Antifibrinolytic and Thrombolytic Agents Flashcards
What are the two clinical situations in
which antifibrinolytic drugs are used ?
- to prevent bleeding when it is anticipated that normal or enhanced fibrinolysis may overwhelm a weakened hemostatic system
- ex. open heart surgery, liver transplantation, hemophilia with surgery
- to stop bleeding in situations where fibrinolysis is enhanced
Note: antifibrinolytic therapy can enhance thrombosis
What are the two classes of antifibrinolytic drugs ?
- lysine binding analogues
- block fibrinolysis by competing for the sites on tPA, plasminogen and plasmin that bind to fibrin
- drugs:
- Aminocaproic acid (EACA)
- Tranexamic acid (TXA)
- can be given IV, orally or topically
- cleared by the kidney
- tPA, plasminogen, and plasmin bind to these drugs and prevent fibrin breakdown
- plasmin inhibitor
- drug: Aprotenin (only approved one)
- binds to and inhibits the active site of plasmin
- given IV, some studies for topical use
- cleared by the kidney
What is a common side affect of Aprotinin ?
- potentially fatal anaphylaxis and other hypersensitivity reactions
- more frequent with repeated use
Why is Aprotinin only used now in research
settings rather than a clinical basis ?
- studies showed an increased risk of post-op MI, renal failure and death
How is fibrinolysis enhanced during cardiovascular surgery ?
- activation of the contact system while going through the pump leads to increased bradykinin and tPA release
- hence increased plasmin generation and fibrinolysis
- most antifibrinolytics are given at the start of surgery and maintained throughout
How is fibrinolyisis enhanced in liver transplantation ?
- increased during anhepatic and reperfusion phases
- caused by reduced clearance of tPA
- reduced PAI-1 production
- worse in patients with severe cirrhosis
How does antifibrinolytic therapy help in liver transplantation ?
- therapy during transplantation has NOT been shown to alter periop mortality, long-term mortality, primary graft function or retransplantation
What is the correlation between fibrinolysis and trauma ?
- magnitude of fibrinolysis correlates with poor clinical outcome
- TEG is not sensitive enough to detect fibrinolysis in trauma
What are other indications for
antifibrinolytic therapy ?
- alpha2-antiplasmin deficiency
- PAI-1 deficiency
- Quebec platelet disorder
- they have abnormal increase in urokinase plasminogen activator elvels in the alpha granules
- hemophilia
- vWD
- topical application in oral surgery
How are antifibrinolytic drugs usually monitored ?
- usually not monitored
What is the purpose of thrombolytic therapy ?
- dissolve or lyse occlusive arterial or venous thrombi
- maintain vessel patency
- must use other agents along with thrombolytic therapy to accomplish this
- anticoagulant - usually LMWH
- antiplatelet agents - aspirin or clopidogrel
Note: thrombolytic therapy can lead to hemorrhage
What is the mechanism of thrombolytic drugs ?
- some form of plasminogen activator
- accelerate the conversion of plasminogen to plasmin
- leads to plasmin mediate lysis of fibrin in the thrombus
- example drugs:
- tPA, alteplase
- reteplase
- tenecteplase
- urokinase
- streptokinase
What are the contraindications for the use
of Thrombolytic agents ?
- active internal bleeding
- history of CVA
- recent intracranial or intraspinal surgery or trauma
- intracranial neoplasm, AVM or aneurysm
- known bleeding diathesis
- severe uncontrolled hypertension
What can potentially block infused tPA ?
- PAI-1 can be markedly increased up to 50 fold because it is an acute phase reactant
- this can cause binding of any excess tPA that is infused
