Disclosures The Perioperative No financial conflicts of interest - - PDF document

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The Perioperative Management of Oral Anticoagulants

Margaret C. Fang, MD, MPH Medical Director, UCSF Anticoagulation Clinic

Disclosures

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No financial conflicts of interest

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Chair of the ABIM Focused-Practice in Hospital Medicine Self Examination Process committee

◆ No exam questions will be disclosed in the

presentation

Anticoagulants and Invasive Procedures

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Approximately 2 – 3 million people in the U.S. take anticoagulants

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Each year, ~10-20% of these patients need to temporarily stop their anticoagulants for an invasive procedure

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This is a common situation!

Session Objectives

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Learn when and how to stop and restart oral anticoagulants for patients undergoing invasive procedures

◆ Warfarin ◆ Direct oral anticoagulants (DOACs)

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Review risk factors for thrombosis and procedure- related bleeding

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Understand when should you use “bridging” anticoagulation

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Goals of Periprocedural Anticoagulation

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Minimize thrombotic risk in patients who require temporary interruption of anticoagulation

◆ Requires estimating the unique thrombotic risk of

patients with atrial fibrillation (AF), mechanical heart valves, and venous thromboembolism (VTE)

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Minimize procedural complications related to anticoagulation

◆ Requires estimating the bleeding risk and potential

consequences of procedural-bleeding

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Determine who should be “bridged”

◆ Use of an anticoagulant with a faster offset (e.g.,

intravenous heparin or LMWH) during temporary interruption of a longer-acting anticoagulant

◆ Bridging ~triples the risk of periprocedural bleeding

Estimating Periprocedural Bleeding Risk

■ Bleeding risk is related to both

patient-specific and procedure-specific factors

Patient-related Bleeding Risk Factors

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HAS-BLED variables (hypertension, abnormal renal/liver function, prior stroke, prior bleeding, labile INR, age>65, drug/alcohol use, antiplatelets)

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Recent bleed (within 3 months) or history of bleeding with prior bridging or similar procedure

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Quantitative or qualitative platelet abnormality (e.g., uremia)

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Elevated/supratherapeutic INR on warfarin

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BleedMAP periprocedural bleeding risk score

◆ Mitral mechanical valve, Active cancer, Bleeding

history, Platelets<150,000, Moderate / High bleeding risk procedure, Restarted bridging within 24 hours

Tafur et al, 2012 J Thromb Haemostasis

Procedure-Related Bleeding Risk Factors

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High bleeding risk procedures

◆ Most cardiothoracic and vascular surgeries ◆ Major abdominal surgeries ◆ Major orthopedic surgeries

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Procedures where bleeding can be catastrophic

◆ Intracranial/Spinal/Neuraxial procedures ◆ Biliary sphincterotomy, variceal treatment ◆ Kidney biopsy, urologic surgery

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Lower risk procedures

◆ Laparoscopic cholecystectomy, hernia repair ◆ Arthroscopy ◆ Biopsies (thyroid, breast, lymph node, prostate)

* Comprehensive list available in 2017 ACC Periprocedural Anticoagulation Pathway Appendix

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Procedures That Can Be Performed on Uninterrupted Anticoagulation

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Dental extractions, root canals, cleaning

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Diagnostic endoscopy or bronchoscopy without biopsy

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Diagnostic gynecologic procedures

◆ Colposcopy, hysteroscopy, endometrial biopsy, IUD

insertion

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Minor skin procedures (biopsy, suturing)

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Cataract surgery

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Some vascular procedures (e.g., IVC filter placement, PICC lines, venography)

Some Cardiac Procedures Can Be Performed on Anticoagulation

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Catheter ablation (COMPARE trial)

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Pacemaker or defibrillator implantation (BRUISE CONTROL trial)

◆ In both trials, bridging had worse outcomes than

uninterrupted warfarin

✦ Higher rates of TE and bleeding after ablation ✦ 4x the rate of pocket hematomas after device

implantation

◆ On-DOAC vs interrupted DOAC (BRUISE CONTROL-2)

✦ Similar and low rates of bleeding in both arms ■

If a patient is at high thromboembolism risk à do the procedure on warfarin rather than bridge. May not need to interrupt DOAC as well.

Estimating Thrombotic Risk

■ Atrial fibrillation

◆ CHA2DS2-VASc stroke risk score ◆ Recent stroke/TIA

■ Venous thromboembolism

◆ History and timing of previous VTE ◆ Risk factors for VTE: active cancer, hypercoagulable

states

■ Mechanical heart valves

◆ Type and position of prosthetic valve ◆ Concomitant AF and stroke risk factors

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Reserve bridging anticoagulation for patients with high thrombotic risk

No Bridging Bridging P value Arterial thromboembolism (stroke/TIA/peripheral embolism) 0.4% 0.3% 0.73 Major bleeding 1.3% 3.2% 0.005 Minor bleeding 12% 21% <0.001 Death 0.5% 0.4% 0.88

— 1813 patients with AF randomized to bridging vs. no bridging

— Mean CHADS2 = 2.3 (only 3% had CHADS2

5-6)

Douketis JD et al. NEJM 2015

The BRIDGE Trial

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Atrial Fibrillation

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DON’T bridge patients at low TE risk

◆ CHA2DS2-VASc ≤ 4 and no prior TE

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MAYBE bridge patients at intermediate TE risk IF no significant bleeding risk

◆ CHA2DS2-VASc 5 or 6 and TE not recent (>3 months) ◆ If no history of TE, advise not bridging ◆ If high bleeding risk, advise not bridging

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CONSIDER bridging patients at high TE risk

◆ CHA2DS2-VASc ≥ 7 or recent TE (within 3 months) ◆ Delay elective surgeries if possible in patients with

recent TE

2017 ACC Periprocedural Anticoagulation Pathway

No Bridging N=1257 Bridging N=555 P value Recurrent VTE at 30 days 0.2% 0.0% 0.56 Clinically relevant bleeding at 30 days 0.2% 2.7% 0.01

— Observational study of 1178 patients with VTE comparing bridging to no bridging

Clark et al. JAMA Intern Med 2015

Bridging for VTE

— Bridging increased bleeding risk without reducing VTE risk — No difference by baseline VTE risk

— Only 3% were categorized as high VTE risk

Venous Thromboembolism

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DON’T bridge patients at low VTE risk

◆ Distant history of VTE (> 12 months prior)

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MAYBE bridge patients at intermediate VTE risk IF no significant bleeding risk

◆ Active cancer ◆ History of recurrent VTE ◆ Non-severe thrombophilia (e.g., Factor V Leiden)

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CONSIDER bridging patients at high VTE risk

◆ Recent VTE (within 1-3 months) ◆ Severe thrombophilia (e.g., APLAS) ◆ History of VTE during interruption of anticoagulation ◆ Delay elective surgeries if possible in patients with

recent VTE (within 3 months)

Witt et al., 2016 Journal of Thrombosis and Thrombolysis

Mechanical Heart Valves

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DON’T bridge patients with low risk valves

◆ Bileaflet aortic valves without AF or other risk factors

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CONSIDER bridging patients at intermediate risk

◆ Bileaflet aortic valve with ≥ 1 of the following: AF,

prior stroke/TIA, heart failure, HTN, diabetes, age≥75

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DO bridge patients at high risk

◆ Mitral valve prosthesis ◆ Caged-ball or tilting disc aortic valves ◆ Recent stroke/TIA (within 6 months) ◆ Multiple prosthetic valves Douketis et al. ACCP Guidelines 2012

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Developing a Periprocedural Anticoagulation Plan Periprocedural Warfarin Management

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First determine the goal INR for procedure

◆ Consider whether the procedure can be done on

uninterrupted or reduced-dose warfarin

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Hold warfarin for the number of days needed to achieve the target INR

◆ For full reversal of anticoagulant effect (INR<1.5),

usually hold for 5 days

◆ May need to hold longer in patients with higher INR

baseline therapeutic ranges

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If bridging, start parenteral agent ~24-48 hours after last dose of warfarin, or when INR < 2

INR Targets for Common Inpatient Procedures

Low Bleeding Risk Moderate Bleeding Risk High Risk, Difficult to Detect or Control Bleeds GOAL INR ≤2.0 <1.5 <1.5 Vascular procedures Dialysis access IVC filter placement PICC line placement Central line removal Venography Tunneled lines Port placement Angiography TIPS Non-vascular procedures Drainage catheter exchange Thoracentesis Paracentesis Superficial abscess drainage Intra-abdominal biopsies/drain Lung biopsy Liver biopsy G-tube placement Renal biopsy Biliary interventions Nephrostomy tube Lumbar punctures 2012 Society of Interventional Radiology Consensus Guidelines

Periprocedural Warfarin Management

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In high bleeding risk patients, check INR prior to procedure to ensure within acceptable range

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Post-procedure: can usually restart warfarin the evening after procedure (takes days to become therapeutic)

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If using bridging anticoagulation

◆ Administer VTE prophylaxis (if indicated) ◆ Full-dose bridging once hemostasis is achieved

✦ Usually no sooner than 48-72 hours after high bleeding

risk procedures

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Example: High Thrombotic Risk and High Bleeding Risk

PRE-PROCEDURE

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Hold warfarin for 5 days

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Start bridging anticoagulant (e.g., enoxaparin) 4 days before procedure

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Stop bridging anticoagulant prior to procedure, accounting for clearance

✦ 1 mg/kg q12 à last dose 24 hours prior to procedure ✦ 1.5 mg/kg qday à last dose 36 hours prior to procedure ■

Check INR within 24 hours prior to procedure

Example: High Thrombotic Risk and High Bleeding Risk

POST-PROCEDURE

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Start appropriate VTE prophylaxis after surgery

◆ Prophylactic dose enoxaparin

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Can start warfarin 24 hours after procedure

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Start full-dose bridging anticoagulant 48-72 hours after surgery if bleeding risk acceptable

◆ Wait longer if very high bleeding risk

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Stop bridging anticoagulant when goal INR achieved

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Always discuss periprocedural anticoagulation plan with the proceduralist!

Periprocedural DOAC Management

■ Bridging generally not needed

◆ DOACs wear off more quickly than warfarin (1-3

days)

◆ When restarted, anticoagulation effect is rapid

(within hours)

■ PT/INR testing is not useful

◆ If you really need to know whether there is

residual anticoagulation on day of surgery, obtain a thrombin time for dabigatran or an anti-Factor Xa level for rivaroxaban/apixaban/edoxaban

■ Be sure to account for renal function

◆ Impaired renal function may delay clearance of

anticoagulation; may need to hold for a longer period

Periprocedural DOAC Management in Patients with Normal Renal Function

Connolly et al. J Thromb Thrombolysis. 2013

■ Low bleeding risk procedures

Ø Hold DOAC for 24 hours Ø Resume DOAC 24 hours after procedure

■ High bleeding risk procedures

Ø Hold DOAC for 48 hours Ø Resume DOAC 48-72 hours after procedure when

bleeding risk acceptable

■ If very high bleeding risk procedures

(neurosurgery, neuraxial, etc), may need to hold longer (3-5 days)

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Agent Recommended Interval Between Last Dose and Procedure Post- procedure Initiation

Dabigatran

hold 3-5 days 48-72 hrs

Rivaroxaban

CrCl 30-50 mL/min: hold 48 hrs CrCl 15-29 mL/min: hold 72 hrs 48-72 hrs

Apixaban

hold 72 hrs 48-72 hrs

Renal Insufficiency and High Bleeding Risk Procedures

Periprocedural DOAC Management

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Know the half life of the DOAC you are managing

◆ Hold 4-5 half-lives for high bleeding risk

procedures/patients

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Know the renal function of your patient

◆ Patients with impaired kidney function may need

longer interruption of DOAC

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Bridging is usually not indicated for DOACs

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Residual anticoagulant effect can be measured if needed

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Urgent reversal of DOACs for procedures

◆ Idarucizumab for dabigatran ◆ Andexanet for Factor Xa inhibitors

Summary

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Learned how to estimate periprocedural bleeding risk to determine whether interruption of anticoagulation is needed

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Stratify patients with AF, VTE, and mechanical heart valves by thrombotic risk to determine which patients may benefit most from bridging

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Develop a periprocedural anticoagulation management plan for patients on warfarin and DOACs