Periprocedural Management of Oral Anticoagulation

Home , Bridge therapy

Nicole Hlavacek, PharmD candidate; Drew McMillan, PharmD Periprocedural management candidate; Jeremy Vandiver, PharmD, BCPS University of Wyoming of oral anticoagulation: School of Pharmacy, Laramie (Ms. Hlavacek, Mr. McMillan, and Dr. Vandiver); When and how to hit “pause” Swedish Family Medicine Residency, Littleton, Colo (Dr. Vandiver) Here’s how best to assess patients’ bleeding and

[email protected] thrombotic risks and 5 key questions to ask as you

The authors reported no consider withholding oral anticoagulants. potential conflict of interest relevant to this article.

CASE 1 u PRACTICE Debra P is a 62-year-old African American woman who calls RECOMMENDATIONS your office to report that she has an upcoming routine colo- ❯ Don’t stop oral antico- noscopy planned in 2 weeks. She has been taking warfarin agulation for procedures with for the past 2 years for ischemic stroke prevention secondary minimal bleeding risk, such as minor dermatologic, dental, to atrial fibrillation (AF), and her gastroenterologist recom- or ophthalmic procedures. C mended that she contact her family physician (FP) to discuss periprocedural anticoagulation plans. Ms. P is currently tak- ❯ Reserve periprocedural ing warfarin 5 mg on Mondays, Wednesdays, and Fridays, bridging with a parenteral anticoagulant for those patients and 2.5 mg all other days of the week. Her international nor- on warfarin who are at high- malized ratio (INR) was 2.3 when it was last checked 2 weeks est risk for thromboembolism ago, and it has been stable and within goal range for the past (those with severe thrombo- 6 months. Her medical history includes AF, well-controlled philia, active thrombosis, or hypertension, and type 2 diabetes mellitus, as well as gout and mechanical heart valves). B stage 3 chronic kidney disease. Ms. P denies any history of stroke ❯ Stop direct oral anticoagu- or transient ischemic attack (TIA). She is requesting instructions lants 24 to 48 hours prior to on how to manage her warfarin before and after her upcoming most invasive procedures, colonoscopy. and do not employ periprocedural bridging. C CASE 2 u

Strength of recommendation (SOR) Jerry Q is a 68-year-old Caucasian man with longstanding os- A Good-quality patient-oriented teoarthritis who is scheduled to undergo a total left knee ar- evidence throplasty in one week. His orthopedic surgeon recommended B Inconsistent or limited-quality that he contact his FP for instructions regarding managing patient-oriented evidence apixaban perioperatively. Jerry has been taking apixaban 5 mg C Consensus, usual practice, opinion, disease-oriented bid for the past 9 months due to a history of recurrent deep evidence, case series vein thrombosis (DVT) and pulmonary embolism (PE) (both unprovoked). Mr. Q had been taking warfarin following his first DVT 4 years ago, but, after reporting that INR monitoring was a burden, he was started on apixaban. The patient has normal renal function and is relatively healthy otherwise. How should apixaban be managed before and after his upcoming surgery?

210 THE JOURNAL OF FAMILY PRACTICE | APRIL 2018 | VOL 67, NO 4 Countless decisions must be made by health care providers each year regarding if, when, and how to pause and resume oral anticoagulation. And these decisions are not always straightforward.

ach year, approximately 15% to 20% of 4. When should the patient resume his patients taking an oral anticoagulant or her oral anticoagulant after the pro- undergo a procedure that carries a cedure, and at what dosage? E 1,2 heightened risk for bleeding. Stopping oral 5. Will bridging with a parenteral anticoagulation is often necessary before— anticoagulant be necessary after the and sometimes briefly after—many of these procedure? procedures in order to minimize the risk of bleeding.3 This means that countless decisions Before addressing these 5 questions, must be made by health care providers each though, physicians must assess patients’ year regarding if, when, and how to pause and thrombotic and bleeding risks.4-6 resume oral anticoagulation. These decisions are not always straightforward, especially when you consider the risks for thrombosis Anticoagulant regimens and and bleeding that are unique to the procedure the risks of discontinuing them and to the individual patient. The 2 most common indications for long- With these variables in mind, the health term oral anticoagulation are venous throm- care provider must make decisions regarding boembolism (VTE), which occurs in ap- anticoagulation during the periprocedural proximately one million Americans every period based on the following 5 questions: year, 7,8 and stroke prevention in the setting 1. Will this patient need to have his/her of AF (AF occurs in 3-6 million US adults per oral anticoagulant stopped prior to year).6 the procedure? Warfarin is also often used in patients

IMAGE: © JOE GORMAN 2. If the patient’s oral anticoagulation with mechanical heart valves for long-term needs to be held, when should it be stroke prevention; however, direct oral anti- stopped and for how long? coagulants (DOACs) are not recommended 3. Will periprocedural bridging with a for patients with mechanical heart valves be- parenteral anticoagulant be necessary cause trials have not yet demonstrated their prior to the procedure? safety or efficacy in this population.4,5,9 CONTINUED

MDEDGE.COM/JFPONLINE VOL 67, NO 4 | APRIL 2018 | THE JOURNAL OF FAMILY PRACTICE 211 TABLE 1 Patients at high risk for thromboembolism3,5,6,9-11

Venous thromboembolism Atrial fibrillation Mechanical heart valve High-risk characteristics Acute VTE within the past 90 days † Mitral valve position CHADS2 score of 5 or 6 Active malignancy Older generation valve in CHA2DS2-VASc score of 7-9 aortic position (caged-ball or Severe thrombophilia* Stroke within the past 90 days tilting disc) Aortic position with additional risk factors‡ Annual risk (without 10% or higher anticoagulation) VTE, venous thromboembolism. *Severe thrombophilia includes protein C or S deficiency, antithrombin deficiency, antiphospholipid antibody syndrome, and more than one type of thrombophilia. † CHADS2 and CHA2DS2-VASc are tools used to determine a patient’s risk of stroke in the presence of atrial fibrillation. They are discussed in greater detail in TABLE 2. ‡Additional risk factors include atrial fibrillation, heart failure, hypertension, history of stroke or transient ischemic attack, and advanced age.

Who’s at highest risk of the CHA2DS2-VASc scoring tool for making for an acute thromboembolic event? decisions regarding perioperative bridging in When planning for interruptions in oral patients with AF.11 anticoagulation, it is important to identify ❚ Patients with previous VTE. Multiple patients at highest risk for an acute throm- aspects of a patient’s past medical history boembolic event. Patients with 10% or higher need to be taken into account when estimat- annual risk for VTE or ischemic stroke are ing annual and acute risk for VTE. Patients at generally placed into this high-risk category the highest risk for VTE recurrence (annual (TABLE 13,5,6,9-11).3 Keep in mind that the ab- VTE risk ≥10%) include those with recent solute risk for thromboembolism during a VTE (past 90 days), active malignancy, and/- brief period of oral coagulation interruption or severe thrombophilias (TABLE 13,5,6,9-11).3,5,6 is relatively low, even in those patients con- Patients without any of these features can sidered to be at high risk. Using a mathemati- still be at moderate risk for recurrent VTE, as cal approach (although simplistic), a patient a single VTE without a clear provoking fac- with a 10% annual risk for a thromboembolic tor can confer a 5% to 10% annualized risk event would have <0.3% chance for develop- for recurrence.12,13 Previous proximal DVT ing such an event in the acute phase, even if and PE are associated with a higher risk for their anticoagulation was withheld for up to recurrence than a distal DVT, and males have 10 days ([10%/365 days] × 10 days). a higher recurrence risk than females.5,12 ❚ Patients with mechanical heart There are scoring tools, such as DASH valves. Nearly all patients with a mechani- (D-dimer, Age, Sex, Hormones) and the “Men cal heart valve are at moderate to high risk for Continue and HERDOO2,” that can help es- ischemic stroke.3 timate annualized risk for VTE recurrence; ❚ For patients with AF, the CHADS2 and however, they are not validated (nor particu-

CHA2DS2-VASc scoring tools can be used to larly useful) when making decisions in the estimate annual thrombosis risk based on perioperative period.14,15 the presence of risk factors (TABLE 210,11).6,9-11 ❚ Additional risk factors. Consider ad- It should be noted, however, that these scor- ditional risk factors for thromboembolism, ing tools have not been validated specifically including estrogen/hormone replacement for periprocedural risk estimations. Nonethe- therapy, pregnancy, leg or hip fractures, im- less, the latest 2017 American College of Car- mobility, trauma, spinal cord injury, cen- diology (ACC) guidelines recommend the use tral venous lines, congestive heart failure,

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TABLE 2 Patient has atrial fibrillation? Consider these tools for stroke risk assessment10,11 Tool Features Point value Interpretation Ischemic stroke risk

CHADS2 score Congestive heart failure 1 Score of ≥1 merits consideration of long-term anticoagulation Hypertension 1 Score of 5 or 6: Highest risk for Age ≥75 years 1 thromboembolism (≥10% per Diabetes mellitus 1 year) History of ischemic stroke or transient ischemic attack 2

CHA2DS2-VASc score Congestive heart failure 1 Score of ≥1 merits consideration of long-term anticoagulation Hypertension 1 Score of 7-9: Highest risk for Age ≥75 years 2 thromboembolism (≥10% per Diabetes mellitus 1 year) History of ischemic stroke or transient ischemic attack 2 History of vascular disease 1 Age 65-74 years 1 Female sex 1 Bleeding risk HAS-BLED Hypertension (uncontrolled) 1 Score of ≥3: Highest risk for surgical and nonsurgical major Abnormal liver or renal function (severe) 1 bleeding (≥4% per year) History of stroke 1 Bleeding history or predisposition (anemia) 1 Labile INR 1 Elderly patients >65 years 1

Drugs that increase bleeding risk (antiplatelets, 1 NSAIDs, corticosteroids) or heavy alcohol use INR, international normalized ratio; NSAIDs, nonsteroidal anti-inflammatory drugs.

thrombophilia, increased age, obesity, and a procedure is imperative prior to urgent and varicose veins.5,16 elective surgeries to help determine when In addition, some surgeries have a higher in- anticoagulation therapy should be discontin- herent risk for thrombosis. Major orthopedic ued and reinitiated, as well as whether bridg- surgery (knee and hip arthroplasty, hip frac- ing therapy is appropriate. The 2012 CHEST ture surgery) and surgeries for major trauma guidelines state that bleeding risk should be or spinal cord injuries are associated with assessed based on timing of anticoagulation an exceedingly high rate of VTE.17 Similarly, relative to surgery and whether the anticoagu- coronary artery bypass surgery, heart valve re- lation is being used as prophylaxis for, or treat- placement, and carotid endarterectomies car- ment of, thromboembolism.3 Categorizing ry the highest risk for acute ischemic stroke.3 procedures as having a minimal, low, or high risk for bleeding can be helpful in making an- Who’s at highest risk for bleeding? ticoagulation decisions (TABLE 3).3,18-21 Establishing the bleeding risk associated with In addition to the bleeding risk

MDEDGE.COM/JFPONLINE VOL 67, NO 4 | APRIL 2018 | THE JOURNAL OF FAMILY PRACTICE 213 associated with procedures, patient-specific stroke within the past 3 months, consider factors need to be considered. A bleeding postponing the invasive procedure until event within the past 3 months, platelet ab- the patient is beyond this period of highest normalities, a supratherapeutic INR at the thrombotic risk.11 time of surgery, a history of bleeding from previous bridging, a bleed history with a similar procedure, and a high HAS-BLED How far in advance of the (Hypertension, Abnormal renal or liver 2 procedure should the oral function, Stroke, Bleeding history or pre- anticoagulant be withheld? disposition, Labile INR, Elderly, Drugs or Warfarin may need to be stopped anywhere alcohol usage) score are all factors that from 2 to 5 days prior to the procedure, de- elevate the risk for perioperative bleeding.10,11 pending on a number of variables. Although validated only in patients taking Warfarin has a half-life of approximately warfarin, the HAS-BLED scoring system can 36 hours, so it can take 3 to 5 days for war- be utilized in patients with AF to estimate an- farin concentrations to drop to safe levels for nual risk for major bleeding (TABLE 210,11).10 procedures with low to moderate bleeding With this risk information in mind, it’s risk and 5 to 7 days for procedures with high time to move on to the 5 questions you’ll bleeding risk.21 The 2012 CHEST guidelines need to ask. recommend that warfarin therapy be discon- Previous tinued 5 days prior to surgery to minimize proximal deep the risk for bleeding.3 The Anticoagulation vein thrombosis Should the patient’s oral Forum, a leading expert panel that produced and pulmonary 1anticoagulation be stopped a set of useful anticoagulation guidelines in embolism are prior to the upcoming procedure? 2016, recommends stopping warfarin 4 to associated with The answer, of course, hinges on the patient’s 5 days prior to a procedure.21 If the provider a higher risk risk of bleeding. chooses to withhold warfarin before a proce- for recurrence Usually, it is not necessary to withhold dure with minimal bleeding risk, it should be than a distal any doses of oral anticoagulation if your pa- stopped 2 to 3 days prior.3 DVT, and males tient is scheduled for a procedure with mini- ❚ Consider checking INR values the week have a higher mal risk for bleeding (TABLE 33,18-21).3 However, before. A 2017 consensus statement from the recurrence risk it may be reasonable to stop anticoagulation ACC recommends that the timing of warfarin than females. if your patient has additional features that discontinuation be based on an INR value predispose to high bleeding risk (eg, hemo- taken 5 to 7 days prior to the surgical proce- philia, Von Willebrand disease, etc). The dure.11 This allows for a more tailored approach CHEST guidelines recommend adding an to preparing the patient for surgery. If the INR oral prohemostatic agent (eg, tranexamic is below goal range, warfarin may need to be acid) if anticoagulation will be continued withheld for only 3 to 4 days prior to a proce- during a dental procedure.3 dure. Conversely, INRs above goal range may If your patient is undergoing any other require warfarin to be held 6 or more days, de- procedure that has a low to high risk for bleed- pending on the degree of INR elevation. ing, oral anticoagulation should be withheld While not always feasible in clinical prior to the procedure in most instances,3,11 practice, the CHEST guidelines recommend although there are exceptions. For example, obtaining an INR value the day prior to the cardiac procedures, such as AF catheter procedure to determine if the INR value is ablation and cardiac pacemaker placement, low enough to proceed with surgery, or if a are often performed with uninterrupted oral low dose of oral vitamin K needs to be ad- anticoagulation despite their bleeding risk ministered to ensure that the INR is in a safe category.3 range the following day.3 When in doubt, discuss the perceived bleeding and clotting risks directly with DOACs the specialist performing the procedure. In DOACs can be withheld for much shorter du- patients who have had a VTE or ischemic rations preoperatively than warfarin.

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TABLE 3 Bleeding risk stratification by surgery type3,18-21

Minimal bleeding risk Low bleeding risk High bleeding risk • Most dental procedures, • Abdominal hernia repair • Any major surgery including extraction of 1-2 >45 minutes in duration • Axillary node dissection teeth, periodontal surgery, • Abdominal aortic aneurysm incision of abscess, implant • Biopsies: Cutaneous and repair positioning bladder/prostate/thyroid/- breast/lymph node • Biliary sphincterotomy • Minor dermatologic procedures, including abscess • Bronchoscopy +/- biopsy • Bladder resection incision, small dermatology • Cardiac electrophysiologic • Bowel resection excisions studies or radiofrequency • Cancer surgery • Endoscopy without plan for ablation biopsy or tissue removal • Cardiac surgery, including • Carpal tunnel repair coronary artery bypass, • Cataract or glaucoma • Cholecystectomy heart valve replacement, procedures pacemaker or implantable • Complicated dental proce- • Central venous catheter cardioverter defibrillator dures (3+ tooth extractions) removal device implantation • More invasive dermatologic • Endoscopic fine-needle procedures (skin cancer aspiration Major excision) orthopedic • Head and neck surgeries • Dilatation and curettage surgery and • Hepatic surgeries or liver • Gastrointestinal endoscopy surgeries for biopsy or colonoscopy +/- biopsy major trauma • Intracranial surgery • ERCP without or spinal cord sphincterotomy • Joint arthroplasty injuries are • Biliary/pancreatic stent • Laser ablation and coagulation associated with without endoscopic an exceedingly • Kidney biopsy sphincterotomy high rate • Laminectomy • Enteroscopy of venous • Nephrectomy thromboembolism. • Endosonography without fine-needle aspiration • Neurosurgeries • Noncataract eye surgery • PEG placement • Hemorrhoidal surgery • Polypectomy • Hydrocele repair • Pneumatic dilation • Hysterectomy • Reconstructive plastic surgery • Noncoronary angiography • Surgeries in highly vascularized organs • Spinal surgery • Splenic surgeries • Transurethral prostate resection • Variceal treatment • Vascular surgeries ERCP, endoscopic retrograde cholangiopancreatography; PEG, percutaneous endoscopic gastrostomy.

When withholding anticoagulants, the procedures and a nominal amount of anti- goal is to have a low amount of anticoagu- coagulant effect (3%-6%) present for high- lant effect (12%-25%) present during low-risk risk procedures.20 DOACs have much shorter

MDEDGE.COM/JFPONLINE VOL 67, NO 4 | APRIL 2018 | THE JOURNAL OF FAMILY PRACTICE 215 half-lives than that of warfarin (7-19 hours vs high risk for thromboembolism (>10% annual 36-48 hours, respectively), so they can be risk) and consideration of bridge therapy in withheld for much shorter durations preop- the setting of moderate clotting risk (5%-10% eratively.20 For patients undergoing proce- annual risk), depending on specific patient dures that are considered to have a minimal and procedural risk factors (TABLE 13,5,6,9-11).3 risk for bleeding (such as minor dental and ❚ In 2015, a landmark clinical trial was dermatologic procedures), DOACs do not published that significantly shaped how generally need to be withheld; however, it patients taking warfarin are managed peri- may be ideal to time the procedure when the procedurally.22 The Bridge (Bridging antico- DOAC is at a trough concentration (before agulation in patients who require temporary the next dose is due).3 interruption of warfarin therapy for an elec- DOACs generally need to be withheld for tive invasive procedure or surgery) trial only 1 to 3 days prior to major surgical pro- was the first prospective, randomized con- cedures in patients with normal renal func- trolled trial to assess the efficacy and safety tion (creatinine clearance [CrCl] >30 mL/min of parenteral bridging in patients with AF using the Cockcroft-Gault formula).20 The taking warfarin and undergoing an elective available oral direct factor Xa inhibitors surgery. (apixaban, rivaroxaban, and edoxaban) Patients in the trial received either dalte- should generally be stopped 24 hours prior to parin at a therapeutic dose of 100 IU/kg or a Coronary artery a procedure that has a low bleeding risk, and matching placebo administered subcutane- bypass surgery, 48 hours prior to procedures with high bleed- ously bid from 3 days before the procedure heart valve ing risk (TABLE 411,20).20 These medications until 24 hours before the procedure, and then replacement, may need to be withheld for an additional for 5 to 10 days after the procedure. The in- and carotid 1 to 2 days in patients with acute kidney incidence of thromboembolic events was not endarterecto- jury or stage IV kidney disease.20 significantly lower in the dalteparin group mies carry the ❚ Dabigatran. About 80% of dabigatran than in the placebo group (0.3% vs 0.4%, highest risk for is excreted by the kidneys, so its elimination respectively; P=.73), while major bleeding acute ischemic is much more dependent on renal function rates were nearly 3-fold higher in the dalte- stroke. than is that of the oral direct factor Xa in- parin group (3.2% vs 1.3%; P=.005). The trial hibitors.20 Therefore, it generally needs to be concluded that placebo “was noninferior to withheld for at least 1 to 2 days longer than perioperative bridging with LMWH for the the oral factor Xa inhibitors unless CrCl is prevention of arterial thromboembolism and >80 mL/min (TABLE 411,20).20 decreased the risk of major bleeding.”22 Patients excluded from the trial included those with a mechanical heart valve, or a re- Is preoperative bridging with cent (within 3 months) embolism, stroke, or 3 parenteral anticoagulation TIA, and only 3% of enrolled patients would necessary? have been classified as having a high clotting In certain instances, patients who have a high risk according to CHEST guidelines.3,22 thromboembolic risk and are discontinuing ❚ A prospective observational registry warfarin therapy may require bridging ther- study produced similar findings and found apy with a low-molecular-weight heparin that those patients who received bridging had (LMWH) or unfractionated heparin (UFH). If more bleeding events and a higher incidence a patient’s CrCl is <30 mL/min, then UFH is the of myocardial infarction, stroke or systemic preferred agent for perioperative bridging.21 embolism, major bleeding, hospitalization, But before any decision is made, it’s best or death within 30 days than those who did to have a good understanding of what the not receive bridging.23 Other retrospective co- guidelines—and the literature—have to say. hort studies comparing bridging to no bridging strategies in patients taking warfarin for Key studies and guidelines VTE, mechanical heart valves, or AF have also The 2012 CHEST guidelines recommend failed to show a reduction in the incidence of providing bridge therapy for any patient at thrombotic events with LMWH bridging.24,25 CONTINUED

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TABLE 4 When to hold DOACs before procedures in patients with CrCl >15 mL/min*11,20 Hold this number of doses DOAC CrCl (mL/min) Procedures with LOW Procedures with HIGH bleeding risk bleeding risk Apixaban ≥30 2 4 15-29 4 6 Rivaroxaban ≥30 1 2 Edoxaban 15-29 2 3 Dabigatran ≥80 2 6 30-79 4 6-8 15-29 6-8 10-12 CrCl, creatinine clearance; DOACs, direct oral anticoagulants. *Individuals undergoing procedures with minimal bleeding risk do not require that their DOAC be held. It’s preferable to schedule the procedure for a trough of the DOAC. When a patient is undergoing a procedure with a low or high bleeding risk, his or her individual history of patient-specific bleeding risk may mandate longer anticoagulant withholding times than indicated by this table. All of these recommendations are made according to the estimated half-lives of the drugs, with 2-3 11 half-lives for procedures with low bleeding risk and 4-5 half-lives for procedures with high bleeding risk. When withholding anticoagulants, ❚ In 2016, the European Society of Car- in accordance with the bleeding risk of the the goal is to diology suggested that “bridging does not procedure (ie, prophylactic doses may be have a low seem to be beneficial, except in patients with appropriate within 24 hours postprocedure, amount of mechanical heart valves.”26 Similarly, the while full treatment doses may need to be anticoagulant 2016 Anticoagulation Forum guidelines state delayed for 48 to 72 hours if surgical bleed- effect (12%-25%) that “most patients with VTE can safely inter- ing risk is high).3 UFH bridge therapy may be present during rupt warfarin for invasive procedures with- stopped 4 to 6 hours prior to surgery.3 low-risk out bridge therapy,” and that bridge therapy ❚ DOACs. Given the rapid onset and rela- procedures and should be “reserved for those at highest re- tively short half-lives of DOACs, use of a paren- a nominal current VTE risk (eg, VTE within the previous teral bridging agent is generally not necessary amount (3%-6%) month; prior history of recurrent VTE during or recommended before or after an invasive present for high- anticoagulation therapy interruption; under- procedure in patients taking a DOAC.20 risk procedures. going a procedure with high inherent risk for VTE, such as joint replacement surgery or major abdominal cancer resection).”21 They When should oral anticoagula- go on to state that even in these high-risk 4 tion be resumed postoperatively, groups, the clinical decision to use bridging and at what intensity? therapy needs to carefully weigh the benefits Warfarin can generally be resumed the same against the potential risks of bleeding.21 day as the procedure (in the evening), assum- ❚ Controversy also surrounds the in- ing there are no active bleeding complica- tensity of LMWH bridging. The Anticoagu- tions.3,11 Once fully reversed, it generally takes lation Forum guidelines state that the use of around 5 days for warfarin to become fully prophylactic rather than therapeutic dose therapeutic, so it can be started soon after LMWH may be considered, while the CHEST surgery without increasing the risk for early guidelines do not make a firm recommenda- postoperative bleeding.20 tion regarding LMWH dose while bridging.3,21 ❚ DOACs. Consider the patient’s individ- Ultimately, in patients who receive perioper- ual and procedural risks for bleeding when ative bridging with LMWH, the CHEST guide- determining when to resume a DOAC post- lines recommend that it should be stopped operatively. That’s because unlike warfarin, 24 hours prior to the procedure and resumed which takes several days to take full effect,

MDEDGE.COM/JFPONLINE VOL 67, NO 4 | APRIL 2018 | THE JOURNAL OF FAMILY PRACTICE 219 DOACs provide a nearly immediate antico- colonoscopy to guide how many doses need agulation effect.20,21 For procedures that have to be withheld; however, given the patient’s a low bleeding risk, it is recommended to re- tight INR control over the previous 6 months, sume therapeutic anticoagulation 24 hours you can assume her INR will be in goal range after the procedure has ended.3,11,20 For pro- at that check. As a result, you recommend that cedures that have a high risk for bleeding, she avoid an extra INR check and stop taking resumption of therapeutic anticoagulation her warfarin 5 days prior to the colonoscopy.

should be delayed until 48 to 72 hours after Ms. P has a CHA2DS2VASc score of 3, which the procedure has ended.3,11,20 puts her at a relatively low risk for acute ischemic stroke over the next 1 to 2 weeks. Given the results of the BRIDGE trial, you recom- Is postoperative bridging with mend no parenteral bridging agent before 5 parenteral anticoagulation or after her procedure. You also recommend necessary? that the patient resume her usual dose of war- Warfarin. If a patient was deemed to be at farin the same day as her procedure (in the sufficient VTE risk to be bridged preopera- evening) unless her gastroenterologist recom- tively, then that patient likely also should be mends otherwise. You schedule her for a fol- bridged postoperatively, particularly if the low-up INR 5 to 7 days after her colonoscopy. surgery itself is associated with a heightened Cohort thrombotic risk. While warfarin can gener- CASE 2 u studies ally be resumed postoperatively the same day Mr. Q’s total knee arthroplasty (TKA)—a pro- involving as the procedure, full therapeutic doses of a cedure associated with a high risk of bleed- patients taking LMWH should not be initiated sooner than ing—requires an interruption in his apixaban warfarin for VTE, 24 hours postoperatively, and initiation should therapy. Additionally, he is at high risk for re- mechanical heart be delayed for 48 to 72 hours for procedures current thromboembolism, given his history valves, or atrial with the highest bleeding risk (such as neu- of recurrent, unprovoked DVTs; however, he fibrillation have rosurgery).3,11,21 Prophylactic doses of LMWH is past the highest risk period (VTE within the failed to show can generally be resumed as early as 12 hours past 3 months; his last one was 9 months ago). a reduction in postoperatively for procedures with high VTE He is otherwise healthy and has normal renal the incidence risk (such as major orthopedic surgery).17 function, so his apixaban should be withheld of thrombotic ❚ DOACs. In patients undergoing a pro- for a total of 4 doses (48 hours) prior to his events with cedure that carries both a high thromboem- procedure. He should resume his full dose of LMWH bridging. bolic and high bleeding risk (such as major apixaban 48 to 72 hours after his procedure to orthopedic surgery), initiation of a full-dose minimize the risk for bleeding. DOAC may need to be delayed for 2 to 3 days; However, given that a TKA is a procedure however, more immediate VTE prophylaxis is associated with a high rate of postoperative usually necessary.3,17 Prophylaxis after such VTE, initiate prophylactic anticoagulation procedures can begin 12 hours after the pro- (such as enoxaparin 40 mg subcutaneously cedure with a low-intensity LMWH, which daily or apixaban 2.5 mg PO bid) approximately should be continued until it is deemed safe 12 hours after the procedure and continue it to resume full-intensity DOAC therapy.3,17,18 until full-dose apixaban is resumed. JFP If the patient is undergoing major orthopedic CORRESPONDENCE surgery, an FDA-approved prophylactic dose Jeremy Vandiver, PharmD, BCPS, University of Wyoming of a DOAC could be a temporary alternative School of Pharmacy, 1000 E. University Ave., Dept. 3375, Laramie, WY 82071; [email protected]. to LMWH.27

CASE 1 u Ms. P’s upcoming colonoscopy may require a References biopsy and would be classified as a procedure 1. Connelly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran ver- sus warfarin in patients with atrial fibrillation. N Engl J Med. with low bleeding risk (per TABLE 3), so warfa- 2009;361:1139-1151. rin should be withheld prior to her procedure. 2. Steinberg BA, Kim S, Piccini JP, et al. Use and associated risks of concomitant aspirin therapy with oral anticoagulation in patients You could check her INR 5 to 7 days before her with atrial fibrillation: insights from the Outcomes Registry for

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