Hemostasis Introduction Part II Flashcards
What are Serpins?
SERine Protease INhibitorS (we are particularly interested in Antithrombin which is a Serpin)
Why are Serpins sometimes called suicide protease inhibitors?
They form a covalent bond with the serine protease (or coagulation factor) which alters the structure of both proteins.
What does Antithrombin inactivate (most importantly)?
Factor Xa and IIa
Heparin is a key co-factor for ______
antithrombin. This accelerates its rate of protease inactivation greatly
The long tail of unfractionated Heparin allows it to interact with what? How is this different from low molecular weight heparin and pentasaccharide?
unfractionated binds Thrombin. Wraps around antithrombin and can hold it in. With the other two kinds of heparin it can still bind factor X but it can’t affect thrombin.
Why would it be better to use Low molecular weight heparin over unfractionated heparin?
It is more predicatable.
Use the _____ test to measure effectiveness of warfarin (coumadin) and the _____ test to measure effectiveness of Heparin.
PT
PTT
What factors are Vitamin K dependent again??
2, 7, 9, 10, c, s
How does thrombin play a role in anticoagulation (all steps)?
Factor IIa binds thrombomodulin which can then go and bind protein C. Protein C becomes APC (activated protein C-ase). APC binds Protein S (a co-factor which just enhances the rxn). APC now inactivates proteins Va and VIIIa. Stops the Coag. cascade
Why is factor V leiden a risk factor for venous thromboembolism?
It is a mutation in factor V that makes it resistant to Protein C inactivation.
TFPI inhibits what pathway?
Tissue Factor Pathway Inhibitor. It inhibits the extrinsic pathway by binding to X, VII, and Tissue Factor on the cell surface.
What activates plasminogen to plasmin, the key enzyme in fibrinolysis?
Tissue Plasminogen activator (tPA) or Urokinase (UPA). tPA is the most important though
Explain how plasminogen can lead to the formation of D-dimers in the blood?
Plasminogen attaches to fibrin. In presence of fibrin it is much more easily activated. tPA activates plasminogen. Plasmin chops up fibrin. In a formed clot covalent bonds attach the D ends of two fibrin molecules, so D-dimers form.
Presence of D-dimers in the blood is evidence of what?
Clot formation and chopping up.
How does Thrombin-activatable fibrinolysis inhibitor (TAFI) work?
It is cleaved to its active form through binding to the thrombin-thrombomodulin complex. It works by removing Arg and Lys residues from C terminal of proteins. Targets fibrin molecules so that plasminogen has no where to bind and break up fibrin.
