Coagulation Flashcards
Activated platelets at the site of injury release what vasoconstrictors?
Thromboxane A2 and serotonin
What initiates platelet tethering?
Glycoprotein receptor 1ba (GP1ba) binds exposed vWF
What occurs immediately after platelet tethering?
GPVI binds collagen in ECM
What occurs after GPVI binds collagen in platelet adhesion and activation?
Factors released by platelets bind to G protein coupled receptors on platelets already bound to injury site - positive feedback activation
What leads to the ability of platelets to bind fibrinogen?
Conformational change in GPIIa/IIIb following platelet activation
What acts as a molecular glue between activated GPIIa/GPIIIb on platelets?
Fibrinogen
What facilitates platelet-platelet interactions?
GPIIa/IIIb
What is an example of autocrine signaling in platelet activation?
Thromboxane A2 receptor activated by TXA2
What activates protease activated receptors (PARs)?
Thrombin
What are the ligands for glycoproteins on platelets?
Collagen, vWF, fibrinogen
What are the ligands for G protein coupled receptors on platelets?
TXA2, ADP, thrombin
What are the roles of NO and PGI2?
- Vasodilation 2. Anti-platelet adhesion
What cleaves fibrinogen to form fibrin monomers?
Thrombin
What clotting factor does thrombin activate?
XIII
What does factor XIIIa do?
Induces fibrin fibers to cross link to form stable insoluble clot
What is the name of clotting factor 1?
Fibrinogen
What is the name of clotting factor 2?
Prothrombin
What is the name of clotting factor 3?
Tissue factor
What is the name of clotting factor 4?
Calcium
What is the (start of) the common clotting pathway?
Prothrombin —-> thrombin mediated by factor Xa and Va
What is the role of factor Va?
Combines with factor Xa to speed up thrombin production 1000x
What does exposure of tissue factor (III) do?
- Activates factor VII 2. Activates factor X 3. Both of these activate factor X
What initiates the intrinsic pathway?
Factor XII is exposed to collagen (activated)
What is the activation cascade after factor XII in the intrinsic pathway?
12 –> 11 –> 9 –> 10 –> Prothrombin / thrombin
What is the tenase complex?
- Made up of factor VIIIa + IXa2. Accelerates activation of Xa
Hemophilia is a deficiency in which clotting factor?
8
What are the vitamin K cofactors in the clotting cascade?
10, 9, 7, 2
What does activated partial thromboplastin time monitor?
Speed of intrinsic pathway
What does the prothrombin time assay measure?
Extrinsic pathway
What are the two anticoagulation mechanisms?
- Preventing thrombin mediated clot 2. Destroying preformed thrombin
Degrading what two clotting factors will significantly reduce thrombin formation?
Va and VIIIa
What is the result of a protein c deficiency?
Hypercoagulation
What is the result of a thrombomodulin deficiency?
Hypercoagulation
How does the tissue factor pathway inhibitor reduce thrombin formation?
Inhibiting factor VIIa / tissue factor complex
What must antithrombin do to speed thrombin proteolysis 1000x?
Bind to heparin sulfate
What is the main protease that cleaves fibrin?
Plasmin
