lec 8 : Natural Anticlotting & Fibrinolytic System Flashcards
Anti-Clotting Mechanisms
- Rapid flow of blood
- Endothelial factors
- Anticoagulant proteins
- Thrombin Removal from Blood
- Heparin
- Clot Lysis
Endothelial Factors for Anti-Clotting
- smooth endothelium
- glycocalyx on endothelium
- Balance between prostacyclin (PGI2) and thromboxane A2
- Thrombomodulin
- Tissue factor pathway inhibitor (TFPI)
Smooth Endothelial Lining of the Blood Vessel
Prevents activation of intrinsic pathway & platelets
Balance between Prostacyclin (PGI2) & Thromboxane A2 (TxA2) lead to ……………………
Keeps clot formation at site of injury only and rest of vessel lumen free of clot
Thrombomodulin-thrombin complex activates ……………………. that act as anticoagulant
protein C
Tissue Factor Pathway Inhibitor (TFPI) made by ……………………Inactivates………….. ,……………………….
made by the endothelial cell.
•Inactivates
♣ Tissue factor / factor VIIa complex
♣ Factor X
Anticoagulant Proteins
- Protein C (PC)
- Protein S
- Antithrombin III
The activation of protein C is enhanced by …………………….. which acts as a cofactor.
protein S
Activated Protein C (APC)
Inactivates active factors VIII, V
Inactivates inhibitors of plasminogen
activators
↑ formation of plasmin → helps lysis of fibrin
• Is vitamin K-dependent hemostatic protein
protein S
PC cofactor
protein S
Anti-thrombin III (Heparin cofactor I)
- Inactivation of thrombin
- Inactivation of active factors II, IX, X, XI, XII
- Its action is facilitated by heparin
Thrombin Removal from Blood Is mediated by
Fibrin fibers
Antithrombin III
……………………% of thrombin is bound to fibrin,
► Remaining amount is bound to ……………………..
85 –90% ,
antithrombin-III.
Heparin + Antithrombin III complex
→……………………………………………………………………………
→ Removal of thrombin & active factors XII, XI, X, IX
Clot lysis is mediated by ………………………
Fibrinolytic system
Plasminogen (profibrinolysin)
•Is an…………………………..
•Produced by……………..
•Circulates in plasma as a……………………
- inactive globulin
- liver
- plasma protein
Plasminogen is converted to plasmin (fibrinolysin) by
♠ Thrombin ♠ Tissue plasminogen activator (t-PA) is released very slowly from damaged tissues and vascular endothelium ♠ Urokinase plasminogen activator (u-PA)
Plasmin is a proteolytic enzyme that digests
♣ Fibrin and fibrinogen
→ fibrin degradation products (FDP)
→ inhibit thrombin
♣ inhibit→ Prothrombin, factor V, factor VIII and factor XI
function fibrin degradation products (FDP)
•Inhibits thrombin
•Inhibits interaction between fibrinogen &
thrombin
•Inhibits platelets activation and aggregation
•APC along with its cofactor PS inactivates:
♦ Active Factors V & VIII
♦ Inhibitors of t-PA
→ increase formaCon of plasmin
Thrombomodulin-thrombin complex activates…………….
protein C
inactivates factor V and VIII?
Protein C
The action of which one of the following is enhanced by heparin?
ATIII
vitamin K synthesis factors ……… , ……….. , …………….., …………….
II , VII , IX , X