Drugs affecting haemostasis

Question 1

What are the drug targets of haemostasis?

Answer 1

• Anticoagulants: for those who have a tendency to clot. People with acute coronary syndromes, stent thrombosis, cerebral ischaemic attacks, hospitalised patients with limited mobility, patients undergoing invasive surgery
• Goal: prevent thrombosis (formation of the blood clot)

Question 2

What are the 5 commonly prescribed drugs affecting haemostasis?

Answer 2

Here are the types of anticoagulants

1. Platelet inhibitors
   ○ COX inhibitors
   ○ ADP receptor antagonists
   ○ GP IIb/IIIa antagonists
2. Directly acting anticoagulants
3. Indirectly acting anticoagulants; interferes with the synthesis of coagulation proteins
4. Thrombolytics: activate plasminogen to dissolve thrombin. Example: tranexamine
5. Fish oil: reduces primary haemostasis by reducing platelet aggregation

Question 3

Platelet inhibitors: COX inhibitors

Answer 3

• Example is aspirin

In low doses, it irreversibly inhibits COX 1, thus affecting the synthesis of platelets

Question 4

Platelet inhibitors: ADP receptor antagonists

Answer 4

• Can be reversible or irreversible
• Theyblock ADP-induced platelet aggregation and activation
• (Have GREL as suffix)
Clopidogrel, prasugrel (irreversible); ticagrelor (reversible)

Question 5

Platelet inhibitors: GP IIb/IIIa antagonists

Answer 5

• Abciximab
• Inhibit of the GpIIb/IIIa receptor on the surface of the platelets
• GP IIb/IIIa is a receptor on platelets which binds to fibrinogen and vWF fibres, thus it aids in platelet activation
• Stops platelet from binding to vWF

Question 6

Directly acting anticoagulants: dabigatran

Answer 6

• Directly inhibits thrombin (which is the activator for fibrin)

Question 7

Directly acting anticoagulants: Factor Xa inhibitors

Answer 7

• Factor Xa is an enzyme in the coagulation cascade. It is the last step before the formation of prothrombin, then thrombin
• Thus, drugs block factor Xa
• Rivaroxaban, Apixaban, Edoxaban, Betrixaban (suffix xaban)
Remember: ban = stop, thus you are banning cofactor Xa: Xaban

Question 8

What type of anticoagulant is aspirin?

Answer 8

Platelet inhibitor:

COX inhibitors

Question 9

What type of anticoagulant are Clopidogrel, prasugrel (irreversible); ticagrelor (reversible)

Answer 9

Platelet inhibitor:

ADP receptor antagonists

Question 10

What type of anticoagulant are abciximab?

Answer 10

Platelet inhibitor:

GP IIb/IIIa antagonists

Question 11

What type of anticoagulant is Dabigatran?

Answer 11

Directly acting anticoagulants

Question 12

What type of anticoagulant is Rivaroxaban, Apixaban, Edoxaban, Betrixaban ?

Answer 12

Directly acting anticoagulants:

Factor Xa inhibitors

Question 13

What type of drug is warfarin?

What type of drug is heparin?

Answer 13

Warfarin: Indirectly acting anticoagulants

Heparin: Directly acting anticoagulants

Question 14

Describe the common adverse effects of anticoagulants.

Answer 14

• Blood in urine
• Blood in stool
• Severe bruising
• Prolonged nose bleeds
• Bleeding gums
• Vomiting/ coughing blood
• Chest pain
• Severe back pain
• Heavy bleeding during periods

Question 15

What are measures used to assess clotting times?

Answer 15

• Measures how quickly individuals clot/ produces thrombin
• aPTT: measures intrinsic pathway (lon(er pathway, longer name)
• PT: measures extrinsic pathway (shorter pathway, shorter name)
• Healthy amount: around 1

Question 16

What do you do when excessive bleeding occurs in the clinical settings?

Answer 16

• Try to induce natural haemostasis by applying pressure, electrocautery, cooling, sutures. Give them adrenaline as this induces vasoconstriction
• Aid with clotting by providing things like gelatin, cellulose, collagen so that a physical matrix can be made. Alternatively, you can apply topical thrombin, fibrin sealants, antifibrinolytics (stops lysing of fibrin/ blood clot)