Coagulation Flashcards
Plasminogen can be proteolytically activated to _________ .
Plasmin
Which form of this protein, plasminogen or plasmin, is freely circulating when you are NOT clotting?
Plasminogen
Which form of this protein is the active, protein plug (clot) forming form? Fibrinogen or fibrin
Fibrin. Aggregates to form a fiber plug.
What kicks off the clotting cascade?
Cells that do not normally come into contact with RBC and other blood products, now come into contact with these and release signals to alert other cells that there is a problem. Signals for vasoconstriction and clotting.
What is the role of TXs in mitigating bleeding?
Assist platelet aggregation
How does our body prevent coagulation downstream of original injury to the endothelium?
The endothelial cells downstream of the cut display anti-coag proteins, bind anti-coag proteins, and destroy the accelerators of the coagulation reaction.
Endothelial cells also produce Prostacyclins that dilate vessels downstream to inhibit platelet aggregation.
Thrombin plays an important role in forming a platelet plug and in activating the enzyme Factor XIIIa (fibrin stapler) to _________ fibrin.
Cross-link
Does Thrombin activate platelets
Yes
What protein is responsible for making Fibrinogen insoluble so that its active form, Fibrin, will begin to polymerize?
Thrombin
What protein cross-links Fibrin, making it a rigid & strong mesh for helping platelets form clots to plug holes in endothelium?
Factor XIIIa
What protein activates Factor XIII to Factor XIIIa?
Thrombin
What protein activates platelets to change surface receptors and initiate shape change?
Thrombin
Upon injury, subendothelial cells at the site of injury release _________ that binds to Factor VIIa.
Tissue Factor
When the Tissue factor/Factor VIIa complex binds to Factor X, Factor X is activated forming Factor Xa which then activates small quantities of _________ .
Thrombin
Factors XI, V and VIII have a +ive feedback loop that increases the activation of ___________ x10,000
Prothrombin
The complex of Factors _____ & _______ activate Prothrombin to Thrombin x10,000 faster than Xa alone.
Xa & Va
Accelerators of coagulation are found on the cell surface of _________ .
Platelets
List the 3 steps in clot formation and maintenance
- Initiation
- Amplification
- Propagation & Stabilization
What keeps the clot localized, preventing clots from over-propagating or causing emboli?
- Limiting initiation: LACI (lipoprotein associated coag factor)
- Limit amplification: anti-thrombin/heparin
- Limit propagation: protein C-S destroys accelerators
- Dissolve/digest clots with plasmin
LACI does what to limit initiation of clot formation?
inactivates TF-VIIa-Xa to limit and terminate initiation
What keeps the coag localized?
Platelet adhesion to the site
What is the action of Antithrombin III in limiting amplification of clotting?
inactivates Thrombin, Factor Xa and IXa if they flow away from the injured site
Plasmin digests clots by digesting which protein aggregate?
Fibrin
Plasmin is activated by activated protein ____ and ________ _________ .
Protein C; plasminogen activator
Endothelial cells express ____________ , a transmembrane protein that binds to thrombin and protein C. Activated C-S complexes inactivate the coag amplifiers Va and VIIIa.
thrombomodulin
What protein and proteoglycan bind to Thrombin, Xa and IXa, inactivating them?
Anti-thrombin III & Heparin
What protein inhibits the Tissue Factor-VIIa complex from activating factor Xa?
LACI
What complex on endothelial cell surfaces binds Factors Va and VIIIa and digests them as well as releasing plasmin to digest the clot?
C-S complex. (proteins C & S)
Do all the protein-protein interactions occur freely in the plasma?
No, they all occur on the extracellular surface of subendothelial cells, endothelial cells or platelets.
