What are the 3 elements of Virchow's triad?
- the blood vessel
- the circulating elements
- speed of blood flow
How does the blood vessel relate to coagulation?
- exposed subendothelium activates platelets
- tissue factor is released from subendothelium, forms a complex with VIIa and activates coagulation
- vessel wall contains thrombomodulin, tPA and uPA to promote anticoagulation
How do the circulating elements relate to coagulation?
- platelets, clotting factors, prothrombin, and fibrinogen become activated by factors and enzymes also in the blood
- antithrombin, protein C, protein S, and plasminogen promote anticoagulation once activated by the coagulation cascade
How does blood flow relate to coagulation?
- slow, turbulent blood activates coagulation
- fast, laminar blood keeps coagulation factors diluted adn inactivated
What causes platelets to adheree to the vessel?
- exposed endothelium attracts platelets
- GP-1b receptors on platelet surfaces facilitate attachment to subendothelium through von Willebrand factor
- adherence activates the platelets which release procoagulants into the blood to attract more platelets and expose GP-IIb/IIIa receptors
- platelets use these receptors to bond to one another
- the exposed endothelium also releases tissue factor to bind factor VII and activate the coagulation cascade
What medications target GP-IIb/IIIa to stop platelet aggregation?
How does the tissue factor - VIIa complex activate factor X?
- directly activates factor X to Xa
- indirectly by activating factor IX to IXa which then activates factor X to Xa
What medications target factor X?
- Warfarin (II, VII, IX, X)
- Heparin (IIa, Xa)
- LMWH (IIa, Xa)
- Fondaparinux (Xa)
How does the formation of thrombin lead to continued propagation of the clot?
- thrombin converts fibrinogen to fibrin, which is stabilized and cross linked by factor VIIIa
- thrombin also activates factors V and VIII
- factor VIIIa activates factor X, leading to thrombin production
- factors Va and Xa convert prothrombin to thrombin
What medications target thrombin (IIa)?
How does formation of thrombin lead to activation of anticoagulation?
- thrombin binds thrombomodulin receptors on the endothelium and is converted to a Protein C activator
- Protein C inactivates Va and VIIIa, which decreases production of thrombin
What substance causes fibrinolysis?
plasmin degrades the fibrin mesh in to soluble products
How is plasmin activated?
plasminogen is activated to plasmin by tPA and uPA which are released by endothelial cells
What medications target fibrinolysis?
What substances inhibit fibrinolysis?
- plasminogen activator type-1 (PAI-1) blocks release of tPA
- Alpha-2 antiplasmin complexes with non-fibrin-bound plasmin, inactivating it
- thrombin activatable fibrinolysis inhibitor (TAFI) changes the end structure of fibrin which decreases plasmin's ability to bind fibrin
How do Factor V Leiden and Prothrombin G20210A mutations impact clot formation?
- factor V Leiden results in decreased factor V degredation by Protein C
- Prothrombin G20210A results in difficulty in degrading prothrombin mRNA
What is the effect of Protein C, Protein S, or antithrombin deficiency?
more blood clots