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How is blood clotting activated?

A cascade of zymogen activations


What is a zymogen?

A zymogen is an inactive precursor molecule that is made active by the cleavage of one or more peptide bonds


What are zymogens most often cleaved by for activation?

Serine proteases in the liver cleave zymogens for activation most often


What is the function of platelets?

To migrate to the site of injury and aggregate with clotting factors to form a clot


What are the main steps to the instrinsic pathway of blood clotting?

Kininogen + (kaloprine?) are released --> 12a --> 11a --> 9a --> 10a --> 2a (thrombin) --> 1a (fibrin) --> fibrin cross linking


What are the assistant steps in the intrinsic pathway of blood clotting?

1) 8a assists 9a in converting 10 to 10a
2) 5a assists 10a in converting 2 to 2a (prothrombin to thrombin)
3) 13a assists 1a (fibrin) to form covalent cross-linking


What activates the assistant steps in the intrinsic pathway of blood clotting?

Thrombin converts:
1) 8 to 8a
2) 5 to 5a
3) 13 to 13a
4) 7 to 7a


What steps require calcium?

1) 9 to 9a
2) 10 to 10a
3) 2 to 2a
4) 7 to 7a
5) Cross-linking of fibrin fibers


What factors require vitamin K to produce their inactive forms?

1) 9
2) 10
3) 2
4) 7


What is the extrinsic pathway for blood clotting?

In the presence of tissue damage, a tissue factor can be activated to convert 7 to 7a (thrombin assists in this conversion). 7a can then convert 10 to 10a


What does Vitamin K do to activate prothrombin?

Vitamin K adds a gamma carboxyl group to Prothromboglutamate, which attracts prothrombin to the platelet membrane where prothrombin is cleaved by proteases to form thrombin


What inhibits vitamin K action?

Coumarins (Coumadin)


What about fibrinogen makes it unsuitable for forming a clot?

It has a negative charge that keeps the molecule extended, however you want a compact molecule for a clot


How exactly is fibrinogen activated to fibrin and how does it form cross links?

1) Fibrinogen contains 2 (A- alpha B- Beta and gamma) groups
2) Thrombin cleaves fibrinogen at arginine and glycine to release A- and B-
3) alpha, Beta, and gamma monomers then aggregate to form a clot


How is the clotting cascade regulated?

1) Antithrombin 3 binds to thrombin and cleaves thrombin
2) Antithrombin 3 binds to 12a, 11a, 9a, and 10a
This prevents the clotting cascade from being activated when you don't need it


What does Heparin do?

Heparin enhances the action of antithrombin 3


How are clots dissolved?

1) Kringle domain on the Tissue type Plasminogen Activation (TPA) binds to the clot
2) Serine domain cleaves plasminogen to plasmin
3) Plasmin dissolves the clot


What are the steps to treating a patient having a heart attack?

1) Insert a stent to open any clogged arteries (may also use some heparin to prevent clotting)
2) Heparin is given through IV, whereas Lovonox only requires a local injection, making it an easier treatment option
3) Patient goes home on aspirin and plavix (inhibits platelet aggregation)


What is given to treat an atrial fibrilation patient?



What are new alternatives to coumadin?

1) Pradaxa - inhibits thrombin
2) Xarelto - inhibits 10a