Platelet receptors Gp1a-2a (glycoprotein), and Gp VI bind directly to subendothelial collagen tissue
Platelets adhesion to collagen indirect (major site) way:
Platelets bind indirectly to collagen tissue (subendothelial layer) via GP1b to von Willebrand factor secreted by endothelial cells
What is the major substance needed for platelet adhesion that is secreted by endothelial cells?
Von Willebrand factor
How is thromboxaneA2 produced?
Upon adhering to collagen, platelets will change shape (activating Gp2b/3a) and this shape change exposes phospholipid membrane which is precursor to thromboxane synthesis
T/F: When blood reaches subendothelial collagen, platelets get signaled to come bind to the endothelium
False; platelets binds to the subendothelial collagen via GP1b to vWF, as well as to collagen directly via GP6 and GP1a and 2a
Thrombin is factor___, and this causes vaso_____
Major stimulators of platelet activation:
ADP (From dense granule)
Thrombin (formed from phospholipid membrane, like TxA2)
What receptor on the activated platelets form bridging crosslinks with fibrinogen?
vWF can also help to form these bridging crosslinks in high shear blood flow conditions
What is the significance of crosslinking fibrinogen via GP2b/3a?
Leading to platelet aggregation
What can inhibit platelet aggregation?
Nitric oxide and prostacyclin produced by endothelial cell inhibit platelet aggregation and cause vasodilation
Most clotting factors are made in the _____
Liver needs _____ to make 4 clotting factors:
Factors II, VII, IX, X.
What are two natural anticoagulants formed by the liver requiring Vitamin K?
T/F: Clotting factors circulate in the blood in the active form
False-mostly; circulating clotting factors are in inactive form. Except actually for Factor VII (7) that one is actually in its active form In the blood
T/F: vitamin K dependent clotting factor needs vitamin K to be oxidized so the precursor molecule (glutamic acid) gets de-carboxylated and this allows a calcium molecule to interact with it to anchor the factor to phospholipid membrane of activated platelets
False; glutamic acid gets carboxylated.
Formation of a fibrin clot- cement platelet plug in place
Coagulation cascade: contact activation pathway is ____ pathway. Tissue factor pathway is the ___ pathway.
Tissue factor is factor ___. Calcium is factor ___
Extrinsic and intrinsic pathways converge at the activation of factor _____ into the ___ pathway which activates ____ and leading to ___
Cross-linked fibrin clot
Extrinsic pathway: Factors _____
VII and Tissue factor (III)
Intrinsic pathway: factors____
What is the Hageman factor?
Factor XII, part of the intrinsic factor
T/F: the intrinsic pathway is the most physiologically relevant pathway for the initiation of coagulation
False; the extrinsic pathway is, not the intrinsic pathway. Extrinsic pathway is activated by tissue factor (F III) expressed at sites of injury vs intrinsic pathway is when blood interacts with a negatively charged surface like glass
Warfarin is monitored via ___ coagulation tests reported as____, associated with ____ pathway
T/F: The intrinsic pathway should not be completely ignored even though it is relatively unimportant, but patients with coronary catheter and other blood-contacting medical devices could likely have activation of this intrinsic pathway
Blood clotting can be prevented by _____
Calcium chelators such as EDTA
In initiation phase, small amount of thrombin are formed, what do these thrombin go on to make?
Mainly Factors 5a, 8a, 11a and up-regulation of platelets
Tissue factor pathway inhibitor would disrupt which phase of coagulation?
Initiation phase would be turned off
Following the initiation phase comes the ____ phase, which takes place on _____.
Activated phospholipid membrane of the platelets
Major cofactor of intrinsic tenase is ______
In amplification phase, Factor ___ from _____ tenase comes to the intrinsic tenase, requiring cofactor _____. And this would produce factor _____ which goes to the ________ , joining factor ____ which leads to ___ burst
Factor Va (co-factor/accelerator)
4 main things needed for thrombin burst during amplification phase:
Factors 5a, 10 a, 2a
Formation and growth and stabilization of fibrin clot is the _____ phase
Function of thrombin in the propagation phase?
Convert fibrinogen to fibrin
Activates factor XIIIa
Which factor is in charge of crosslinking fibrin polymers?
Co-factor, enzyme and product of Extrinsic tenase, intrinsic tenase and prothrombinase:
Extrinsic tenase: tissue factor, Factor VIIa, Factors IXa and Xa (co-factor, enzyme, product)
Intrinsic tenase: facot VIIIa, Factor IXa, Factor Xa
Prothrombinase: Factor Va, Factor Xa, Thrombin (Factor IIa)
How does fibrinolysis occur?
Endothelial cell makes plasminogen activator (t-PA) which activates fibrinolysis
How does plasminogen gets converted into plasmin?
Upon binding to fibrin, it can be converted to plasmin by plasminogen activator (t-PA)
T/F: Plasminogen is a zymogen of plasmin that is produced in the kidneys
False; it is produced in the liver and circulates in the blood in a form that is activation-resistant
What is the function of alpha2-antiplasmin?
Pick up free plasmin that has escpeted the site
What is D-dimer?
It is a fibrin degradation product. That’s why we test for D-dimer to see whether there is clot
Thrombin can activate Protein _____, which is a natural____. And it will bind to co-factor Protein _____ forming a complex which will inactivated Factor _____ and Factor _____. This will lead to inhibition of further blood coagulation
Thrombin can bind to _____ expressed on the endothelial cells, which will inactivate thrombin, and activate ____
Protein C (a natural anticoagulant)
Antithrombin III binds to ____ on endothelial cells and inhibits the activity of ______ and factors ___, ____, ___, _____.
Heparan (heparin-like molecules)
IXa, Xa, XIa, and XIIa
What are the 7 ways of controlling blood clotting?
1 factors activation is restricted to sites of exposed phospholipids
2 Antithrombin III presence to inhibit thrombin and 9a, 10a, 11a, 12a
3 Thrombomodulin binds and inactivate thrombin
4 activating protein C and S which inactivate Va and VIIIa
5 endothelial secrete Tissue factor pathway inhibitor that inactivate factor 10a and TF-VIIa complexes
6 endothelial secretion of NO and prostacyclin inhibit platelet aggregation
7 activation of fibrinolysis by endothelial secretion of TPA