Warfarin Protocol

See Also

Indications

Management
INR variability

See Warfarin Drug Interactions
Vitamin K supplementation significantly helps stabilize INR levels
1. Vitamin K 100-150 mcg orally daily
2. (2007) Blood 109: 2419-33 [PubMed]
Medical conditions that increase INR levels
1. Hyperthyroidism
2. Diarrhea
3. Congestive Heart Failure
4. Liver Disease
Medical conditions that decrease INR levels
1. Hypothyroidism

Protocol
Starting Warfarin in elderly inpatients

General
1. Safe (no patient had an INR >4)
2. Therapeutic INR achieved within 6-7 days
Initial Dose: 4 mg daily for first 3 days
Dosing protocol after day 3 based on daily INR
1. INR <1.3: Warfarin 5 mg
2. INR 1.3-1.4: Warfarin 4 mg
3. INR 1.5-1.6: Warfarin 3 mg
4. INR 1.7-1.8: Warfarin 2 mg
5. INR 1.9-2.4: Warfarin 1 mg
6. INR >2.4: Hold Warfarin, check INR daily
References
1. Siguret (2005) Am J Med 118:137 [PubMed]

Protocol
Starting Warfarin in general patients

Indications for starting with concurrent Heparin (Lovenox)
1. Thrombophilic state (e.g. known Protein C Deficiency)
2. Thromboembolism (DVT, PE) within last 3 months
3. Atrial Fibrillation with Cerebrovascular Accident within last 3 months
4. Atrial Fibrillation with CHADS2-VASc Score >6
5. Mechanical Heart Valve patients (depending on valve)
Indications for starting Warfarin without Heparin
1. Chronic stable Atrial Fibrillation
Precautions
1. Do not use DOAC (e.g. Rivaroxaban) for bridging to Warfarin (use Lovenox or similar LMWH instead)
2. When starting DOAC, may stop Warfarin and start DOAC without overlap
3. Exception
  1. Transitioning from DOAC to Warfarin may warrant overlapping until Warfarin near therapeutic
  2. In all other cases, LMWH (e.g. Lovenox) is the standard for bridging Warfarin
4. References
  1. (2019) Presc Lett 26(2):9-10
Starting dose of Warfarin
1. Standard dose: 5 mg orally daily
  1. Anticipate therapeutic by day 4-5
2. High Dose: 10 mg daily for 2 days, then drop to standard dosing
  1. Indicated for urgency to reach therapeutic level
    1. Consider for young patients with Thromboembolism
    2. Avoid in chronic Atrial Fibrillation (no urgency to get to level)
  2. Study: 10 mg start was therapeutic 1.4 days earlier
    1. Kovacs (2003) Ann Intern Med 138:714-9 [PubMed]
3. Low dose: 2.5 mg orally daily (or use 4 mg protocol as described above)
  1. Elderly, frail or malnourished
  2. Serious liver disease
  3. High risk of bleeding
  4. Serious comorbidity
  5. Significant warfarin Drug Interaction
Protocol
1. Monitor daily INR (typically starting at day 3-4)
2. Stop Heparin when 2 consecutive INRs therapeutic
3. Monitor INR 2-3 times per week for 1-2 weeks
4. Monitor INR every 2-4 weeks when stable
5. Consider less frequent monitoring in stable patients
  1. Indications
    1. Stable INR without Warfarin dose change for 12 weeks
    2. Compliant patient, without other Bleeding Diathesis or serious comorbidity
  2. Protocol
    1. Consider spacing monitoring of INR to every 12 weeks
  3. References
    1. Schulman (2011) Ann Intern Med 155(10):653-9 [PubMed]
INR 2.2 to 2.3 associated with lowest overall mortality
1. Oden (2002) BMJ 325:1073-5 [PubMed]

Protocol
Adjust Warfarin (based on INR 2 to 3)

See Warfarin for other target INR indications
INR less than 2
1. Increase weekly Warfarin dose by 5 to 20%
INR 3 to 3.5
1. Decrease weekly Warfarin dose by 5 to 15% or
2. Maintain same dose and recheck in 7 days
  1. Banet (2003) Chest 123:499-503 [PubMed]
INR 3.6 to 5.0
1. Consider withholding one Warfarin dose
2. Decrease weekly Warfarin dose by 10 to 15%
INR 5.0 to 10.0
1. Withhold 1 to 2 Warfarin doses
2. Decrease weekly Warfarin dose by 10 to 20%
3. Indications for Vitamin K
  1. Bleeding or high bleeding risk: Vitamin K 1.0 to 2.5 mg orally for 1 dose
  2. Surgery in 24 hours: Vitamin K 2 to 4 mg orally x1 dose
INR exceeds 10.0
1. Hold Warfarin
2. Vitamin K 2.5 to 5 mg orally for 1 dose
3. Monitor INR daily and consider repeating Vitamin K
4. Anticipate significantly lower INR within 24-48 hours

Protocol
Mild to moderate bleeding risk (INR >5-10)

Hold Warfarin per protocols above
Vitamin K
1. Mild bleeding: Vitamin K 2.5 mg orally
2. Moderate-severe bleeding: Vitamin K 5-10 mg orally or IV
  1. Oral route is preferred in all but cases of threatened life or limb
  2. Oral Vitamin K has consistent absorption with excellent efficacy
  3. Intravenous Vitamin K risks Anaphylaxis reaction with infusion rates faster than 15-30 min

Protocol
Serious or Life-threatening bleeding (esp. INR >20)

Replace Clotting Factors (first-line)
1. Prothrombin Complex Concentrate 4 (PCC4, Kcentra or outside U.S. Octaplex, Beriplex)
  1. Preferred if available
  2. FFP-like serum extract that is 25 fold more potent than FFP
  3. Formulation in United States was PCC3 (without Factor 7) until 2013
  4. Cost is 20 times that of the $250 FFP dose (but faster acting and fewer reactions than FFP)
  5. Avoid in DIC
  6. Dose: 50 Units/kg
2. Fresh Frozen Plasma (FFP)
  1. Indicated if PCC is not available
  2. Fresh Frozen Plasma (FFP) 15 ml/kg (roughly 1 to 1.5 liters for most patients)
    1. Typical empiric adult dose: FFP 4 units
  3. INR of Fresh Frozen Plasma is 1.7
    1. Do not expect INR to drop below 1.6 following FFP administration
  4. Each FFP unit replaces 5% of Clotting Factors
  5. Anticipate 45 minutes to thaw FFP and 6 hours to completely transfuse the full 4 unit dose
3. Factor Eight Inhibitor Bypass Activity (FEIBA)
  1. Similar mechanism and components to PCC
4. Older regimens (not recommended)
  1. Factor VIIa replacement is no longer recommended
Reverse Warfarin effect
1. Vitamin K 5-10 mg by slow IV infusion (do not use subcutaneous dosing due to inconsistent absorption)
2. Anticipate Warfarin resistance after dose
3. Avoid in Valve Replacement
4. Anaphylaxis risk to IV Vitamin K is reduced with newer preparations from prior 3 events per 100,000
5. Anticipate 16 hour delay in effect
  1. Consider repeat INR at that time
  2. Consider repeating Vitamin K at 12 hours
References
1. (2013) Presc Lett 20(10): 57
2. Lex and Orman in Majoewsky (2013) EM:Rap 13(4): 4-5

Dosing Adjustment
Decreased Dosing

Decrease Dosing by 20% (27.5 mg per week)
1. Warfarin 2.5 mg PO on Monday, Wednesday, Friday
2. Warfarin 5 mg PO all other days
Decrease Dosing by 15% (30 mg per week)
1. Warfarin 2.5 mg PO on Monday and Friday
2. Warfarin 5 mg PO all other days
Decrease Dosing by 5% (32.5 mg per week)
1. Warfarin 2.5 mg PO on Monday
2. Warfarin 5 mg PO all other days

Dosing Adjustments
Standard Dosing

Warfarin 5 mg PO qd (35 mg per week)

Dosing Adjustments
Increased Dosing

Increase Dosing by 5% (37.5 mg per week)
1. Warfarin 7.5 mg PO on Monday
2. Warfarin 5 mg PO all other days
Increase Dosing by 15% (40 mg per week)
1. Warfarin 7.5 mg PO on Monday and Friday
2. Warfarin 5 mg PO all other days
Increase Dosing by 20% (42.5 mg per week)
1. Warfarin 7.5 mg PO on Monday, Wednesday, Friday
2. Warfarin 5 mg PO all other days

Resources

Point of Care Guide by Mark Ebell, MD
1. http://www.aafp.org/20050515/pocform.html

References