Weber Warfarin

Question 1

Determine appropriate therapeutic goal INR ranges for specific indications

Answer 1

• INR goal 1.5-2.0: aortic valve replacement-mechanical on-x
• INR goal 2.0-3.0: prophylaxis & treatment of VTE, mechanical heart valve (aortic)
• INR goal 2.5-3.5: mechanical heart valve (mitral, caged ball, high risk), oral anticoagulant to prevent recurrent MI

Question 2

Identify common gene mutations associated with warfarin metabolism

Answer 2

CYP2C9*1,2,3
* *2 & 3: decr S-warfarin clearance –> lower dose req

VKORC1 (gene that encodes the Vit K reductase enzyme)
* A: incr warfarin sensitivity –> lower dose req
* G: incr warfarin resistance –> higher dose req

2&3 don’t need me (need less)
A little bitch (sensitivity->lower dose)
G’s get high (need higher dose)
lower dose for all except G

Question 3

Warfarin genetic testing

Answer 3

Pt must meet all 3 reqs
1. pt is warfarin naive
2. genetic tests available before 6th dose
3. pt at high risk of bleeding if INR is elevated (usually from concomitant therapy)

Question 4

Identify common drug interactions of concern

Answer 4

Vit K reverses effects of warfarin, so consistency is key
aspirin and NSAIDs incr bleeding risk but no effect on INR
cipro, metronidazole, bactrim, fluconazole, amiodarone incr INR
rifampin decr INR
* Vit K: reverses effects of warfarin
* Aspirin & NSAIDs: incr bleeding risk, no effect on INR
* Cipro, metronidazole, bactrim, fluconazole, amiodarone: incr INR (so decr warfarin dose)
* Rifampin: decr INR (so incr warfarin dose)

Question 5

Provide appropriate education to a patient who is initiating therapy

Answer 5

inform Dr about meds taking (including aspirin, ibuprofen, antibacterial), alc consumption, Vit K consumption

Question 6

frequency of INR monitoring

Answer 6

• 1 INR in first week
• 1 INR in second week
• once 2 INRs are at goal, then incr freq to 2 weeks, then 4 weeks

Question 7

tablet strengths

Answer 7

1, 2, 2.5, 3, 4, 5, 6, 7.5, and 10 mg

Question 8

surgery

Answer 8

• stop warfarin 5 days before surgery
• give LMWH or UFH until procedure
• stop LMWH 24 hr before
• stop UFH 4-6 hr before
• warfarin resumed 12-24 hrs after surgery

Question 9

coagulation cascade

Answer 9

1. Initiation
   * damage to blood vessel -> collagen exposed to TF -> activates factor VII
2. Amplification
   * factors IX and X are activated -> X is activated to Xa -> prothrombinase complex formed (Xa, V, Ca2+) -> prothrombin converted to thrombin -> thrombin converts fibrinogen (I) into fibrin -> forms blood clot
3. Propagation
   * thrombin promotes activation of platelets and coagulation factors -> Factor XIII cross-links the fibrin strands -> stabilizes clot

Question 10

Warfarin MOA

Answer 10

• Works in liver & blocks synthesis of Vit K dependent clotting factors (II, VII, IX, X) & protein C, S; inhibits Vit K reductase
• only works to prevent new factors from forming, not already existing factors so it takes about 2-5 days to see effects of warfarin

Question 11

CHA2DS2-VASc

Answer 11

risk factors for stroke or systemic VTE; only score for pts with Afib
score of 2 means to initiate anticaog therapy

• Congestive heart failure (1)
• Hypertension (1)
• Age 75 or older (2)
• Diabetes (1)
• Stroke/TIA (2)
• Vascular disease (1)
• Age 65-74 (1)
• Female (1)

Question 12

Vitamin K-depending clotting factors

Answer 12

• Factors II, VII, IX, X
• Remember: 2+7=9, not 10