Anticoagulants, anti-thrombotics and thrombolytics

Question 1

How are haemorrhages prevented and how?

Answer 1

Vasospasm - restricts blood flow and facilitates platelet aggregation

Question 2

What is the difference between primary and secondary homeostasis?

Answer 2

Primary - formation of a platelet plug via aggregation restricting blood loss
Secondary - Formation of a fibrin clot - reinforces plug

Question 3

What does a low and high platelet count cause?

Answer 3

Low - excessive bleeding
High - increased risk of thrombosis

Question 4

What are the five steps in the platelet aggregation mechanism?

Answer 4

1. Endothelial Injury
2. Exposure
3. Adhesion
4. Activation
5. Aggregation (Primary haemostasis)

Question 5

What is haemostasis?

Answer 5

A process to prevent bleeding/haemorrhage

Question 6

What does healthy endothelial cells generate to maintain platelets in inactive state?

Answer 6

Nitric oxide, prostacyclin (PGI2), Expression of CD39

Question 7

What are the two pathways of secondary haemostasis (coagulation cascade)?

Answer 7

Intrinsic and Extrinsic pathways (both can be activated independently)

Question 8

What four components regulate the coagulation cascade?

Answer 8

Protein C, Anti-thrombin 3, Tissue factor pathway inhibitor, Plasmin

Question 9

What commonly causes arterial and venous thrombi and how are they treated?

Answer 9

Arterial - rupture of atherosclerotic plaque - antiplatelets and anticoagulants
Venous - adhesion of blood cells on endothelium - anticoagulants

Question 10

What three classes of drugs target blood coagulation?

Answer 10

Antiplatelets, anticoagulants and thrombolytic agents

Question 11

What does aspirin inhibit and how does it prevent and treat arterial thromboembolic disorders?

Answer 11

COX (Irreversibly), inhibiting synthesis of prostaglandins from arachidonic acid (mainly thromboxane A2), inhibiting platelet activation and aggregation

Question 12

What is the main side effect of aspirin?

Answer 12

It can cause an increased bleeding risk

Question 13

What other class of drugs are COX Inhibitors?

Answer 13

NSAIDS

Question 14

What are examples of ADP receptor inhibitors, how do they work and what is their main side effect?

Answer 14

Clopidogrel, prasugrel, ticagrelor

Block ADP binding to platelet P2Y12 receptors -> prevents thrombus formation and increases bleeding time

They increase risk of bleeding

Question 15

What is an example of a vitamin K antagonist and how does it work?

Answer 15

Warfarin, it’s structurally similar and it inhibits Vitamin K-dependent synthesis of coagulation factors (Factors 2,7,9,10)

Question 16

How would you reverse warfarins effects and what are its side effects?

Answer 16

Supplementation with vitamin K

Excessive bleeding risk, contraindicated in pregnancy, interacts with CYP450 drugs

Question 17

What are examples of antithrombin 3 potentiators and what do they inhibit?

Answer 17

• Heparin - thrombin and active factor X
• Enoxaparin (LMWH) - active factor X
• Fondaparinux

Question 18

How are heparin, enoxaparin and fondaparinux administered?

Answer 18

Parenterally,
Heparin - IV
Enoxaparin/Fondaparinux - SC

Question 19

What is an example of a direct thrombin inhibitor?

Answer 19

Dabigatran etexilate

Question 20

What is an example of an active factor X inhibitor?

Answer 20

Apixaban and Rivaroxaban

Question 21

What thrombolytic agents are derived from tPA, how are they administered and what do they bind to?

Answer 21

Alteplase, Reteplase, Tenecteplase.

Administered by IV

Bind to fibrin proteins in a clot

Question 22

What are examples of bacterial-derived thrombolytics and what is their main side effect on repeated administration?

Answer 22

Streptokinase and Anistreplase.

There’s a risk of severe allergic reaction as it is a bacterial immunogen
(Note: tPAs used preferentially)

Question 23

What are thrombolytic drugs used for?

Answer 23

Short Term emergency treatment of pathological thrombosis

Question 24

What are two examples of anti-fibrinolytics, how do they work and what are they used for?

Answer 24

Animocaproic and Tranexamic acid

Promote clotting by slowing down or preventing fibrinolysis

Haemophilia and in surgery to prevent blood loss