Using low molecular weight heparins as "bridging anticoagulant therapy"

April 1, 2005
Wendy Lim, MD
Wendy Lim, MD

,
James D. Douketis, MD
James D. Douketis, MD

Volume 5, Issue 4

Abstract: Bridging anticoagulant therapy is used to minimize the risk of thromboembolic complications when warfarin therapy must be temporarily interrupted because of surgery or another procedure. The decision to use this strategy depends on the patient's risk of thromboembolic complications and the risk of bleeding associated with the specific procedure. One approach is to withhold 4 or 5 daily doses of warfarin before surgery and initiate low molecular weight heparin (LMWH) 3 or 4 days before surgery. The last dose of LMWH is administered at least 24 hours before the procedure. After the procedure, prophylactic-dose LMWH can be administered subcutaneously once daily. The use of therapeutic-dose LMWH should be deferred until at least 24 or 48 hours after procedures that have a low or moderate risk of bleeding and until 48 or 72 hours after high-risk procedures. (J Respir Dis. 2005;26(4):170-172)

The temporary interruption of oral anticoagulant therapy in patients undergoing surgery or other invasive procedures is a frequently encountered clinical problem. Few prospective studies have evaluated the use of low molecular weight heparins (LMWHs) in the perioperative or periprocedure setting and, consequently, there are no universally accepted management recommendations at present.1,2

The use of perioperative anticoagulation, or "bridging anticoagulant therapy," refers to the administration of therapeutic doses of short-acting anticoagulants in the days preceding the surgery or procedure, during which time warfarin therapy is interrupted or its anticoagulant effect is subtherapeutic. Bridging anticoagulant therapy is used to minimize the risk of thromboembolic complications, including stroke, mechanical valve thrombosis, and venous thromboembolism (VTE).

In this article, we will address the question, "What approach do you recommend for using LMWH in patients who require temporary interruption of warfarin therapy?" We will present an approach that is currently used at our institu- tion, which has been standardized and evaluated for its efficacy and safety.3

Assessing thromboembolic risk

The decision to use bridging anticoagulant therapy depends on an assessment of 2 clinical features:

• The patient's risk of thromboembolic complications while he or she is not receiving anticoagulants.

• The risk of bleeding associated with the procedure.

The risk of thromboembolic complications depends on the presence of thromboembolic (stroke) risk factors and the indication for warfarin therapy. Risk factors for stroke include atrial fibrillation, left ventricular dysfunction, hypertension, age over 75 years, diabetes mellitus, and a previous history of stroke or transient ischemic attack (TIA).4,5 The most common indications for long-term anticoagulation include the presence of mechanical heart valves, chronic atrial fibrillation, and VTE.

• Mechanical heart valves: For patients with mechanical heart valves, the following features indicate high risk: recent (within the previous month) stroke or TIA, a mechanical mitral valve, or a caged-ball or single-leaflet tilting disk aortic valve. Patients at moderate risk include those with a bileaflet aortic valve and 2 or more risk factors for stroke. Low-risk patients are those with a bileaflet aortic valve and fewer than 2 risk factors for stroke.

• Chronic atrial fibrillation: Patients at high risk for thromboembolic complications include those with recent (within 1 month) stroke or TIA and those with rheumatic mitral valvular disease. Moderate-risk patients include those with 2 or more stroke risk factors, while low-risk patients have fewer than 2 risk factors.

• VTE: Patients at high risk include those who have had a recent (within the previous month) episode of VTE or who have ongoing risk factors for VTE, including active cancer (they have received treatment within 6 months or are receiving palliative care) and antiphospholipid antibodies (anticardiolipin antibody or lupus anticoagulant/nonspecific inhibitor).6,7 Moderate-risk patients include those who had VTE within the previous 6 months or who have had VTE in the perioperative setting. Low-risk patients are those with none of the above-mentioned features.

Periprocedure anticoagulant management

To minimize the duration that anticoagulant therapy will be interrupted, we recommend withholding 4 or 5 daily doses of warfarin before surgery. This will result in an international normalized ratio (INR) of 1.3 or less in the vast majority of patients after 5 days, which is generally acceptable for most procedures.

We routinely measure the patient's INR the day before surgery to ensure that it has normalized (INR of 1.3 or less). If the INR is 1.5 or higher, we administer vitamin K, 1 mg orally, to ensure that the INR will normalize for surgery, and we may remeasure the patient's INR the morning of surgery.

In general, bridging anticoagulant therapy should be used in patients who are at high risk for thromboembolic complications. It may be considered in patients at moderate risk and is optional for those at low risk. LMWHs are usually started 3 or 4 days before surgery, during which time the patient's INR would be expected to be subtherapeutic (INR less than 2.0 for most clinical indications).

Because of their pharmacokinetic properties, LMWHs may be administered subcutaneously with use of weight-adjusted doses (Table). The following LMWH preparations and dose regimens can be used: dalteparin, 200 IU/kg once daily or 100 IU/kg twice daily; enoxaparin, 1.5 mg/kg once daily or 1 mg/kg twice daily; nadroparin, 171 IU/kg once daily; or tinzaparin, 175 IU/kg once daily. (Nadroparin is not commercially available in the United States.)

Since anticoagulant monitoring is not required, LMWHs may be administered out-of-hospital, which simplifies the bridging anticoagulation process. Most patients can be taught self-administration, or outpatient nursing may be arranged.

The last dose of LMWH is administered at least 24 hours before the start of the procedure. If once-daily LMWH is used, the last pre-procedure dose should be given before 8 am the day before surgery, whereas if twice-daily LMWH is used, the evening dose the day before surgery should be held. This approach may decrease the likelihood that a residual anticoagulant effect from LMWH would occur at the time of the procedure.

Assessing the risk of postoperative bleeding

The risk of postoperative bleed- ing depends on several factors, including the type of surgery or procedure and a number of patient-specific factors. In general, the procedures and their associated postoperative bleeding risk can be categorized as follows:

• High risk: The high-risk procedures include major neurosurgical procedures (craniotomy, spinal cord procedures); major cardiovascular procedures (coronary artery bypass, major peripheral vascu- lar surgery); urologic procedures (prostatectomy, bladder tumor resection); and minor procedures at vascular sites (renal biopsy, cervical cone biopsy, bowel polypectomy).

• Moderate risk: The moderate-risk procedures include major intra-abdominal surgery, intrathoracic surgery, and major orthopedic surgery.

• Low risk: Cataract extraction, most cutaneous surgery, laparoscopic abdominal surgery (cholecystectomy, hernia repair), and single dental extraction are considered low-risk procedures.

The decision to reinitiate anticoagulation should be made with the surgeon and is made after hemostasis has been achieved following a noncomplicated procedure.

Postprocedure anticoagulation management

Because the bleeding risks are higher following a procedure, we recommend use of prophylactic-dose LMWH, administered subcutaneously once daily. Possible regimens are dalteparin, 5000 IU; enoxaparin, 40 mg; nadroparin, 38 IU/kg; and tinzaparin, 75 IU/kg. This is started the evening of the day of surgery in patients undergoing low- and moderate-risk procedures and may be given after 24 or 48 hours in those undergoing procedures associated with a high bleeding risk.

The use of therapeutic-dose LMWH should be deferred until at least 24 or 48 hours after procedures that have a low and moderate risk of bleeding, and until 48 or 72 hours after high-risk procedures. Alternatively, therapeutic-dose LMWH can be avoided altogether in patients undergoing high-risk procedures.

The patient's usual dose of warfarin may be started the evening of the day of surgery, since the anticoagulant effect of warfarin requires 4 to 5 days to reach therapeutic levels. Once the INR is in the target therapeutic range, the bridging LMWH should be discontinued. In patients who also take aspirin, this can be resumed at the same time as warfarin.

References:

REFERENCES


1. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery.

N Engl J Med.

1997;336:1506-1511.
2. Douketis JD. Perioperative anticoagulation management in patients who are receiving oral anticoagulant therapy: a practical guide for clinicians.

Thomb Res

. 2002;108:3-13.
3. Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen.

Arch Intern Med.

2004;164:1319-1326.
4. Gage BF, Waterman AD, Shannon W, et al. Validation of clinical classification schemes for predicting stroke: results from the National Registry of Atrial Fibrillation.

JAMA

. 2001;285:2864-2870.
5. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation: analysis of pooled data from five randomized controlled trials.

Arch Intern Med.

1994;154: 1449-1457.
6. Douketis JD, Foster GA, Crowther MA, et al. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy.

Arch Intern Med

. 2000;160: 3431-3436.
7. Schulman S, Svenungsson E, Granqvist S, and the Duration of Anticoagulation Study Group. Anticardiolipin antibodies predict early recurrence of thromboembolism and death among patients with venous thromboembolism following anticoagulant therapy.

Am J Med.

1998;104:332-338.