Safe Use of Anticoagulants

Effective July 1, 2019, some new requirements have been added to the National Patient Safety Goals (NPSG 3.05.01).11 New is a requirement for policies for DOAC initiation and maintenance (including laboratory monitoring), due to an increase in adverse events involving them.11 Institutions will also need to develop protocols for bleeding management, and perioperative management of anticoagulants, including DOACs.11 Patients/caregivers will also need to be educated on adherence, follow-up (including labs), drug/drug and drug/food interactions, and adverse effects of anticoagulants, including DOACs.11 Hospital processes for identifying adverse events and evaluation of safety practices will need to include DOACS. The toolbox below provides information and resources to help you update or develop your institution’s policies and protocols for use of DOACs and other anticoagulants at your institution. Note that these requirements do not apply to short-term prophylactic anticoagulation (e.g., VTE prevention in medical or surgical inpatients).11 Tips for nurses for improving anticoagulant safety can be found in our chart, Preventing Anticoagulation Errors. For more information on the changes to the NPSG 3.05.01, see

Abbreviations: BID = twice daily; CrCl = creatinine clearance; DOAC = direct-acting oral anticoagulant; MI = myocardial infarction VTE = venous thromboembolism


Pertinent information and resources

Ensure appropriate anticoagulant choice based on indication.

Pick the correct anticoagulant for the desired indication (indications below based on U.S. labeling; also consult institution-specific protocols):1,5,6,7,8,9,10

  • A Fib: apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (Savaysa), rivaroxaban (Xarelto), warfarin, heparin
  • VTE treatment/prevention of recurrence: apixaban (Eliquis), dabigatran (Pradaxa), edoxaban (treatment), rivaroxaban (Xarelto), warfarin, enoxaparin, dalteparin, fondaparinux, heparin
  • VTE prevention post-arthroplasty: apixaban (Eliquis), dabigatran (hip), rivaroxaban (Xarelto), warfarin, enoxaparin, dalteparin (hip), fondaparinux (also hip fracture surgery)
  • VTE prevention in at-risk medical (nonsurgical) patients: betrixaban (Bevyxxa), enoxaparin, dalteparin
  • Cardiovascular risk reduction in coronary or peripheral artery disease: rivaroxaban (Xarelto)
  • Mechanical heart valve: warfarin
  • Post-MI risk reduction: warfarin
  • Myocardial infarction or unstable angina: enoxaparin, dalteparin (unstable angina, non-Q-wave MI)
  • Percutaneous coronary interventions: bivalirudin
  • VTE prevention post-abdominal surgery: enoxaparin, dalteparin, fondaparinux
  • Disseminated intravascular coagulation: heparin
  • Prevention of clotting in arterial and cardiac surgery: heparin
  • Prevention and treatment of peripheral arterial embolism: heparin
  • Anticoagulant in blood transfusions, extracorporeal circulation, and dialysis: heparin
  • Heparin-induced thrombocytopenia: argatroban, bivalirudin (patients undergoing percutaneous coronary intervention)

Use our toolbox, Appropriate Use of Oral Anticoagulants, for more help choosing of anticoagulant for a given indication.

Ensure appropriate anticoagulant choice for special populations

Most DOACs are either not recommended in severe renal impairment (based on U.S. labeling), or dosing information is unavailable in such patients.1 Edoxaban is not for use for A Fib in patients with CrCl >95 mL/min. Fondaparinux is contraindicated if CrCl <30 mL/min.7 See our chart, Comparison of Oral Anticoagulants, for more information.

Most DOACs have warnings/cautions regarding use in liver impairment (per U.S. labeling):1

  • Apixaban: not recommended in severe liver impairment
  • Betrixaban: avoid in liver impairment
  • Edoxaban: not recommended in moderate or severe liver impairment
  • Rivaroxaban: avoid in moderate or severe liver impairment or liver disease with coagulopathy

For obstetrical populations, see our chart, Anticoagulants in Pregnancy.

Some anticoagulants may have special cautions in advanced age or underweight patients. Our toolbox, Appropriate Use of Oral Anticoagulants, covers these. Warfarin may be a better choice in such patients.4

For information on choice of anticoagulant for cancer-related thrombosis, see our chart, Cancer-Related Thrombosis FAQs.

For information on anticoagulant choice in valvular heart disease, see our chart, Antithrombotics and Valvular Heart Disease: FAQs.

Use our toolbox, Appropriate Use of Oral Anticoagulants, for more information to guide anticoagulant choice in special populations.

Ensure appropriate anticoagulant dosing for a given patient.

Use only oral unit-dose, prefilled syringes, or premixed bags of anticoagulants when available.11

Require DOAC indications on orders to help prevent dosing errors.

Choose the correct anticoagulant dose for the patient’s renal function (renal dosing below based on U.S. labeling):1

  • Apixaban: for A Fib, dose reduction (2.5 mg BID) is needed for patients with two or more of the following: age ≥80 years, weight ≤60 kg, serum creatinine ≥1.5 mg/dL.
  • Betrixaban: dose reduction (80 mg x 1, then 40 mg once daily) is needed for CrCl 15 to <30 mL/min (calculated using actual body weight). No information on dosing in patients with more severe impairment.
  • Dabigatran: for A Fib, dose reduction (75 mg BID) is needed for CrCl 15 to 30 mL/min.
  • Edoxaban: for A Fib, the dose is 60 mg once daily for CrCl >50 to ≤95 mL/min, or 30 mg once daily for CrCl 15 to 50 mL/min. For VTE treatment, the dose is 30 mg once daily for CrCl 15 to 50 mL/min.
  • Rivaroxaban: for A Fib, 15 mg with evening meal for CrCl ≤50 mL/min.
  • LMWH: See our chart, LMWH Dosing in Special Populations,

Ensure DOACs are given with a meal, if appropriate: betrixaban, rivaroxaban doses >10 mg.1

Be aware that some DOACs have initial dosing that is different from maintenance dosing:1

  • Apixaban: for DVT/PE treatment, 10 mg BID for seven days, then 5 mg BID. For prevention of recurrence, 2.5 mg BID after at least six months of treatment.
  • Betrixaban has a one-time loading dose.
  • Dabigatran: for VTE treatment, dabigatran is started after an initial 5 to 10 days of an injectable anticoagulant. For VTE prevention post-arthroplasty, use 110 mg (half the usual maintenance dose) if started on the day of surgery.
  • Edoxaban: for VTE treatment, edoxaban is started after an initial 5 to 10 days of an injectable anticoagulant.
  • Rivaroxaban: DVT/PE treatment (15 mg twice daily [with food] x 3 weeks, then 20 mg once daily [with food to improve absorption]. For prevention of recurrence, 10 mg once daily after at least six months of treatment.

See our chart, Comparison of Oral Anticoagulants, for more information on DOAC and warfarin dosing.

Our chart, LMWH Dosing in Special Populations, covers dosing in overweight, pregnancy or lactation, renal impairment, and underweight or frail patients.

Administer heparin infusions using a programmable pump.11 Nurse-driven heparin protocols may help get patients titrated to their goal faster, and stay at their goal dose longer, than prescriber-driven protocols. Our chart, Nurse-Driven Heparin Protocol Safety, lists how to prevent errors with nurse-driven heparin protocols, how to monitor heparin therapy, and how to manage side effects that can occur with heparin.

Identify and respond to potential drug interactions with anticoagulants.

Most DOACs are not good choices in patients who require use of drugs that strongly induce their metabolism (e.g., through CYP3A4 and/or p-glycoprotein rifampin, phenytoin, carbamazepine). See our chart, Comparison of Oral Anticoagulants, for details.

Ensure DOAC doses are adjusted for drug interactions:1 DOACs are often significantly affected by p-glycoprotein inhibitors and inducers. Additionally, apixaban and rivaroxaban may interact with CYP3A4 inducers/inhibitors.1

Identify patients who are taking both an antiplatelet and anticoagulant, and determine if both are appropriate. Engage nurses in this process with our chart, Anticoagulants vs Antiplatelets.

Perform appropriate baseline and follow-up labs.

Develop a policy addressing need for baseline and ongoing lab tests to monitor and adjust anticoagulant therapy.11

To guide DOAC dosing, check renal function at baseline and repeat as clinically indicated.1 Also consider monitoring liver function.11 Other labs may be appropriate in specific situations11 (e.g., patient is bleeding or requires emergency/urgent surgery. See our chart, Managing Bleeding with Direct Oral Anticoagulants).

INR should be used to monitor warfarin, and activated partial thromboplastin time (aPTT) should be used to monitor heparin.11

In warfarin patients, confirm acceptable INR before neuraxial anesthesia.3

Monitor complete blood count to detect problems such as heparin-induced thrombocytopenia, increased bleeding risk, or subclinical bleeding.

Switch between anticoagulants safely.

See our chart, Comparison of Oral Anticoagulants, for details on switching to/from DOACs and warfarin.

Information on switching between other anticoagulants can be found at

Manage bleeding in patients taking anticoagulants.

Develop protocols for anticoagulant reversal. For help, see our chart, Managing Bleeding with Direct Oral Anticoagulants and for nurses, Agents for Reversing Anticoagulants.

For information on warfarin reversal, see our algorithm, How to Manage High INRs in Warfarin Patients. Use our chart, Kcentra for Emergent Warfarin Reversal: Fixed Versus Variable Dosing, to help you develop protocols for Kcentra use at your institution.

Manage anticoagulants perioperatively.

Develop protocols that address perioperative use of anticoagulants. Consult our resources for help:

Educate patients and families about anticoagulation (including DOACs).

Points that must be addressed in education include adherence, follow-up (e.g., next INR), interactions (with foods and drugs), and adverse effects.11

Customize our patient handout, Why It’s Important to Take Your Blood Thinning Meds, and use it to reinforce verbal education of patients and caregivers about any anticoagulant.

Suggest tools to promote anticoagulation adherence, such as phone apps like Medisafe ( or Mango Health (

Ensure safe use of anticoagulants at transitions of care.

If a patient is admitted on a DOAC, ensure that the dose is adjusted based on any changes in renal function. Also ensure that the anticoagulant is still needed for its originally prescribed indication (i.e., VTE treatment) and that the dose is appropriate.

Ensure anticoagulants prescribed solely for VTE prevention in at-risk medical patients are discontinued before discharge.2 Inform new provider of time of last dose of discontinued anticoagulants, due to possibility of persistent effect.12

Ensure outpatient provider or transfer facility is aware of date of next INR and the INR target.12

Document renal function (preferably as CrCl) in communication to outpatient providers.12

Iron out any issues with 3rd party DOAC coverage or cost barriers before discharge. This might involve discharge planners and the patient’s outpatient pharmacist.

Include indication and time of last dose on discharge orders/prescriptions for oral anticoagulants.12

If an anticoagulant is prescribed for a finite duration (e.g., VTE treatment, VTE prevention post-arthroplasty), ensure that the outpatient prescriber, patient/caregiver, and pharmacist are aware of the stop date and any need for step-down in dosage (e.g., for VTE treatment, rivaroxaban dose reduction from 15 mg BID to 20 mg once daily after three weeks).

Use our Monitoring Checklist for the New Oral Anticoagulants, at admission and/or discharge.

Project Leader in preparation of this clinical resource (350217): Melanie Cupp, Pharm.D., BCPS


  1. Clinical Resource, Comparison of Oral Anticoagulants. Pharmacist’s Letter/Prescriber’s Letter. December 2018.
  2. Clinical Resource, Venous Thromboembolism. Pharmacist’s Letter/Prescriber’s Letter. January 2019.
  3. Clinical Resource, Antithrombotic Management in Regional Anesthesia. Pharmacist’s Letter/Prescriber’s Letter. June 2018.
  4. Clinical Resource, Appropriate Use of Oral Anticoagulants. Pharmacist’s Letter/Prescriber’s Letter. March 2018.
  5. Prescribing information for Lovenox. Sanofi-Aventis. Bridgewater, NJ 08807. December 2018.
  6. Prescribing information for Fragmin. Pfizer Labs. New York, NY 10017. June 2017.
  7. Prescribing information for Arixtra. Mylan Institutional. Rockford, IL 61103. August 2017.
  8. Prescribing information for heparin sodium and dextrose. Hospira. Lake Forest, IL 60045. December 2018.
  9. Prescribing information for Angiomax. The Medicines Company. Parsippany, NJ 07054. March 2016.
  10. Prescribing information for argatroban. Teva. Pharmaceuticals USA. New Wales, PA 19454. August 2017.
  11. The Joint Commission. R3 Report. Requirement, rationale, reference. National Patient Safety Goal for anticoagulant therapy. December 7, 2018. (Accessed January 18, 2019).
  12. Triller D, Myrka A, Gassler J, et al. Defining minimum necessary anticoagulation-related communication at discharge: consensus of the care transitions task force of the New York State Anticoagulation Coalition. Jt Comm J Qual Patient Saf 2018;44:630-40.

Cite this document as follows: Clinical Resource, Safe Use of Anticoagulants. Hospital Pharmacist’s Letter/Prescriber’s Letter. February 2019.

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