Perioperative management of warfarin and antiplatelet therapy

November 1, 2009|Cleveland Clinic Journal of Medicine

ABSTRACT

Perioperative management of patients on warfarin or antiplatelet therapy involves assessing and balancing individual risks for thromboembolism and bleeding. Discontinuing anticoagulant and antiplatelet therapy is usually necessary for major surgery but increases the risk of thrombotic events. Bridge therapy, the temporary perioperative substitution of low-molecular-weight heparin or unfractionated heparin in place of warfarin, is an effective means of reducing the risk of thromboembolism but may increase the risk of bleeding. The timing of warfarin withdrawal and timing of the preoperative and postoperative components of bridge therapy are critical to balancing these risks. Perioperative management of antiplatelet therapy requires special care in patients with coronary stents; the timing of surgery relative to stent placement dictates management in these patients.

KEY POINTS

Determining when and how to use bridge anticoagulation therapy depends on the patient’s risk for thromboembolism, which is in turn based on the indication for warfarin—ie, a mechanical heart valve, atrial fibrillation, or prior venous thromboembolism.
Factor patient preference into whether and how to use bridge therapy: many patients are more concerned about stroke risk than bleeding risk, regardless of the relative frequency of these events.
Anticoagulation with warfarin often does not need to be interrupted for patients undergoing minor surgery, such as some ophthalmic, dental, dermatologic, and gastrointestinal procedures.
Premature discontinuation of antiplatelet therapy in surgical patients with recent coronary stent placement significantly raises the risk of catastrophic perioperative stent thrombosis.

CHOICE OF AGENT FOR BRIDGE THERAPY

LMWH appears to offer cost advantage over UFH

For cost reasons, managed care organizations often recommend LMWH, which can be administered subcutaneously in outpatient settings, over IV UFH administered in the hospital. A retrospective analysis of medical costs from the 1990s in a managed care organization found that bridge therapy with LMWH prior to elective surgery cost an average of $13,114 less per patient (in total cost of care) than did bridge therapy with UFH.¹⁸

LMWH safety issues in valve patients are a myth

Clinical outcomes were not statistically significantly different for patients receiving LMWH or UFH in the above study.¹⁸ Nevertheless, there is a widely held notion that LMWH is not safe to use as bridge therapy for patients with mechanical heart valves. Recent prospective bridge studies do not support that view, demonstrating that LMWH used as bridge therapy is associated with low risks for thromboembolism and major bleeding even in patients with mechanical valves.^9,10,12–14 In contrast, recent data on the use of IV UFH for bridging is minimal, with most bridge studies dating to the 1970s. Accordingly, the latest ACCP guidelines for perioperative management of patients on antithrombotic therapy recommend therapeutic-dose LMWH over IV UFH for bridge therapy, including in patients with mechanical heart valves.¹ Likewise, 2006 guidelines from the American College of Cardiology and American Heart Association on management of patients with valvular heart disease endorse LMWH as an option for bridge therapy.¹⁹

A PRACTICAL APPROACH TO BRIDGE THERAPY

A bridge therapy protocol for patients receiving warfarin has been successfully used at the Cleveland Clinic, where I previously practiced. Essentials of the protocol²⁰ are summarized here, followed by commentary that draws on additional sources.

Before surgery

Discontinue warfarin 5 days before surgery (ie, hold four doses) if the preoperative international normalized ratio (INR) is 2 to 3, and 6 days before surgery (hold five doses) if the INR is 3 to 4.5.
For bridge therapy, start LMWH (enoxaparin 1 mg/kg or dalteparin 100 IU/kg subcutaneously every 12 hours) beginning 36 hours after the last dose of warfarin.
Give the last dose of LMWH approximately 24 hours prior to surgery.

After surgery

For minor surgery, reinitiate LMWH at full dose approximately 24 hours after surgery. For major surgery and for patients at high risk of bleeding, consider using prophylactic doses on the first two postoperative days.
Discuss the timing of anticoagulant reinitiation with the surgeon.
Restart warfarin at preoperative dose 1 day after surgery.
Order daily prothrombin time/INR tests until the patient is discharged and periodically after discharge until the INR is within the therapeutic range.
Order a complete blood cell count with platelets on days 3 and 7.
Discontinue LMWH when the INR is between 2 and 3 for 2 consecutive days.

Additionally, the plan should be discussed in advance with the patient, surgeon, and anesthesiologist, along with the risks and benefits associated with LMWH. The patient should receive written instructions for self-administration and information about signs and symptoms of bleeding and thromboembolism.

When to stop warfarin

Warfarin should be discontinued far enough in advance of surgery to achieve a preoperative target INR of less than 1.2.²¹ Patients with an initial INR of 2 to 3 tend to achieve that target after discontinuation of warfarin for about 5 days (four doses). A longer wait (6 days, or five doses) is necessary for patients with an initial INR of 3 to 4. Age is associated with a slower rate of decrease in the INR, and there is wide interpatient variation. The INR should always be checked prior to surgery.²¹

Warfarin need not be stopped for all procedures

It is commonly assumed that warfarin should be discontinued for any procedure, including minor surgery. But several procedures, listed in Table 4, can be performed safely without discontinuing long-term anticoagulation, as suggested by several literature reviews and comparative studies.^22–25 Additionally, a 2003 systematic review concluded that major bleeding with continuation of therapeutic oral anticoagulation was rare for patients undergoing dental procedures, arthrocentesis, cataract surgery, upper endoscopy, or colonoscopy.²⁶

If warfarin is stopped for minor procedures, bridging may be counterproductive

At the same time, a recent prospective observational study evaluated the effects of brief (≤ 5 days) interruption of warfarin among more than 1,000 patients undergoing minor outpatient procedures and found low rates of both thromboembolism (0.7%) and major bleeding (0.6%).²⁷ The risk of major bleeding was significantly higher among the small proportion of patients who received bridge therapy with UFH or LMWH. The study concluded that interrupting warfarin for 5 days or less for minor outpatient procedures carries a low risk of thromboembolism and that the risk of clinically significant bleeding should be weighed before bridge therapy is considered in this setting.

When to stop bridge therapy preoperatively

Bridge therapy with LMWH is commonly discontinued 12 hours before surgery, but it is preferable to discontinue 24 hours before surgery. In a study of preoperative anticoagulant activity in 80 patients, LMWH (enoxaparin 1 mg/kg) was administered twice daily and discontinued the night before surgery.²⁸ Blood anti–factor Xa levels were measured shortly before surgery, at which time 68% of patients still had therapeutic levels of anti–Xa. This suggests that discontinuing LMWH too close to the time of surgery can increase the risk of bleeding.

Consistent with these findings, consensus guidelines from the American Society of Regional Anesthesia and Pain Medicine (ASRA) recommend that needle placement for regional anesthesia take place 12 hours after the last dose of LMWH if prophylactic dosing is used and 24 hours after the last dose of LMWH if therapeutic dosing is used (ie, ≥ 1 mg/kg of enoxaparin every 12 hours).²⁹

Dosing and timing of postoperative bridge therapy

Postoperative use of full-dose bridge therapy is associated with increased risks of bleeding, according to a multicenter study of approximately 500 patients who received various doses of UFH or LMWH for bridge therapy.¹⁴ Patients who received full-dose LMWH or UFH after surgery had a fivefold to sixfold increase in the incidence of major bleeding compared with patients who received prophylactic doses. The study centers that frequently used full-dose bridge protocols were four times as likely to report major bleeding events. In light of these findings, waiting a couple of days after surgery to initiate full-dose bridge therapy is recommended, and prophylactic dosing may be considered in the interim.

The ASRA consensus guidelines recommend that indwelling catheters be removed prior to postoperative reinitiation of twice-daily dosing of LMWH. The first dose of LMWH should be given no sooner than 2 hours after catheter removal. Once-daily dosing of LMWH (European dosing) is acceptable under the ASRA guidelines, but the first dose should be given 6 to 8 hours after surgery and the second dose no sooner than 24 hours later. The guidelines state that once-daily (but not twice-daily) LMWH dosing is acceptable in patients with indwelling catheters; neurological status should be monitored in these patients, and the catheter should be removed 12 to 24 hours after the last dose of LMWH.²⁹

References

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