Anticoagulation

Sarah Fittro

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).
  • Target INR:
    • 2.0–3.0: For most indications (e.g., AF, DVT, PE).
    • 2.5–3.5: For mechanical heart valves or certain other conditions.
  • Renal dose: No change needed
  • PPX: 5000u Q8H
  • Monitoring: Requires regular INR checks (initially daily or every few days, then weekly/monthly once stable).
  • Hold prior to procedure: Several days (Goal INR <1.5)
  • Notes: Affected by diet, drug interactions, and genetics (e.g., CYP2C9, VKORC1 variants).
  • Reversal agent: Vitamin K (phytonadione). 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
      • INR 4.5-10: 1- 2.5 mg PO Vitamin K
      • INR >10: 2.5 - 5mg PO Vitamin K
    • Minor bleeding (e.g., epistaxis, hematuria): 5–10 mg PO or IV (over 30 minutes). Consider FFP.
    • Major bleeding (e.g., intracranial hemorrhage, GI bleed): Give 10mg IV Vitamin K over 30 minutes. Combine with PCC or FFP for immediate reversal.
  • Rapid reversal INR > 5 prior to surgery: 5mg Vit K IV (24 hours prior to procedure)
  • FFP: 15 ml/kg (e.g. 4 units/70 kg person) if need reversal <24 hrs, plus give Vitamin K
  • 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 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).
  • Renal dose: No change needed
  • PPX: 5000u Q8H
  • Monitoring: aPTT every 6 hours initially (automatic in order set)
  • Hold prior to procedure: 6 hours
  • 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: Monitor anti-Xa levels if CrCl <30 mL/min.
  • Monitoring: Anti-Xa levels may be checked in renal impairment, obesity, or pregnancy (target 0.5–1.0 IU/mL for twice-daily dosing).
  • Hold prior to procedure: 12 hours
  • Reversal Agent: Protamine Sulfate (Partial). 1 mg IV per 1 mg enoxaparin (or 100 units dalteparin) given in the last 8 hours. Incomplete reversal; additional measures (e.g., FFP) may be needed for severe bleeding.

Indirect Factor Xa Inhibitor

Fondaparinux (Arixtra)

  • DVT/PE Treatment dose: HEMATOLOGY-ONCOLOGY 199
    • 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.
  • Cardioversion If refractory to medical management
  • Treatment of underlying cause if identifiable
    • Ischemia, electrolyte disturbances, heart failure, drugs

Direct Oral Anticoagulants (DOACs)

Apixaban (Eliquis) 

  • Tx Dose:
    • DVT/PE Treatment: 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, or serum creatinine ≥1.5 mg/dL.
  • Renal dose: Caution in severe renal impairment (CrCl <15 mL/min); not typically recommended.
  • Hold prior to procedure: At least 48 hours
  • Reversal Agent: Andexanet Alfa (Andexxa). Very $$$. Not on VUMC formulary but is on the VA formulary.

Dabigatran (Pradaxa) 

  • Tx Dose:
    • DVT/PE Treatment: 150 mg twice daily (after 5–10 days of parenteral anticoagulation, e.g., heparin).
    • AF (stroke prevention): 150 mg twice daily
  • Renal dose: Reduce to 75 mg twice daily if CrCl 15–30 mL/min. Contraindicated if CrCl <15 mL/min.
  • Hold prior to procedure: At least 48 hours
  • Reversal Agent: Idarucizumab (Praxbind). 5 g IV (given as two 2.5 g doses, 15 minutes apart). Monoclonal antibody that binds dabigatran, neutralizing its effect. Rapid onset (within minutes). Consult Hematology

Rivaroxaban (Xarelto)

  • Tx Dose:
    • DVT/PE Treatment: 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.
  • Hold prior to procedure: At least 48 hours
  • Reversal Agent: Andexanet Alfa (Andexxa). Very $$$. Not on VUMC formulary but is on the VA formulary.

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
  • Renal dose: 30mg QD for CrCl 15-50 mL/min. Avoid if CrCl <15 mL/min.
  • Hold prior to procedure: At least 48 hours

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”
  • Hx of GI bleed: Apixiban (Eliquis) has the best GI safety profile among DOACs. Avoid dabigatran, rivaroxaban, edoxaban (may have higher risk of GI bleed). Warfarin has higher risk of GI bleed than apixaban but lower than dabigatran or rivaroxaban in some analyses (e.g., GI bleeding rate ~1–3% per year, depending on INR control).
  • 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.
  • Duration: Varies by condition (e.g., 3–6 months for provoked DVT, lifelong for AF or recurrent events).

Transitioning between Anticoagulants with DOACs

From

To

Timing
DOAC Warfarin Low-moderate risk DVT/PE: start warfarin while pt is on DOAC, stop DOAC on day 3 of warfarin therapy, and check INR on day 4
High risk DVT/PE: start LMWH or UFH, then start warfarin
DOAC LMWH Stop DOAC and start LMWH when due for next DOAC dose
DOAC UFH Start IV heparin with bolus when next DOAC dose is due
LMWH Warfarin LMWH and warfarin given simultaneously until INR is therapeutic for 24h
LMWH DOAC Stop LMWH and start DOAC when due
UFH DOAC Start DOAC when IV stopped (30min prior to cessation if high risk for thrombosis)
Warfarin DOAC Start DOAC when INR < 2.0

Peri-procedural Management of Anticoagulation 

  • Temporary IVC filter indicated in pts with very recent acute VTE (within 3-4 weeks) if the procedure requires AC delay >12 hours
  • 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

Stop before procedure

Restart after procedure
Warfarin 5 days prior, check INR day of 12 to 24 hours after
Dabigatran 48 hours prior (longer if CrCl 30-50 or procedure is high bleeding risk) 1 day after (2 days if high bleeding risk)
Rivaroxaban
Apixaban
Edoxaban
Heparin Stop infusion 4-5 hours prior 24 hours after
Enoxaparin 12 - 24 hours prior 24 hours after, (48-72 hours if high bleeding risk)
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