12.5 Management of Coagulopathies & Bleeding Disorders

Question 1

Acute vs long-term goals of antiplatelet therapy

Answer 1

Acute: Stop progression of acute thrombus
Long-term: prevent recurrence of CVA, MI etc.

Question 2

Acetylsalicylic acid is also known as…

Answer 2

Aspirin

Question 3

“Low-Dose Aspirin” is the typical dosage in Australia; how much is it, and how often is it taken?

Answer 3

• 100mg
• Once daily

Question 4

Describe the mechanism of aspirin

Answer 4

Inhbits COX-1 enzyme, prevents synthesis of Thromboxane A2, which is otherwise used for autocrine platelet activation, thus inhibiting platelet aggregration.

Question 5

Clopidogrel mechanism

Answer 5

IRREVERSIBLY binds to ADP receptor

Question 6

Ticagrelor mechanism

Answer 6

REVERSIBLY binds to ADP receptor

Question 7

Antiplatelets vs anticoagulants

Answer 7

Antiplatelets: stop primary haemostasis
Anticoagulants: stop secondary haemostasis

Question 8

Acute vs long-term goals of anticoagulant therapy

Answer 8

Acute:
- Prevent extension of acute thrombus
- Prevent embolisation
Long-Term:
- Preventing AF-association thromboembolism
- Prevent VTE recurrence

Question 9

Heparin mechanism

Answer 9

• Binds to antithrombin; makes it up to 1000 times more effective (!)
• Increased thrombin breakdown -> decreased fibrin production -> decreased coagulation

Question 10

Warfarin mechanism

Answer 10

• Prevents recycling of vitamin K
• Depletse Vit-K dependent factors from the coagulation cascade

Question 11

Which clotting factors are Vitamin-K Dependent

Answer 11

2, 7, 9, 10

Question 12

Targets of LMW vs unfractionated heparin…

Answer 12

LMW: Predominantly Factor Xa
Unfractionated: both Xa and antithrombin

Question 13

Direct acting anticoagulant (DOAC) mechanism

Answer 13

Binds to and inhibits factor Xa

Question 14

Give two examples of Direct acting anticoagulants

Answer 14

• Apixaban
• Rivaroxaban

Question 15

Common uses of thrombolysis

Answer 15

• Acute ischaemic stroke
• Acute MI
• Acute Limb Ischaemia
• Massive PE

Question 16

How do tissue Plasminogen Activators (tPAs) cause fibrinolysis?

Answer 16

• catalyse the activation of plasminogen into plasmin

Question 17

Give some examples of tPAs

Answer 17

• Tenecteplase
• Alteplase

Question 18

How is gene therapy used in Factor IX replacement therapy?

Answer 18

• Viral vector carries gene to liver
• Cause expression of gene to synthesise protein

Question 19

Indications for antiplatelets

Answer 19

Arterial thrombotic disease:
- Cardio (such as in coronary PCI)
- Cerebrovascular disease
- Peripheral vascular disease
- Pre-eclampsia prevention

Question 20

Contraindications for antiplatelets

Answer 20

• Avtice/recent haemorrhage
• Upcoming/recent surgery
• Thrombocytopaenia

Question 21

Side effects of antiplatelets

Answer 21

• Blood loss
• GI irritation

Question 22

What are three specific side effects associated with ticagrelor

Answer 22

• Dyspnoea
• Bradycardia
• Gout

Question 23

Can most procedures be done on aspirin? What about dual platelet therapy?

Answer 23

• MOST (not necessarily all) can be done on aspirin
• Usually, allow one antiplatelet to wash out of system for 5-7 days before surgery if on dual

Question 24

Which has higher bleeding risk: anticoagulants or antiplatelets?

Answer 24

Anticoagulants

Question 25

What advice would you give to a patient who you are prescribing anticoagulants to?

Answer 25

- No contact sports :( - High-risk occupations - Important to keep doses consistent/don't miss them

Question 26

Indications for prophylactic vs therapeutic heparin

Answer 26

Prophylaxis: VTE prevention Therapeutic: treatment of VTE, acute arterial events, or mechanical valve prophylaxis

Question 27

Contraindications for heparins

Answer 27

- Active/recent haemorrhage - Severe thrombocytopaenia

Question 28

Side effects of heparins

Answer 28

- Heparin-induced thrombocytopaenia syndrome (HIITS) - Bleeding; liver enzyme elevation - Long term: alopecia, osteoporosis

Question 29

Describe Heparin-Induced Thrombocytopaenia Syndrome

Answer 29

- Antibodies formed against platelets - Leads to antibody destruction, and yet HYPERthrombotic state

Question 30

Benefits/limitations of LMW heparin

Answer 30

Benefits: - Subcutaneous (can be used for outpatients) - Fixed dosage - No monitoring needed Limitations: - Only partially reversible - Short half life

Question 31

Benefits/limitations of unfractionated heparin

Answer 31

Benefits: - Fully reversible - Independent of renal function Limitations: - IV (so only for inpatients) - Requires frequent monitoring - Complex dosing algorithm

Question 32

What are some rare circumstances where a patient requires monitoring for being on LMW heparin

Answer 32

- Obesity - Pregnancy - Renal impairment

Question 33

Indications for therapeutic vs prophylactic DOACs

Answer 33

- Prophylaxis: VTE prevention - Therapeutic: VTE or AF treatment

Question 34

Contraindications for DOACs

Answer 34

- Renal impairment - Recent haemorrhage - Severe thrombocytopaenia - Pregnancy

Question 35

Risks of DOACs

Answer 35

- No reversal agent currently - Rivaroxaban also has higher risk of menorrhagia than apixaban

Question 36

Indications for warfarin

Answer 36

- Mechanical heart valve (arterial thrombi prophylaxis) - Anticoagulation in renal disease

Question 37

Contraindications for warfarin

Answer 37

- Active/recent haemorrhage - Severe thrombocytopaenia - Pregnancy

Question 38

Side effects of warfarin

Answer 38

- Bleeding - Long-term: alopecia, hepatic dysfunction

Question 39

Importance of diet in warfarin prescription

Answer 39

If suddenly changed, vitamin K levels could change, altering drug effectiveness

Question 40

Why do you start enoxaparin when you start warfarin?

Answer 40

Because, initially warfarin depletes Protein C before is inhibits vitamin K recycling, creating a prothrombotic state. The enoxaparin prevents this from causing acute thrombotic events.

Question 41

Describe factor replacement therapy in Haemophilia A and Haemophilia B

Answer 41

H. A: Recombinant Factor VIII H. B: Recombinant Factor IX

Question 42

Describe factor replacement therapy for von Willebrand's Disease

Answer 42

- First, give desmopressin, which increases endothelial release of vWF - If not enough, give purified vWF with Factor VIII

Question 43

What is the function of Tran Examic Acid (TXA)?

Answer 43

- Opposes the function of tPA; opposes conversion of plasminogen into plasmin

Question 44

What are some indications for antifibrinolytic therapy?

Answer 44

- GI bleeding - Menorrhagia - Gum/dental bleeding - Epistaxis

Question 45

Describe novel therapy of Haemophilia A

Answer 45

- Synthetic replacement of Factor VIII by using a bi-specific antibody that binds factors IX and X