Antiplatelets, Anticoagulants & Thrombolysis

Question 1

What is the difference between a venous thrombus and an arterial thrombus.

Answer 1

Venous - ‘red’ - RBC and fibrin rich, platelet low.

Arterial - ‘white’ - platelet rich, fibrin low.

Question 2

How does treatment differ for arterial and venous thrombosis?

Answer 2

Arterial - use antiplatelets and fibrinolytic drugs.

Venous - use anticoagulants.

Question 3

Describe the production of prostaglandins and thromboxanes.

Answer 3

Tissue damage during the inflammatory process produces phospholipase A2, which converts phospholipids in the membrane into arachidonic acid. Oxidation of arachidonic acid by COX enzymes produces eicosanoids such as thromboxanes, prostaglandins and leukotrienes.

Question 4

What is the rate limiting enzyme in the eicosanoid generation?

Answer 4

Phospholipase A2.

Question 5

How is thromboxane A2 formed and what are its effects?

Answer 5

Formed by COX-1

Causes vasoconstriction and promotes platelet aggregation

Question 6

How is PGI-2 produced and what are its effects?

Answer 6

Produced by COX-2

Causes vasodilation and inhibits platelet aggregation

Question 7

Name 3 COX-1 selective inhibitors.

Answer 7

Aspirin
Ibuprofen
Naproxen

Question 8

What is the MOA of COX-1 inhibitors.

Answer 8

Inhibit COX-1 enzyme, reducing TXA2 synthesis, therefore inhibits platelet aggregation.

Question 9

What is the MOA of COX-2 inhibitors?

Answer 9

Inhibit COX-2 enzymes, reducing PGI2 synthesis, which promotes platelet aggregation.

Question 10

Name a COX-2 selective inhibitor.

Answer 10

Celecoxib

Question 11

Name a non-selective COX inhibitor.

Answer 11

Diclofenac

Question 12

State a side effect of aspirin.

Answer 12

Prolonged bleeding time due to reduced TXA 2 synthesis and reduced platelet aggregation.

Question 13

What are P2Y12 inhibitors used for? What is their MOA?

Answer 13

Antiplatelet agents

Inhibit binding of ADP to P2Y12 receptors, inhibits activation of GPIIb/IIIa receptors.

Question 14

What drug class are clopidogrel and ticagrelor?

Answer 14

P2Y12 receptor antagonists, both are prodrugs.

Question 15

What are Glycoprotein IIb/IIIa inhibitors used for? What is their MOA?

Answer 15

Antiplatelet agents
Antibody irreversibly blocks receptor, preventing fibrinogen binding to IIb/IIIa receptors on platelets, reduces platelet aggregation.

Question 16

Name a GIIb/IIIa inhibitor.

Answer 16

Abciximab.

Question 17

What drug class is dipyramidole and what is it used for?

Answer 17

Phosphodiesterase inhibitor - used as an antiplatelet.

Question 18

What is the MOA of dipyramidole?

Answer 18

Prevents cAMP and cGMP degradation, which inhibits expression of GPIIb/IIIa, reducing platelet aggregation.

Question 19

What are streptokinase, alteplase and reteplase used for? What is their MOA?

Answer 19

Fibrinolytic

Increase fibrinolysis.

Question 20

What is the MOA of tranexamic acid?

Answer 20

Anti-fibrinolytic
Inhibits fibrinolysis, slows breakdown of clots, which helps to prevent prolonged bleeding.
Often used for menorrhagia.

Question 21

What is the MOA of warfarin?

Answer 21

Stops production of active vitamin K, reducing synthesis of vitamin K-dependent clotting factors - II (prothrombin), VII, IX and X.

Question 22

What is heparin cover?

Answer 22

When warfarin is taken, there is a delay in onset of action as active circulating clotting factors will be present for several days. During this time, heparin can be given.

Question 23

Is warfarin taken orally or IV? Why?

Answer 23

Orally as it has 100% bioavailability and good GI absorption.

Question 24

How can warfarin be monitored?

Answer 24

• INR (internal normalised ratio - ratio of speed of someone’s clotting action compared to standardised value).
• prothrombin time

Question 25

Is warfarin safe in pregnancy?

Answer 25

No, as it can cross the placenta.

Question 26

What is the main side effect of warfarin?

Answer 26

Bleeding.

Question 27

What is the most effective antidote to bleeding caused by warfarin?

Answer 27

Vitamin K1 | Also stop warfarin

Question 28

In a patient with PE, which drugs should be given?

Answer 28

- immediate heparinisation - stops thrombus propagation - oral anticoagulant e.g. Warfarin or DOAC e.g. Rivaroxiban for 3 months - fibrinolytic e.g. Streptokinase

Question 29

In patients who cannot be given anticoagulant drugs, which surgical intervention can be used?

Answer 29

IVC filter - collects any clots coming up from the legs.

Question 30

What is a d-dimer test?

Answer 30

Positive result indicates that there has been significant thrombus formation and breakdown in the body e.g. May have had a PE. (D-diner is a fibrin degradation product released into the blood when a thrombus is degraded by fibrinolysis).

Question 31

What would happen if you gave warfarin and aspirin together?

Answer 31

Dual action of inhibiting platelet function/thinning blood can lead to bleeding.

Question 32

What is a parenteral anticoagulant?

Answer 32

Means that it doesn't enter the GI tract e.g. Heparin, which is given IV.

Question 33

Name the 2 types of heparin that can be given.

Answer 33

Unfractionated heparin | Low molecular weight heparin

Question 34

Name some uses for heparin.

Answer 34

- DVT - PE - AF - pregnancy (doesn't cross the placenta)

Question 35

What is heparin reversal?

Answer 35

Protamine sulphate can be given as an antidote to heparin, it dissociates heparin from ATIII, often given following surgery.

Question 36

What is heparin induced thrombocytopenia (HIT)?

Answer 36

When heparin-dependent IgG antibodies activate platelets and produce a hypercoagulable state.

Question 37

What is the MOA of unfractionated heparin?

Answer 37

Binds to AIII (antithrombin), inactivating IIa and Xa. To inhibit IIa, heparin needs to simultaneously bind to ATIII and IIa (thrombin). To inhibit Xa, only needs ATIII binding.

Question 38

What is the MOA of low molecular weight heparin?

Answer 38

Binds to AIII (antithrombin) to inactivate Xa.

Question 39

Name 2 LMWHs.

Answer 39

Dalteparin | Enoxaparin

Question 40

Of UFH and LMWH, which is more likely to cause thrombocytopenia?

Answer 40

UFH

Question 41

What is the MOA of Fondaparinux?

Answer 41

Anticoagulant that selectively inhibits Xa by binding to ATIII.

Question 42

What is a DOAC?

Answer 42

Direct oral anticoagulant: Rivaroxaban, apixaban, that inhibits both free Xa and that bound with ATIII. Has no effect on IIa. Argatroban and dabigartran both inhibit IIa.