Evidence-Based Management Of Anticoagulant Therapy

Publication Date: February 1, 2012
Last Updated: March 14, 2022


VKA—Initiation of Therapy

Initial Dose Selection—Loading Dose

For patients sufficiently healthy to be treated as outpatients, we suggest initiating VKA therapy with warfarin 10 mg daily for the fi rst 2 days followed by dosing based on INR measurements rather than starting with the estimated maintenance dose. (2, C)

Initial Dose Selection and Pharmacogenetic Testing

For patients initiating VKA therapy, we recommend against the routine use of pharmacogenetic testing for guiding doses of VKA. (1, B)

Initiation Overlap for Heparin and VKA

For patients with acute VTE, we suggest that VKA therapy be started on day 1 or 2 of LMWH or UFH therapy rather than waiting for several days to start. (2, C)

Maintenance Treatment With VKAs

For patients taking VKA therapy with consistently stable INRs, we suggest an INR testing frequency of up to 12 weeks rather than every 4 weeks. (2, B)

Management of the Single Out-of-Range INR

For patients taking VKAs with previously stable therapeutic INRs who present with a single out-of-range INR of 0.5 below or above therapeutic, we suggest continuing the current dose and testing the INR within 1 to 2 weeks. (2, C)

Bridging for Low INRs

For patients with stable therapeutic INRs presenting with a single subtherapeutic INR value, we suggest against routinely administering bridging with heparin. (2, C)

Vitamin K Supplementation

For patients taking VKAs, we suggest against routine use of vitamin K supplementation. (2, C)

Anticoagulation Management Services for VKAs

We suggest that health-care providers who manage oral anticoagulation therapy should do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dosing decisions.
(Best Practice Statement) (, )

Patient Self-Testing and Self-Management

For patients treated with VKAs who are motivated and can demonstrate competency in self-management strategies, including the selftesting equipment, we suggest PSM rather than usual outpatient INR monitoring. (2, B)

For all other patients, we suggest monitoring that includes the safeguards in our Best Practice Statement (above).


Dosing Decision Support

For dosing decisions during maintenance VKA therapy, we suggest using validated decision support tools (paper nomograms or computerized dosing programs) rather than no decision support. (2, C)

VKA Drug Interactions to Avoid

For patients taking VKAs, we suggest avoiding concomitant treatment with NSAIDs, including COX-2-selective NSAIDs, and certain antibiotics. (2, C)
For patients taking VKAs, we suggest avoiding concomitant treatment with antiplatelet agents except in situations where benefi t is known or is highly likely to be greater than harm from bleeding, such as patients with mechanical valves, patients with acute coronary syndrome, or patients with recent coronary stents or bypass surgery. (2, C)


Optimal Therapeutic INR Range

For patients treated with VKAs, we recommend a therapeutic INR range of 2.0 to 3.0 (target INR of 2.5) rather than a lower (INR <2) or higher (INR 3.0-5.0) range. (1, B)

Therapeutic Range for High-Risk Groups

For patients with antiphospholipid syndrome with previous arterial or venous thromboembolism, we suggest VKA therapy titrated to a moderate-intensity INR range (INR 2.0-3.0) rather than higher intensity (INR 3.0-4.5). (2, B)

VKA—Discontinuation of Therapy

For patients eligible to discontinue treatment with VKA, we suggest abrupt discontinuation rather than gradual tapering of the dose to discontinuation. (2, C)

Parenteral Anticoagulants

UFH—Dose Adjustment by Weight

For patients starting IV UFH, we suggest that the initial bolus and the initial rate of the continuous infusion be weight adjusted (bolus 80 units/kg followed by 18 units/kg per h for VTE; bolus 70 units/kg followed by 15 units/kg per h for cardiac or stroke patients) or a fixed-dose (bolus 5,000 units followed by 1,000 units/h) rather than alternative regimens. (2, C)

UFH—Dose Management of SC UFH

For outpatients with VTE treated with SC UFH, we suggest weight-adjusted dosing (fi rst dose 333 units/kg, then 250 units/kg) without monitoring rather than fi xed or weight-adjusted dosing with monitoring. (2, C)


Should the Therapeutic Dose of LMWH Be Modified for Decreased Renal Function?

For patients receiving therapeutic LMWH who have severe renal insuffi ciency (calculated creatinine clearance <30 mL/min), we suggest a reduction of the dose rather than using standard doses. (2, C)


Fondaparinux Dose Management by Weight

For patients with VTE and body weight over 100 kg, we suggest that the treatment dose of fondaparinux be increased from the usual 7.5 mg to 10 mg daily subcutaneously. (2, C)

Prevention and Management of Anticoagulant Complications

Vitamin K for Patients Taking VKAs With High INRs Without Bleeding

(a) For patients taking VKAs with INRs between 4.5 and 10 and with no evidence of bleeding, we suggest against the routine use of vitamin K. (2, B)
(b) For patients taking VKAs with INRs >10.0 and with no evidence of bleeding, we suggest that oral vitamin K be administered. (2, C)

Clinical Prediction Rules for Bleeding While Taking VKA

For patients initiating VKA therapy, we suggest against the routine use of clinical prediction rules for bleeding as the sole criterion to withhold VKA therapy. (2, C)

Treatment of Anticoagulant-Related Bleeding

For patients with VKA-associated major bleeding, we suggest rapid reversal of anticoagulation with four-factor PCC rather than with plasma. (2, C)
We suggest the additional use of vitamin K 5 to 10 mg administered by slow IV injection rather than reversal with coagulation factors alone. (2, C)

Recommendation Grading




Evidence-Based Management Of Anticoagulant Therapy

Authoring Organization

Publication Month/Year

February 1, 2012

Last Updated Month/Year

May 15, 2023

Document Type


External Publication Status


Country of Publication


Document Objectives

High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices.

Target Patient Population

Patients with conditions requiring anticoagulant therapy

Inclusion Criteria

Male, Female, Adolescent, Adult, Older adult

Health Care Settings

Ambulatory, Emergency care, Hospice, Long term care, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Treatment, Management, Prevention

Diseases/Conditions (MeSH)

D054556 - Venous Thromboembolism, D020246 - Venous Thrombosis, D000925 - Anticoagulants, D056824 - Upper Extremity Deep Vein Thrombosis


anticoagulation, Antithrombotic Agents, Venous Thromboembolism, deep vein thrombosis, deep venous thrombosis, Anticoagulation

Supplemental Methodology Resources

Data Supplement