FIBRINOLYTIC SYSTEM AND

ANTICOAGULANTS
FATHIMA.A
OBJECTIVES
 HEMOSTASIS

•Hemostasis is the formation of blood clots in the walls of damaged blood vessels
•It prevents blood loss while maintaining blood in fluid state within the vascular
system
VASCULAR
CONSTRICTION

FORMATION OF
PLATELET PLUG

FORMATION OF BLOOD CLOT

AND FIBROUS TISSUE
DEPOSITION

CLOT RETRACTION

FIBRINOLY
 FIBRINOLYTIC SYSTEM
•FIBRINOLYSIS:Fibrinolysis refers to the process that brings about the dissolution of fibrin.
=>as the vessels heal,the clots dissolve to restore fluidity
=>it is body’s defence against occlussion of blood vessels
COMPONENTS
PLASMINOGEN:
• Plasminogen is a β-globulin produced by the liver
•Activation of plasminogen occurs from cleavage by
plasminogen activators of the bond between
arginine and valine at 560 and 561
Thus, plasminogen is converted into plasmin, an active protease.
 PLAMINOGEN ACTIVATORS

UROKININASE PLASMINOGEN
TISSUE PLASMINOGEN ACTIVATOR ACTIVATOR

=>released from thevascular endothelium. =>The UPA is found in a number of tissues

=>Release depends upon the release of including endothelial cells,
serotonin from platelets and adrenaline in renal cells and tumour cells
blood =>more effective than tissue plasminogen
=>normally it is poor plasminogen activator but activator
in the presence of fibrin the activity increases

PLASMINOGEN ACTIVATOR INHIBITORS

 PAI-1: Rapidly acting inhibitor of tpa and Upa.

Present in liver monocytes,endothelial cells and adipocytes
PAI-2: Less effective
Secreted by placenta ,monocytes and tumor cells
 PLASMIN
• Plasmin is a powerful protease formed from its precursor, the plasminogen.
• It lyses fibrin and fibrinogen into fragments known as fibrin degradation
products (FDP) that inhibit thrombin
• FDP is also known as D Dimers
• =>D Dimers help clinically to diagnose presence of a clot
• Digests fibrinogen ,factor V ,factor VIII,prothrombin and factor XII
• =>inhibited by alpha antiplasmin,alpha macroglobulin
 MECHANISM OF FIBRINOLYSIS

Blood coagulation automatically initiates anticlotting mechanisms so

that clot does not spread beyond site of injury
1.ACTIVATION OF PROTEIN C
2.ACTIVATION OF PLASMIN
3.FIBRINOLYSIS
Activation of Protein C
• Thrombin which is produced by clotting mechanism acts as an enzyme to activate protein C to its active form.
The anticlotting mechanism activated by thrombin can also beinitiated by thrombomodulin, a hormone
secreted from endothelial cells of blood vessel. Thrombomodulin activates protein C

Activation of Plasmin
• Activated protein C inactivates the inhibitors of plasmin activator. This, in turn, activates plasminogen
activator which promotes formation of plasmin from plasminogen.
• Activated protein C along with its cofactor protein S also inactivates Va and VIIIa into their respective
inactive
• forms. This aids in prevention of coagulation.
Fibrinolysis
• Plasmin acts as an enzyme to cause fibrinolysis (lysis of clot).
• 1. This process is facilitated by cofactors thrombin, tissue- type plasminogen activator and urokinase-
typeplasminogen activator.
• 2. Fibrin is degraded by plasmin to fibrin degradation products (FDP)
 PHYSIOLOGICAL SIGNIFICANCE OF
FIBRINOLYTIC SYSTEM
1. Cleaning the minute clots of tiny vessels.
in physiological conditions the clotting system of the plasma is continually forming small amounts
of fibrin, which are deposited to form a thin layer on vascular endothelium and that the fibrinolytic
system is constantly in action to prevent excessive fibrin formation.
2. Promote normal healing process. Lysis of clot formed as a result of tissue injury helps to
promote normal healing process.
3 . Liquefaction of menstrual clot in the vagina is carried out by fibrinolytic system.
4. Liquefaction of sperms in the epididymis
when seminal ejaculation does not occur is caused by the fibrinolysin system.
5. Role in inflammatory response.In addition to its fibrinolytic activity, plasmin can form plasma
kinins (bradykinins and kallidin) and thus contribute to the vascular and sensory features (pain) of
the inflammatory response to injury.
 ANTICOAGULANTS
• Anticoagulants refer to the substances which delay or prevent the process of
coagulation of blood

FOR LAB PRESERVING BLOOD IN Therapeutic NATURA

INVESTIGATION BLOOD BANK
L
S

•Sodium citrate •Acid citrate dextrate ORAL

•Endothelial
INTRAVENOU
•Double oxalate •Citrate phosphate S surface factors
Vitamin K •Antithrombin II
•EDTA dextrose antagonists
•Sodium sulphate •Protein c
•Heparin

(remove) calcium from the blood by forming insoluble salts

with calcium or by chelating calcium
NATURAL ANTICOAGULANTS
Endothelial surface factors
• (1) the smoothness of the endothelial cell surface, which prevents contact
activation of the intrinsic clotting system;
• (2) a layer of glycocalyx on the endothelium which repels clotting factors and
platelets, thereby preventing activation of clotting; and
• (3) the thrombomodulin-thrombin complex slows clotting process by removing
thrombin and also activates protein C, that acts as an anticoagulant by inactivating
activated Factors V and VIII.
Antithrombin III.
• It is a present in plasma and endothelium
• It binds to thrombin and clotting factors active from of IX, X, XI and XII and
inactivates them
HEPARIN
• Produced in mast cells and basophils
Heparinactivates antithrombin III Heparin anti thrombin iii complexbinds to
clotting factors of intrinsic and extrinsic factors and inactivates them=>inhibitd
thrombin and factor X
• Used for osmotic fragility test,pH assays

• PROTEIN C
• Protein C is a plasma protein synthesized in liver. It, along with thrombomodulin and
protein-S constitute an important negative feedback pathway that keeps the coagulatory
process under control
 THERAPEUTIC
=>Used for treatment or prevention of thrombosis
• ORAL ANTICOAGULANTS:These agents occupy vitamin K receptor sites in the liver
and prevent vitamin K from carrying out its normal physiological function, Thus, these
substances inhibit synthesis of vitamin K-dependent factors, i.e. factors VII, IX and X.
These include coumarin derivatives (e.g. dicoumarol), warfarin, phenindioneand
nicoumalone
REFERENCES
• Guyton and hall
• G K pal
• Indu Khurrana