Anticoagulation: When to Start,When to Stop Ebtisam Bakhsh, MD; and James D. Douketis, MD, FRCPC Presented at McMaster University s Thrombosis and Hematology Update, October 2006. CASE IN... Anticoagulation The management of patients who require an interruption of warfarin because of surgery or an invasive procedure is a common clinical problem as there are over two million people in North America with chronic atrial fibrillation, a mechanical heart valve or venous thromboembolism who are receiving long-term warfarin therapy. 1 In most patients, perioperative anticoagulation is managed in an outpatient setting, in part because most of the procedures that patients undergo (e.g., endoscopy or minor surgery), do not require hospitalization. The availability of low-molecular-weight heparins (LMWHs), which Copyright can be administered subcutaneously by the patient or a caregiver, facilitates the use of outpatient bridging. 2,3 Bridging anticoagulation refers to the administration of a therapeutic-dose of anticoagulation therapy before and after a procedure, Not for Sale or Commercial Distribution Unauthorised use prohibited. Authorised users can download, display, view and print a single copy for personal use during the time warfarin therapy is interrupted and its anticoagulant effect is below the target therapeutic range. This is typically used in patients at higher risk for thromboembolism. In recent years, there have been several non-randomized trials that have assessed the use of LMWH as a form of bridging in patients who require warfarin interruption. 4 These studies provide a framework of how to bridge patients and demonstrated that when bridging is done according to a standardized management protocol, the incidence of stroke is low (approximately 1%) and, importantly, the incidence of serious bleeding is also low (approximately 3%). Meet Tracey Tracey, 55, weighs 75 kg and has rheumatic heart disease as well as a mechanical mitral valve. She is scheduled to have laparoscopic cholecystectomy, with a planned discharge from the hospital on the evening after her surgery. Her risk factors for thromboembolism include atrial fibrillation and a mechanical heart valve. Tracey has no prior history of stroke, transient ischemic attack (TIA), hypertension, diabetes, or congestive heart failure. Case management Based on the type of surgery, warfarin will require temporary interruption. Tracey is considered to be at high-risk for thromboembolism (Figure 1), bridging anticoagulation is warranted. Management for this type of patient includes stopping warfarin 5 days before surgery and bridging with low-molecular-weight heparin (LMWH) (e.g., 100 IU/kg of dalteparin b.i.d., rounded off to a 7,500 IU pre-filled dose), which is started 3 days before surgery and with the last dose given on the morning of the day before surgery (i.e., at least 24 hours before surgery). After surgery, there is adequate hemostasis, based on intraoperative blood loss and good postoperative wound hemostasis. Warfarin is resumed on the evening after surgery and LMWH is resumed the next day, at least 24 hours after surgery (i.e., 7,500 IU b.i.d.). LMWH is continued for 3 more days until the INR is > 2.0. For a second case, look to page 23. The Canadian Journal of CME / November 2007 21
Is the planned surgery/procedure elective or urgent? Elective Urgent Is the interruption of warfarin needed prior to the elective surgery/invasive procedure? < 24 hours > 24 hours No Bleeding risk associated with surgery/procedure is very low Yes Bleeding risk associated with surgery/procedure is intermediate or high Administer vitamin K, 2 mg to 4 mg IV (± fresh frozen plasma) Administer vitamin K: 2 mg to 4 mg IV, or 5 mg to 10 mg p.o. No need to stop warfarin before surgery/procedure Is bridging anticoagulation needed when warfarin is interrupted? No Yes Patient is at low-risk for thromboembolism Patient at intermediate or high-risk for thromboembolism Day -5: Stop warfarin (last dose day -6) Day -1: International normalized ratio (INR) testing (if INR > 1.5, give, 1 mg to 2 mg of vitamin k p.o.) Day 0: Resume warfarin on evening after surgery if patient is drinking fluids Day +1 to +3: Resume warfarin when patient is drinking fluids Figure ±: With 1. Perioperative or without management of anticoagulant ther- ±: With or without Figure 1. Perioperative management of anticoagulant therapy. Day -5: Stop warfarin (last dose on day -6) Day -3: Start subcutaneous LMWH Day -1: INR test (if INR > 1.5, give, 1 mg to 2 mg of vitamin k p.o.); stop LMWH on the morning before surgery (omit evening dose with twice daily dosing; reduce total dose by 50% with daily dosing) Day 0: Assess postoperative surgical site hemostasis; resume warfarin on evening after surgery if patient is drinking fluids Day +1 to +3: Resume LMWH when hemostasis is secured and not earlier than 12 hours after surgery; resume warfarin when patient is drinking fluids Day +5 to +6: Stop LMWH when INR is therapeutic 22 The Canadian Journal of CME / November 2007
CASE IN... Anticoagulation Table 1 Suggested patient risk stratification for perioperative thromboembolism High-risk (bridging anticoagulation is recommended) Mechanical mitral valve Cage-ball or tilting disc mechanical aortic valve Recent (< 3 months) arterial thromboembolism (stroke, TIA, or systemic embolism) Recent (< 3 months) venous thromboembolism High-risk thrombophilia (deficiency of protein C, protein S or antithrombin or antiphospholipid antibodies) Intermediate-risk (bridging anticoagulation is suggested, but is optional) Bileaflet mechanical aortic valve Bioprosthetic aortic valve Chronic atrial fibrillation and at least 1 major risk factor for stroke (prior stroke/tia, left ventricular dysfunction, hypertension, diabetes, or age > 75 years) Prior venous thromboembolism within the last 3 to 12 months Low-risk (bridging anticoagulation is not recommended) Chronic atrial fibrillation and no major risk factors for stroke Prior venous thromboembolism (> 12 months ago) Assessing a patient In assessing a patient who requires warfarin interruption prior to surgery, the first question to consider is: does this patient need an interruption of warfarin? Many minor procedures, such as dental extractions, skin biopsies or cataract removal can be done without the interruption of warfarin. In patients who are undergoing surgery that necessitates the interruption of warfarin, the next question is: does this patient need bridging anticoagulation? In general, the need for bridging is dependent on patient s risk for perioperative thromboembolism. As shown in Table 1, bridging anticoagulation is recommended in patients who are at high-risk for thromboembolism; whereas bridging is optional in patients at moderate-risk for thromboembolism and is not necessary in patients who are at low-risk for thromboembolism. A more detailed discussion of the rationale for this approach has been described elsewhere. 1-3 Meet Harry Harry, 73, has chronic atrial fibrillation and is scheduled to undergo dental extractions. His only major risk factor for stroke is hypertension, which is controlled with medical therapy. Based on the procedure, an interruption of warfarin is not necessary because, in general, it is not required for most minor dental procedures. 5 However, to mitigate the risk for post-extraction bleeding, patients can receive a mouthwash rinse containing tranexamic acid, which is an antifibrinolytic agent that promotes local hemostasis. Dr. Bakhsh is a Clinical Fellow, Department of Hematology, McMaster University and St. Joseph s Healthcare, Hamilton, Ontario. Dr. Douketis is an Associate Professor of Vascular Medicine, Department of Medicine at McMaster University, Hamilton, Ontario. The Canadian Journal of CME / November 2007 23
St. Joseph s Healthcare Hamilton McMaster University 50 CHARLTON AVENUE EAST, HAMILTON, ONTARIO, CANADA LBN 4A6 PHONE (905) 522-1155 Date Days relative Antithrombotic management Blood testing (d/m/y) to surgery -7 STOP acetylsalicylic acid/clopidogrel/ticlopidine CBC, INR, creatinine -6-5 STOP warfarin (i.e., no warfarin on this day) INR -4-3 LMWH units, q.d. or b.i.d. -2 LMWH units, q.d. or b.i.d. -1 LMWH units, q.d. or b.i.d. (last dose 24 hours before surgery) INR SURGERY At bedtime, when there is adequate postoperative hemostasis warfarin mg +1 LMWH units, q.d. or b.i.d. (at least 24 hours after surgery, when there is adequate postoperative hemostasis) warfarin mg +2 LMWH units, q.d. or b.i.d. warfarin mg +3 LMWH units, q.d. or b.i.d. INR, CBC Warfarin mg +4 LMWH units, q.d. or b.i.d. (if required) Warfarin mg +5 LMWH units, q.d. or b.i.d. (if required) INR, CBC Warfarin mg Figure 2. Sample bridging anticoagulation patient information form. 24 The Canadian Journal of CME / November 2007
CASE IN... Anticoagulation Take-home message 1. Most patients who require a temporary interruption of warfarin before an elective surgical or other invasive procedure can be managed as an outpatient 2. Patient management should be individualized, addressing whether warfarin requires interruption and, if so, whether bridging anticoagulation, typically with LMWH, is needed before and after surgery 3. In patients who require bridging anticoagulation, a standardized management protocol should be used that minimizes the time patients are not therapeutically anticoagulated and this minimizes the risk of bleeding complications Many minor procedures, such as dental extractions, skin biopsies or cataract removal, can be done without the interruption of warfarin. Perioperative anticoagulation management In our practice, approximately 90% of bridged patients are taught to self-administer LMWH or to have it administered by a family member. The overall objective of this standardized perioperative management protocol is to minimize the time patients are not therapeutically anticoagulated, thereby minimizing the risk for thromboembolism and to minimize the risk for bleeding complications. This latter issue is key because the occurrence of a bleed can lead to short-term morbidity, but perhaps more importantly, it delays the resumption of anticoagulation for one to four weeks, depending on the extent and site of bleeding, which then exposes a patient to an increased risk for thromboembolism. References 1. Douketis JD. Perioperative Anticoagulation Management in Patients Who Are Receiving Oral Anticoagulant Therapy: A Practical Guide for Clinicians. Thromb Res 2002;108(6):3-13. 2. Jaffer A. Anticoagulation Management Strategies For Patients On Warfarin Who Need Surgery. Cleve Clin J Med 2006; 73 (Suppl 1): S100-105. 3. Spyropoulos AC, Turpie AG: Perioperative Bridging Interruption with Heparin for the Patient Receiving Long-Term Anticoagulation. Curr Opin Pulm Med 2005; 5:373-80. 4. 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(12): 1319-1326. 5. Wahl MJ: Dental Surgery in Anticoagulated Patients. Arch Intern Med. 1998;158(1):1610-6. Tracey and Harry s cases demonstrate perioperative anticoagulant management. These cases represent typical patients assessed requiring perioperative management of anticoagulant therapy. An algorithm for general patient management is provided in Figure 1. In addition, a sample Bridging Anticoagulation Patient Information Form is provided in Figure 2, that can be given to patients (with copies faxed to the patient s family doctor and surgeon/interventionist) and which provides clear instructions in regards to stopping and resuming warfarin and LMWH. The Canadian Journal of CME / November 2007 25
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