Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy Principal Developer: J. Douketis Secondary Developers: M. Crowther, M. Kovacs Scope The management of patients who are assessed for temporary interruption of warfarin therapy is challenging for two reasons1,2. First, warfarin interruption may expose patients to an increased risk for perioperative arterial or venous thromboembolism whereas continuation of warfarin in the perioperative period may increase the risk for bleeding complications. Second, the patient population is heterogeneous, both in terms of perioperative bleeding and thromboembolic risk. Chapter Objectives • • •

to provide a clinical guide for stratifying patients according to surgical bleeding risk, thereby identifying patients in whom warfarin interruption is needed to provide a clinical guide for stratifying patients according to thromboembolic risk, thereby identifying patients in whom bridging anticoagulation is needed during temporary interruption of warfarin to provide a clinical guide that will facilitate the management of patients who require urgent surgery and prompt reversal of anticoagulation with warfarin

Other Related Documents in this Educational Monograph • • •

Initiation and Maintenance of Warfarin Therapy Treatment of Patients Overanticoagulated with Warfarin Warfarin: A Guide for Patients

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Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy

Overview of Perioperative Management of Warfarin Therapy before and after Surgery or other Invasive Procedures Is surgery an elective or emergency/urgent?

Elective

Emergency/Urgent

24 hours

Administer IV vitamin K1, 2-4 mg

Bleeding risk associated with procedure is intermediate or high

Is bridging anticoagulation needed during warfarin interruption?

No

Patient is at low risk for thromboembolism

Day -5: stop warfarin (last dose Day -6) Day -1: INR testing (if INR >1.5, administer vitamin K1, 1.0 to 2.0 mg orally) Day 0: resume warfarin on evening after surgery if patient drinking fluids Day +1 to +3: resume warfarin when patient drinking fluids

Yes

Patient is at intermediate or high risk for thromboembolism

Day -5: stop warfarin (last dose on Day -6) Day -3: start intravenous UFH or subcutaneous LMWH Day -1: INR testing (if INR >1.5, administer vitamin K1, 1.0 to 2.0 mg orally); stop LMWH on the morning before surgery (omit evening dose with b.i.d. dosing; reduce total daily dose by 50% with o.d. dosing) Day 0: stop UFH 4 hours before surgery; assess postoperative surgical site hemostasis; resume warfarin on evening after surgery if patient drinking fluids Day +1 to +3: resume UFH or LMWH when hemostasis secured and not earlier than 12 hours after surgery; resume warfarin when patient drinking fluids Day +5 to +6: stop UFH or LMWH when INR therapeutic -2-

Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy Patient Assessment and Management 1) Is warfarin interruption needed in patients who are undergoing elective surgery? Deciding whether a patient needs interruption of warfarin therapy is based on the bleeding risk associated with the surgical or invasive procedure. As outlined in the Table below, procedures can be classified according to their risk for bleeding, as very low, low, intermediate, high or very high risk. Most patients will require warfarin interruption. Patient Stratification for Bleeding Risk Very High-Risk • neurosurgery (intracranial or spinal surgery) • cardiac surgery (coronary artery bypass or heart valve replacement) High-Risk • major vascular surgery (abdominal aortic aneurysm repair, aortofemoral bypass) • major urologic surgery (prostatectomy, bladder tumour resection) • major lower limb orthopedic surgery (hip/knee joint replacement surgery) • lung resection surgery • intestinal anastomosis surgery • permanent pacemaker insertion or internal defibrillator placement • selected invasive procedures (kidney biopsy, prostate biopsy, cervical cone biopsy, pericardiocentesis, colonic polypectomy) Intermediate-Risk • other intraabdominal surgery • other intrathoracic surgery • other orthopedic surgery • other vascular surgery Low-risk • laparoscopic cholecystectomy • laparoscopic inguinal hernia repair • dental procedures • dermatologic procedures • ophthalmologic procedures • coronary angiography • gastroscopy or colonoscopy • selected invasive procedures (bone marrow aspirate and biopsy, lymph node biopsy, thoracentesis, paracentesis, arthrocentesis) Very Low-risk (warfarin interruption not needed) • single tooth extraction or teeth cleaning • selected skin biopsy or skin cancer removal • selected cataract removal

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Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy

ecommendation 1: In patients undergoing a procedure associated with a very low risk for bleeding, warfarin interruption is R not needed before the procedure. In other patients undergoing a major surgical or other invasive procedure, warfarin therapy should be interrupted before the procedure. 2) Is bridging anticoagulation needed in patients who require warfarin interruption? For patients who require warfarin interruption, the next issue is whether ‘bridging anticoagulation’ is needed before and after the procedure. Bridging anticoagulation refers to the administration of a short-acting anticoagulant, typically with therapeuticdose unfractionated heparin (UFH) or low-molecular-weight heparin (LWMH), before and after surgery to minimize the time that patients are not therapeutically anticoagulated and, thereby, minimize the risk of thromboembolism1-3. Although the risk for thromboembolism during warfarin interruption is low (i.e., 75 years

•

prior venous thromboembolism within last 3 to 12 months

Low-Risk (bridging anticoagulation not recommended) •

chronic atrial fibrillation (valvular or nonvalvular) and no major stroke risk factors

•

prior venous thromboembolism over 12 months ago

†Consider a temporary inferior vena cava filter, to be inserted after warfarin interruption and prior to surgery for patients in whom surgery is planned within 1 month of thromboembolic episode); it can be left in situ for 1-2 weeks until therapeutic anticoagulation is re-established. For patients in whom bridging anticoagulation is considered, treatment options consist of: •

i ntravenous UFH, administered to achieve a therapeutic activated partial thromboplastin time (aPTT), defined according to local laboratory parameters

•

subcutaneous therapeutic-dose LMWH (enoxaparin, 1 mg/kg b.i.d. or 1.5 mg/kg o.d., dalteparin,100 IU/kg b.i.d. or 200 IU/kg o.d., or tinzaparin, 175 IU/kg o.d.)

•

i n patients having a surgery or procedure associated with a high-risk for bleeding, an alternate postoperative management is subcutaneous low-dose LMWH (enoxaparin, 40 mg o.d.; dalteparin 5000 IU o.d.; or tinzaparin, 4500 IU o.d.)

•

i n patients having a surgery associated with a very high-risk for bleeding, postoperative therapeutic-dose LMWH/UFH should be avoided; postoperative management options are low-dose LMWH or resuming warfarin alone -4-

Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy ecommendation 2: Bridging anticoagulation is recommended in patients at high-risk for thromboembolism, is suggested (but R optional) in patients at intermediate-risk for thromboembolism, and is not recommended in patients at low-risk for thromboembolism. 3) What is the perioperative anticoagulant management after warfarin interruption? As a convention, Day -5 refers to 5 days before surgery, Day 0 refers to the day of surgery, Day +1 refers to the day after surgery. ecommendation 3A: In patients at high-risk or intermediate-risk for thromboembolism in whom bridging anticoagulation is to R be administered, the following perioperative management is recommended: •

Day -5: stop warfarin (last dose on Day -6)

•

Day -3: start intravenous UFH or subcutaneous LMWH

•

Day -1: INR testing (if INR >1.5, administer vitamin K1, 1.0-2.0 mg orally)12; stop LMWH on the morning before surgery (omit evening dose with b.i.d. dosing; reduce total daily dose by 50% with o.d. dosing)13

•

Day 0: stop UFH 4 hours before surgery; assess postoperative surgical site hemostasis; resume warfarin on evening after surgery if patient drinking fluids

•

Day +1 to +3: resume UFH or LMWH when hemostasis secured and not earlier than 12 hours after surgery; resume warfarin when patient drinking fluids

•

Day +5 to +6: stop UFH or LMWH when INR within therapeutic range

ecommendation 3B: In patients at low-risk for thromboembolism in whom bridging anticoagulation is not to be administered, R the following perioperative management is recommended: •

Day -5: stop warfarin (last dose on Day -6)

•

Day -1: INR testing (if INR >1.5, administer vitamin K1, 1.0-2.0 mg orally)

•

Day 0: resume warfarin on evening after surgery if patient drinking fluids

•

Day +1 to +3: resume warfarin when patient drinking fluids

4) When is it safe to resume bridging anticoagulation after surgery/procedure? Deciding on when to resume bridging anticoagulation is important to minimize the risk for bleeding, which occurs at the surgical site in >90% of cases4-8. Minimizing bleeding is important because of morbidity associated with bleeding (i.e., emergency reoperation, blood transfusion). Furthermore, a bleed will delay the resumption of warfarin for 1-4 weeks, thereby exposing patients to an increased risk for thromboembolism4-8. The resumption of bridging anticoagulation after a procedure is dependent on the bleeding risk of the procedure, as shown in the Table below, and is predicated on adequate postoperative hemostasis. Assessing postoperative hemostasis is subjective and includes inspecting wound bandages and drainage tubes to detect bleeding. Adjunctive measures to minimize the risk for perioperative bleeding include good suturing technique, wound-site pressure (e.g., pressure dressings), use of ice packs and, when indicated, use of anti-fibrinolytic agents (e.g., tranexamic acid mouthwash for dental procedures).

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Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy Postoperative Resumption of Bridging Anticoagulation: Treatment Options Very-High Risk Bleeding Procedure • low-dose LMWH, starting 12-24 hours after surgery (i.e., day after surgery) • alternate management: resume warfarin alone with no postoperative LMWH/UFH High-Risk Bleeding Procedure • therapeutic-dose LMWH/UFH, starting 48-72 hours after surgery • alternate management: low-dose LMWH, starting 12-24 hours after surgery (i.e., day after surgery) Moderate-Risk Bleeding Procedure • therapeutic-dose LMWH/UFH, starting 24-48 hours after surgery Low-Risk Bleeding Procedure • therapeutic-dose LMWH/UFH, starting 12-24 hours after surgery (i.e., day after surgery) 5) How to manage patients who require warfarin reversal for urgent surgery? or patients who require urgent or emergency surgery, management is predicated on the timing of the surgery. Also, reversal of F anticoagulation with warfarin requires administration of vitamin K1, irrespective of whether fresh frozen plasma is administered as clotting factors in fresh frozen have a shortened half-life and their pro-hemostatic effects will diminish after several hours. Vitamin K1 is, therefore, needed to eliminate the residual effect of warfarin which, otherwise, can persist for >48 hours after it is stopped. Recommendation 4A: In patients who require emergency surgery, within 24 hours, the anticoagulant effect of warfarin should be reversed with vitamin K1, 2.0-4.0 mg intravenously and, if required, transfusion of 2-4 units fresh frozen plasma. Recommendation 4B: In patients who require urgent surgery, after more than 24 hours, the anticoagulant effect of warfarin should be adequately reversed with vitamin K1, 2.0-4.0 mg intravenously without the need for transfusion of fresh frozen plasma. 6) Perioperative management of patients who are receiving aspirin and/or clopidogrel? atient management is similar to that of warfarin-treated patients in that the need for aspirin/clopidogrel interruption should be P initially addressed. Antiplatelet drugs probably can be continued for patients undergoing very low or low bleeding risk procedures. In patients undergoing intermediate or high bleeding risk procedures, antiplatelet therapy should be interrupted. Because aspirin and clopidogrel irreversibly inhibit platelet function, 7-10 days (platelet lifespan) is required after treatment interruption to eliminate a residual antiplatelet effect prior to surgery. Interrupting aspirin/clopidogrel 3-4 days before surgery will result in ~50% of platelets have normal function and this may be sufficient for some procedures. There is no known short-acting antiplatelet drug that can be used, like UFH or LMWH, as bridging antiplatelet therapy. In patients who require urgent surgery that necessitates eliminating the antiplatelet effects of aspirin/clopidogrel, administering 5-10 units of platelets can be done although this is preferable only for patients who have active life-threatening bleeding. Recommendation 5: For patients undergoing elective surgery and require interruption of aspirin and/or clopidogrel, treatment should be stopped at least 3-4 days before surgery and should be stopped 7-10 days before surgery to ensure there is no residual antiplatelet effect at the time of surgery. Practical Aspects of Perioperative Anticoagulant Management erioperative anticoagulant management involves a team of health care providers which include the surgeon/interventionist, P anesthetist, internist/hematologist, clinic/home care nurse and the patient. Effective communication of planned management among health care providers and with the patient is essential to optimize patient care. •

the anesthetist and internist/hematologist should communicate about planned anesthesia since the type used (i.e., general vs. spinal/epidural) will have implications on ensuring no residual antithrombotic effect at the time of surgery and the type of postoperative anticoagulation

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•

the internist/hematologist and surgeon/interventionist should confer on the adequacy of postoperative hemostasis and safe time to resume postoperative bridging anticoagulation

•

the patient should be provided with clear instruction regarding the perioperative stopping/starting of warfarin and LMWH

To facilitate communication on patient management, a standardized bridging anticoagulation patient information form, an example of which is provided in the Appendix below, can be given to patients at the time of their visit, and faxed or e-mailed to other caregivers (surgeon, interventionist, anesthetist, family doctor).

Appendix. Sample Bridging Anticoagulation Patient Information Form

Date (d/m/y)

Days in Relation to Surgery -7

Antithrombotic Management STOP aspirin/clopidogrel/ticlopidine

Blood Testing CBC, INR, creatinine

-6 -5

STOP warfarin (i.e., no warfarin on this day)

INR

-4 -3 -2 -1

SURGERY

LMWH ____ units, once- or twice-daily LMWH ____ units, once- or twice-daily LMWH ____ units, once-or twice-daily (last dose 24 hours before surgery) (at bedtime, when there is adequate postoperative hemostasis) warfarin ____ mg

+2

LMWH ____ units, once- or twice-daily (at least 24 hours after surgery, when there is adequate postoperative hemostasis) warfarin ____ mg LMWH ____ units, once- or twice-daily warfarin ____ mg

+3

LMWH _____ units, once- or twice-daily warfarin ____ mg

+1

+4

+5

INR

LMWH _____ units, once- or twice-daily (if required) warfarin ____ mg LMWH _____ units, once- or twice-daily (if required) warfarin ____ mg

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INR CBC

INR CBC

Perioperative Management of Patients who are Receiving Warfarin or Antiplatelet Therapy References 1. D unn AS, Turpie AG. Perioperative management of patients receiving oral anticoagulants: a systematic review. Arch Intern Med 2003;163:901-8. 2. Douketis JD. Perioperative anticoagulation management in patients who are receiving oral anticoagulant therapy. A practical guide for clinicians. Thromb Res 2002;107:3-13. 3. Hirsh J, Raschke R. Heparin and low-molecular-weight heparin: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:188S-203S. 4. Kovacs MJ, Kearon C, Rodger M, Anderson DR, Turpie AG, Bates SM, Desjardins L, Douketis J, Solymoss S, Wells PS. Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin. Circulation 2004;110:1658-63. 5. Douketis JD, Johnson JA, Turpie AG. Low-molecular-weight heparin as bridging anticoagulation in patients who require temporary interruption of warfarin for an elective surgical or invasive procedure: assessment of a standardized peri-procedural anticoagulation regimen. Arch Intern Med 2004;169:1319-26. 6. Spyropoulos AC, Turpie AG, Dunn AS, Spandorfer J, Douketis J, Jacobson A, Frost F, for the 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 Haemost 2006;4:1246-52. 7. Dunn AS, Spyropoulos AC, Sirko SP, Turpie AG. Perioperative bridging therapy with enoxaparin in patients requiring interruption of long-term oral anticoagulant therapy: a multicenter cohort study. Blood 2004;104:488a. 8. Turpie AG, Douketis JD. Enoxaparin is effective and safe as bridging anticoagulation in patients with a mechanical prosthetic heart valve who require temporary interruption of warfarin because of surgery or an invasive procedure. Blood 2004;104:202a. 9. Martinelli J, Jiminez A, Rabago G, Artiz V, Fraile J, Farre J. Mechanical cardiac valve thrombosis: is thrombectomy justified? Circulation 1991;84 (Suppl III):70 10. Longstreth WT, Bernick C, Fitzpatrick A, Cushman M, Knepper L, Lima J, Furberg CD. Frequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study. Neurology 2001;56:368-75. 11. Kearon C, Hirsh J. Management of anticoagulation before and after elective surgery. N Engl J Med 1997;336:1506-11. 12. Crowther MA, Ageno W, Schnurr T, Manfredi E, Kinnon K, Garcia D, Douketis JD. Oral vitamin K produces a normal INR within 24 hours of its administration in most patients discontinuing warfarin. Haematologica 2005;90:137-9. 13. 13. D ouketis JD, Woods K, Foster GA, Crowther MA. Bridging anticoagulation with low-molecular-weight heparin after interruption of warfarin therapy is associated with a residual anticoagulant effect prior to surgery. Thromb Haemost 2005;94:52831.

Created February 2009 -8-