Coagulant & AntiCoagulant Haemostasis (arrest of blood loss) and blood coagulation involve complex interaction between the injury vessel wall, platelets and coagulation factors

1. Presented By – Gyanendra Kumar Prajapati
1st year M.Pharm
Department of Pharmacology
KLE University’s College of Pharmacy,
Bengaluru
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2. Haemostasis (arrest of blood loss) and blood coagulation involve
complex interaction between the injury vessel wall, platelets and
coagulation factors.
Blood clotting, or coagulation, is an important process that prevents
excessive bleeding when a blood vessel is injured. Platelets (a type of
blood cell) and proteins in plasma (the liquid part of blood) work
together to stop the bleeding by forming a clot over the injury.

3.  Typically, body will naturally dissolve the blood clot after
the injury has healed. Sometimes, however, clots form on
the inside of vessels without an obvious injury or do not
dissolve naturally. These situations can be dangerous and
require accurate diagnosis and appropriate treatment.
 Clots can occur in veins or arteries, which are vessels that
are part of the body's circulatory system.
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4.  Am I at Risk?
 The risk factors for developing a venous clot
are different from those for an arterial clot, and
people at risk for getting one are not
necessarily at risk for getting the other.
Different risk factors or events can cause
unnatural clotting; however, each factor may
initiate clotting in a different way.
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5. The following factors increase your risk of developing a
venous blood clot:
 Obesity
 Pregnancy
 Immobility (including prolonged inactivity, long trips by
plane or car)
 Smoking
 Oral contraceptives
 Certain cancers
 Trauma
 Certain surgeries
 Age (increased risk for people over age 60)
 A family history of blood clots
 Chronic inflammatory diseases 5Department of Pharmacology

6. What Are the Symptoms of a Blood Clot?
In addition to knowing risk factors, it is also important to
be aware of the symptoms of blood clots, which vary
depending upon where the clot is located:
 Heart - chest heaviness or pain, discomfort in other
areas of the upper body, shortness of breath, sweating,
nausea, light-headedness.
 Brain - weakness of the face, arms or legs, difficulty
speaking, vision problems, sudden and severe headache,
dizziness.
 Arm or Leg - sudden or gradual pain, swelling,
tenderness and warmth.
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7.  Lung - sharp chest pain, racing heart, shortness of breath,
sweating, fever, coughing up blood.
 Abdomen - severe abdominal pain, vomiting, diarrhea.
How Are Blood Clots Treated?
 Blood clots are treated differently depending on
the location of the clot and your health.
 Anticoagulants - medicine that prevents clots
from forming
 Thrombolytics - medicine that dissolves blood
clots
 Catheter-directed thrombolysis - a procedure in
which a long tube, called a catheter, is surgically
inserted and directed toward the blood clot
where it delivers clot-dissolving medication
 Thrombectomy - surgical removal of a clot
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9. Mechanism of Blood Clotting:
 Blood Clotting is one of three mechanisms that reduce
the loss of blood from broken blood vessels.
The three Mechanisms are:
1.Vascular Spasm:
 The smooth muscle in blood vessel walls contracts
immediately the blood vessel is broken. This response
reduces blood loss for some time, while the other
haemostatic mechanisms become active.
2.Platelet Plug Formation:
 When blood platelets encounter a damaged blood vessel
they form a “platelet plug” to help to close the gap in
the broken blood vessel. (The key stages of this process
are called platelet adhesion, platelet release reaction,
and platelet aggregation) 9Department of Pharmacology

10. 3.Coagulation:
 Following damage to a blood vessel, vascular spasm
occurs to reduce blood loss while other mechanisms
also take effect. Blood platelets congregate at the site of
damage and a mass to form a platelet plug. This is the
beginning of the process of the blood “breaking down”
from its usual liquid form in such a way that its
constituents play their own parts in processes to
minimize blood loss.
 This blood clotting is a complex process involving
many clotting factors (incl. calcium ions, enzymes,
platelets, damaged tissues) activating each other.
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12.  Stages of Blood Clotting:
 1. Formation of Prothrombinase:
 Prothrombinase can be formed in two ways, depending of
which of two “systems” or “pathways” apply.
 I. Intrinsic System:
 This is initiated by liquid blood making contact with a foreign
surface, i. e. something that is not part of the body; or
 II.Extrinsic System:
 This is initiated by liquid blood making contact with damage
tissue.
 Both the intrinsic and the extrinsic systems involve interactions
between coagulation factors. These coagulation factors have
individual names but are often referred to by a standardized set
of Roman Numerals, e.g. Factor VIII (anti-haemophilic factor),
Factor IX (Christmas factor).
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13.  2. Prothrombin Converted Into the Enzyme
Thrombin:
 Prothrombinase (formed in stage 1.) converts
prothrombin, which is a plasma protein that is formed in
the liver, into the enzyme thrombin.
 3. Fibrinogen (Soluble) Converted to Fibrin
(Insoluble):
 In turn, thrombin converts fibrinogen (which is also a
plasma protein synthesized in the liver) into fibrin.
 Fibrin is insoluble and forms the threads that bind the
clot
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14. There are two pathways that lead to the conversion of
prothrombin to thrombin:
(1) The intrinsic pathway and
(2) The extrinsic pathway.
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15. (1) Intrinsic Pathway:
 The intrinsic pathway, which is triggered by elements
that lie within the blood inself (intrinsic to the blood),
occurs in the flowing way. Damage to the vessel wall
stimulates the activation of a cascade of clotting factors
(for the sake of simplicity we will not consider the
individual factors).
 This cascade results in the activation of factor X.
 (2) Extrinsic Pathway:
 The extrinsic pathway is triggered by tissue damage
outside of the blood vessel. This pathway acts to clot
blood that has escaped from the vessel into the tissues.
Damage to tissue stimulates the activation of tissue
thromboplastin, an enzyme that catalyzed the activation
of factor X. 15Department of Pharmacology

16.  3. Clotting of Blood:
 The blood contains about a dozen clotting factors. These
factors are proteins that exist in the blood in an inactive
state, but can be called into action when tissues or blood
vessels are damaged.
 Blood clotting is the transformation of liquid
blood into a semisolid gel. Clots are made from
fibers (polymers) of a protein called fibrin.
Fibrin monomers come from an inactive
precursor called fibrinogen.
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17.  Drugs used clinically to remove clot include:
 1. Tissue plasminogen activator (TPA) was recently
cloned and is now produced in mass quantities by the
biotech fig, Amgen. It is used clinically to dissolved
clots in coronary arteries following a heart attack. It is
also used to dissolved clots in the brain following
stroke.
 2. Streptokinase is an enzyme that directly dissolved
blood clots. It is produced by streptococcus bacteria.
The bacteria use streptokinase to dissolve clots that
negatively affect their growth in the human host. This
clot dissolving enzyme is apparently as effective as
recombinant TPA.

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18. References
 Beckman et al. Venous Thromboembolism: A Public
Health Concern. AJPM April 2010.
 Raskob et al. Surveillance for Deep Vein Thrombosis
and Pulmonary Embolism: Recommendations from a
National Workshop. AJPM April 2010.
 David Lillicrap; Nigel Key; Michael Makris; Denise
O'Shaughnessy (2009). Practical Hemostasis and
Thrombosis. Wiley-Blackwell. pp. 1–5. ISBN 1-
4051-8460-4.
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