Drugs affecting haemostasis and thrombosis

Question 1

Describe some of the features of Tranexamic acid

Answer 1

It is an Anti-fibronolytic drug which inhibits the activation of plasminogen to plasmin.
-Therefore can be used in trauma, GI bleeding and post op/delivery of babies.

Question 2

How does Warfarin work?

Answer 2

Inhibiting the reduction of oxidised vitamin K. Reduced vitamin K acts as a catalyst in the generation of clotting factors and becomes oxidised during the reaction, however the oxidised form cannot act as a catalyst.

Question 3

What are some of the positive and negative aspects of warfarin?

Answer 3

Positive - Cheap, easily measurable effect and can be revered with vitamin K or factor concentrate

Negatives - Lots of drug interactions, slow onset, unpredictable dose, needs regular blood testing, risk of bleeding and narrow therapeutic window

Question 4

What are the some of drug interactions with Warfarin?

Answer 4

Increasing the effects of warfarin - Amoxycillin (reduce gut vit K), Erythromycin, statins and alcohol intake (enzyme inhibition), Aspirin and NSAIDs (increased risk of bleeding)
Decreasing the effects of Warfarin - Phenytoin and chronic alcohol use (enzyme induction)

Question 5

What are some of the indications for warfarin

Answer 5

DVT and PE, prosthetic heart valve replacement and arterial fibrillation to reduce stroke.

Question 6

Name two types of Direct Oral Anticoagulants (DOACs) and some examples

Answer 6

• Xa inhibitors (rivaroxaban, apixaban and edoxaban)

- Direct thrombin inhibitors (dabigatran)

Question 7

With warfarin over DOAC what are the reasons to favour DOAG’s?

Answer 7

• Good evidence it can be more effective than warfarin and with fewer side effects
• No monitoring needed
• Lower bleeding risk
• Effective for stroke prevention
• Reversible agents but super expensive
• Short half life

Question 8

Describe how Heparin works

Answer 8

It is a naturally occurring anticoagulant which binds to and activates anti-thrombin, reducing thrombin generation.

Question 9

What are the two types of heparin and their half lives

Answer 9

Unfractionated - half life = an hour

Low molecular weight (LMWH) half life = 12 hours

Question 10

How is IV heparin monitored?

Answer 10

By APTT plasma testing

Question 11

What are some of the adverse side effects of heparin

Answer 11

• Pain at injection site
• Increase risk of bleeding
• Osteoporosis with prolonged use
• Heparin induced thrombocytopenia

Question 12

Describe how aspirin is used to modify platelet function, the risks and when is it used

Answer 12

• Low doses irreversible inhibit cycooxygenase so less thromboxane A2 is produced so less aggregation of platelets.
• Typically used after transient ischaemic attack (TIA) or myocardial infarction
• Increase risk in GI bleed and Dyspepsia

Question 13

Describe some of the features of Clopidogrel

Answer 13

• works by inhibiting ADP induced platelet aggregation
• Used with aspirin to prevent recurrent myocardial infarction
• Used in ischaemic strokes and TIAs
• Increase risk of GI bleed and dyspepsia
• No reversal agents

Question 14

Describe some of the features of Thrombolytic drugs

Answer 14

• Increase activation of plasminogen to plasmin
• Causes breakdown of fibrin and fibrinogen
• Increased risk of bleeding
• Stent and clot removals are alternative treatments