Anticoagulation

Vitamin K Antagonist

Warfarin (Coumadin)

• Tx Dose: Highly individualized; typically started at 2–5 mg orally once daily, then adjusted based on INR (International Normalized Ratio). Consult pharmacy to aid with dosing. 
• INR goal by indication:

• Renal dose: No change needed 
• Monitoring: Requires regular INR checks (initially daily or every few days, then weekly/monthly once stable). 
• Notes: Affected by diet, drug interactions, and genetics (e.g., CYP2C9, VKORC1 variants). 
• Reversal agents: Vitamin K (phytonadione), PCC, FFP. Onset within a few hours but takes 24-48 hrs for full effect.

No bleeding and elevated INR 

• INR <4.5: Vitamin K not recommended; HOLD warfarin until INR in range 
• INR 4.5-10: HOLD warfarin AND 1- 2.5 mg PO Vitamin K 
• INR >10: HOLD warfarin AND 2.5 - 5mg PO Vitamin K

Bleeding on warfarin

• Major bleeding (bleeding at critical site such as CNS, GI sites, bleeding causing HDUS, Hb drop >/= 2, requiring >/=2 units pRBCs): Hold warfarin, Give 10 mg IV Vitamin K and give PCC dosed by INR: 
• INR 2-3.9: 25 units/kg 
• INR 4-6: 35 units/kg 
• INR >6: 50 units/kg 
• Note: Use FFP 10-15 mL/kg if PCC is unavailable 
• Minor bleeding (not meeting major bleeding criteria; such as epistaxis, hematuria): Hold warfarin until hemostasis achieved. Give Vitamin K for elevated INR as you would for a non-bleeding patient. 
• Rapid reversal prior to surgery (emergent): Give PCC/FFP based on INR as you would in the setting of major bleeding
• Rapid reversal prior to surgery (within 24 hours): 1-2.5mg Vit K IV; repeat INR pre-operatively and give PCC/FFP based on INR as you would in the setting of major bleeding 
• KCentra ($$$): Contains Factors II, VII, IX, and X with Protein C, Protein S, and heparin 
• Given instead of plasma when insufficient time for plasma/Vit K to work (i.e. for life threatening hemorrhage) 
• Avoid giving in HIT 
• Administer with Vitamin K

Heparins 
Unfractionated Heparin (UFH) 

• Tx Dose: IV bolus of 60-80 U/kg (or 5,000 units), followed by continuous infusion of 18 U/kg/hour, adjusted to target aPTT (typically 1.5–2.5 times control, or 60–80 seconds, though depends on indication). 
• Renal dose: No change needed 
• PPX: 5000u Q8H 
• Monitoring: aPTT every 6 hours initially (automatic in order set) 
• Notes: Short half-life; used in hospital settings. 
• Reversal Agent: Protamine Sulfate. 1 mg IV /100 units of heparin given in the last 2–3 hours (max 50 mg). Rapid onset.

Low molecular weight heparin (LMWH)

• Enoxaparin (Lovenox) treatment dose: DVT/PE Treatment: 1 mg/kg subQ q12h, or 1.5 mg/kg QD. Renal adjustment: 1 mg/kg once daily if CrCl <30 mL/min. 
• Dalteparin (Fragmin) treatment dose: DVT/PE Treatment: 200 units/kg subQ QD. Renal Adjustment: Avoid altogether or monitor anti-Xa levels if CrCl <30 mL/min. 
• PPX: Lovenox 40 mg qDay. 30 mg qDay if CrCl <30 mL/min. Dalteparin 2,500-5,000 units qDay. 
• Monitoring: Anti-Xa levels may be checked in renal impairment, obesity, or pregnancy (target 0.5–1.0 IU/mL for twice-daily dosing). 
• Reversal Agent: Protamine Sulfate (Partial). 1 mg IV per 1 mg enoxaparin (or 100 units dalteparin) given in the last 8 hours. An additional dose of 0.5 mg IV per 1 mg or 100 units may be given for persistent bleeding after the first dose. Incomplete reversal; additional measures (e.g., PCC/FFP) may be needed for severe bleeding.

Indirect Factor Xa Inhibitor 
Fondaparinux (Arixtra) 

• DVT/PE Treatment dose: 
  • Weight <50 kg: 5 mg subcutaneously once daily. 
  • Weight 50–100 kg: 7.5 mg subcutaneously once daily. 
  • Weight >100 kg: 10 mg subcutaneously once daily. 
• Renal Adjustment: Contraindicated if CrCl <30 mL/min.

Direct Oral Anticoagulants (DOACs) 

Note: Multiple recent studies have shown that eliquis has lower bleeding risk than dabigatran, edoxaban, and rivaroxaban. In addition, a recent study demonstrated lower risk of recurrent VTE against rivaroxaban. Apixaban is generally the preferred DOAC, though rivaroxaban has the benefit of once-daily dosing and may be a better option in patients with adherence issues.

Apixaban (Eliquis) 

• Tx Dose: 
  • DVT/PE Treatment: if loading - 10 mg twice daily for 7 days, then 5 mg twice daily. 
  • AF (stroke prevention): 5 mg twice daily; reduce to 2.5 mg twice daily if ≥2 of: age ≥80, weight ≤60 kg, and/or serum creatinine ≥1.5 mg/dL. 
• Renal dose: Caution in severe renal impairment (CrCl <25 mL/min); not typically recommended. Consider dose decrease to 2.5 mg BID. 
• Reversal Agent: Andexanet Alfa (Andexxa) was removed from the US Market in December 2025. Use PCC 25-50 units/kg prior to urgent surgery or with major bleeding.

Rivaroxaban (Xarelto) 

• Tx Dose: 
  • DVT/PE Treatment: if loading - 15 mg twice daily with food for 21 days, then 20 mg once daily with food. 
  • AF (stroke prevention): 20 mg once daily with evening meal 
• Renal dose: Reduce to 15 mg once daily if CrCl 15–50 mL/min. Avoid if CrCl <15 mL/min. 
• Reversal Agent: Andexanet Alfa (Andexxa) was removed from the US Market in December 2025. Use PCC 25-50 units/kg prior to urgent surgery or with major bleeding.

Edoxaban (Savaysa) 

• Tx Dose: 
  • DVT/PE Treatment: 60 mg once daily (after 5–10 days of parenteral anticoagulation); reduce to 30 mg once daily if CrCl 15–50 mL/min or weight ≤60 kg. 
  • AF (stroke prevention): 60 mg once daily. Consider 30 mg once daily in patients with age >/= 65 years or weight

Additional Information 

• VA is starting to move towards rivaroxaban and apixaban for extended secondary thromboprophylaxis 
  • Write in your PADR for apixaban citing “pt uses a pillbox and cannot use dabigatran” 
• Pregnancy: UFH/LMWH (other agents may cross the placenta). Warfarin is a known teratogen in 1st trimester and has fetal bleeding risk in 2nd/3rd trimester. DOACs cross placenta and there is limited human data, animal studies suggest fetal harm. 
• BMI >40: Consider LMWH (dose is weight based) or warfarin (able to target INR). Fixed-dose regimens (e.g., DOACs) may underperform in extreme obesity. Apixaban or rivaroxaban can be used per ISTH guidelines (but avoid dabigatran and edoxaban) 
• GI malabsorption (e.g. Crohn's): Caution with DOACs, consider LMWH or warfarin.

Transitioning between Anticoagulants with DOACs

Peri-procedural Management of Anticoagulation 

• Temporary IVC filter indicated in pts with very recent acute VTE (within 3-4 weeks) for urgent/emergent surgery if the procedure requires AC delay >12 hours. Delay elective surgery. - For those at high risk of thromboembolism: 
• Consider continuing AC for low-bleeding-risk procedures like dental procedures, cutaneous biopsy/excision, ICD placement, and endovascular procedures. 
• Can bridge with LMWH or heparin drip