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What are the 3 elements of Virchow's triad?
- the blood vessel
- the circulating elements
- speed of blood flow
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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
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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
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How does blood flow relate to coagulation?
- slow, turbulent blood activates coagulation
- fast, laminar blood keeps coagulation factors diluted adn inactivated
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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
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What medications target GP-IIb/IIIa to stop platelet aggregation?
- abciximab
- eptifibatide
- tirofiban
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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
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What medications target factor X?
- Warfarin (II, VII, IX, X)
- Heparin (IIa, Xa)
- LMWH (IIa, Xa)
- Fondaparinux (Xa)
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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
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What medications target thrombin (IIa)?
- lipirudin
- bivalirudin
- argatroban
- dabigatran
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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
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What substance causes fibrinolysis?
plasmin degrades the fibrin mesh in to soluble products
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How is plasmin activated?
plasminogen is activated to plasmin by tPA and uPA which are released by endothelial cells
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What medications target fibrinolysis?
- alteplase
- reteplase
- streptokinase
- tenecteplase
- urokinase
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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
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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
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What is the effect of Protein C, Protein S, or antithrombin deficiency?
more blood clots
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