PROCESS FOR DISSOLVING CLOT FIBRIN

1. Name: Sanjog Bam
HUMAN BIOLOGIST
Msc. Medical Physiology

2. I. INTRODUCTION
• SUMMARY
• PLASMINOGEN ACTIVATORS
II. ROLE OF FIBRINOLYSIS IN HOMEOSTASIS
III. MECHANISM OF FIBRINOLYSIS
IV. REGULATION OF FIBRINOLYSIS
V. FIBRIN DEGRADATION PRODUCTS
VI. FIBRINOLYTIC INHIBITORS

3.  System where fibrin clot is systematically and gradually gets dissolved.
 Ultimate substrate for fibrinolysis reaction is fibrin clots
 Main enzyme PLASMIN (active) PLASMINOGEN(zymogen).
 Plasminogen : synthesis in Liver
: inactive form , cannot cleave fibrin but has affinity to it
: incorporated into the clot when it is formed
: activated by the plasminogen activators, regulates the fibrinolytic
system.
: receptors located on the surfaces of different types of cell and are
plentiful on endothelial cells.

4.  Main proteolytic enzyme in fibrinolysis, also called fibrinolysin.
 It cleaves the fibrin clots, the product of coagulation.
 Formed from plasminogen by the action of plasminogen activators and thrombin
 Lysis fibrin with production of different fibrin degradation products that inhibits
thrombin
 Also digests fibrinogen, factor V, factor VIII, prothrombin and factor XII
 Catalyzes the formation of the pre kallikrein activators from active factor XII

5.  Tissue type plasminogen activator(t-PA) and urokinase-type plasminogen
activator(u-PA).
 t-PA :endothelial cells
: higher affinity to plasminogen in presence of fibrin
: metabolized in liver after forming complex with LDL like protein
• u-PA : monocytes ,macrophages , renal tubular epithelium and vascular
epithelium.
: found in plasma and urine
:lower affinity for plasminogen and doesnot require fibrin as cofactor
• Both have short half life in circulation :4-8 minutes

7.  As the vessels heals temporary clot get dissolve to
restore the blood fluidity
 Is the body’s defense against occlusion of blood
vessels
 Remove minute clots from millions of tiny peripheral
vessels
 There are number of substances involve in
fibrinolysis

8.  Intrinsic plasminogen
activation
 Extrinsic plasminogen
activation
 Exogeneous plasminogen
activation
 Plasminogen activation in
secretory ducts

10.  Plasmin degrades fibrin within the clot forming specific molecular fragments
called fibrin degration products(FDPs) or fibrin split products(FSPs)
 FDPs are X,Y,D-dimers(common)and E
 Their levels in blood provides a measure of the amount of fibrin formation and
lysis.
 D-dimers is specific indication of fibrinolysis(intravascular thrombin formation
leading to fibrin formation and its subsequent degradation)
 High level of FDPs in blood is associated with disseminated intravascular
coagulation.
 These are removed by reticuloendothelial cells and other organs.
 Abnormal level of FDPs suggests that there is problem in fibrinolysis or clot
formation process.
 Helps to determine deep vein thrombosis, pulmonary embolism, leukemia
,kidney disease

11.  Prevents excess unregulated plasmin or plasminogen activators activity
 Neutralizes circulating plasmin and plasminogen activators
 Serine protease inhibitors(serpins)
 Plasminogen activator inhibitor-1
 Plasminogen activators inhibitor-2
 Alpha-2-antiplasmin: acts on plasmin that free in plasma
 non-serpine plasmin inhibitors
 alpha-2-macroglobulin :acts on plasmin after alpha-2-antiplasmin depletion
 thrombin activated fibrinolysis inhibitors : reduces the no. of available
plasminogen binding sites in fibrin