Starting and Managing Warfarin/Coumadin for Initial Treatment of DVT/PE
from the ACCP Guidelines, 9th Ed.
The ACCP’s new 9th edition of their clinical practice guidelines for prevention and treatment of DVT/PE were published in February 2012. Here we review their update on how to start a patient on warfarin (Coumadin) for deep venous thrombosis or pulmonary embolism (DVT/PE). See also our reviews of the other sections of the ACCP 9th edition recommendations on management of DVT/PE.
Answered here: What’s the best initial Coumadin dose? How often should the INR be checked, how should you adjust the Coumadin dose, and what’s the best way to manage bleeding due to high INR?
In this section of the ACCP’s 9th Edition recommendations, there are only two strong evidence-based recommendations (both are Grade 1B, meaning a strong recommendation with moderate evidence):
- Use a target INR of 2.5 (range 2.0 – 3.0). This applies to all patients, including those at high risk (e.g., antiphospholipid antibody syndrome with previous arterial or venous thrombus, although they downgraded that particular recommendation to Grade 2B).
- Don’t use pharmacogenetic testing to guide warfarin dosing; it’s not validated and appropriate for widespread use.
The others are categorized as weak recommendations, based on moderate or weak evidence (Grade 2B or 2C); here’s a summary.
How to Start Warfarin for DVT/PE:
- Start patients on warfarin 10 mg daily for 2 days, then dose by INR (rather than choosing the dose you think they’ll need at the outset). There is no need to treat with heparin for several days before starting warfarin therapy (the supposed threat of warfarin skin necrosis is a bogeyman that unnecessary delays therapy, they advise). You can safely start warfarin on day 1 or 2 of heparin therapy. (Grade 2C)
- When considering whether someone is a “candidate” for warfarin, don’t disqualify them on the basis of a clinical prediction rule’s rating them as having a high risk of bleeding — not on this alone, at least; use broader clinical judgment. (Grade 2C)
How to Follow & Adjust Warfarin/Coumadin Dose According to Changes in INR:
- Patients who are able to do it properly should self-test at home. People with stable INRs can be rechecked as infrequently as once every 3 months (12 weeks). (Grade 2B)
- When making changes in warfarin dosing, don’t wing it: use a validated decision support tool like an online calculator or smartphone app for warfarin dose adjustment. (Grade 2C)
- INR should be allowed to fluctuate up to 0.5 below or above therapeutic range (e.g., an INR of 1.5 to 3.5 for DVT/PE) without any change in dose — just recheck INR in 1-2 weeks. There is no need to bridge with heparin in this situation. (Grade 2C)
Warfarin/Coumadin Interactions With Aspirin and Plavix (clopidogrel):
Antiplatelet drugs like aspirin and clopidogrel (Plavix) significantly increase the risk for major bleeding when taken with Coumadin. Aspirin or Plavix should only be added to warfarin when there is a clear or highly likely benefit: patients with acute coronary syndrome, mechanical valves, or recent bypass surgery or coronary artery stents. NSAIDs also increase bleeding risk when taken with coumadin, and should be avoided. (Grade 2C)
Warfarin/Coumadin and Other Food/Drug Interactions:
- People who regularly enjoy foods high in vitamin K should keep eating them — but they should take care to habitually eat about the same amount. (From the text; not graded.)
- There are more than 700 drugs that might interact with warfarin, and not only can no one keep them all straight, there’s little known about the pharmacokinetic interactions of each individual one, because many were described in small case series. In addition, the interactions probably vary between patients, just as warfarin kinetics do. About the best one can do is be aware of the danger when starting new medicines, and check them using an online warfarin interaction calculator or the drug interaction table included in the ACCP publication.
- Don’t give routine vitamin K supplements to people taking warfarin. (Grade 2C)
How to Stop Warfarin/Coumadin:
Abruptly stop warfarin when the treatment period is over. Don’t slowly taper it down; there’s no need. (Grade 2C)
What to Do About High INRs, With or Without Bleeding
- For INRs up to 10, if there is no evidence of bleeding, don’t give vitamin K or plasma products. Just hold warfarin and recheck INR frequently. (Grade 2B)
- For INRs greater than 10 without evidence of bleeding, give oral vitamin K (Grade 2C)
- For patients with major bleeding while taking warfarin at any dose, rapidly reverse the coagulopathy using four-factor prothrombin complex (NOT fresh frozen plasma, they recommend) and vitamin K 5 or 10 mg given IV by slow injection. (Grade 2C)
Guyatt GH et al. Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Executive Summary. CHEST 2012; February 2012; 141 (2 suppl).