8.1 - Thrombolytic, Platelet, anticoagulant Therapies

Question 1

Explain the physiological mechanism by which thrombi are cleared

Answer 1

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.

Question 2

What are the 2 methods by which fibrinolytic drugs can work? Give examples of the 2 types.

Answer 2

Generating plasmin themselves e.g. alteplase or by binding to and activating endogenous plasminogen e.g. strptokinase.

Question 3

Explain why streptokinase can only be used once.

Answer 3

It is a bacterial product and therrefore produces an immune response. Body produces antibodies to it.

Question 4

Why is a slow infusion of streptokinase recommended?

Answer 4

To prevent or counteract the transient hypotension that occurs upon infusion

Question 5

Give 2 examples of recombinant tPA (r-tPA)

Answer 5

alteplase, reteplase

Question 6

What situations would fibrinolytic drugs be indicated for?

Answer 6

acute MI, major PE, acute ischaemic stroke

Question 7

What is the window of opportunity for fibrinolysis in an acute MI and an ischaemic stroke? Why is there a time frame?

Answer 7

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.

Question 8

What are the ADRs of fibrinolytic agents?

Answer 8

increased risk of haemorrhage.

Question 9

What are the major contra-indications for fibrinolytic therapy?

Answer 9

history of haemorhagic stroke, active peptic ulcer, recent surgery, uncontrolled hypertension, known coagulation defect

Question 10

How would you diagnose a CVA after fibrinolytic therapy?

Answer 10

CT or MRI diagnosis

Question 11

How would you treat serious bleeding post fibrinolytic therapy

Answer 11

transfusion of blood and inhibition of fibrinolytics and administration of tranexamic acid which competitively inhibits activation of plasmin.

Question 12

What is the mechanism of action of vitamin K antagonists?

Answer 12

Vitamin K promotes synthesis of prothrombin and factors VII, IX, and X.

Antagonise these to prevent synthesis of prothrombin

Question 13

Give an example vit K antagonist

Answer 13

warfarin

Question 14

How is vit K antagonist administered?

Answer 14

Orally

Question 15

How is vit K antagonist monitored? How long does it take to take effect?

Answer 15

monitored with INR

Gradual onset and persisting anticoagulant action on cessation of treatment

Question 16

What ADRs are associated with vit K antagonists?

Answer 16

excessive bleeding or bruising. Teratogenic

Question 17

How would you reverse vit K antagonists?

Answer 17

administration of IV vit K

Question 18

How does heparin work?

Answer 18

heparin binds to antithrombin, increasing inhibition of thrombin and Xa

Question 19

How is heparin administered? How long does it take to take effect? how is it monitored

Answer 19

Monitored with APTT (activated partial thrombin time)

Rapid onset and offset

IV or subcutaneous

Question 20

What are the ADRs of heparin?

Answer 20

bleeding, thrombocytopenia, osteoporosis (long term)

Question 21

How is heparin reversed?

Answer 21

Protamine sulphate causes dissociated of heparin/antithrombin complex and binds irreversibly to heparin

Question 22

What are the 3 types of antiplatelet agents? Give examples of each

Answer 22

Thromboxane A2 inhibition - aspirin, dipyridamole

Platelet ADP receptor antagonist - ticlopidine, clopidogrel

GPIIb/IIa inhibitor

Question 23

What is the mechanism of action of thromboxane A2 inhibitors

Answer 23

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

Question 24

How do platelet ADP receptor antagonists work?

Answer 24

ADP to ADP receptor interaction is one of the stimuli needed for platelet aggregation. Antagonising.

Question 25

How do GpIIa/IIb inhibitors work?

Answer 25

inhibit the final common pathway of platelet aggregation

Question 26

What is anticoagulation therapy?

Answer 26

Prevention of thromboembolism

Question 27

What is fibrinolysis

Answer 27

Breakdown existing clot

Question 28

What is antiplatelet therapy?

Answer 28

Preventing platelet aggregation

Question 29

What is the difference between anticoagulants and antiplatelets?

Answer 29

Anticoagulants target clotting factors

Antiplatelets target platelets