Explain the physiological mechanism by which thrombi are cleared
Cleared via plasmin which cleaves fibrin to fibrin fragments.
Plasmin formed from circulating plasminogen which binds to fibrin strands. tPAs convert plasminogen to plasmin and are regulated by PAI-1. tPA released after endothelial damage.
What are the 2 methods by which fibrinolytic drugs can work? Give examples of the 2 types.
Generating plasmin themselves e.g. alteplase or by binding to and activating endogenous plasminogen e.g. strptokinase.
Explain why streptokinase can only be used once.
It is a bacterial product and therrefore produces an immune response. Body produces antibodies to it.
Why is a slow infusion of streptokinase recommended?
To prevent or counteract the transient hypotension that occurs upon infusion
Give 2 examples of recombinant tPA (r-tPA)
What situations would fibrinolytic drugs be indicated for?
acute MI, major PE, acute ischaemic stroke
What is the window of opportunity for fibrinolysis in an acute MI and an ischaemic stroke? Why is there a time frame?
MI - 12 hours
Stroke - 3 hours
Time frame because the thrombus becomes more resistant to lysis as it ages, where as the risks remain constant.
What are the ADRs of fibrinolytic agents?
increased risk of haemorrhage.
What are the major contra-indications for fibrinolytic therapy?
history of haemorhagic stroke, active peptic ulcer, recent surgery, uncontrolled hypertension, known coagulation defect
How would you diagnose a CVA after fibrinolytic therapy?
CT or MRI diagnosis
How would you treat serious bleeding post fibrinolytic therapy
transfusion of blood and inhibition of fibrinolytics and administration of tranexamic acid which competitively inhibits activation of plasmin.
What is the mechanism of action of vitamin K antagonists?
Vitamin K promotes synthesis of prothrombin and factors VII, IX, and X.
Antagonise these to prevent synthesis of prothrombin
Give an example vit K antagonist
How is vit K antagonist administered?
How is vit K antagonist monitored? How long does it take to take effect?
monitored with INR
Gradual onset and persisting anticoagulant action on cessation of treatment
What ADRs are associated with vit K antagonists?
excessive bleeding or bruising. Teratogenic
How would you reverse vit K antagonists?
administration of IV vit K
How does heparin work?
heparin binds to antithrombin, increasing inhibition of thrombin and Xa
How is heparin administered? How long does it take to take effect? how is it monitored
Monitored with APTT (activated partial thrombin time)
Rapid onset and offset
IV or subcutaneous
What are the ADRs of heparin?
bleeding, thrombocytopenia, osteoporosis (long term)
How is heparin reversed?
Protamine sulphate causes dissociated of heparin/antithrombin complex and binds irreversibly to heparin
What are the 3 types of antiplatelet agents? Give examples of each
Thromboxane A2 inhibition - aspirin, dipyridamole
Platelet ADP receptor antagonist - ticlopidine, clopidogrel
What is the mechanism of action of thromboxane A2 inhibitors
Thromboxane A2 produced by activated platelets and causes platelet aggregation and vasoconstriction.
Aspirin inhibits COX and therefore platelet thromboxane A2 production
Dipyridamole inhibits platelet phosphodiesterase which inhibits thromoxane A2 production
How do platelet ADP receptor antagonists work?
ADP to ADP receptor interaction is one of the stimuli needed for platelet aggregation. Antagonising.
How do GpIIa/IIb inhibitors work?
inhibit the final common pathway of platelet aggregation
What is anticoagulation therapy?
Prevention of thromboembolism
What is fibrinolysis
Breakdown existing clot
What is antiplatelet therapy?
Preventing platelet aggregation
What is the difference between anticoagulants and antiplatelets?
Anticoagulants target clotting factors
Antiplatelets target platelets