Management of Anticoagulants in the Periprocedural Period for Patients With Cancer

Patients with cancer undergo surgeries and procedures for various purposes, including prophylaxis, diagnosis, staging, cure, debulking, palliation, and reconstruction. The diagnosis of cancer itself, along with the well-established complication of venous thromboembolism (VTE), places these patients at risk for perioperative thromboembolism. It is also well-established that continuing patients on oral anticoagulation therapy during the periprocedural period is associated with an increased risk of bleeding. Rates of periprocedural VTE and major bleeding are significantly higher in patients with cancer, presenting a complex problem for clinicians in terms of periprocedural anticoagulation management. This article reviews the current recommendations regarding periprocedural anticoagulation management in patients with cancer.

An estimated 1,660,290 new cases of cancer were diagnosed in 2013,1 and the incidence of new cases was 463 per 100,000 persons per year. However, the 5-year survival rate continues to increase, from 50.0% in 1975 to 1997 up to 65.8% in 2003 to 2009.1 Patients with cancer undergo surgeries and procedures for various purposes, including prophylaxis, diagnosis, staging, cure, debulking, palliation, and reconstruction.2 The diagnosis of cancer itself, along with its well-established association with venous thromboembolism (VTE), places these patients at risk for perioperative thromboembolism.3 It is also well-established that continuing patients on oral anticoagulation therapy during the periprocedural period is associated with an increased risk of bleeding.4 Rates of periprocedural VTE and major bleeding are significantly higher in patients with cancer,5 presenting a complex problem for clinicians in terms of periprocedural anticoagulation management. This article reviews the current recommendations regarding periprocedural anticoagulation management in patients with cancer with regard to the interruption and resumption of vitamin K antagonists (VKAs), unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) bridging, and target-specific oral anticoagulants (TSOACs).

Thrombotic and Bleed Risk in the Periprocedural Period

Overall, patients with active cancer (treated within the last 6 months or receiving palliative treatment) would be considered to be at moderate risk for perioperative thromboembolism, which implies an annual risk of arterial thromboembolism (ATE) of 5% to 10% and a 1-month VTE risk of 2% to 10%.3 However, patients with advanced-stage cancer, specific cancer histologies (ie, adenocarcinoma), high-risk biomarkers, or certain thrombogenic treatment-related factors, and those who have experienced a recent thrombotic event (within the past 3 months) or have associated severe thrombophilia (eg, protein C, protein S, or antithrombin deficiency; antiphospholipid antibodies) should be considered to be high risk for perioperative thromboembolism (annual ATE risk >10% or 1-month VTE risk >10%; Table 1). Finally, patients with a history of cancer and VTE greater than 12 months and no other risk factors can be considered at moderate risk.35

The procedural bleeding risk can be classified into 2 groups: high risk (with a 2-day risk of major bleeding of 2%–4%) or low risk (with a 2-day risk of major bleeding

Table 1

Clinical Risk Factors and Biomarkers for Cancer-Associated Venous Thrombosisa

Table 1
of 0%–2%).6 Various surgical societies have conducted studies to determine bleeding risk based on operation type.7 Most cardiovascular, vascular, oncologic, and urologic surgeries are considered to be associated with a high risk of bleeding. Operations and procedures associated with a low risk of bleed include cholecystectomy, abdominal hysterectomies or hernia repairs, most laparoscopic procedures, noncoronary angiography, and bronchoscopy with or without biopsy (Table 2).8

No validated risk assessment models are currently available to help clinicians with periprocedural heparin bridging in patients on chronic VKAs with thromboembolic and bleeding risks. Along with thrombotic and bleeding risks, patient- and procedure-related risk factors should also be considered. A recent article by Spyropoulos and Douketis8 presented a schematic of periprocedural antithrombotic management based on a 3-tier thromboembolic risk scheme and a 2-tier bleed risk scheme. In this conceptualized schematic, the thromboembolic risk determines whether a patient needs conservative or aggressive antithrombotic management in the periprocedural period (ie, heparin bridging). The postoperative management for initiation and duration of therapy is determined based on the procedural bleeding risk. For patients with malignancy, most procedures with low bleed risk (ie, ophthalmologic and dental procedures) warrant interruption of VKA therapy, because the bleed risk may be significant. Table 3 shows suggested periprocedural heparin bridging strategies based on thromboembolic and bleeding risks specific to patients with cancer.

Table 2

Procedural Bleeding Risks

Table 2
Other patient-specific factors, such as the development of periprocedural thrombocytopenia or anemia, fall risk, and need for supportive therapy that may affect the hemostatic system, should also be considered in management decisions for patients with cancer, especially in the postprocedural period.

Vitamin K Antagonists

The American College of Chest Physicians (ACCP) has made recommendations for VKA interruption based on the pharmacodynamic effects, specifically the time required for regeneration of vitamin K-dependent coagulation factors and the time to achieve hemostasis.9 Therefore, for warfarin, patients would need approximately 5 days before surgery to remove any effects of the drug. On closer examination, this is a result of the 36- to 42-hour elimination half-life of warfarin; with first-order pharmacokinetics, each half-life correlates to an approximately 50% reduction in the anticoagulant effect. Thus, one half-life decreases the anticoagulant effect by approximately 50.0%, the second half-life is 25.0%, the third half-life is 12.5%, the fourth-half life is 6.25%, and the fifth half-life is 3.125%.10 This finding was validated by studies that examined interruption of VKA therapy and used international normalized ratio (INR) on the day of surgery as a measurable outcome. In a prospective cohort study, INR testing on the day of surgery was conducted in 224 patients, all of which had stopped their warfarin 5 days prior. This study revealed that only 7% of patients had an INR greater than 1.5 on the day of surgery. Through indirect evidence, this supported the theory that discontinuation of VKAs at least 5 days before surgery allows for normalization of INR.11

Low-Molecular-Weight Heparin

Multiple studies reveal that LMWHs have superior efficacy to VKAs in patients with malignancy that require long-term VTE treatment. Romera-Villegas et al12 found that LMWH at full dose (relative risk [RR], 0.37; 95% CI, 0.19–0.74) and intermediate

Table 3

Suggested Periprocedural Heparin Bridging Strategies Based on Thromboembolic and Bleeding Risks in Patients With Cancer in Whom VKA Treatment is Interrupted

Table 3
dose (RR, 0.52; 95% CI, 0.35–0.79) was preferable. They also found a higher risk of recurrent VTE in patients with cancer who received a prophylactic dose of LMWH rather than a therapeutic dose. Therefore, specific considerations for the periprocedural management of patients with cancer undergoing long-term treatment with LMWHs require special review. Clinicians must consider the LMWH dose in patients with renal impairment, because LMWH is contraindicated in patients with stage V chronic kidney disease (CKD) and necessitates a dose adjustment for patients with stage IV CKD (creatinine clearance, 15–30 mL/min).13

TSOAC Use

TSOACs are a new class of drugs that is revolutionizing the management of thrombotic disorders. TSOACs can be separated into direct thrombin inhibitors, such as dabigatran, and direct factor Xa inhibitors, such as rivaroxaban and apixaban. Although the FDA approved these drugs for the prevention and treatment of VTE, the randomized controlled trials on which this approval was based included approximately 5% of patients with malignancy. The concerns are that patients with mucositis will have unpredictable absorption and a higher risk of gastrointestinal bleeding; drug interactions will occur with chemotherapeutic and hormonal agents; and there is no antidote for patients treated with TSOACs. However, guidance on the perioperative management of these patients is continually developing.14 Additionally, studies such as the placebo-controlled pilot trial conducted by Levine et al15 show that drugs such as apixaban were well tolerated in preventing VTE in patients undergoing chemotherapy.

Perioperative Anticoagulation Management

Minor Procedures

Certain dental, dermatologic, and ophthalmologic procedures are considered to have a low bleeding risk. Randomized studies have shown that patients receiving anticoagulation treatment can be guided safely through procedures such as tooth extractions and endodontic and minor reconstructive surgery, without needing to alter their anticoagulation treatment, by using local hemostatic agents, including oxidized cellulose or an oral tranexamic acid mouthwash.16,17 For patients undergoing minor dermatologic procedures, certain studies found that although self-limited episodes of minor bleeding occurred with the continued use of VKA, the incidence of major bleeding was less than 5%.18 Finally, in patients undergoing ophthalmologic procedures, similar results were seen, in that patients continuing on VKA treatment had self-limited episodes of bleeding. These bleeds did not compromise visual acuity.19

Neuraxial Anesthesia

With the introduction of neuraxial anesthesia (epidural and spinal blockades), an associated improvement in morbidity, mortality, and patient outcomes has been seen.20,21 However, the increasing number of patients on antithrombotic therapies warranted concerns regarding a greater risk of bleeding in patients undergoing neuraxial anaesthesia. The American Society of Regional Anesthesia and Pain Medicine (ASRA) updated guidelines in 2010 regarding the use of regional anesthesia in patients receiving antithrombotic or thrombolytic therapy. Their current recommendations for spinal or epidural anesthetic administration and catheter removal should be followed on an individual basis. The patient’s coagulation status should be optimal at the time of neuraxial anesthesia administration, and any indwelling catheter should not be removed in the presence of therapeutic anticoagulation, because this can significantly increase the risk of hematoma with the potential for subsequent neurologic deficits.22

Procedures Requiring Interruption of Oral Anticoagulants

VKA Management

The current ACCP recommendation for patients who require temporary interruption of VKAs before surgery is to stop these agents approximately 5 days before surgery (grade IC evidence). Other considerations regarding the interruption of VKAs include the fact that the decay of warfarin in elderly patients may not be the same as in younger patients,23 and that certain minor procedures that have less anticipated bleeding may require a shorter interruption.24

Most studies have shown that resuming VKA therapy on the evening of surgery or the day after is safe. Douketis et al25 studied 650 consecutive patients who required interruption of warfarin therapy because of an invasive procedure. In patients who underwent a non–high-bleeding-risk procedure with adequate postprocedural hemostasis, warfarin was resumed on the evening of the procedure. Other studies have shown similar results indicating that early resumption of warfarin is safe in the postoperative period.26,27

Use of Heparin Bridging Therapy

Intravenous UFH or LMWH Management: Perioperative management of patients who are receiving heparin bridging during temporary interruption of VKA has the potential to be complex because of multiple factors. The type of anticoagulant (intravenous UFH or LMWH), the intensity of anticoagulation (therapeutic, intermediate, or low dose), and the timing of perioperative administration are all examined.

When analyzing the intensity to prevent thromboembolism, studies have shown that low-dose LMWH or UFH is sufficient enough to prevent VTE after cancer.28 However, evidence is still insufficient regarding whether low-dose heparin regimens are sufficient to prevent ATE. The proximity of anticoagulant interruption and resumption to surgery is also highly considered with heparin products. In patients receiving bridging anticoagulation with intravenous UFH, ACCP recommendations are to stop this treatment 4 to 6 hours before surgery.29 Intravenous UFH would be a safer choice for patients with severe renal insufficiency or those on dialysis, because LMWH is contraindicated. Additionally, intravenous UFH can be resumed postoperatively without a bolus dose and at the same infusion rate as before procedure.

For patients receiving bridging anticoagulation with subcutaneous LMWH, the ACCP recommends administering the last preoperative dose approximately 24 hours before surgery.9 When contemplating initiation of LMWH postprocedure, it has been well documented that the closer to surgery LMWH is given, the greater the potential of its anticoagulant effect.30,31 Thus, although Table 3 depicts a suggested LMWH bridging protocol, clinicians should always assess postoperative hemostasis and delay LMWH bridging with a therapeutic dose until after adequate hemostasis is achieved. Finally, the principles of stopping and restarting LMWH for patients on long-term LMWH follows the same protocol as for those who are on VKA therapy receiving LMWH bridging.

TSOAC Management

For any TSOAC-treated patient, perioperative management is maintained by the following factors: elimination half-life of the TSOAC being used, the patient’s renal function, and the planned surgery and its high or low risk of bleed.32 Postoperative resumption of these TSOACs are based on 3 factors: their rapid onset of action, the potential effect of postoperative bowel dysmotility, and the use of acid-suppressive therapy on drug absorption of these TSOACs.33

Dabigatran has an elimination half-life of 14 to 17 hours in patients with normal or mild renal impairment. Therefore, in patients undergoing a procedure with a high bleed risk, the last dose should be given 3 days before surgery. Based on the dosing of dabigatran at 150 mg twice daily, these patients would be skipping 4 doses. In patients with moderate renal impairment, dabigatran has a half-life of 16 to 18 hours, and therefore the last dose should be given 5 days before surgery (ie, skip 8 doses).34

The cessation of rivaroxaban and apixaban also depends on the drug elimination half-lives. For rivaroxaban, the half-life is 8 to 9 hours, and for apixaban it is 7 to 8 hours. A patient’s renal function is also a factor, because the renal clearance is 33% for rivaroxaban and is 25% for apixaban.35 Both rivaroxaban and apixaban should be discontinued at least 3 to 4 days for procedures with a high bleeding risk. Typically, for patients with more-severe renal impairment, 4 days is necessary. In procedures with a low bleeding risk, 2 to 3 days should suffice.

Table 4

Suggested Perioperative Management of Target-Specific Oral Anticoagulants

Table 4

For postoperative resumption of rivaroxaban and apixaban, clinicians should base reinitiation on bleeding risk and whether hemostasis was achieved. In patients undergoing major surgery, a lower dose of rivaroxaban at 10.0 mg daily or apixaban at 2.5 mg twice daily may be a safer option for the first 2 to 3 days, with treatment dose regimen for the following days. Table 4 shows suggested perioperative management of dabigatran, rivaroxaban, and apixaban based on renal function and bleeding risk.

Conclusions

The periprocedural management of patients with cancer on chronic oral anticoagulant therapy is a common and complex challenge faced by clinicians. Patient-related factors, such as histologic type and stage of malignancy and concomitant risk factors for thrombosis, can complicate this matter greatly. Clinicians must take into consideration not only these factors but also procedural-related risk factors for bleeding. Patients with cancer can be classified into high or moderate risk for perioperative thromboembolism based on factors such as recent VTE, concurrent thrombophilia, and active cancer or chemotherapy treatment. The periprocedural bleeding risk can be classified into high or low risk. Thus, it is helpful to conceptualize a 3-tiered thromboembolism risk scheme and a 2-tiered bleed risk scheme when assessing patients with cancer who will require periprocedural anticoagulation.

Certain minor procedures may not require temporary interruption of oral anticoagulant therapy. In procedures requiring interruption of VKA, the current recommendation is to discontinue treatment 5 days before surgery. Studies have shown that it is safe to resume VKA therapy on the day of surgery or the next day. In any patient with cancer undergoing a procedure with a high risk for bleeding, the current recommendations are to use either intravenous UFH or to use LMWH as bridging therapy, usually in treatment doses. In low-bleed-risk situations, LMWH can be restarted within 24 hours of the procedure, whereas in high-bleed-risk situations, postoperative initiation of anticoagulation with therapeutic-dose LMWH should not be restarted before 48 to 72 hours. In patients with cancer who have a moderate thromboembolic risk, heparin bridging will depend on patient- and surgical-related risk factors for bleeding and thrombosis.

Although much research is still needed in patients with malignancy who are on TSOACs, perioperative management is guided by the half-life of individual TSOACs, renal function of the patient, and operative surgical risk. Further clinical work is needed to establish best practices for patients with cancer who are receiving antithrombotic therapy and require surgery.

Dr. Pudusseri has disclosed that she has no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors. Dr. Spyropoulos is a consultant for Bayer, Janssen, Boehringer Ingelheim, Sanofi, Bristol-Myers Squibb, and Pfizer, and is a member of the steering committee of the NHLBI Bridge Trial.

References

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    HowladerNNooneAMKrapchoM eds. SEER Cancer Statistics Review 1975-2010National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2010/ based on November 2012 SEER data submission posted to the SEER web site April 2013. Accessed November 10 2014.

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    DouketisJDFosterGACrowtherMA. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med2000;160:34313436.

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    CaliendoFJHalpernVJMariniCP. Warfarin anticoagulation in the perioperative period: is it safe?Ann Vasc Surg1999;13:1116.

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    TafurAJWysokinskiWEMcBaneR. Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients. Ann Onc2012;23:19982005.

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    • Export Citation
  • 6

    CollinsRScrimgeourAYusufSPetoR. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med1988;318:11621173.

    • Search Google Scholar
    • Export Citation
  • 7

    WeibertRT. Oral anticoagulant therapy in patients undergoing dental surgery. Clin Pharm1992;11:857864.

  • 8

    SpyropoulosACDouketisJD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood2012;120:29542962.

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    AnsellJHirshJHylekE; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th ed). Chest2012;133(Suppl 6):160S198S

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    PalaretiGLegnaniC. Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations. Clin Pharmacokinet1996;30:300313.

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    KovacsMJKearonCRodgerM. Single-arm study of bridging therapy with low-molecular weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation2004;110:16581663.

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    Romera-VillegasACairols-CastelloteMAVila-CollR. Long-term use of different doses of low-molecular weight heparin versus vitamin K antagonists in the treatment of venous thromboembolism. Ann Vasc Surg2010;24:628639.

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    • Export Citation
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    CarterGGossA. Tranexamic acid mouthwash-a prospective randomized study of a 2-day regimen vs. 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg2003;32:504507.

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    KargiEBabuccuOHosnuterM. Complications of minor cutaneous surgery in patients under anticoagulant treatment. Aesthetic Plast Surg2002;26:483485.

    • Search Google Scholar
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    LipJYDurraniOMRoldanV. Perioperative management of ophthalmic patients taking antithrombotic therapy. Int J Clin Pract2011;65:361371.

    • Search Google Scholar
    • Export Citation
  • 20

    LiuSCarpenterRLNealJM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology1995;82:14741506.

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    RodgersAWalkerNSchugS. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomized trials. BMJ2000;321:1493.

    • Search Google Scholar
    • Export Citation
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    HorlockerTTWedelDJRowlingsonJC. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. Reg Anesth Pain Med2010;35:64101.

    • Search Google Scholar
    • Export Citation
  • 23

    HylekEMReganSGoAS. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med2001:135:393400.

    • Search Google Scholar
    • Export Citation
  • 24

    MariettaMBertesiMSimoniL. A simple and safe nomogram for the management of oral anticoagulation prior to minor surgery. Clin Lab Haematol2003;25:127130.

    • Search Google Scholar
    • Export Citation
  • 25

    DouketisJDJohnsonJATrupieAG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med2004;164:13191326.

    • Search Google Scholar
    • Export Citation
  • 26

    DunnA. Perioperative management of oral anticoagulation: when and how to bridge. J Thromb Thrombolysis2006;21:8589.

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    SpyropoulosACTurpieAGDunnAS; REGIMEN Investigators. Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry. J Thromb Haemost2006;4:12461252.

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Article Details

Correspondence: Anita Pudusseri, DO, North Shore-LIJ Health System at Lenox Hill Hospital, 100 East 77th Street, New York, NY 10065. E-mail: apudusseri@nshs.edu

Article Sections

References

  • 1

    HowladerNNooneAMKrapchoM eds. SEER Cancer Statistics Review 1975-2010National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2010/ based on November 2012 SEER data submission posted to the SEER web site April 2013. Accessed November 10 2014.

    • Search Google Scholar
    • Export Citation
  • 2

    RosenbergSA. Surgical oncology: general issues. In: DeVitaVTLawrenceTSRosenbergSA eds. Cancer Principles & Practice of Oncology. 9th ed.Philadelphia, PA: Lippincott Williams & Wilkins; 2011:268276.

    • Search Google Scholar
    • Export Citation
  • 3

    DouketisJDFosterGACrowtherMA. Clinical risk factors and timing of recurrent venous thromboembolism during the initial 3 months of anticoagulant therapy. Arch Intern Med2000;160:34313436.

    • Search Google Scholar
    • Export Citation
  • 4

    CaliendoFJHalpernVJMariniCP. Warfarin anticoagulation in the perioperative period: is it safe?Ann Vasc Surg1999;13:1116.

  • 5

    TafurAJWysokinskiWEMcBaneR. Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients. Ann Onc2012;23:19982005.

    • Search Google Scholar
    • Export Citation
  • 6

    CollinsRScrimgeourAYusufSPetoR. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med1988;318:11621173.

    • Search Google Scholar
    • Export Citation
  • 7

    WeibertRT. Oral anticoagulant therapy in patients undergoing dental surgery. Clin Pharm1992;11:857864.

  • 8

    SpyropoulosACDouketisJD. How I treat anticoagulated patients undergoing an elective procedure or surgery. Blood2012;120:29542962.

  • 9

    AnsellJHirshJHylekE; American College of Chest Physicians. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (9th ed). Chest2012;133(Suppl 6):160S198S

    • Search Google Scholar
    • Export Citation
  • 10

    PalaretiGLegnaniC. Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations. Clin Pharmacokinet1996;30:300313.

  • 11

    KovacsMJKearonCRodgerM. Single-arm study of bridging therapy with low-molecular weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation2004;110:16581663.

    • Search Google Scholar
    • Export Citation
  • 12

    Romera-VillegasACairols-CastelloteMAVila-CollR. Long-term use of different doses of low-molecular weight heparin versus vitamin K antagonists in the treatment of venous thromboembolism. Ann Vasc Surg2010;24:628639.

    • Search Google Scholar
    • Export Citation
  • 13

    SchmidPBrodmannDOdermattY. Study of bioaccumulation of dalteparin at a therapeutic dose in patients with renal insufficiency. J Thromb Haemost2009;7:16291632.

    • Search Google Scholar
    • Export Citation
  • 14

    KaatzSKoudesPAGarciaDA. Guidance on the emergent reversal of oral thrombin and factor Xa inhibitors. Am J Hematol2012;87(Suppl 1):S141145.

    • Search Google Scholar
    • Export Citation
  • 15

    LevineMNGuCLiebmanHA. A randomized phase II trial of apixiban for the prevention of thromboembolism in patients with metastatic cancer. J Thromb Haemost2012;10:807814.

    • Search Google Scholar
    • Export Citation
  • 16

    MorimotoYNiwaHMinematsuK. Hemostatic management of tooth extractions in patients on oral antithrombotic therapy. J Oral Maxillofac Surg2008;66:5157.

    • Search Google Scholar
    • Export Citation
  • 17

    CarterGGossA. Tranexamic acid mouthwash-a prospective randomized study of a 2-day regimen vs. 5-day regimen to prevent postoperative bleeding in anticoagulated patients requiring dental extractions. Int J Oral Maxillofac Surg2003;32:504507.

    • Search Google Scholar
    • Export Citation
  • 18

    KargiEBabuccuOHosnuterM. Complications of minor cutaneous surgery in patients under anticoagulant treatment. Aesthetic Plast Surg2002;26:483485.

    • Search Google Scholar
    • Export Citation
  • 19

    LipJYDurraniOMRoldanV. Perioperative management of ophthalmic patients taking antithrombotic therapy. Int J Clin Pract2011;65:361371.

    • Search Google Scholar
    • Export Citation
  • 20

    LiuSCarpenterRLNealJM. Epidural anesthesia and analgesia. Their role in postoperative outcome. Anesthesiology1995;82:14741506.

  • 21

    RodgersAWalkerNSchugS. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomized trials. BMJ2000;321:1493.

    • Search Google Scholar
    • Export Citation
  • 22

    HorlockerTTWedelDJRowlingsonJC. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy. Reg Anesth Pain Med2010;35:64101.

    • Search Google Scholar
    • Export Citation
  • 23

    HylekEMReganSGoAS. Clinical predictors of prolonged delay in return of the international normalized ratio to within the therapeutic range after excessive anticoagulation with warfarin. Ann Intern Med2001:135:393400.

    • Search Google Scholar
    • Export Citation
  • 24

    MariettaMBertesiMSimoniL. A simple and safe nomogram for the management of oral anticoagulation prior to minor surgery. Clin Lab Haematol2003;25:127130.

    • Search Google Scholar
    • Export Citation
  • 25

    DouketisJDJohnsonJATrupieAG. Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin: assessment of a standardized periprocedural anticoagulation regimen. Arch Intern Med2004;164:13191326.

    • Search Google Scholar
    • Export Citation
  • 26

    DunnA. Perioperative management of oral anticoagulation: when and how to bridge. J Thromb Thrombolysis2006;21:8589.

  • 27

    SpyropoulosACTurpieAGDunnAS; REGIMEN Investigators. Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry. J Thromb Haemost2006;4:12461252.

    • Search Google Scholar
    • Export Citation
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