FIBRINOLYSIS Flashcards
The last stage of coagulation
Fibrinolysis
Fibrinolysis is Comprised of
A systemic hydrolytic digestion of cross-linked fibrin polymers by bound plasmin.
the physiologic process of removing unwanted fibrin deposits , represents a gradual progressive enzymatic cleavage of fibrin to soluble fragments.
Fibrinolysis
Fribrinolysis fragments are then removed by
the fixed macrophages of the MPS. (mononuclear phagocytic system).
Components of Fibrinolysis
- Plasminogen - Plasmin
- Tissue plasminogen activator (TPA)
- Urokinase
- Streptokinase
- Plasminogen activator inhibitor-1 (PAI-1)
- A2- antiplasmin
Produced by liver (Components of fibrinolysis)
PLASMINOGEN
A2-Antiplasmin
Serine Protease (components of Fibrinolysis)
TPA
UROKINASE
Produced by activated endothelium
TPA
What component of fibrinolysis id being produce by Kidneys
Urokinase
Plasminogen half life
24-26 hours
Streptokinase is produced by
B-hemolytic strep
PAI-1 is produced by
Endothelium
Inhibits TPA
PAI-1
Inhibits plasmin
A2-antiplasmin
The fibrinolytic system is mediated mainly by the enzyme plasmin, which acts primarily on fibrin to produce lysis of the clot.
Plasminogen
Plasmin is generated from the inactive zymogen
Plasminogen
Plasminogen is activated to plasmin by
TPA AND OTHER SUBSTANCES
Plasminogen is synthesize by
Liver
Half life of plasminogen
2 days
Plasminogen 2 forms
Lys
Glu
What form of plasminogen is more readily converted to active plasmin.
Lys
ENDOGENOUS ACTIVATORS
FACTOR XIa , XIIa and Kallikrein
EXOGENOUS ACTIVATORS
Tissue plasminogen activator
Urokinase
Streptokinase
the main activator of plasmin in-VIVO (sulod).
TPA
Potent fibrinolytic agent by activating
plasminogen.
TPA
acts as the major release inducer.
Thrombin
minor role in in-VIVO fibrinolysis.
Urokinase
Genitourinary system product
Urokinase
Has Lower a nity with fibrin
Urokinase
Produced by B-hemolytic streptococci
Streptokinase
Indirectly activates plasminogen
Streptokinase
A group of substances referred to as
Serpins (Serine Protease inhibitors)
Primary inhibitor of tPA and Urokinase.
Plasminogen activator inhibitor-1
has the ability to proteolytically degrade both fibrin and fibrinogen in clots formed and native fibrinogen in the circulation.
Plasmin
The degraded products of plasmin is collectively termed as
FIBRIN/FIBRINOGEN DEGREDATION PRODUCTS
Proteolytically cleave and render inactive factors
V and VIII and XII
Plasmin Proteolytically cleave
GPIB complexes.
The earliest recognizable unit fragment is
FRAGMENT X
The Y fragment is further degraded to produce and additional D fragment and a single
E fragment
Fragment X gets cleaved further by plasmin to yield unclottable fragment
Y and D.
Crosslinked fibrin cleavage will produce the
D-dimer
exhibits anticoagulant e ect by competing with fibrinogen for thrombin.
Fragment X
forms abnormal complexes with fibrin monomers as it polymerizes.
Fragment D
no known anticoagulant
Fragment E
the major in-vivo plasmin inhibitor.
A2- plasmin inhibitor
A2- macroglobulin
Has a role in plasmin inhibition during Normal hemostasis.
Participates only when a2-antiplasmin inhibitor binding sites are saturated.
A2- macroglobulin
Inhibits fibrinolysis by hydrolyzing lysine from the carboxyl end of fibrin.
Thrombin-activatable fibrinolysis inhibitor (TAFI)
Activated by Thrombin-thrombomodulin complex.
Thrombin-activatable fibrinolysis inhibitor (TAFI)
Fragment X gets cleaved further by plasmin to yield unclottable fragment
fragment Y and D.
