8. Perioperative Management of Anticoagulant and Antiplatelet Therapy

7th Edition – 2020 UPDATED

Definitions

Type of surgery or procedure and bleeding risk category:

A high-bleed-risk surgery or procedure includes major abdominal surgery (e.g., cancer resection), major thoracic surgery, major orthopedic surgery, and any cardiac, spinal, or intracranial surgery. Any patient having neuraxial anesthesia is classified as high-bleed-risk because of the risk for spinal epidural hematomas which could cause limb paralysis.
A low to moderate-bleed-risk surgery or procedure includes most surgeries that are <1-hour duration and procedures that do not involve neuraxial anesthesia.
A minimal-bleed-risk surgery or procedure includes tooth extractions, root canal, skin biopsies, cataract surgery, and selected colonoscopies, for which anticoagulants can be continued without interruption. Permanent pacemaker and internal cardiac defibrillator implantation, as well as cardiac catheterization, also can be done without stopping anticoagulants.

Refer to current Thrombosis Canada Guidance and Perioperative Anticoagulant Management Algorithm for additional information.

Recommendations

Patients with atrial fibrillation or a mechanical heart valve who are receiving oral anticoagulant therapy and require a procedure associated with a minimal risk of bleeding (e.g., tooth extraction, skin biopsy, cataract removal, cardiac pacemaker) should not have anticoagulation interrupted around the time of the procedure [Level of Evidence B].
For patients with atrial fibrillation receiving a Direct Oral Anticoagulant (DOAC) for stroke prevention who require temporary DOAC interruption for an elective surgery or procedure, the following approach is recommended [Level of Evidence B]:
1. For a low to moderate-bleed-risk surgery or procedure, stop the DOAC the day before the procedure and the day of the procedure (i.e., skip 2 days total), and restart the day after the procedure.
2. For a high-bleed-risk surgery or procedure, stop the DOAC 2 days before the procedure, the day of the procedure, and one day after the procedure (i.e., skip 4 days total).
For patients with atrial fibrillation receiving warfarin for stroke prevention who require temporary warfarin interruption for an elective surgery or procedure:
1. For patients at low to moderate stroke risk (e.g., CHADS2 score 0-4), warfarin should be stopped for 5 days pre-procedure, and resumed within 24 hours post-procedure, without heparin bridging [Level of Evidence: A].
2. For patients at high stroke risk (e.g., CHADS2 score 5-6 or prior perioperative stroke), heparin bridging is suggested during warfarin interruption, typically with twice-daily subcutaneous injections of low-molecular-weight heparin for 3 days before and 3 days after the surgery or procedure [Level of Evidence: B] If bridging is used pre-operatively, it is recommended to forego post-operative bridging in selected patients, especially those undergoing high-bleed-risk procedures [Level of Evidence: B]. Refer to current Thrombosis Canada Guidance and Perioperative Anticoagulant Management Algorithm for additional information.
For patients with a mechanical heart valve who are receiving warfarin for stroke prevention and require temporary warfarin interruption for elective surgery or procedure, stopping warfarin 5 days pre-procedure is recommended and should be resumed within 24 hours post-procedure [Level of Evidence: A].
- Heparin bridging is recommended for selected patients with a mitral valve prosthesis and for high-risk patients with an aortic valve prosthesis (e.g., with additional risk factors for stroke) [Level of Evidence: B].
- If bridging is used pre-operatively, it is recommended to forego post-operative bridging in selected patients, especially those undergoing high-bleed-risk procedures [Level of Evidence: B].
For patients receiving acetylsalicylic acid for stroke prevention who require an elective or urgent (within 7 days) carotid endarterectomy or coronary artery bypass surgery, acetylsalicylic acid should be continued without interruption [Level of Evidence: B].
For patients who are receiving dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 inhibitor (e.g., clopidogrel, ticagrelor) for secondary stroke prevention who require urgent carotid endarterectomy (within 7 days), acetylsalicylic acid and a P2Y12 inhibitor should be continued perioperatively [Level of Evidence C].
For patients undergoing other types of surgery, continuing acetylsalicylic acid could be considered before a low/moderate-bleed-risk surgery or procedure. Interrupting acetylsalicylic acid before a high-bleed-risk surgery or procedure could be considered for 7-10 days [Level of Evidence C].

Section 8 Clinical Considerations

Perioperative management of patients undergoing a minimal-bleed-risk procedure

For patients undergoing minor procedures that are considered minimal-bleed-risk (refer to definition above), it is not routinely necessary to stop anticoagulants. However, there are some caveats to the management of such patients:
1. Any of the minimal-bleed-risk procedures could be considered as having a higher bleed risk warranting anticoagulant interruption (e.g., tooth extraction in a patient with poor dentition or cataract surgery with retrobulbar anesthesia) based on individual patient circumstances.
2. In patients receiving a DOAC who are undergoing a minimal bleed-risk procedure, it is prudent to omit the morning DOAC dose just before the procedure because the peak anticoagulant effect, occurring 1-3 hours after intake, may coincide with the timing of the procedure and may increase the risk for bleeding.
3. For pacemaker or ICD implantation, patients can continue warfarin, but the international normalized ratio (INR) should be <3.0 at the time of the procedure.
4. For coronary angiography, continuing anticoagulants if a femoral artery approach is used may not be advisable as such patients are at increased risk for developing a hematoma or false aneurysm
5. For colonoscopy, anticoagulation can be continued in selected patients where the likelihood of polypectomy or multiple biopsies is low.
6. For dental procedures, oral tranexamic acid mouthwash can be used before and 2-3 times daily after the procedure to reduce bleeding since such oral bleeding, although not clinically important, may cause distress to patients.

Perioperative management of patients undergoing a moderate to high-risk procedure

Patients having a high-bleed-risk surgery or procedure only need to be off DOACs for 2 days before the procedure, corresponding to a 60–68-hour interval between the last DOAC dose and the time of surgery, which means there is little to no residual anticoagulant effect at surgery given the 12–15-hour half-life of DOACs.
Patients having a low/moderate-bleed-risk surgery or procedure only need to be off DOACs for 1 day before the procedure, corresponding to a 36–42-hour interval between the last dose and the surgery
For all patients, no DOAC should be taken on the day of surgery/procedure.
The exception to this approach is patients on dabigatran with impaired renal function (creatinine clearance <50 mL/minute). Because dabigatran is cleared primarily by the kidneys, a longer interruption interval is needed (4 days before a high-bleed-risk surgery: 2 days before a low/moderate-bleed-risk surgery).
Postoperative resumption of DOACs should wait at least 24 hours after a low/moderate-bleed-risk surgery or procedure and 48-72 hours after a high-bleed-risk surgery or procedure.
There are caveats to postoperative DOAC management: First, the 48–72-hour resumption interval can be extended if there is greater than expected postoperative bleeding, which is important because the full anticoagulant effect of DOAC is almost immediate after oral intake. Second, in patients who are unable to take medications by mouth and who are at high risk for venous thromboembolism, low-dose LMWH can be given for the initial 1-3 postoperative days

Rationale +-

The perioperative management of patients receiving anticoagulant therapy is a common issue. The aim is to minimize the risk of stroke and other thromboembolic events while simultaneously minimizing the risk of clinically important (major) bleeding.

System Implications +-

Processes in place for access to pre-operative consultation prior to invasive surgery or procedures to optimize patient safety.

Performance Measures +-

Percentage of people with a history of stroke on antithrombotic agents who experience a perioperative/peri-procedural stroke.
Median length of stay people for with a history of stroke on antithrombotic agents who experience a perioperative/peri-procedural stroke compared to same population without peri-operative stroke.

Implementation Resources and Knowledge Transfer Tools +-

Patient Information

Summary of the Evidence +-

Perioperative Management of Anticoagulant and Antiplatelet Therapy
Recommendations Evidence Table and Reference List

Heparin bridging and warfarin interruption.

Heparin bridging is used in selected warfarin-treated patients and, typically, consists of giving a low-molecular-weight heparin (LMWH), such as enoxaparin 1 mg/kg BID or dalteparin 100 IU/kg BID, for 3 days before a surgery, during warfarin interruption. The premise of heparin bridging is that it shortens the time around the surgery that patients are not fully anticoagulated, while warfarin is interrupted and resumed, with the aim of mitigating the risk for stroke and systemic embolism.

In patients with atrial fibrillation who are receiving warfarin, there is evidence from the BRIDGE trial that heparin bridging had no effect on preventing arterial thromboembolism but increased the risk for major bleeding. Rates of arterial thromboembolism were 0.3% and 0.4% in patients who were bridged and not bridged, but rates of major bleeding were significantly higher in patients who were bridged: 3.2% vs. 1.3%. One caveat to the study findings is that heparin bridging might be considered in selected high-risk patients, including those with a CHADS2 score of 5-6 or those who have had perioperative thromboembolism during prior interruption of warfarin. In patients with a mechanical heart valve who require warfarin interruption, heparin bridging is suggested, especially in patients with a mitral valve prosthesis or any older tilting disc or caged-ball prosthesis. However, in selected patients, especially those having a high-bleed-risk surgery or procedure, we suggest omitting post-operative heparin bridging. Preoperative INR testing is not routinely needed but can be done in patients having a high-bleed-risk surgery or neuraxial anesthesia. An INR >1.5 on the day before the surgery can be managed by giving 1-2 mg oral vitamin K. After surgery, INR testing can be done in patients who are receiving heparin bridging can be stopped once the INR is >2.0.

Perioperative management of DOAC therapy

In DOAC-treated patients who require treatment interruption for an elective surgery or procedure, patient management is based on the estimated bleed risk associated with the surgery or procedure. Thromboembolic risk is less of a concern because the duration of anticoagulant interruption is short as DOACs have a rapid offset and onset of action. Perioperative heparin bridging and coagulation function testing are not routinely needed for perioperative DOAC management. There are selected patients in whom low-dose LWWH can be used after surgery, typically if they are at increased risk for venous thromboembolism and cannot take their DOAC medication by mouth.

Postoperative management of DOAC therapy

Postoperative resumption of DOACs should mirror preoperative interruption, so as to wait at least 24 hours after a low/moderate-bleed-risk surgery or procedure and 48-72 hours after a high-bleed-risk surgery or procedure. This approach was assessed in a prospective study, PAUSE, which studied 3,007 DOAC-treated patients (1,257 on apixaban, 668 on dabigatran and 1,082 on rivaroxaban) who required an elective surgery or procedure. The strategy of standardized DOAC interruption and resumption, no perioperative bridging and no preoperative coagulation function testing appeared safe as the 30-day postoperative rates of arterial thromboembolism, and major bleeding were <1% and <2%, respectively.

In summary, a quick way to remember perioperative DOAC management for an elective surgery or procedure is: “1 day off before and after a low/moderate-bleed-risk procedure and 2 days off before and after a high-bleed-risk procedure”.

Perioperative management of antiplatelet therapy

The perioperative management of patients receiving antiplatelet therapy such as acetylsalicylic acid, clopidogrel or both, and require an elective surgery/procedure is common because of the widespread use of these drugs for the secondary prevention of stroke and myocardial ischemia. The aim of perioperative antiplatelet management is to minimize the risk of stroke and myocardial ischemia while simultaneously mitigating the risk of bleeding which, if it occurs, can lead to prolonged antiplatelet interruption that, in turn, may increase the risk for stroke or cardiovascular events.

Most antiplatelet drugs (acetylsalicylic acid, clopidogrel, prasugrel) irreversibly inhibit platelet function for the lifespan of the platelet, which is 7-10 days. Consequently, platelet function is restored by 10-15% for each day such agents are interrupted. Ticagrelor reversibly inhibits platelets and, consequently, normalization of platelet function occurs within 2-3 days after interruption. Dipyridamole, a pyridopyridamine derivative with antiplatelet and anticoagulant properties and a half-life of 8 hours, has reversible antiplatelet effects but when it is combined with acetylsalicylic acid for secondary stroke prevention, this reversibility is nullified. There are few high-quality randomized trials to inform perioperative antiplatelet management and these studies have focused on patients who are receiving acetylsalicylic acid alone. Studies assessing patients who are receiving acetylsalicylic acid and a P2Y12 inhibitor and require an elective surgery are mainly retrospective studies.

Taken together, these studies suggest that in patients taking acetylsalicylic acid who need non-cardiac surgery, acetylsalicylic acid should be continued perioperatively in selected patients at increased risk for cardiovascular events, such as those with a prior stroke or coronary stent. Caution is warranted when continuing ASA without interruption in patients undergoing a high-bleed-risk surgery/procedure.

For patients taking acetylsalicylic acid who need coronary artery bypass or carotid artery surgery, acetylsalicylic acid is continued perioperatively. If a patient is also taking a P2Y12 inhibitor, this is typically interrupted for 5 days before coronary artery bypass surgery and 7 days before other non-cardiac surgery. For patients taking acetylsalicylic acid and a P2Y12 inhibitor who need urgent carotid artery surgery, typically within 1-2 weeks of a stroke syndrome, there is limited evidence from retrospective studies suggesting benefit with continuing both antiplatelet agents but with an associated increase in perioperative bleeding. In such patient’s pre-operative discussion with the surgeon of the benefits and risks of this management is advisable.

Sex and Gender Considerations

No studies were found that address sex and gender differences on this topic.

8. Perioperative Management of Anticoagulant and Antiplatelet Therapy

Definitions

Recommendations

Section 8 Clinical Considerations

Stroke Resources