Anticoagulation, Anticoagulant, Direct Oral Anticoagulant, DOAC, Direct Acting Anticoagulant, Non-Vitamin K Antagonist Oral Anticoagulant, NOAC

  • Definitions
  1. Direct Oral Anticoagulants (DOACs) or Non-Vitamin K Antagonist Oral Anticoagulant (NOACs)
    1. Direct Thrombin Inhibitors (e.g. Dabigatran)
    2. Factor Xa Inhibitors (e.g. Rivaroxaban, Apixaban, Edoxaban)
  • Drug Interactions
  1. Anticoagulants have significant Drug Interactions
  2. Greatest risk for Drug Interaction is with Warfarin
    1. See Warfarin Drug Interactions
  3. Direct Oral Anticoagulants (e.g. Dabigatran, Rivaroxaban) also have significant Drug Interactions
    1. Review specific agents for Drug Interactions (e.g. P-Glycoprotein, CYP3A4)
      1. Highest risk: Ketoconazole, Fluconazole, Ritonavir, Amiodarone
    2. Unknown safety and bleeding risk when combined with antiplatelet agents
    3. Reducing DOAC dose due to Drug Interaction risk may render it ineffective
  1. Direct Oral Anticoagulants (DOACs) may result in inaccurate results on clot and coagulation based assays
  2. Tests impacted by DOACs with alternative options
    1. Lupus Anticoagulant panel
      1. Consider ELISA Anticardiolipin Antibody and anti-beta2 GP1 Antibody as an alternative
    2. Activated Protein C resistance
      1. Consider Factor V Leiden as an alternative
  3. Tests impacted by DOACs (test when DOAC at trough level before next dose and interpret with caution)
    1. Protein C Activity
    2. Protein S Activity
    3. Antithrombin Activity
  4. References
    1. Choosing Wisely (American College of Clinical Pathology)
    2. Adcock (2015) Thromb Res 136(1):7-12 +PMID:25981138 [PubMed]
    3. Murer (2016) Lab Med 47(4): 275-78 +PMID:27474775 [PubMed]
  • Management
  • Venous condition prevention and treatment
  1. See Anticoagulation in Thromboembolism
  2. See Anticoagulation in Atrial Fibrillation
  3. See Anticoagulation in Surgical Patients
  4. See Valve Replacement and Anticoagulation
  5. Conditions: Venous Thromboembolism
    1. Deep Vein Thrombosis
    2. Pulmonary Embolism
    3. Atrial Fibrillation
    4. Artificial Heart Valve Replacement
  6. Preparations: Agents affecting Clotting Pathway (PTT or INR)
    1. Warfarin (Coumadin)
    2. Unfractionated Heparin
    3. Low Molecular Weight Heparin
    4. Direct Oral Anticoagulants (DOACs) or Non-Vitamin K Antagonist Oral Anticoagulant (NOACs)
      1. Direct Thrombin Inhibitors (e.g. Dabigatran)
        1. Bind to Thrombin active site, preventing Fibrinogen conversion to Fibrin
      2. Factor Xa Inhibitors (e.g. Rivaroxaban, Apixaban, Edoxaban)
        1. Bind Factor Xa, preventing Thrombin generation
  7. Preparations: Acute event in an unstable patient or prevention of complications
    1. Thrombolytic (e.g. t-PA, Streptokinase)
  8. Preparations: Preventing complications from Venous Thromboembolism
    1. Greenfield Filter
  • Management
  1. See Emergent Reversal of Anticoagulation
  2. Routine follow-up at least every 6 months
  3. Review compliance and adherence
    1. Review risk of thrombosis with non-compliance (e.g. Drug-eluting Stent thrombosis, VTE)
    2. Most Direct Oral Anticoagulants (e.g. Pradaxa, Eliquis) have short half-lives
    3. Review specific medication guidelines for when to take a forgotten dose
  4. Review bleeding risk
    1. Falls or other Trauma
    2. Gastrointestinal Bleeding, excessive Bruising
    3. Control Blood Pressure (manage Severe Hypertension aggressively)
    4. Exercise caution in age 75 years or older, and those who are significantly underweight
  5. Renal dysfunction (GFR <30 ml/min)
    1. Obtain Serum Creatinine before starting Anticoagulation
    2. Previously Warfarin was recommended instead of Direct Oral Anticoagulants if GFR <30 ml/minute
      1. However, Warfarin associated bleeding risk also increases with decreased GFR
    3. Avoid Dabigatran (Pradaxa) if GFR <30 ml/min (80% renally excreted)
    4. Apixiban may be preferred when GFR <30 ml/min (lower overall bleeding risk, 25% renally excreted)
      1. See Apixiban for Renal Dosing (2.5 mg orally twice daily) indications
      2. Approved for use in Hemodialysis patients
    5. Rivaroxaban is also a good choice in Renal Insufficiency (if GFR >15 ml/min)
      1. See Rivaroxaban for Renal Dosing
      2. Approved for use in Hemodialysis patients
    6. References
      1. Swaminathan and Hayes in Herbert (2019) EM:Rap 19(8):10-11
      2. Weber (2019) Eur J Haematol 102(4): 312-8 +PMID:30592337 [PubMed]
  6. Consider Drug Interactions
    1. Review specific medication P450 interactions
    2. Avoid NSAIDs
    3. If Aspirin is being used, confirm appropriate and at low dose (i.e. 81 mg daily)
  7. Restarting Anticoagulation after major Hemorrhage (e.g. Hemorrhagic CVA)
    1. Risk of embolic CVA in Atrial Fibrillation, Prosthetic Heart Valve versus risk of recurrent major bleeding
    2. Intracranial HemorrhageIncidence 1 in 250 on Anticoagulants yearly (and 15% recurrence rate)
    3. If Anticoagulation restarted, wait at least 4 weeks after Intracranial Hemorrhage (8-10 weeks if higher risk)
    4. Indications to restart Anticoagulation
      1. Prosthetic Heart Valve
      2. CHADS2-VASc Score 4 or higher (no studies to support a specific score for restarting Anticoagulation)
      3. Intracranial Hemorrhage predisposing risks have since been mitigated (e.g. Hypertension control)
  8. Anticoagulant selection and dosing adjustments - special circumstances
    1. Obesity (weight >120 kg or BMI >40)
      1. Warfarin (preferred)
      2. Apixaban (Eliquis)
      3. Rivaroxaban (Xarelto)
      4. Avoid Dabigatran (Pradaxa) and Edoxaban (Savaysa)
    2. Low body weight (<60 kg)
      1. Apixaban (Eliquis) 5 mg twice daily (2.5 mg twice daily if age >80, or Serum Creatinine >1.5 mg/dl)
      2. Edoxaban (Savaysa)
    3. Dialysis
      1. Apixaban (Eliquis) based on limited data
      2. Avoid other DOACs in Dialysis patients
  9. References
    1. (2015) Presc Lett 22(10): 55-6
    2. (2017) Presc Lett 24(5): 28
    3. (2017) Presc Lett 24(7)
  • Prevention
  • Bleeding Home Management
  1. Education
    1. Educate patients on prevention and control of minor bleeding
    2. Immediate evaluation for Head Injury, significant injury or bleeding that does not stop after 30 minutes
    3. Also seek medical care for Hematuria, Gastrointestinal Bleeding or Hemoptysis
    4. Bleeding may be a sign of excess Anticoagulation (e.g. supratherapeutic INR with Warfarin use)
    5. Avoid NSAIDS and Herbals that increase bleeding risk (e.g. Garlic, Ginkgo)
  2. Epistaxis
    1. Consider frequent Nasal Saline use to prevent Epistaxis
    2. If Epistaxis occurs, to pinch the nose in the soft region inferior to the nasal bridge for 10-15 min
    3. May use intranasal Oxymetazoline or Phenylephrine for up to 3 days if Nasal bleeding recurrs
  3. Skin Lacerations
    1. Employ strategies to avoid Skin Trauma (e.g. electric razor instead of razor blade)
    2. Elevate and apply pressure for 15 min to bleeding sites
    3. Consider Hemostatic Agents for recurrent bleeding (e.g. styptic pencil, woundSeal)
  4. References
    1. (2020) Presc Lett 27(9): 50-1