 Chronic myelogenous leukemia (CML). With this form,
you might not have noticeable symptoms. You might not
be diagnosed with it until you have a routine blood test.
People 65 and older have a higher risk of this type.
Signs and symptoms  Weakness or fatigue
 Bruising or bleeding easily

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LOM Hematology Notes

 Fever or chills
 Infections that are severe or keep coming back
 Pain in your bones or joints
 Headaches
 Vomiting
 Seizures
 Weight loss
 Night sweats
 Shortness of breath
 Swollen lymph nodes or organs like your spleen
Diagnosis/ Investigation  Blood tests -A complete blood count (CBC) looks at the
number and maturity of different types of blood cells. A
blood smear looks for unusual or immature cells.
 Bone marrow biopsy
 Spinal tapCT
 MRI
 PET scans
Treatment  Chemotherapy
 Radiation
 Biologic therapy
 Targeted therapy
 Stem cell transplant
 Surgery
Complication 

Topic Description
Disease Mononucleosis
Definition Infection with the Epstein-Barr virus (EBV, human herpesvirus
4, HHV-4) in which there is an increase of white blood cells
that have a single nucleus (monocytes).
Cause  Epstein-Barr virus (EBV)
Risk factor  Sharing drinks, toothbrushes, or anything that touches
the mouth and saliva.
 Sexual contact.
 Having a blood transfusion.
 Receiving a transplanted organ.
Signs and symptoms  Fatigue
 Sore throat, perhaps misdiagnosed as strep throat, that
doesn't get better after treatment with antibiotics
 Fever

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LOM Hematology Notes

 Swollen lymph nodes in your neck and armpits


 Swollen tonsils
 Headache
 Skin rash
 Soft, swollen spleen
Diagnosis/ Investigation  Physical exam
 Antibody test
 WBC Count
Treatment  Nonsteroidal anti-inflammatory drug
 Relieves pain, decreases inflammation and reduces
fever.
 Analgesic
 Relieves pain.
 Fluid replacement
 Supplies or replenishes water and nutrients in the body.
Complication  Hepatitis
 Jaundice
 Anemia
 Thrombocytopenia
 Heart problems
 Swollen tonsils

DISEASE OF BONE MARROW CELLS

Topic Description
Disease Multiple myeloma
Definition A bone marrow cancer that involves a type of white blood cell
called a plasma (or myeloma) cell. The tumor cells in myeloma
can form a single collection (plasmacytoma) or many tumors
(multiple myeloma).
Cause  Unknown
Risk factor  Age
 Race
 Sex
 Family history
 Obesity
Signs and symptoms  Fatigue - As myeloma cells replace bone marrow, body
has to work much harder with fewer disease-fighting
cells, and tire more easily.
 Bone problems. Myeloma can prevent body from making
new bone cells, causing problems like bone pain,

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LOM Hematology Notes

weakened bones, and broken bones.


 Kidney problems. Myeloma cells produce harmful
proteins that can cause kidney damage and even failure.
 Low blood counts. Myeloma cells crowd out healthy blood
cells, leading to low red blood counts (anemia) and low
white blood cells (leukopenia). Unhealthy blood cell
levels make it harder to fight infections.
 Frequent infections. Fewer antibodies in your blood
make fighting infections more difficult.
 nausea
 weight loss
 constipation
 loss of appetite
 weakness or loss of feeling in your legs
 swelling in your legs
 increased thirst
 frequent urination
 dizziness
 confusion
 pain, especially in your back or belly
Diagnosis/ Investigation  Blood test
 Urine Test - Bence Jones proteins
 MRI
 CT
Treatment  Biological
 Chemotherapy
 Corticosteroids
 Bone marrow transplant
Complication  Frequent infections
 Anemia
 Bone problems
 Reduced kidney function

DIAGNOSTIC INVESTIGATIONS/LABORATORY TESTS AND CLINICAL


PROCEDURES

LABORATORY TESTS

Antiglobulin test (Coombs' test):

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LOM Hematology Notes

Demonstrates whether the patient's erythrocytes are coated with antibody and is useful
in determining the presence of antibodies in infants of Rh women or in patients with
autoimmune hemolytic anemia.

Bleeding time:
Time it takes for a small puncture wound to stop bleeding.
Normal time is 8 minutes or less. Bleeding time is prolonged with use of aspirin and in
platelet disorders such as thrombocytopenia.

Complete blood count (CBC):


This usually includes the following studies: red blood cell count, white blood cell count
(with differential), platelet count, hemoglobin test, hematocrit, and red cell indices, MCV,
MCH, and MCHC.

Coagulation (clotting) time:


Time required for venous blood to clot in a test tube. Normal time is less than 15 minutes.

Erythrocyte sedimentation rate (sed rate):


Speed at which erythrocytes settle out of plasma. Venous blood is collected, anticoagulant
is added and the blood is placed in a tube in a vertical position. The distance that the
erythrocytes fall in a given period of time is the sedimentation rate. The rate is altered in
disease conditions, such as infections, joint inflammation and tumor that increase the
immunoglobulin content in blood.

Hematocrit:
Percentage of erythrocytes in a volume of blood. A sample of blood is spun in a centrifuge
so that the erythrocytes fall to the bottom of the sample.

Hemoglobin test:
Total amount of hemoglobin in a sample of peripheral blood.

Partial thromboplastin time:


Measures the presence of factors that act at early points in the coagulation pathway.

Platelet count:
Number of platelets per cubic millimeter.

Prothrombin time:
This is a test of the ability of blood to clot. It measures the time elapsed between the
addition of calcium to a plasma sample and the appearance of a visible clot. The test is
used to follow patients taking blood thinners (anticoagulants).

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LOM Hematology Notes

Red blood cell count (RBC):


Number of erythrocytes per cubic millimeter of blood. The normal number is 4-6 million
per cubic millimeter.

Red blood cell morphology:


A stained blood smear is examined to determine the shape or form of individual red cells.
The presence of anisocytosis, poikilocytosis, sickle cells, and hypochromia can be noted.

White blood cell count:


This test determines the numbers of different types of leukocytes (immature and mature
forms). The cells are stained and counted under a microscope by a technician. A minimum
of 100 cells is counted and the percentages for neutrophils, lymphocytes, monocytes,
basophils, and eosinophils are given. The term shift to the left is used to describe a
condition in which there is an increase in immature neutrophils and a decrease in mature
forms in the blood.

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LOM Hematology Notes

CLINICAL PROCEDURES

Apheresis:
Separation of blood into its parts. It is performed to remove toxic substances or
autoantibodies from the blood or to harvest blood cells.
Plateletpheresis and plasmapheresis are examples.

Blood transfusion:
In this procedure, whole blood or cells are taken from a donor and after appropriate
testing to assure a close match of red cell or platelet type, the whole blood or cells are
infused into a patient. Prior to transfusion, tests are performed to assure that the
specimen is free from hepatitis or acquired immunodeficiency syndrome virus. Autologous
transfusion is the collection and later reinfusion of a patient's own blood or blood
components.

Bone marrow biopsy:


A needle is introduced into the bone marrow cavit and a small amount of marrow is
aspirated. The marrow is then examined under the microscope. This procedure is helpful
in the diagnosis of blood disorders such as anemia, cytopenias and leukemia.

Bone marrow transplant:


Bone marrow cells from a donor whose tissue and blood cells closely match those of the
recipient are infused into a patient with leukemia or aplastic anemia.

ABBREVIATIONS

ABO: Three main blood groups

ALL: Acute lymphocytic leukemia

AML: Acute myelogenous leukemia

Baso: Basophils

BMT: Bone marrow transplant

CBC: Complete blood count

CLL: Chronic lymphocytic leukemia

CML: Chronic myelogenous leukemia

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LOM Hematology Notes

Diff.: Differential count (white blood cells)

Eos: Eosinophils

ESR: Erythrocyte sedimentation rate

G-CSF: Granulocyte colony-stimulating factor

GM-CSF: Granulocyte macrophage colony-stimulating factor

Hct: Hematocrit

IgA, IgD, IgE, IgG, IgM: Immunoglobulins

Lymphs: Lymphocytes

MCH: Mean corpuscular hemoglobin

MCHC: Mean corpuscular hemoglobin concentration

MCV: Mean corpuscular volume

Mono: Monocyte

Poly: Polymorphonuclear leukocyte

PMN, PMNL: Polymorphonuclear leukocyte

PT: Prothrombin time

PTT: Partial prothrombin time

RBC: Red blood cell

Sed rate: Erythrocyte sedimentation rate

Segs: segmented, mature white cells

WBC: White blood cell

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LOM Hematology Notes

DRUGS

Drugs for anemia

 Anadrol (oxymetholone)
 Cytoxan (cyclophosphamide)
 Epogen (epoetin alfa)
 Feosol (ferrous sulfate)
 Fumerin (ferrous fumarate)
 Procrit (epoetin alfa)
 Sytobex (cyanocobalamin)

Drugs for factor IX deficiency

 AlphaNine SD (factor IX complex)


 BeneFix (factor IX complex)
 Hemonyne (factor IX complex)
 Profilnine (factor IX complex)
 Proplex (factor IX complex)

Drugs for factor VIII deficiency (hemophilia)

 Alphanate (antihemophilic factor)


 Hemofil (antihemophilic factor)
 Monarc-M (antihemophilic factor)

Names of a few drugs for hematologic disorders

 Acthar (corticotropin)
 Aristocort (triamcinolone)
 Atolone (triamcinolone)
 Decadron (dexamethasone)
 Dexasone (dexamethasone)
 Kenacort (triamcinolone)
 Medrol (methylprednisolone)

Drugs for hemophilia

 Hyate C (antihemophilic factor porcine)


 Stimate (desmopressin acetate)

Drugs for iron deficiency anemia

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LOM Hematology Notes

 Ferrlecit (ferric gluconate)

Drugs for lymphomas

 Adriamycin (doxorubicin)
 Blenoxane (bleomycin)
 Platinol (cisplatin)
 Cytoxan (cyclophosphamide)
 Matulane (procarbazine)
 Rituxan (rituximab)

Drugs for myasthenia gravis

 Enlon (edrophonium)
 Reversol (edrophonium)
 Tensilon (edrophonium)
 Mestinon (pyridostigmine)
 Regonol (pyridostigmine)

Drugs for thrombocytopenic purpura

 Oncovin (vincristine)
 Vincasar PFS (vincristine)

Drugs for thrombocytopenia

 Ceredase (alglucerase)
 Neumega (oprelvekin)

Drugs for thrombocytosis

 Droxia (hydroxyurea)
 Hydrea (hydroxyurea)
 Mylocel (hydroxyurea)

Drugs for thromboembolic disorders/anticoagulants

 Abbokinase (urokinase)
 Activase (alteplase)
 Coumadin (warfarin)
 Fragmin (dalteparin)

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LOM Hematology Notes

 Hep-Lock (heparin)
 Lovenox (enoxaparin)

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