SACCM 166: Thrombolytic Agents

Question 1

What are the 3 different activators of Plasminogen?

Answer 1

tissue-type plasminogen activator (tPA)
urinary-type plasminogen activator (uPA)
contact plasminogen activator pathway (FXII, prekallikrein, kininogen)

Question 2

What are the steps of Fibrinogen cleavage by plasmin?

Answer 2

1. alpha chains are cleaved –> alpha chain fragments –> X fragment left (D-E-D)
2. D fragment cleaved, Y fragment left (D-E)
3. cleaved to single D and E fragments –> fibrin degradatin products

Question 3

Why do D-dimers indicate presence of previous clots?

Answer 3

D dimers are a complex of D-D with a concurrent free E complex
remnants of Y-chain needed to create D-D complex (i.e., D-dimer) –> Y-chain formed when fibrin binds with other fibrin

Question 4

What are the 3 most important plasmin inhibitors and where are they synthesized?

Answer 4

• PAI-1 (platelet alpha granules)
• alpha-2 antiplasmin (liver)
• TAFI (liver)

Question 5

How does TAFI inhibit fibrinolysis?

Answer 5

fibrin residues –> C terminal lysine –> usually have a positive feedback on ongoing plasmin binding to fibrin
TAFI –> removes C-terminal lysine fibrin residues

Question 6

How is streptokinase produced?

Answer 6

by streptococci

Question 7

What is the half-life of tissue plasminogen activator?

Answer 7

5 minutes

Question 8

what does PAI-1 bind to?

Answer 8

directly inhibits uPA and tPA

Question 9

What does alpha-2 anti-plasmin bind to?

Answer 9

plasminogen or plasmin AND fibrin - crosslink and prevents binding of tPA

Question 10

What is the structure of fibrinoge and how does the structure change matter when using FDP versus d-diemr cc to differentiate DIC?

Answer 10

D-E-D domains and extending alphaC domains/chains

broken down into FDPs (separate D, E) by plasmin

if fibrinogen can first be activated to fibrin monomers and cross link with FXIIIa (i.e., form an actual clot) - the D domains of different fibrins will cross link and a D-D (d-dimer) complex can form