Dr Mahvash Khan
MBBS, MPhil
◦ Occurs inside the blood vessels, it is also called
fibrinolysis
◦ Occurs due to a substance known as plasmin
(fibrinolysin)
◦ Plasmin is formed from plasminogen
(profibrinolysin)
◦ Plasmin is a proteolytic digestive enzyme
◦ Plasmin digests fibrin fibers, Factor V, factor Vlll,
prothrombin, factor Xll
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Significance of the lysis
◦ Reopening of the affected vessels
◦ Prevents development of infarction
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Intravascular anti coagulants
◦ Flow of blood
◦ Endothelial surface factors
 Smoothness of endothelial cell surface
Prevents contact activation of the intrinsic clotting system
 Layer of glycocalyx
Muccopolysaccharide adsorbed to the vascular surfaces
repels clotting factors and platelets
◦ Thrombomodulin
 Protein bound to endothelial membrane
 Binds thrombin
 Thrombomodulin –thrombin complex also activates a
plasma protein complex known as protein C
 Acts as anticoagulant by inactivating activated factors V &
VII
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Antithrombin Action of Fibrin & Antithrombin
III
◦ Most important anticoagulants are those that
remove thrombin
 Fibrin fibers-formed during the process of clotting
 Antithrombin lll
 Antithrombin-heparin cofactor
 Thrombin formed from prothrombin gets adsorbed to the
fibrin fibers
 Helps prevent spread of thrombin into the remaining
blood
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Powerful anticoagulant which is a negatively
charged polysaccharide
Used widely as a pharmacological agent
Under physiological condition its concentration
is low
When it combines with antithrombin III the
effectiveness of antithrombin III increases
The complex removes other activated
coagulation factors----XII,XI,X & IX
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Vitamin K deficiency
Hemophilia
Thrombocytopenia
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Fat soluble vitamin
Required for synthesis of clotting factors
Action
◦ Acts as a cofactor at a late stage in the synthesis by
liver of coagulation proteins
 Prothrombin, VII, IX& X
 Causes gamma carboxylation of glutamate residues in
the synthesis of clotting factors
◦ Continually synthesized in GIT
◦ Deficiency seldom occurs
◦ Deficiency can occur because of the failure of the
liver to secrete bile
Hemophilia is a bleeding (hemorrhagic)
disease occurs almost exclusively in males.
Types
1. Hemophilia
A Or Classic hemophilia:
because of abnormality or deficiency of
factor VIII(1/1000 male in USA suffering
from disease).
2. Hemophilia
B Or Christmas disease:
because of deficiency of factor IX.
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Very low quantity of platelets in circulating
blood is called Thrombocytopenia.
Bleeding occurs in small venules & capillaries
so the hemorrhage occurs through out all
body tissues.
Platelets normal, 150,000-300,000
Bleeding occurs in < 50,000/ µl
Lethal count
< 10,000/ µl
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A pathological process in the body where the
blood starts to coagulate throughout the
whole body. This depletes the body of its
platelets and coagulation factors, and there is
a paradoxically increased risk of hemorrhage.
It occurs in critically ill patients, especially
those with Gram-negative sepsis (particularly
meningococcal sepsis) and acute
promyelocytic leukemia
Thrombi: An abnormal clot that develops in
blood vessel
Emboli: freely flowing clot is known as emboli
Continuous flow of blood passes the clot away
from its attachment & causes the clot to flow
with the blood .
Emboli originating from large arteries & left
side of heart can flow to periphery & plug
arteries or arterioles in brain, kidney or else
where.
Emboli originating from venous system or
right side of heart generally flow into the lungs
to cause pulmonary embolism.
1.
2.
Roughened endothelial surface of vessels: This is
because of arteriosclerosis, infections or trauma,
these factors initiating coagulation
Slow flowing of blood
Use of t-PA in treating intravascular clot: Tissue
plasminogen activator when delivered directly to a
thrombosed area through a catheter it activates
plasminogen to plasmin & dissolve i/v clot.
Uses: In 1st hour of heart attack or after the
thromboembolic occlusion of coronary artery the
heart saved from serious damage.
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