VTE: Injectable Factor Xa Inhibitors and DTI

Question 1

Fondaparinux

Answer 1

Prophylaxis following THA, TKA, hip replacement, or abdominal surgery

Treatment of DVT or PE

Prophylaxis: 2.5 mg SQ once daily

Question 2

Fondaparinux Considerations

Answer 2

Do not use if have renal dysfunction (CrCl < 30 ml/min)

Do not use for prophylaxis with low body weight (<50 kg)

Can be used in HIT

No routine monitoring for therapeutic efficacy

Pregnancy category B

Question 3

IV Direct Thrombin Inhibitors

Answer 3

Lepirudin: HIT
Bivalirudin: HIT, UFH alternative during PCI
Argatroban: HIT

Question 4

NOAC Approved Indications

Answer 4

Dabigatran: Postoperative prophylaxis (Hip), Non-valvular Afib, DVT/PE treatment

Rivaroxaban: Postoperative prophylaxis, non-valvular afib, DVT/PE treatment, secondary prevention of recurrent DVT/PE, VTE prophylaxis

Apixaban: post op prophylaxis, non-valvular afib, dvt/pe treatment, secondary prevention of recurrent dvt/pe

Edoxaban: non-valvular afib, DVT/PE treatment

Question 5

Warfarin available strengths

Answer 5

1
2
2.5
3
4
5
6
7.5
10

all tabs are the same color

Question 6

Challenges of Warfarin

Answer 6

narrow therapeutic window

considerable inter-subject variability

drug and diet interactions

labs difficult to standardize

good PK/PD understanding by both patient/provider

Question 7

Warfarin MOA

Answer 7

Does not affect circulating factors or previously formed thrombi

Inhibits enzymes responsible for cyclic conversion of VIT-K

Inhibits synthesis of VIT-K dependent clotting factors
Factors 2, 7, 9, and 10
Proteins C AND S

Question 8

PK/PD and Half-lives

Answer 8

anticoagulant effect within 24 hours
- peak effect 72-96 hours
- duration of action fromm single dose: 2-5 days

hepatically metabolized
- CYP P450
- S: 2C9, 2C19, 2C18
- R: 1A2, and 3A4
DRUG INTERACTIONS

Factor 2: 60-100 h
Factor 7: 4-6 h
Factor 9: 20-30 h
Factor 10: 24-40 h