Determining a safe INR level for surgery in patients anticoagulated with coumadin
E. Crosby MD
Increases in the INR with coumadin therapy occur as a result of reductions of three of the
four vitamin K-dependent pro-coagulant clotting factors (II, VII, IX, X). The INR is most sensitive
to the levels of factors VII and X and is relatively insensitive to factor II levels. Levels of factors II,
VII, and X are reduced by coumadin at a rate proportional to their respective half-lives. FVII has
a half-life of ~6 hours and prolongation of the INR will occur 24-36 hours (4-6 half lives) after the
administration of coumadin (the anticoagulant effect of coumadin). Prolongation of the INR to
greater than 1.2 occurs when FVII activity is reduced to ~55% of the baseline; an INR of 1.5 is
associated with a FVII activity of <40%. The antithrombotic effect of coumadin to depends largely
on the clearance of prothrombin (FII); with a half-life of 60-72 hours, it will take a minimum of 2T2
(~ 5 days) to fully express an antithrombotic effect.
Clinical experience with patients who are deficient in factors II, IX, or X suggests that
factor activity level of ~40% is adequate for normal or near normal hemostasis; bleeding may
occur when the level of any clotting factor is decreased to <40% of baseline. Thus an INR of <1.5
should reflect adequate levels of factors II, VII, and X and be associated with normal hemostasis.
These same principles apply during recovery of normal hemostasis upon discontinuation of
coumadin therapy. FVII activities will rapidly increase, as demonstrated by a decrease in the INR
but FII and FX activities will require more time to be restored to normal.
Kreppel, after a literature review and meta-analysis, concluded that hemorrhagic
complications occur about three times more often following epidural anesthesia than after spinal
anesthesia. The incidences of hematoma were estimated at 1/150,000 for epidural anesthesia
and 1/220,000 for spinal anesthesia. Kearon and Hirsch suggested it was safe to perform
surgery on patients who had been receiving coumadin and once the coumadin had been
discontinued and the INR returned to <1.5. This “safe INR value” was based on their own
experience as well as a number of older studies involving a limited number of patients.
Warfarin Reversal Consensus Guidelines (Australasian Society of Thrombosis and
Hemostasis) suggests that coumadin can be withheld for five days before elective surgery,
allowing the INR to fall <1.5, at which time surgery may be conducted safely. The AHA/ACC
Guide to Warfarin Therapy also suggests that for patients who are currently at therapeutic INR
levels (INR 2-3), the dose of coumadin can be held four to five days in advance of elective
surgery to allow the INR to fall to normal or near normal (<1.5) at the time of surgery.
Although there seems to be consensus that an INR of 1.5 is generally considered not to
increase the risk of perioperative bleeding, the American Society of Regional Anesthesia
Consensus Guidelines recommends an INR of <1.5 for neuraxial blockade, and for neurosurgical
procedures an INR closer to 1.0. Consistent with that position, the American College of Chest
Physicians Consensus Guidelines on Perioperative Anticoagulation also state that surgery can
safely be performed with an INR ~1.5. No explicit recommendation is made with respect to these
patients other than a caution that they are at higher risk of developing epidural or spinal
hematoma. The European Society of Regional Anaesthesia is modestly more liberal than its
American counterpart in advising that it is safe to proceed with neuraxial block once the INR is <
1.5.
There seems to be consensus opinion that in patients who have been chronically treated
with coumadin and who require surgery, the INR should be decreased to <1.5 at the time of
surgery. This can usually be achieved in elective situations by withholding coumadin for five days
in patients normally managed to INR levels of 2.5-3 and 6-7 days if INR is >3. In patients
requiring urgent or emergent surgery as well as those who have experienced significant trauma,
vitamin K (10 mg iv), frozen plasma (3-4 units), or octaplex (2 vials) may be administered to
decrease the INR to a level of <1.5. Once INR levels <1.5 are achieved proceeding to surgery
and administration of a neuraxial block, if indicated and/or desired, should be safe.
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