Targeting The Coagulation And Fibrinolytic Pathways - From Classic Inhibitors To Specific Ones Flashcards
Name the classical inhibitors of the coagulation/fibrinolytic pathways
Heparin and hydroxycoumarin
What role does Heparin perform?
Heparin increases the activity of serpins (such as ATIII)
What role does Hydroxycoumarin play?
It’s a vitamin K analougue and inhibits the enzyme vitamin k reductase which recycles vitamin K back to its active form.
What happens if Vitamin K is not recycled?
Without vitamin K the GLA domain is not modified post-transitionally and will not lead to a properly functioning molecule - this diminishes or impairs the function of factors 7, 9, 10, prothrombin, protein C and protein S. Thus it indirectly inhibits coagulation
Why is hydroxycoumarin dangerous?
Because the intake of vitamin K is via the diet, and one can significantly change the ratio between the inhibitor and the active co-enzyme depending on what they eat. And consequently changing the level of inhibition on the coagulation cascade
Which process (in coagulation) do the new approaches to theapy aim to target?
The binding of factor 7 to tissue factor
Which 2 methods are the newer specific therapies utilising?
- Antibodies specific to Tissue Factor (which block its binding site to factor 7)
- Specific inhibitors of factor 7 through its specificity pockets (this way they would not target other factors)
Another protein therapy would provide synthetic ______ to add to the natural one
tPA
What would the effect of additional tPA be?
Thrombolysis (by conversion of plasminogen to plasmin)
What are the time limits for tPA administration?
Administration is allowed until:
- 3H after cerebral thrombosis (stroke)
- within 12H from onset of cardiac thrombosis
What is the target of therapies against thrombosis
Factor 12 inhibitors to inhibit the intrinsic pathway - which has a major role in thrombi formation
