FIBRINOLSIS SYSTEM
DR MOHAMMED SAIEMALDAHR
Faculty of Applied Medical Sciences
Medical Technology Dep.
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FIBRINOLSIS SYSTEM
Fibrinolysis System in Homeostasis
 In 1937 MaCfarlane reported that damage tissues release a
substance (activator that activates the inert precursor
called Plasminogen).
 Plasminogen: is normally circulates in the plasma to its
active form called, Plasmin.
 Plasmin is anon-specific Proteolytic enzyme capable of
degrading fibrin as well as fibrinogen and factors V & VIII.
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FIBRINOLSIS SYSTEM
Function of Fibrinolysis in Homeostasis
 Fibrinolysis is the system whereby the temporary fibrin clot
is systematically and gradually dissolved as the vessel heals
in order to restore normal blood flow.
 Is the body’s defense against occlusion of blood vessels
 There are number of substances responsible for fibrinolysis
(Fig).
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FIBRINOLSIS SYSTEM
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FIBRINOLSIS SYSTEM
 FIG. Simple overview of Fibrinolytic pathway.
 Tissue plasminogen activators activate plasminogen within
clot to plasmin, which slowly dissolves fibrin clot.
 Inhibitors are neutralized by protein C—S complex, thus
enhancing fibrinolysis.
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FIBRINOLSIS SYSTEM
 Tissue Plasminogen Activators, which convert Plasminogen
to Plasmin are released from injured vessel walls.
 Plasmin is trapped within the clot, and clot lysis begin
slowly as soon as the clot is formed, with fibrin degradation
products being released in the plasma.
 Lysis is slow because of fibrin clot stabilization by factor
XIII.
 Protein S and C are two substance that enhance fibrinolysis
and inactivate Tissue Plasminogen Activators (tPA
inhibitor).
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FIBRINOLSIS SYSTEM
Physiologic Fibrinolysis
Many similarities exist between Coagulation and Fibrinolytic
systems.
• AS there are checks and balances in the formation of clot
• There are similar mechanism for dissolution of the clot to
promote wound Healing.
• Important that bleeding does not recur because of
premature lysing of the clot.
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FIBRINOLSIS SYSTEM
Activation of Plasminogen to Plasmin
 Fibrinolysis is dependent on the enzyme PLASMIN
Normally is not present in the blood in an active form.
Can digest or destroy fibrinogen, fibrin and factors V & VIII
Promotes Coagulation and activates the Kinine and
Complement systems.
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FIBRINOLSIS SYSTEM
Plasmin's Roles
Comments
Activates Fibrinolysis
Cleaves Fibrin and Fibrinogen to
fibrin (ogen) degradation products
X, Y and D-E
Activates Intrinsic Coagulation
Pathway
Factors XII----XIIa is amplified
indirectly by plasmin
Interferes with intrinsic and
common pathways
Destroys factors VIII and V
Block Thrombin conversion of
fibrinogen to fibrin
FDP interfere with thrombin
influence on fibrinogen
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FIBRINOLSIS SYSTEM
 Activation of Plasminogen to Plasmin
• A zymogen known as Plasminogen which normally present
in plasma is converted to Plasmin by the action of specific
enzyme called Plasminogen Activators.
• Plasminogen is a single-chain glycoprotein with a Mwt of
90,000 d
• Synthesized in the liver
• Increased concentrations are found in association with
inflammation.
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FIBRINOLSIS SYSTEM
Activation of Plasminogen can occurs due to
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• Intrinsic Plasminogen Activation
• Extrinsic Plasminogen Activation
• Exogenous Plasminogen Activation
• Plasminogen Activation in Secretory Ducts. (Fig)
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FIBRINOLSIS SYSTEM
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FIBRINOLSIS SYSTEM
 For therapeutic destruction of thrombosis, Urokinase, a
trypsin-like protease, may be administered to a patient to
activate plasminogen to plasmin and induce Fibrinolysis.
 Streptokinase is another agent used to activate
Plasminogen to plasmin
 Tissue Plasminogen activator (tPA) is an agent used for the
treatment of thrombosis. It released in vivo on endothelial
cell damage and can be manufactured in vitro through
recombinant DNA techniques.
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FIBRINOLSIS SYSTEM
 Summary
 Fibrinolysis is dependent on the enzyme PLASMIN
 Tissue Plasminogen Activators, which convert Plasminogen
to Plasmin are released from injured vessel walls.
 Plasminogen (A zymogen) which normally present in
plasma is converted to Plasmin by the action of specific
enzyme called Plasminogen Activators.
 Activation of Plasminogen can occurs due to
 Intrinsic, Extrinsic, Exogenous Plasminogen Activation,
andActivation in Secretory Ducts.
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FIBRINOLSIS SYSTEM
 Plasminogen is a part of any clot because of the tendency
of fibrin to absorb plasminogen from the plasma in normal
circumstances.
 When plasminogen activators performed their function,
plasmin is formed within the clot, which gradually
dissolves the clot while leaving time for tissue repair.
 Free Plasmin is released to the plasma, however, antiplasmin is there immediately destroy any plasmin released
from the clot.
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FIBRINOLSIS SYSTEM
 When Pathologic Coagulation processes are involved,
excessive free plasmin is released to the plasma
 In these situation, the available anti-plasmin is depleted
and plasmin begins destroying components other than
fibrin, including, fibrinogen, factor V and VIII and other
factors.
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FIBRINOLSIS SYSTEM
FIBRIN(OGEN) DEGRADATION by PLASMIN
 In the process of fibrinogen or fibrin degradation by
plasmin within a clot, specific molecular fragments are
produced called Fibrin (ogen) Degradation Products (FDP)
or Fibrin (ogen) Split Products (FSP)
 These degradation products are removed by the
reticuloendothelial system and other organs.
 The sequence of reaction in the degradation of Fibrin(ogen)
by plasmin are X, Y, D (D-D dimer) and E.
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FIBRINOLSIS SYSTEM

Fibrin(ogen) Degradation by Plasmin
 Fragment X and Y are referred to as early degradation
products
 Fragment D and E are late degradation products
 Fragment X is the first and the largest fragment formed
(Mwt 250,000 d)
 Fragment X is the results of Plasmin (P) cleavage of the
terminal portion of the alpha (α) chains from a fibrin
polymer
 Fragment X is cleaved by Plasmin (P) to form two
fragments called Y (YY) and an intermediate complex
(DXD)
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FIBRINOLSIS SYSTEM
 This complex is further cleaved into intermediate
complexes DED and DY/DY until finally, fragment E and D
(D-D dimer) are formed.
 A single fragment D has Mwt 90,000 d and that the D-D
dimer is 180,000 d
 Presence of D-D dimer is a specific indication of in vivo
fibrinolysis, namely, intravascular thrombin formation
leading to fibrin formation and its subsequent degradation
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FIBRINOLSIS SYSTEM
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Pathologic Effect of FDPs
The FDPs are significant because of their haemostatic
effects, which include;
Anti-thrombin activity
Interference with polymerization of fibrin monomer
Interference with platelet activity
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FIBRINOLSIS SYSTEM
The early and large fragments (X and Y) along with the
intermediate FDPs, are important in exerting anticoagulant
Effect
• Fragment Y and D inhibit fibrin polymerization
• Fragment E is a powerful inhibitor of thrombin
• All four fragments, but particularly low molecular weight
FDP, have an effinity coating platelet membrane and
therefore, cause a clinically significant platelet dysfunction by
inhibiting aggregation.
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FIBRINOLSIS SYSTEM
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Fibrinolytic Inhibitors
1- Alpha-2- Anti-plasmin (α2 anti-plasmin)
An (α2) glyco-protein
Most important naturally occurring inhibitor
The principle inhibitors of fibrinolysis by binding with
plasmin that is free in the plasma (neutralizing plasmin)
Inhibits the clot-promoting activities of plasma kallikrein
Inhibits the serine proteases Xlla, XIa, IIa and Xa
Hereditary deficiencies have been associated with,
Excessive clotting (DIC)
Excessive fibrinolysis
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FIBRINOLSIS SYSTEM
2- Alpha 2 Macroglobulin
 Large naturally occurring plasma GP
 Inhibits component in both the fibrinolysis and coagulation
systems
 Inhibits plasmin after alpha 2 anti-plasmin depletion
3- Alpha 1 Antitrypsin
 The third most important naturally occurring inhibitor of
fibrinolytic system. Inactivates plasmin slowly and does
not bind plasmin until both alpha2 anti-plasmin and alpha
2 macroglobulin are saturated
 Inhibits coagulation by its potent inhibitory effects on
factor XIa
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FIBRINOLSIS SYSTEM
Other Inhibitors
 Anti-thrombin III, inhibits fibrinolysis by inhibiting
plasmin and kallikrein
 The C1 inactivator also inhibits plasmin.
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