An-Najah National University

Faculty of Medicine
Division of Physiology, pharmacology and Toxicology
Medical physiology one
7102201

Dr. Heba Salah, PhD

Dr. Azza Islem, MD, PhD
Dr. Abdalrahman Al Aqra’a, MD, Msc.

Hematology
 Blood components
• Blood is a mixture of cellular components
suspended in a fluid called plasma.

• Plasma carries blood cells, proteins, nutrients,

metabolic wastes, and other molecules being
transported around the body.

• Hematocrit: % of erythrocytes volume to the

total blood volume.

• Normal hematocrit values in healthy males is

47% ± 5% and in females it is 42% ± 5%

• Normal pH between 7.35 and 7.45

 Blood components

Functions of Plasma:
1. Transport of hormones,
vitamins, minerals, and
drugs.
2. Control of capillary
permeability and
maintenance of blood
volume
3. Blood coagulation
4. Immune function
 Blood components
Plasma
• Consists of a number of inorganic and organic substances dissolved in water.
• Plasma components : water, organic solutes and minerals
1. Water: is the major component (90%)
2. Organic solutes, including proteins, nutrients, metabolic waste products,
and hormones (example of these substances glucose, amino acids, urea,
creatinine, and uric acid, measurement of these substances in blood are
useful in clinical diagnosis

• The plasma proteins constitute most of the plasma solutes, by weight.

• They are responsible for the blood osmotic pressure, why and what is the
importance of this pressure?.
• Plasma proteins can be classified into three broad groups: the albumins, the
globulins, and fibrinogen.

Serum: the composition of serum is identical to that of plasma except that it

contains none of the clotting proteins
 Blood components

3. Inorganic component; Mineral electrolytes: blood contains many

more ions than protein molecules

• Na+, K+, Ca2+, Mg2+, Cl-, SO4-, HCO3

• Maintain plasma osmotic pressure and pH
 Blood components
1. Red blood cells
2. White blood cells
3. Platelets
 Erythrocytes (red blood cells)
Functions of the erythrocytes:
1. Oxygen and carbon dioxide transport.
2. Transport hemoglobin
3. They are the acid-base buffer system of the blood since they contain hemoglobin and
large quantity of carbonic anhydrase enzyme

Characteristics of RBCs:
◦ Biconcave disk in shape with a flexible membrane

◦ They have a large surface area which favors diffusion

◦ The RBC is a bag that can be deformed into almost any shape
The above two properties is due to the fact that RBCs have a great excess of cell
membrane for the quantity of material inside
 Erythrocytes (red blood cells)
Characteristics of RBCs:
• Mature RBCs have no nucleus nor organelles: No mitochondria, No DNA, RNA
(so no division of mature RBCs)

• Mature RBCs have cytoplasmic enzymes:

1. Glycolytic enzymes

2. Carbonic anhydrase enzyme

3. Enzymes for the maintenance of

A. Pliability of the cell membrane
B. Membrane transport of ions
C. The iron of the cells’ hemoglobin in the ferrous form rather than ferric form

4. Enzymes for the prevention of oxidation of the proteins in the red cells
 Erythrocytes (red blood cells)
Characteristics of RBCs:
• Concentration of RBCs in the blood: the average number of red blood cells per
cubic millimeter is 5,200,000 (±300,000) in healthy men, and 4,700,000
(±300,000) in women. The number increases in person living at high altitudes

• Quantity of hemoglobin in the cells: RBCs have the ability to concentrate

hemoglobin in the cell fluid up to about 34 grams in each 100 milliliters of
cells. This percentage decreases when the hemoglobin formation is deficient,
and the volume of the red cell may also decrease because of diminished
hemoglobin to fill the cell (microcytic anemia).

• RBCs are synthesized in red bone marrow by the process called Erythropoiesis.

• Erythropoietin (hormone from the kidneys) triggers differentiation of stem cells

to erythrocytes

• RBCs have a short life span and only last about 120 days.

• They are filtered by the spleen and the liver.

 Erythrocytes (red blood cells)
erythropoiesis
Areas of the body that produce red blood cells
1. Yolk sac: In the early weeks of embryonic life. Cells:
primitive, nucleated RBCs

2. Liver (the main one), spleen and lymph nodes: middle

trimester of gestation

3. Exclusively in bone marrow:

• during the last month of gestation and after birth.
• The bone marrow of essentially all bones produces red
blood cells until the age of 5 years .
• Beyond the age of 20 years, most red cells continue to be
produced in the marrow of the membranous bones, such as
the vertebrae, sternum, ribs, and ilia.
• With age, the bone marrow becomes less productive
 Erythrocytes (red blood cells)
erythropoiesis

• The pluripotential hematopoietic stem cell

are the source of all blood cells

• During cell division, a small portion of

these cells remains exactly like the
original pluripotential cells and is retained
in the bone marrow to maintain a supply
of these, although their numbers diminish
with age.
 Erythrocytes (red blood cells)
erythropoiesis
Growth inducers and differentiation inducers
• Multiple proteins called growth inducers control the growth and reproduction of
the different stem cells.

• Differentiation inducers cause one type of committed stem cell to differentiate

one or more steps toward a final adult blood cell

• Formations of growth and differentiation inducers are controlled by factors out

side bone marrow (example: low oxygen, infection)
 Erythrocytes (red blood cells)
erythropoiesis
Stages of differentiation of red blood cells
• Reticulocytes do not have nucleus or ER but it still
contains a small amount of basophilic material,
consisting of remnants of the Golgi apparatus,
mitochondria, and a few other cytoplasmic organelles.

• The reticulocytes pass from the bone marrow into the

blood capillaries by diapedesis (squeezing through the
pores of the capillary membrane), then the remaining
basophilic material disappears, and the cell is then a
mature erythrocyte.

• Reticulocyte cells have a short life, and in normal blood

they account only for less than 1% of all RBC

• Reticulocyte count increases if there is increased RBCs

production, examples?
 Erythrocytes (red blood cells)
erythropoiesis

Requirements for Erythrocyte Production

• Erythropoietin regulates the rate of production of RBCs

• Iron: Component of hemoglobin (heme portion)
• Folic acid: Necessary for DNA replication, thus cell proliferation
• Vitamin B12: Necessary for DNA replication, thus cell proliferation
 Hemoglobin
Normal hemoglobin content of blood:
Men: 13–18 gram / dL
Women: 12–16 gram / dL

 Hemoglobin is made up of the red

heme pigment bound to the protein
globin.

 Globin consists of four polypeptide

chains: two alpha (α) and two beta (β)
—each binding a ring-like heme

 Each heme group bears an atom of

iron in its center

15
 Red Blood Cells
Role of erythropoietin in the regulation of red blood cell production

• The total mass of red blood cells is regulated within narrow

limits that there is adequate red cells to transport oxygen but
not too much RBCs, why?

• Tissue oxygenation is the most essential regulator of RBCs

production.

• Erythropoietin is the principal stimulus for red blood cell

production in low oxygen states.

• Erythropoietin is a circulating hormone, mainly produced in

the kidney, and small amount of it is formed in the liver.

• Erythropoietin production is decreased during renal

impairment

• When the RBCs production increases, the hematocrit

increases
 Red Blood Cells
Role of erythropoietin in the regulation of red blood cell production

Effect of erythropoietin in erythrogenesis

1. Erythropoietin stimulates the production of
proerythroblasts from hematopoietic stem cells

2. it speeds up the rate of differentiation through

the different erythroblastic stages.
 Red Blood Cells
Role of erythropoietin in the regulation of red blood cell production
 Red Blood Cells
Formation of Hemoglobin
• Synthesis of hemoglobin begins in the
proerythroblasts and continues even into the
reticulocytes until they become mature
erythrocytes.

• There are four types of hemoglobin subunits:

Alpha, beta, gamma, and delta chains.

• The most common form of hemoglobin in the

adult human being is hemoglobin A (α2β2)

• Through the heme group, each hemoglobin

molecule can bind loosely with four molecule of
oxygen.

• The types of hemoglobin chains in the

hemoglobin molecule determine the binding
affinity of the hemoglobin for oxygen.
Normal and variant hemoglobin at birth and in older children
 Red Blood Cells

Iron metabolism
Iron is important for the formation of many essential elements in the body
(e.g., hemoglobin, myoglobin, cytochromes, cytochrome oxidase,
peroxidase, catalase).

The total quantity of iron in the body averages 4 to 5 grams:

• 65 % of iron is in the form of hemoglobin
• 4 % is in the form of myoglobin
• 1 % is in the form of the various heme compounds that promote
intracellular oxidation,
• 0.1 percent is combined with the protein transferrin in the blood
plasma
• 15 to 30 percent is stored as ferritin mainly in liver parenchymal cells
and in the reticuloendothelial system of the bone marrow
 Red Blood Cells
Iron metabolism
Absorption of iron from the intestinal tract
• Absorption of iron occurs from all parts of the small intestine.

• The free iron and certain iron compounds, such as hemoglobin

and myoglobin from meat, two of the most important sources
of iron in the diet, bind with apotransferrin forming the
transferrin

• By pinocytosis, the transferrin molecule is absorbed into the

epithelial cells and later released into the blood capillaries in
the form of plasma transferrin.

• Iron absorption is a slow, but it depends on the amount of

stored iron

• The transferrin molecule binds strongly with receptors in the

cell membranes of erythroblasts in the bone marrow leading to
endocytosis
 Red Blood Cells
Iron Storage

1. In the form of ferritin (storage iron): In the cell cytoplasm, iron

combines mainly with a protein, apoferritin, to form ferritin. Ferritin
particles are so small and dispersed that they usually can be seen in
the cell cytoplasm only with the electron microscope

2. In the form of hemosiderin: an extremely insoluble form.

Hemosiderin forms large particles that can be observed
microscopically

• Iron deficiency anemia: microcytic hypochromic anemia

 Red Blood Cells

Filtering and Destruction of Erythrocytes

• RBCs have a short life span and only last about 120 days

• When the RBCs become older, the metabolic systems become progressively less
active and the cells become more and more fragile

• The spleen filters and removes old erythrocytes, and the liver metabolizes
byproducts from breakdown of erythrocytes.

• Spleen macrophages filter blood by phagocytosis of old fragile RBCs.

 Red Blood Cells

Filtering and Destruction of Erythrocytes

• The hemoglobin released from destructed RBCs is phagocytized

almost immediately by macrophages in many parts of the body,
but especially by the Kupffer cells of the liver and macrophages
of the spleen and bone marrow

• Iron is recycled for synthesis of hemoglobin or storage

• In the microphages, the hemoglobin molecule is converted

through a series of stages, into the bile pigment bilirubin, which
will be exerted by the stool or the urine
Fate and Destruction of Erythrocytes

26
 Fate and
Destruction of
Erythrocytes
 Red Blood Cells
Role of vitamin B12 and folic acid in the red blood cell production

• Vitamin B12 and folic acid are important for final maturation of the red blood cells.

• These two vitamins are essential for the synthesis of DNA.

• Deficiency of either vitamin B12 or folic acid causes maturation failure in the process of
erythropoiesis

• The erythroblastic cells of the bone marrow fail to proliferate rapidly, and produce mainly
larger than normal red cells called macrocytes

• Macrocytes are irregular, large, oval cells with weak membrane, they are capable of
carrying oxygen normally, but they have a short life (one-half to one-third normal)

• Megablastic anemia
 Red Blood Cells
Role of vitamin B12 and folic acid in the red blood cell production
 Anemias
deficiency of hemoglobin in the blood, which can be caused by either too few red blood cells or
too little hemoglobin in the cells.
 Anemias
1. Blood Loss Anemia:
• After hemorrhage , replaces the fluid portion of the plasma in 1 to 3 days.
• cell concentration usually returns to normal within 3 to 6 weeks.
• In chronic blood loss - microcytic,hypochromic anemia

2. Aplastic Anemia: Bone marrow aplasia means lack of functioning bone marrow.

3. Megaloblastic Anemia:
• Deficiency of vitamin B12, folic acid, and intrinsic factor from the stomach mucosa
• Atrophy of the stomach mucosa, as occurs in pernicious anemia, or loss of the entire stomach after
surgical total gastrectomy

4. Hemolytic Anemia:
• Hereditary spherocytosis: the red cells are very small and spherical rather than being biconcave discs.
• sickle cell anemia: the cells have an abnormal type of hemoglobin called hemoglobin S, containing faulty
beta chains in the hemoglobin molecule
• Erythroblastosis fetalis: Rh-positive red blood cells in the fetus are attacked by antibodies from an Rh-
negative mother.
 Polycythemia
Increase production of RBCs

Secondary polycythemia:
• Hypoxia of the tissues (high altitudes, or cardiac failure), extra RBCs are formed and the red
cell count commonly rises to 6 to 7 million/mm3, about 30 percent above normal.

• A common type of secondary polycythemia, called physiologic polycythemia, occurs in people

who live at high altitude

Polycythemia vera (erythremia):

• Due to genetic aberration in the hemocytoblastic cells, the blast cells continue to proliferate
without stopping.

• It usually causes excess production of white blood cells and platelets as well. The hematocrit,
blood volume, and the viscosity of the blood all increased in polycythemia
 Effects of anemia and polycythemia on function of
the circulatory system

• Increased cardiac output

Effects of • Increased pumping workload of the heart
• during exercise, extreme tissue hypoxia results, and acute cardiac
Anemia failure ensues

• increased viscosity of the blood , blood flow through the peripheral

blood vessels is sluggish --- decreases the rate of venous return to the
Effect of heart.
• Conversely, the blood volume is greatly increased in polycythemia,
Polycythemia which tends to increase venous return
• cardiac output in polycythemia is not far from normal
 Leukocytes
 Leukocytes (white blood cells) function in the defense of the body.

 Human blood contains 4000–11,000 white blood cells per microliter

 They can be divided into granulocytes and agranulocytes.

– Granulocytes—cytoplasmic granules (polymorphonuclear leukocytes, PMNs)
the most numerous
 Neutrophils
 Eosinophils
 Basophils
– Agranulocytes—no cytoplasmic granules
 Monocytes have abundant agranular cytoplasm and kidney-shaped nuclei
 Lymphocytes have large round nuclei and scanty cytoplasm
Leukocytes functions
Hemostasis
 Hemostasis

• Hemostasis is the physiological mechanisms that stop bleeding

• Hemostasis is achieved by:

1. Vascular spasm
2. Formation of platelet plug
3. Blood coagulation
4. Growth of fibrous tissue into
the blood clot to close the hole
in the vessel
Hemostasis
Sequence of events leading to
formation of a platelet plug and
vasoconstriction following damage
to a blood vessel wall
 Hemostasis
Vascular spasm
• Vasoconstriction minimize blood loss until the other components of
hemostasis start working (this is a protective mechanism to maintain BP).

• The underlying mechanisms

1. The direct damage to the vascular wall causes local myogenic spasm:
the major contributors
2. The traumatized tissues and blood platelets releases local autacoid
factors such as thromboxane A2 released from the platelets
3. Stimulation of the pain nerve endings and other sensory receptor in the
traumatized area initiates nervous reflexes that lead to vasoconstriction

• The degree of the spasm is directly related to the severity of the trauma.

• The spasm can last for many minutes or even hours

 Hemostasis
Formation of platelets plug

• Shape: minute discs 1 to 4 micrometers in diameter, with no

nucleus

• Source: megakaryocytes
 Megakaryocytes is extremely large cells of the hematopoietic
cells in the marrow.
 Megakaryocytes fragment into the minute platelets either in
the bone marrow or soon after entering the blood, especially in
the capillaries.

• Half life : 8-12 days

• Site of elimination: by tissue macrophage system specially in the

spleen

• The normal concentration in the blood : 150,000 -300,000 per

microliter
 Hemostasis
Formation of platelets plug

In the cytoplasm of the platelets:

1. Contractile proteins: actin, myosin molecules , and thrombosthenin.

2. Residuals of the endoplasmic reticulum and the Golgi apparatus for enzymes synthesis
and storage of large quantities of calcium ions

3. Mitochondria and enzyme systems for forming ATP and ADP

4. Enzyme systems for the synthesis of prostaglandins

5. Fibrin-stabilizing factor

6. A growth factor for vascular endothelial cells, vascular smooth muscle cells, and
fibroblasts, this to allow tissue repair of the damaged vascular walls.
 Hemostasis
Formation of platelets plug

The cell membrane of the platelets has:

1. A coat of glycoproteins (glycocalyx) that normally prevents the

adherence of the platelets to normal endothelium by expulsion.
During tissue injury, this coat causes adherence of the platelets to
the exposed collagen from the injured endothelium.

2. Large amounts of phospholipids that activate multiple stages in the

blood-clotting process.
Platelets
plug
 Platelets plug
• Steps in the formation of platelets plug:

1. Platelets adhesion: the contact of the platelets with the damaged endothelium
make them sticky, they adhere to collagen in the tissues and to von Willebrand
factor protein that leaks into the traumatized tissue from the plasma

2. Changing the shape of the platelets: They begin to swell; they assume irregular
forms with numerous irradiating pseudopods protruding from their surfaces

3. Platelets activation and contraction causes the release of granules that contain
multiple active factors; The ADP and thromboxane causes recruitment of the
nearby platelets (positive feedback) to activate them as well, and these platelets
adhere to the original activated platelets, forming the platelets plug

• Importance of formation of platelet plug: many very small vascular holes develop
throughout the body is often closed by a platelet plug rather than by a blood clot
 Hemostasis
Formation of a blood clot

• Clotting = coagulation
• Blood converted into solid gel called clot or thrombus

• Occurs around platelet plug

• Dominant hemostatic defense mechanism

• Factors involved in blood coagulation are

1. Factors that promote coagulation; procoagulants
2. Factors that inhibit coagulation; anticoagulants.

• The balance between these two groups determine

when blood will coagulate.
Blood coagulation

46
 Blood coagulation
Clotting cascade

• Once injury happened, clotting

begins by the two pathways

• The extrinsic pathway can be

explosive

• The intrinsic pathway is much

slower to proceed compared to
extrinsic one

• Calcium is required in multiple

steps of clotting
 Blood coagulation

There are three essential steps in the clot formation

1. Formation of a complex of activated substances collectively called
prothrombin activator
2. The conversion of prothrombin into thrombin by the prothrombin
activator
3. The conversion of fibrinogen into fibrin fibers by the thrombin,
and fibrin then enmesh platelets, blood cells, and plasma to form the
clot
 Homeostasis

Initiation of coagulation: formation of prothrombin activator

• The mechanisms that initiate this first step are :
1. trauma to the vascular wall and adjacent tissues
2. trauma to the blood
3. contact of the blood with damaged endothelial cells or with collagen

• Prothrombin activator is considered to be formed in two ways

1. The extrinsic pathway that begins with trauma to the vascular wall and
surrounding tissues
2. The intrinsic pathway that begins in the blood itself

• We have to know that the two ways interact constantly with each other, and in both
ways different clotting factors are involved, and most of these factors inactive forms
of proteolytic enzymes
 Hemostasis

• The rate-limiting factor in causing blood

coagulation is usually the formation of
prothrombin activator since the steps after
normally occur rapidly to form the clot

• Blood clot is composed of a meshwork of fibrin

fibers running in all directions and entrapping
blood cells, platelets, and plasma. The fibrin
fibers also adhere to damaged surfaces of blood
vessels.
 Hemostasis

Prothrombin and Thrombin:

• Prothrombin is a plasma protein, an alpha2-globulin, which is continuously formed
by the liver, and continuously used in clotting.

• Prothrombin is an unstable protein that can split easily into smaller compounds, one
of which is thrombin.

• Thrombin is an enzyme with weak proteolytic capabilities. It acts on fibrinogen to

form the fibrin monomer that has the automatic capability to polymerize with other
fibrin monomer molecules to form fibrin fibers

• Vitamin K is required by the liver for normal formation of prothrombin, as well as a

few other clotting factors.

• Lack of vitamin K or the presence of liver disease increases the bleeding tendency.
 Hemostasis

• Fibrinogen is a high-molecular-weight plasma

protein, it is synthesized in the liver

• Liver disease can decrease the plasma level of

fibrinogen

• The fibrin-stabilizing factor is an enzyme that is

present in small amounts in normal plasma
globulins but is also released from platelets
entrapped in the clot

• When the fibrin monomers are formed, many

of them polymerize within seconds into long
fibrin fibers that constitute the reticulum of the
blood clot.
 Clot retraction
• Clot retraction: contraction of the clot occurs within a few minutes after a
clot is formed, and expression of most of the fluid (serum) from the clot
occurs within 20 to 60 minutes.

• This retraction allows the edges of the broken blood vessel to be pulled
together.

• Mechanism of clot retraction: platelets pull on fibrin thread:

In the blood clots platelets become attached to the fibrin fibers in such a way
that they actually bond different fibers together. These platelets activate
platelet thrombosthenin, actin, and myosin molecules, causing strong
contraction of the platelet spicules attached to the fibrin. This causes
compression of the fibrin meshwork into a smaller mass. The contraction is
activated and accelerated by thrombin, as well as by calcium ions released
from calcium stores in the mitochondria, endoplasmic reticulum, and Golg
apparatus of the platelets
 Clot lysis
• A large amount of plasminogen is trapped in the clot along
with other plasma proteins

• The injured tissues and vascular endothelium very slowly

release the tissue plasminogen activator (t-PA), which
converts plasminogen to plasmin

• Few days after clot has been formed, plasmin acts as a

proteolytic enzyme that digests digests fibrin fibers and
some other protein coagulants such as fibrinogen, Factor V,
Factor VIII, prothrombin, and Factor XII.

• Streptokinase works as Fibrinolytic or Thrombolytic drug,

it binds and activates human plasminogen

• Engineered tissue plasminogen activator

 Hemostasis
• Prevention of blood clotting in the normal vascular system—intravascular
anticoagulants

1. Endothelial surface factors: the most important factor.

A. The surface of endothelial cells is smooth preventing contact activation of
the intrinsic clotting system.
B. The glycocalyx on the endothelium repels clotting factors and platelets

C. The endothelial membrane has a protein bound called thrombomodulin,

which binds thrombin, this binding remove thrombin, and the complex
also activates a plasma protein, protein C, that acts as an anticoagulant by
inactivating activated Factors V and VIII.

D. The endothelial cells release prostacyclin which prevent platelets

aggregation and causes vasodilation (opposite to thromboxane A2)
 Hemostasis

• Thrombin indirectly inactivates factors VIIIa and Va via

protein C. To activate protein C, thrombin must first bind to a
thrombin receptor, thrombomodulin, on endothelial cells; this
binding also eliminates thrombin’s procoagulant effects
 Hemostasis
2. Antithrombin action of fibrin and antithrombin III.
A. 85 – 90 % of the thrombin formed from the prothrombin becomes adsorbed to the fibrin fibers
as they develop. This prevent the spread of thrombin into the remaining blood and, so,
prevents excessive spread of the clot.

B. The thrombin that does not adsorb to the fibrin fibers soon combines with antithrombin III or
antithrombin-heparin cofactor, (alpha globulin protein)

3. Heparin: normally the concentration of heparin in the blood is low, but it is widely used as a
pharmacological anticoagulant.
 Bleeding disorders

According to pathogenesis, bleeding disorders could be classified into:

1. Coagulopathy:
A. Conginital : Deficiency of coagulation factor VIII (hemophilia A), IX (hemophilia B), XI
(hemophilia C), Deficiency of other coagulation factors (I, II, V, VII, IX, X and XIII) •
Deficiency of protein C and S • Von Willebrand’s disease (angiohemophilia).
B. Aquired: Hypoprothrombinemia (Deficiency of vitamin K or In liver cirrhosis (due to reduced
protein production)), Consumption of coagulation factors or Heparin overdose.

2. Platelet disorder (thrombocytopenia and thrombocytopathy)

A. Thrombocytopathy (normal count but abnormal function): Can be congenital due to deficiency of
membrane glycoprotein or acquired due to intake of antiplatelet agents like aspirin.
B. Thrombocytopenia (decrease in the number of platelets): can be Idiopathic thrombocytopenia
purpura or Drug induced thrombocytopenia
 Thromboembolic diseases
An abnormal clot that develops in a blood vessel is called a thrombus or freely flowing emboli

Causes of Thromboembolic Conditions:

1. A roughened endothelial surface of a vessel—as may be caused by arteriosclerosis,
infection, or trauma—is likely to initiate the clotting process
2. blood often clots when it flows very slowly through blood vessels, where small quantities
of thrombin and other procoagulants are always being formed.

Treatment: Genetically engineered t-PA is available. When delivered through a catheter to an

area with a thrombus, it is effective in activating plasminogen to plasmin, which in turn can
dissolve some intravascular clots.

Disseminated intravascular coagulation:

• Occasionally the clotting mechanism becomes activated in widespread areas of the
circulation.
• This condition often results from the presence of large amounts of traumatized or dying
tissue in the body that releases great quantities of tissue factor into the blood.
• This process occurs especially in patients with widespread septicemia
• A peculiar effect of disseminated intravascular coagulation is that the patient on occasion
begins to bleed … WHY???
 Anti-clotting drugs

Anti-clotting

Anti-platelet Anti-blood
Thrombolytics
aggregation coagulation
Anti-platelets
 Anticoagulants
• These drugs either inhibit the action of the coagulation factors (e.g. Heparin) or inhibit
the synthesis of these factors (e.g. Warfarin).
• Heparin + ATIII forms the Heparin-ATIII complex
• LMWH-ATIII complex inactivate factor Xa only but not Thrombin
Nonfunctional Functional Factors
Factors II, VII, IX, II, VII, IX, X
X

Reduced Vit K Oxidized Vit K

NADP+ NADPH
Warfarin
 Blood tests
• Platelets count (number of platelets)

• Bleeding time (function of platelets)

• Prothrombin Time (PT): evaluate the extrinsic pathway

• INR (standardized PT): evaluate the extrinsic pathway

• PT, INR (used to evaluate warfarin effect)

• Partial Thromboplastin Time (PTT): evaluate the intrinsic pathway (used

to evaluate heparin effect)