Warfarin

Question 1

Warfarin MOA

Answer 1

Inhibits vitamin K oxidase which prevent prothrombin precursor getting converted to prothrombin

• Does not affect existing clotting factors
• Affects factor II, IV, IX, X, protein C and S

Question 2

Half-life of Warfarin

Answer 2

36-42 hours while prothrombin half-life is 60-72 hours

Question 3

Warfarin PK

Answer 3

Highly plasma protein bound
Metabolized by the liver
Substrate of CYP450

Question 4

Warfarin AE

Answer 4

Bleeding
CI in pregnancy
Induced skin necrosis in those with a protein C or S deficiency
Purple toe syndrome dur to microembolization

Question 5

VTE (DVT/PE) INR Range

Answer 5

2.0-3.0

Question 6

A Fib INR Ranges

Answer 6

2.0-3.0

Question 7

AVR INR Ranges

Answer 7

2.0-3.0

Question 8

AVR + A Fib/Low EF/hypercoagulable INR Range

Answer 8

2.5-3.5

Question 9

MVR- mitral valve replacement INR Range

Answer 9

2.5-3.5

Question 10

Warfarin Initial Dose and Bridge Therapy

Answer 10

5 mg once daily
Avoid large loading doses >10 mg
 When initiating warfarin for treatment of acute thrombotic event (eg DVT), overlap IV heparin or LMWH until INR in range for 2 consecutive days (allows for adequate decrease in Factors II and X)

Question 11

Warfarin Drug Interactions

Answer 11

Bactrim (50%)
Metronidazole (50%)
Amiodarone (15-60%)
Rifampin (50%)
Herbals/OTC

Question 12

Warfarin Increased Sensitivity

Answer 12

•	Hyperthyroidism
•	Fever
•	HF exacerbations
•	ESRD
Diarrhea
•	Hepatic dysfunction

Question 13

Warfarin Decreased Sensitivity

Answer 13

Hypothyroidism

Question 14

Warfarin Food Interactions

Answer 14

Vitamin K
Grapefruit
Alcohol
Illness (N/V/D)

Question 15

Define Anticoagulation Management Services (AMS)

Answer 15

Each step is done by one person or small group of people to prevent mix ups

Question 16

AMS Benefits

Answer 16

 Improved time in therapeutic range
 Reduced frequency of bleeding complication and thromboembolic events
 Reduced costs

Question 17

INR Monitoring - When first initiating therapy

Answer 17

• Daily after 2 days on therapy until goal range obtained
• Then 2-3 times over the next week or two to assess stability
• In outpatient setting: Every 2-3 days until stable

Question 18

INR Monitoring - After dosage adjustments

Answer 18

• 5-7 days after change

Question 19

INR Monitoring- Stable patient with last INR in range

Answer 19

• First follow-up 2-4 weeks

* Then, every 4-6 weeks if consistently stable

Question 20

Things to assess with Warfarin Management

Answer 20

 Verify indication and target INR range to use
 Duration of therapy (e.g. post DVT)
 Assess compliance
 Check for any drug-drug interactions (including OTCs and herbals)
 Changes in lifestyle (significant diet changes, alcohol use, cigarette smoking)
 Any bleeding complications (mild, moderate, severe) – watch for bruises
 Any signs/symptoms of thromboembolic event

Question 21

Any potential causes?

Answer 21

• Alcohol
• Drug or food interaction
• Compliance (taking too much or too little)
• Illness (acute illness often raises INRs)

Question 22

***If INR has been very stable and INR is only 0.5 over/under goal range

Answer 22

o No change in dose, recheck INR 1-2 week

o May consider booster dose or 1x dosage decrease

Question 23

***If INR is 0.2-0.5 over or under goal range and patient hasn’t been very stable in recent past or have 2 INRs in a row out of range

Answer 23

o Increase / decrease weekly dose by 5-10%

o Hold 1 dose if supratherapeutic

Question 24

***If INR is 0.6-1.0 over or under goal range

Answer 24

o Increase / decrease weekly dose by 10-15%
o Hold 1-2 doses if supratherapeutic
o Consider extra dose(s) if INR under goal

Question 25

INR Rule of Thumb

Answer 25

10% change in weekly dose will increase/decrease INR by ~0.5

Question 26

INR less than 4.5 without bleeding

Answer 26

o Hold doses (# depends on INR range you want)

Question 27

INR 4.5-10.0 and no bleeding

Answer 27

o Hold and decrease weekly warfarin dose

o Could hold until you get a safer INR level then restart at lower dose (especially if > 6.0)

Question 28

INR > 10 and no bleeding

Answer 28

o Hold warfarin
o Oral Vitamin K: 2.5-5.0 mg x 1, repeat INR 12-24 hours
o May repeat if INR still not significantly lowered

Question 29

CHEST Grading System

Answer 29

1A: strong recommendation, high quality evidence
2C: weak recommendations, low or very low quality evidence

Question 30

AHA/ACC/HRS Grading System

Answer 30

o Class I (lots of benefits), IIa, IIb, III (no benefit)

o Level A (multiple populations), B and C (limited populations)