Gregory YH Lip, MD, FRCPE, FESC, FACC
Lawrence LK Leung, MD
Stephen A Landaw, MD, PhD
INTRODUCTION — The role for warfarin and other anticoagulants in many cardiovascular disorders is well established and their use as prophylaxis against stroke or thromboembolism is increasing. As a result, many patients undergoing elective surgery or an invasive procedure may be taking anticoagulants. The management of anticoagulation in such patients both before and after such procedures will be reviewed here .
Rapid, temporary reversal of excess warfarin anticoagulation, and the possible use of medications affecting hemostasis in the perioperative period are discussed separately. (See “Correcting excess anticoagulation after warfarin”, section on ‘Temporary reversal of warfarin’ and “Perioperative medication management”, section on ‘Medications affecting hemostasis’.)
Issues concerning the risks of continuing warfarin or antiplatelet agents during eye surgery are discussed separately. (See “Cataract in adults”, section on ‘Antithrombotic agents’ and “Anticoagulant, antiplatelet, and fibrinolytic (thrombolytic) therapy in patients at high risk for ocular hemorrhage”, section on ‘Ophthalmic surgery’.)
PROBLEM OVERVIEW — Although continuation of anticoagulation increases the risk of bleeding following invasive procedures, interruption of such therapy increases the risk of thromboembolism in patients taking anticoagulants to prevent thrombosis [2-4]. Accordingly, individual circumstances should be carefully reviewed before an informed decision on modifying anticoagulation therapy is made in the patient undergoing surgery or an invasive procedure. There is also concern about the following issues in anticoagulated patients:
- There is a requirement of several days for the anticoagulant effect to resolve after warfarin therapy is discontinued, potentially delaying more urgent surgery.
- Rebound hypercoagulability may occur following the abrupt cessation of anticoagulation.
- Several days may be required after warfarin therapy is resumed to reestablish a therapeutic and adequate level of anticoagulation.
The importance of these issues varies in part with the indication for anticoagulation (eg, prophylaxis for thromboembolism versus actual treatment for an acute thrombotic episode). Accordingly, there is no general consensus regarding management strategy in patients undergoing elective surgery who are currently taking long-term anticoagulation. The type of procedure may also be important (see ‘Type of surgery or procedure’ below).
THROMBOTIC RISK IF ANTICOAGULATION IS STOPPED — Patients may be taking oral anticoagulation as prophylaxis against the development of new thrombi or embolism (eg, atrial fibrillation, severe myocardial dysfunction, prosthetic heart valve) or as actual treatment of acute thrombus-related problems (eg, deep venous thrombosis or pulmonary embolism).
Cessation of oral anticoagulation used to treat an acute thrombotic event may exacerbate the condition, which may itself be life-threatening. The risk of underanticoagulation varies with the type of thromboembolic event. While recurrent DVT carries some risk of fatal pulmonary embolism, the consequences of arterial thromboembolism from atrial fibrillation or prosthetic heart valves are much more serious, with 20 percent of episodes being fatal and 40 percent causing permanent disability [5-8].
Appropriate use of alternative strategies, such as intravenous heparin or subcutaneous low molecular weight heparin (LMW heparin) to provide antithrombotic coverage (ie, “bridging” anticoagulation) during the period when warfarin is withdrawn or reintroduced has been utilized in an attempt to minimize the risks involved. (See ‘Use of bridging anticoagulation’ below.)
Venous thromboembolism — Long-term anticoagulation is the recommended treatment for patients at high risk of recurrence of venous thromboembolism. Discontinuation of warfarin in such patients is associated with a significant risk of thromboembolism as high as 15 percent per year; warfarin probably reduces this risk by about 80 percent [9-11].
After an acute episode of venous thromboembolism, the recurrence risk is much reduced over the following three months . Without anticoagulation, the early risk of recurrent venous thromboembolism is approximately 50 percent, but treatment with warfarin for one month reduces this risk to 8 to 10 percent, and to 4 to 5 percent after three months of warfarin therapy [11,13]. Thus, discontinuing oral anticoagulation within the first month after an acute venous thromboembolic episode is associated with a high risk of recurrent venous thromboembolism ; this risk is reduced if surgery is delayed and there is a longer period of warfarin treatment.
Patients at risk for arterial thromboembolism — The risk of recurrent arterial embolism from any cardiac source is approximately 0.5 percent per day in the first month after an acute event . This risk is reduced by two-thirds with warfarin.
Arterial thromboembolism is most commonly associated with atrial fibrillation; embolic stroke is fatal or associated with a severe neurologic deficit in over 60 percent of these patients [5,6]. Patients with atrial fibrillation not due to valvular heart disease have an overall risk of systemic embolism of 4 to 5 percent per year in the absence of warfarin therapy; anticoagulation reduces the risk of embolization by about two-thirds in this setting [7,16].
However, patients with atrial fibrillation are not a homogeneous group and the risk of stroke and thromboembolism varies. Management should therefore be tailored to an individual patient’s risk of thromboembolism as compared to the risk of bleeding during surgery. It is possible to risk stratify such patients based upon clinical and echocardiographic criteria. (See “Risk of embolization in atrial fibrillation”.)
Other causes of thromboembolism include a dilated and poorly contractile left ventricle or a left ventricular aneurysm in which intraventricular thrombi may form and embolize [17-19].
- Among patients with left ventricular dysfunction, one report found an 18 percent increase in stroke risk for every 5 percent reduction in left ventricular ejection fraction, although the absolute short-term risk was low . Anticoagulation with warfarin was associated with an 81 percent reduction in total stroke risk while aspirin therapy reduced the risk by 56 percent. (See “Indications for anticoagulation in heart failure”.)
- Among patients with left ventricular aneurysm, the frequency of left ventricular thrombi in aneurysms reported by postmortem studies can range between 14 and 68 percent, a value consistent with findings at the time of surgical aneurysmectomy (50 to 95 percent) .
Recommendations are available elsewhere for the management of patients with atrial fibrillation when temporary cessation of warfarin is considered. (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Temporary cessation of anticoagulation’.)
Prosthetic heart valves — Systemic embolization (predominantly cerebrovascular events) occurs at a frequency of approximately 0.7 to 1.0 percent per patient per year in patients with mechanical valves who are treated with warfarin, 2.2 percent per patient per year with aspirin, and 4.0 percent with no anticoagulation. A major advantage of the bioprosthetic valve is freedom from anticoagulation.
The management of anticoagulation in such patients, both in general and in the perioperative period, is discussed in depth separately. (See “Antithrombotic therapy in patients with prosthetic heart valves”, section on ‘Discontinuing warfarin for surgical procedures’.)
BLEEDING RISK IF ANTICOAGULATION IS CONTINUED — The risk of bleeding occurring with surgery in patients taking anticoagulant therapy is dependent upon patient age, the presence of other disease states, the type of surgery , the anticoagulant regimen and intensity, the length of warfarin therapy, the use of other drugs that affect hemostasis (eg, heparin, aspirin, antiplatelet agents), the stability of anticoagulation, and the degree of anticoagulation as measured by the INR [2,21,22].
Type of surgery or procedure — Prolonged, complex, and major surgery is much more likely to cause significant bleeding problems than short, simple, and minor surgical procedures. As examples:
- Low bleeding risk procedures — Most patients can undergo low-risk surgical procedures (eg, arthrocentesis, cataract surgery, coronary arteriography, outpatient dental surgery, other minor outpatient procedures) without alteration of their anticoagulation regimen [23,24]. In such patients, oral anticoagulation with a vitamin K antagonist can be continued at or below the low end of the therapeutic range (INR ≤2.0). (See “Cataract in adults”, section on ‘Antithrombotic agents’ and “Anticoagulant, antiplatelet, and fibrinolytic (thrombolytic) therapy in patients at high risk for ocular hemorrhage”, section on ‘Ophthalmic surgery’.)
- High bleeding risk procedures — More complex or high-risk surgical procedures (eg, open-heart surgery, abdominal vascular surgery, intracranial or spinal surgery, major cancer surgery, urologic procedures) require discontinuation of oral anticoagulation, followed by temporary perioperative coverage with unfractionated heparin or LMW heparin in those patients who are at high risk of thromboembolism . (See ‘Cessation and resumption of anticoagulation’ below.)
Gastroenterologic procedures — Management of anticoagulation in patients undergoing gastroenterologic procedures depends upon the estimated bleeding risk for the contemplated procedure as well as the estimated thrombotic risk if the patient is temporarily taken off anticoagulation (table 1 and table 2 and table 3) . This subject is discussed in detail separately. (See “Management of anticoagulants in patients undergoing endoscopic procedures”, section on ‘Elective procedures in anticoagulated patients’.)
Dental or excisional cutaneous procedures — In patients undergoing dental extraction, warfarin anticoagulation is associated with a minimal risk of serious bleeding if the INR is within the therapeutic range just prior to the contemplated surgery [27-32]. Tranexamic acid or aminocaproic acid mouthwash, if available (eg, 4.8 to 5 percent aqueous solutions used four times per day for at least two days), can be used to limit local postoperative bleeding [32-37]. The use of aspirin, NSAIDS, or Cox-2 inhibitors for analgesia should be avoided.
However, there are documented cases of serious embolic events when warfarin has been withdrawn prior to dental procedures. In a literature review of 542 documented cases in 493 patients in whom continuous anticoagulation was withdrawn for a dental procedure (without heparin replacement), there were five serious embolic complications (0.9 percent of cases) .
Anticoagulation is generally safe in patients undergoing excisional cutaneous surgery (eg, Mohs surgery) if the INR is maintained within the therapeutic range [20,38-40]. As with dental procedures, cessation of prophylactic anticoagulation (warfarin or antiplatelet therapy) has been associated with a risk of thromboembolic events [38-40].
Use of heparin — The risk of bleeding after the use of heparin is variable. A two-day course of intravenous heparin before surgery is unlikely to cause much in the way of preoperative bleeding. The general risk of bleeding associated with continuous intravenous heparin is less than 5 percent in patients with acute venous thromboembolism; however, in patients with deep vein thrombosis who are judged to be at high risk for bleeding, the incidence of major bleeding is approximately 11 percent during the first five days of intravenous heparin therapy [22,41].
CESSATION AND RESUMPTION OF ANTICOAGULATION
Overview — After the cessation of oral warfarin, it usually takes a few days for the INR to fall to below 2.0. One study prospectively evaluated 22 patients with a baseline INR of 2.6 in whom it was deemed safe to discontinue warfarin . In these patients the mean INR was 1.6 and 1.2 at 2.7 and 4.7 days after discontinuation of warfarin, respectively.
Once the INR is 2.0 or below, surgery can be performed with relative safety in most cases. Following surgery and after warfarin is restarted, it takes about three to four days for the INR to rise above 2.0. It is therefore estimated that if warfarin is withheld for four days before surgery and is restarted as soon as possible afterwards, patients would have a subtherapeutic INR for approximately two days before surgery and two days after surgery .
A slight elevation of the INR to about 1.5 should theoretically provide partial protection against thromboembolism [43,44]. In support of this hypothesis, ultra-low dose warfarin (1 mg/day) has been successfully used to prevent deep venous thrombosis in patients with malignancy in association with a marginal rise in the INR . (See “Drug-induced thrombosis and vascular disease in patients with malignancy”, section on ‘Prophylactic anticoagulation’.)
If the patient has been adequately anticoagulated for some time prior to cessation of warfarin, it is generally assumed that almost any preexisting thrombus would have either resolved or be endothelialized, thereby minimizing the risk of embolism . Among patients with nonvalvular atrial fibrillation, for example, over 85 percent of thrombi resolve after four weeks of warfarin therapy as determined by transesophageal echocardiography .
Nevertheless, although the INR itself may not be a good guide to a reduced risk of thromboembolism, some patients have a significant reduction in their usual anticoagulant intensity during surgery and a minor increase in the risk of thromboembolism is probably unavoidable . Among patients with atrial fibrillation, chronic low dose warfarin plus aspirin is much less effective than adjusted dose warfarin in preventing embolic events (figure 1 and figure 2), demonstrating that such lesser degrees of anticoagulation do not provide optimal protection . (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”.)
Reversing warfarin — Reversing the activity of vitamin K antagonists depends upon the amount of time available before the surgical or invasive procedure. The following guidelines are most appropriate :
Fully elective surgery — In patients with an INR between 2.0 and 3.0 who are undergoing elective surgery that requires temporary cessation of anticoagulation, warfarin should be withheld for approximately three to four days to allow the INR to fall to a level of 1.5 to 2.0 before surgery [14,42,47]. Warfarin should be withheld for approximately five days if the surgeon feels it is necessary to reduce the INR to a lower or normal level in order to reduce the risk of bleeding (eg, less than 1.5) .
Semi-urgent surgery — If more rapid reversal of warfarin anticoagulation is required (eg, over one to two days), warfarin should be withheld and a small dose (eg, 1.0 to 3.0 mg) of intravenous vitamin K1 administered. (See “Correcting excess anticoagulation after warfarin”, section on ‘Temporary reversal of warfarin’.)
Urgent surgery — If urgent reversal of warfarin anticoagulation is required (eg, less than one day), warfarin should be withheld and a higher dose (eg, 2.5 to 5.0 mg) of intravenous vitamin K1 administered. If more immediate correction is required (eg, minutes to hours), this can be achieved via the use of those prothrombin complex concentrates which contain adequate amounts of factor VII or fresh frozen plasma, in addition to vitamin K . A discussion of how such rapid reversal of the warfarin effect can be accomplished can be found elsewhere. (See “Correcting excess anticoagulation after warfarin”, section on ‘Significant or life-threatening bleeding’.)
The risk of rebound hypercoagulability — As mentioned above, rebound hypercoagulability may occur following the abrupt cessation of anticoagulation. Accordingly, alternative preoperative and/or postoperative prophylaxis against thromboembolism with unfractionated heparin (UFH) or LMW heparin should be considered in high risk patients (eg, prosthetic valve in the mitral position, venous thromboembolism within the previous four weeks, or active malignancy) for the period during which the INR is less than 2.0 [49-51].
The clinical effects of rebound hypercoagulability after stopping warfarin are unlikely to be significant, despite biochemical evidence for this phenomenon and the recommendation by some investigators that warfarin should be withdrawn gradually [52-54].
- In one study of 19 patients, for example, thrombin and fibrin formation increased after abrupt cessation of warfarin therapy but no patient had a thromboembolic event .
- In another report, however, 32 patients were randomly assigned to receive abrupt or gradual withdrawal of warfarin . Very high levels of thrombin activation were seen in a few patients treated with abrupt withdrawal, two of whom developed a thrombotic event (one recurrent deep vein thrombosis and one thrombosis in a varicose vein).
Surgery itself increases the risk of thromboembolism as documented by changes in hemostatic markers, which are also part of the acute phase response and wound healing process . High levels of hemostatic markers, such as fibrin D-dimer, an index of intravascular thrombogenesis and fibrin turnover, are predictive of postoperative thrombosis [56,57]. Although there is evidence that surgery increases the risk of venous thromboembolism, there is no evidence that surgery itself increases the risk of arterial thromboembolism, apart from risks associated with particular procedures, such as carotid surgery .
Use of bridging anticoagulation — The risk of a short period of underanticoagulation is uncertain, especially since randomized studies of heparin versus placebo bridging among warfarin-treated patients who need procedures have not been conducted. Because of the lack of evidence-based information indicating those patients in whom bridging anticoagulation is or is not warranted, there is considerable variation in the use of this modality .
Of the available non-randomized studies of this question [25,49,60-68], the following prospective observational cohort studies are instructive concerning the thrombotic and hemorrhagic risks attendant to the use or non-use of bridging therapy in this setting.
The first study involved a cohort of 1024 individuals whose warfarin therapy was temporarily withheld on 1293 different occasions for an outpatient invasive procedure (colonoscopy; oral, dental, or ophthalmic surgery; epidural injection; prostate or breast biopsy; dermatologic procedure). The following observations were made :
- The duration of warfarin therapy interruption was variable, although >80 percent had warfarin therapy withheld for ≤5 days. Bridging therapy with heparin or LMW heparin was given in only 8.3 percent of the procedures.
- Six patients (0.6 percent; 95% CI 0.2-1.3) experienced major bleeding and an additional 17 patients (1.7 percent; 95% CI 1.0-2.6) experienced a clinically significant, nonmajor bleeding episode. Four of the six patients with major bleeding and 10 of the 17 patients with nonmajor clinically significant bleeding had received periprocedural bridging therapy, for an overall bleeding rate in bridged patients of 13 percent.
- Postprocedural thromboembolism within 30 days occurred in seven patients (0.7 percent; 95% CI 0.3-1.4). None of the seven patients had received periprocedural bridging therapy; two of these patients would have been considered to be at high risk for thromboembolism (ie, recent VTE or active malignancy).
The authors concluded that perioperative anticoagulation may be unnecessary for a significant proportion of low- to intermediate-risk outpatients who have undergone long-term anticoagulation, whose warfarin therapy must be interrupted for a brief period (ie, ≤5 days), and that bridging therapy with unfractionated or LMW heparin may result in significant and potentially avoidable perioperative hemorrhage.
Similar conclusions were reached in a second study involving a cohort of 345 individuals with nonvalvular atrial fibrillation undergoing an invasive procedure. Warfarin therapy was temporarily withheld on 342 different occasions for a mean period of 6.6 days. The decision to use bridging anticoagulation with therapeutic doses of either intravenous unfractionated heparin or LMW heparin was individualized, but was generally given only to those patients deemed to be at high risk for stroke. The following observations were made :
- The three-month cumulative incidence of thromboembolism was 1.1 percent and did not differ significantly between those who did or did not receive bridging therapy.
- Of interest, despite not receiving bridging therapy after brief warfarin cessation, none of the 43 patients with a prior thromboembolic event, and none of the 51 patients with a CHADS2 score ≥3 developed postoperative thromboembolism during the three-month follow-up period.
- The three-month cumulative incidence of major bleeding was 2.7 percent for those receiving bridging therapy. Of the 10 episodes of major bleeding, six occurred in five patients given bridging therapy with LMW heparin.
The authors indicated that they currently utilize bridging with LMW heparin only for those patients at highest risk (eg, prior stroke, CHADS2 score ≥4) while taking into account the procedure-associated risk of bleeding. (See ‘Type of surgery or procedure’ above.)
Use of subtherapeutic doses of LMW heparin — Two nonrandomized studies employing bridging with sub-therapeutic doses of LMW heparin are discussed below.
In the first study, subtherapeutic doses of LMW heparin (eg, 3800 IU of nadroparin or 4000 IU of enoxaparin once daily the night before the procedure for those at low risk of thrombosis or 3800 or 4000 IU of these agents twice daily for those at high thrombotic risk) were employed in 103 patients undergoing surgery and in 225 non-major invasive procedures. Results included :
- The overall incidence of a thromboembolic event was 1.8 percent and was not significantly different between those in the low-risk (0.54 percent) or high-risk (3.4 percent) groups.
- The overall incidence of major bleeding was 2.1 percent and was not significantly different between those in the low-risk (0.5 percent) or high-risk (4.1 percent) groups. All of the major bleeding events occurred in those undergoing major surgery.
The second study was a report from a prospective registry of 198 consecutive patients receiving oral anticoagulation with phenprocoumon and a planned surgery . The majority of patients (88 percent) were judged to be at intermediate thromboembolic risk. Phenprocoumon was stopped seven days before surgery. All patients received enoxaparin in a half-therapeutic dose (1 mg/kg per day) starting when the INR was <2.0 and continuing until the day before surgery. Enoxaparin was restarted after the procedure at the same total daily dose (in two divided doses) and phenprocoumon was resumed within the first 14 postoperative days, depending upon the bleeding risk. Only one patient (0.5 percent) developed a postoperative arterial thromboembolic event, and one patient (0.5 percent) required a second surgical intervention due to severe bleeding.
Both sets of authors concluded that the use of bridging anticoagulation with subtherapeutic doses of LMW heparin was safe and effective.
Resumption of warfarin — Warfarin therapy should be restarted 12 to 24 hours post-surgery, provided that surgical hemostasis has been achieved .
Unfractionated heparin — The biologic half-life of intravenous unfractionated heparin (UFH) is approximately 45 minutes [37,70]. Thus, most bridging anticoagulation studies have suggested that intravenous UFH should be stopped 4 to 5 hours before the planned surgery or procedure, a time interval that is approximately 5 elimination half-lives of UFH.
LMW heparin — The biologic half-life of subcutaneous LMW heparin is approximately 4 to 6 hours [37,70]. Thus, most bridging anticoagulation guidelines have suggested that the last dose of subcutaneous LMW heparin should be given 24 hours before the planned surgery or procedure, a time interval that is approximately 5 elimination half-lives of LMW heparin.
However, because some studies have shown residual anticoagulant effect at 24 hours after stopping therapeutic-dose LMW heparin [12,71], it has been recommended that, on the day before surgery or the procedure, therapeutic-dose LMW heparin should be administered at one-half of the usual total daily dose .
Resumption of treatment — The onset of anticoagulation after both UFH and LMW heparin is similar, at around one hour after administration, with peak anticoagulant activity at around three to five hours. Thus, if post-operative or post-procedural anticoagulation is contemplated, these agents should not be employed too early following the operation, in order to insure that hemostasis has been secured at the operative or procedural site . This requires both a pre-procedural estimate of the anticipated risk of bleeding as well as a post-procedural determination of the adequacy of hemostasis .
However, for most minor procedures associated with a low bleeding risk, therapy with LMW heparin or UFH can usually be resumed at 24 hours post-procedure, whereas for those undergoing major surgery or those with a high bleeding risk procedure, such treatment should be delayed for 48 to 72 hours after hemostasis has been secured .
Dabigatran — Dabigatran is an orally active thrombin inhibitor. It has a time to peak anticoagulant activity of two to three hours after ingestion and a half-life elimination of 12 to 14 hours in normal subjects and approximately 28 hours in those with severe renal impairment . (See “Anticoagulants other than heparin and warfarin”, section on ‘Dabigatran’.)
These pharmacokinetic parameters affect the timing of cessation and resumption of treatment with this agent, as follows [74,75]:
- Cessation prior to invasive or surgical procedures: For those with a creatinine clearance ≥ 50 mL/minute, discontinue dabigatran 1 to 2 days before the procedure. For those with a creatinine clearance <50 mL/minute, discontinue this agent 3 to 5 days before the procedure. Longer periods should be considered for those undergoing major surgery, spinal puncture, placement of a spinal or epidural catheter or port, in whom complete hemostasis may be required.
- Conversion to a parenteral anticoagulant: Wait 12 hours (Clcr ≥30 mL/minute) or 24 hours (Clcr <30 mL/minute) after the last dose of dabigatran before initiating a parenteral anticoagulant.
- Resumption following procedure: Therapy with dabigatran should be initiated when hemostasis has been achieved, since its onset of action (2 to 3 hours) is rapid.
- Resumption following use of heparin or LMW heparin: Initiate dabigatran ≤2 hours prior to the time of the next scheduled dose of the parenteral anticoagulant (eg, enoxaparin) or at the time of discontinuation for a continuously administered parenteral drug (eg, intravenous heparin)
SPECIAL CONSIDERATIONS — A number of clinical situations require special consideration. These are discussed below.
Venous thromboembolism — The management of anticoagulation in patients with previous venous thromboembolic disease depends upon the temporal relationship to surgery or an invasive procedure (table 4).
- Within the first month after an acute episode of venous thromboembolism, the incidence of recurrence without anticoagulation is about 1 percent per day. While postoperative intravenous heparin doubles the rate of bleeding, there is a net reduction in serious morbidity in such patients, since the risk of postoperative recurrent venous thromboembolism is high. Thus, heparin therapy is recommended both before and after surgery .
- By two to three months after an acute episode of venous thromboembolism, the risk of recurrence is significantly reduced so that preoperative heparin therapy is probably not justified unless there are other risk factors for thromboembolism (eg, prolonged hospitalization and confinement to bed) . However, because of an expected increase in the risk of venous thromboembolism after surgery, these patients should be treated postoperatively with heparin.
- At more than three months after an episode of venous thromboembolism, preoperative anticoagulation is not needed and postoperative intravenous heparin is also probably not necessary. (See “Treatment of lower extremity deep vein thrombosis”, section on ‘Length of treatment’.)
In this setting, the bleeding associated with postoperative intravenous heparin offsets any beneficial effect from the prevention of major thromboembolic events . Prophylactic measures that reduce the thrombotic risk, such as subcutaneous LMW heparin or compression stockings, are associated with a lower risk of bleeding than intravenous heparin and are safer alternatives .
Arterial thromboembolism — The approach is somewhat different in patients at risk for arterial thromboembolism, because the thromboembolic risk is similar both before and after surgery. Furthermore, the risk of bleeding is much higher in such patients after surgery if heparin is continued or the INR is maintained at around 2.0. Thus, preoperative treatment with intravenous heparin is advised if oral anticoagulation is stopped. Postoperative therapy with intravenous heparin is probably useful for patients undergoing minor surgery where the risk of bleeding is low. In contrast, the net benefit of using intravenous heparin in reducing long-term disability after major surgery is small because of the high risk of serious bleeding.
If the risk of acute arterial thromboembolism is low, as in patients with nonvalvular atrial fibrillation receiving warfarin for thromboprophylaxis, postoperative intravenous heparin therapy probably increases, rather than decreases, serious morbidity. Restarting warfarin on the second postoperative day and the use of low risk regimens, such as subcutaneous heparin, if warfarin was discontinued preoperatively, are preferable to minimize the risk of bleeding.
- Unfractionated heparin should be stopped four hours before surgery with the expectation that the anticoagulation effect will have worn off at the time of surgery . If LMW heparin has been used, it should be stopped, preferably 24 hours before surgery , with the same expectation.
These recommendations may not apply to patients undergoing minor procedures such as skin biopsy or dental extractions [28,34,38]. However, it is important to confirm that the INR does not exceed the therapeutic range. Although uninterrupted anticoagulation may be continued in most patients, we and many other clinicians withhold warfarin for two to four days prior to the procedure, and reinstitute therapy after the procedure .
- Elective surgery should be avoided in the first month after arterial thromboembolism. If surgery is essential, preoperative and postoperative heparin therapy is recommended as described above for venous thromboembolism, but only if the risk of postoperative bleeding is low.
- In patients receiving warfarin as prophylaxis against arterial embolization, such as low risk patients with a prosthetic heart valve or nonvalvular atrial fibrillation, the risk of thromboembolism is not high enough to warrant routine preoperative or postoperative therapy with intravenous heparin, especially in view of the bleeding risk [7,78].
If the surgical intervention itself is associated with a high risk of postoperative venous thromboembolism (VTE), the brief use of subcutaneous low-dose heparin or LMW heparin in doses used for prophylaxis against VTE has been suggested . (See “Antithrombotic therapy to prevent embolization in nonvalvular atrial fibrillation”, section on ‘Temporary cessation of anticoagulation’ and “Prevention of venous thromboembolic disease in surgical patients”, section on ‘Risk factors for VTE’.)
The approach is different in high risk patients with atrial fibrillation (eg, prior thromboembolism, rheumatic heart disease, left ventricular dysfunction) or prosthetic heart valves (eg, those with older generation mechanical valves or atrial fibrillation), in whom there is a delicate balance between the risks of bleeding and thromboembolism [7,78]. In this setting, a number of options exist and the appropriate treatment of such patients is unclear and controversial [76,78].
However, it is our preference in this setting to administer intravenous heparin until five to six hours before the procedure, to be restarted as soon as surgical hemostasis has been assured ; the dose is adjusted to achieve an activated PTT that is 2.0 times control. Warfarin is then reinstituted prior to discharge from the hospital; the INR should be in the therapeutic range for at least 48 hours before heparin is discontinued.
Pacemaker insertion — A substantial number of patients who require the insertion of a permanent pacemaker are receiving oral anticoagulation and/or antiplatelet therapy for various reasons. Elective pacemaker insertion is often performed in the outpatient setting and the issue of anticoagulation is an important concern . One study compared the outcome of 37 patients undergoing outpatient pacemaker implantation while continuing on warfarin therapy with 113 patients not receiving warfarin; there was no difference in the incidence of any complications, including those related to the wound . The use of a cut-down technique, rather than a subclavian puncture, to gain venous access is preferred and a catheter electrode with a small cross sectional area and small introducer should be used to reduce the probability of venous damage; pocket hemostasis must be meticulous.
Mechanical prosthetic heart valves — Recommendations regarding the perioperative management of anticoagulation in patients with prosthetic heart valves are presented separately. (See “Antithrombotic therapy in patients with prosthetic heart valves”, section on ‘Discontinuing warfarin for surgical procedures’.)
Percutaneous coronary intervention — Management of anticoagulation as well as antiplatelet therapy in patients undergoing percutaneous coronary intervention is discussed separately. (See “Antithrombotic therapy for intracoronary stent implantation: General use”, section on ‘Patients who require warfarin’.)
SUMMARY AND RECOMMENDATIONS — The risk of thromboembolism in patients who discontinue anticoagulation before an invasive procedure must be weighed against the risk of bleeding if these agents are continued or bridging anticoagulation is employed. Accordingly, individual circumstances should be carefully reviewed before an informed decision on modifying anticoagulation therapy is made in the patient undergoing surgery or an invasive procedure. (See ‘Problem overview’ above.)
Low risk surgical procedures — Most patients can undergo low-risk surgical procedures without alteration of their anticoagulation regimen, provided that their INR is within the therapeutic range. (See ‘Type of surgery or procedure’ above and ‘Bleeding risk if anticoagulation is continued’ above.)
Patients at risk for bleeding — For patients with a high risk of procedural bleeding, the pre-procedural INR should be ≤1.5. We recommend that patients at low risk for thrombosis stop warfarin five days preoperatively rather than for a shorter interval (Grade 1B). This will allow adequate time for the INR to normalize. (See ‘Warfarin’ above.) Once surgical hemostasis has been achieved, we recommend that warfarin therapy be resumed 12 to 24 hours post-surgery, rather than for a shorter or longer interval (Grade 1C). (See ‘Resumption of warfarin’ above.)
Patients at risk for thrombosis
- Elective surgery should be avoided, if at all possible, in the first month after an acute episode of venous thromboembolism.
- For patients at high or intermediate risk for thrombosis, we recommend the use of bridging anticoagulation with intravenous heparin or LMW heparin over no bridging during temporary interruption of oral anticoagulation (Grade 1C). Clinical judgement is required to determine the dose of these agents (ie, therapeutic, sub-therapeutic, or prophylactic dosing) as the quality of evidence for making this choice is poor. (See ‘Venous thromboembolism’ above and ‘Use of bridging anticoagulation’ above.)
- For patients at low risk for thrombosis, we suggest either bridging anticoagulation with prophylactic dose or subtherapeutic dose LMW heparin or no bridging anticoagulation over bridging with therapeutic dose LMW heparin (Grade 2C). (See ‘Use of bridging anticoagulation’ above.)
- If acute venous thromboembolism has occurred within two weeks AND the risk of bleeding associated with the use of bridging anticoagulation is high, the temporary use of a vena caval filter should be considered. (See “Inferior vena cava filters”.)
- Elective surgery should be avoided, if at all possible, in the first month after arterial thromboembolism. If surgery is essential, bridging anticoagulation is recommended as described above for venous thromboembolism. (See ‘Arterial thromboembolism’ above and ‘Use of bridging anticoagulation’ above.)
Stopping and starting bridging anticoagulation
- Bridging anticoagulation with unfractionated heparin should be stopped four to five hours before surgery. If LMW heparin has been used, it should be stopped 24 hours before surgery. (See ‘Heparin products’ above.)
- We suggest that heparin or LMW heparin in therapeutic doses should not be restarted postoperatively until at least 24 hours after surgery and delayed longer if there is any evidence of bleeding (Grade 2C). (See ‘Heparin products’ above.)
- Guidelines for stopping and restarting dabigatran have been formulated on the known pharmacokinetics of this agent, and are described in the text. (See ‘Dabigatran’ above.)
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