Anti-coagulants

Question 1

what is the MOA of UH? of LMWH?

Answer 1

UH:

1. forms complex between anti-thrombin III and thrombin - inactivates thrombin
2. increase anti-thrombin III activity against factor Xa

LMWH:
1. increase anti-thrombin III activity against factor Xa

Question 2

name examples of LMWH

Answer 2

dalteparin, enoxaparin, tinzaparin

Question 3

how are heparins administered?

Answer 3

UH: IV bolus + IV infusion
LMWH: S/C injection

Question 4

name characteristic side effects of heparin

Answer 4

1. bleeding
2. hyperkalaemia (inhibition of aldosterone secretion)
3. heparin-induced thrombocytopenia (autoimmune reaction as heparin is immunogenic) - less with LMWH
4. osteoporosis (long-term use) - less with LMWH

Question 5

how would you monitor UH and LMWH use? how would you reverse effcts if required?

Answer 5

UH:

• APTT ratio (check 6 hrs after dose change and 24 hourly once pt established within therapeutic range)
• check platelet count regularly between day 5-14

LMWH:
- anti-Xa assay - not required routinely

Reversal: protamine sulphate (only partially effective in LMWH)

Question 6

what is the MOA of warfarin?

Answer 6

inhibits vitamin K epoxide reductase… inhibits production of vitK-dependent clotting factors (II, VII, IX and X)

Question 7

name common ADRs of warfarin

Answer 7

1. bleeding

2. teratogenic

Question 8

what can interfere with warfarin action?

Answer 8

• vitK found in health foods, supplements, large amounts of leafy green veg or green tea
• pomegranate - increased INR in response to warfarin

Question 9

which parameters should be monitored with warfarin use?

Answer 9

1. baseline PT

2. INR measured daily in early days of Tx, then at longer intervals, then up to 12 wks

Question 10

what is target INR for the different indications of warfarin?

Answer 10

INR 2.5 for:

• DVT or PE
• AF or cardioversion
• dilated cardiomyopathy
• MI
• bioprosthetic valve

INR 3.5 for:

• recurrent DVT or PE
• mechanical valve

Question 11

how would you reverse warfarin therapy if:

1. INR <8 and no/minor bleeding
2. INR >8 and no/minor bleeding
3. major bleeding

Answer 11

1. stop warfarin (restart when INR <5)
2. stop warfarin (restart when INR <5) and give 0.5-2.5 mg oral vitK if other bleeding risk factors present
3. stop warfarin, give PT complex concentrate or FFP and give 5 mg oral/IV vitK

Question 12

describe the MOA of the different DOACs

Answer 12

• dabigatran: direct competitive thrombin inhibitor

- apixaban/rivaroxaban/edoxaban: factor Xa inhibitors