to bridge or not to bridge: guide to clinicians hazem elewa, rph, phd, bcps assistant professor,...

To Bridge or Not to Bridge: Guide to Clinicians

Hazem Elewa, RPh, PhD, BCPSAssistant Professor, College of Pharmacy,

Qatar University

Disclosures

I have no financial disclosures to report

Important concepts

• Bridging anticoagulation: To give a short-acting anticoagulant, usually low-molecular-weight heparin (LMWH) for 10 to 12 days around the periprocedural period, when warfarin is interrupted and its anticoagulant effect is not optimal

• Bridging aims to reduce patients’ thromboembolic (TE) risk, but may also increase patients’ risk for developing bleeding complications after surgery

• Bridging has become a common practice due to increased convenience and decreased cost of LMWH

Douketis et al. Chest 2012;141;e326S-e350SThe bridge study investigators. Circulation. 2012;125:e496-e498

1. Perform patient anticoagulation assessment 7+ days prior to procedure2. Categorize procedure-related bleeding risk 3. Categorize underlying thrombosis risk 4. Build bridging recommendation after weighing the risk of bleeding against the risk of thromboembolism5. View specific guidance for novel oral anticoagulants (NOACs) and antiplatelets

A stepwise guide

Douketis et al. Chest 2012;141;e326S-e350S

High risk

• MVR; Caged-ball or tilting-disc AVR; Recent stroke or TIA • AF with CHADS2 of 5-6; Rheumatic valvular heart disease• Recent VTE (within 3 months); Severe thrombophilia

Moderate risk

• Bileaflet AVR + one more of the following: AF; Stroke or TIA; HTN; DM; CHF; older than 75 years

• AF with CHADS2 of 3-4• VTE within 3-12 months; Recurrent VTE; Active cancer; Non-

severe thrombophilia

Low risk

• Bileaflet AVR without AF; No other risk factors for stroke• AF with CHADS2 of 1-2 assuming no history of stroke or TIA• VTE more than 12 months and no other risk factors

Risk of TE


Risk of bleedingHigh bleeding risk procedures Low bleeding risk procedures Minimal bleeding

risk procedures

Cancer surgeryMajor orthopedic surgeryReconstructive plastic surgery

Minor dental proceduressimple dental extractions, restorations, prosthetics, endodontics

Dental cleaningsDental filling

Transurethral prostate resection, bladder resection or tumor ablationNephrectomy, kidney biopsyColonic polyp resectionBowel resectionPercutaneous endoscopic gastrostomy (PEG) placement, endoscopic retrograde cholangiopancreatography

Cutaneous/lymph node biopsiesShoulder/foot/hand surgeryCoronary angiographyGastrointestinal endoscopy +/- biopsyColonoscopy +/- biopsyAbdominal hysterectomy

Minor dermatologic procedures(excision of basal andsquamous cell skin cancers,actinic keratoses)

Cardiac, intracranial, or spinal surgerySurgery in highly vascular organs (kidneys, liver, spleen)Any major operation (procedure duration >45 minutes)Pacemaker or cardioverter-defibrillator device implantation

Laparoscopic cholecystectomyAbdominal hernia repairHemorrhoidal surgeryBronchoscopy +/- biopsyEpidural injections with INR <1.2Pacemaker battery changeArthroscopy

Cataract procedures and other minor ophthalmologic procedures


Decision to bridge

Minimal bleeding risk

No YesWhat is the

thromboembolic risk

Continue warfarin

Stop warfarin. No need to

bridgeBridge

Weigh benefits Vs.risks of warfarin interruption/

bridging

Decision to bridgeHigh bleeding risk procedures

Low bleeding risk procedures

Minimal bleeding risk procedures

Warfarin interruption: Yes

Bridging with LMWH: Yes

Warfarin interruption: Yes/No

Bridging with LMWH: Yes/No

Warfarin interruption: No

Bridging with LMWH: No



Warfarin interruption: Yes/No










Weigh benefits Vs.risks of warfarin interruption/ bridging

Bridge No Bridge

Patient preference

Thromboembolic risks:Patient-related

Procedure-related

Cost

Bleeding risks:Patient-related

Procedure-related

How to bridge with LMWH

• Stop warfarin for five days before the procedure and restart in the evening of the procedure provided hemostasis is adequate.

• LMWH is started three days prior to the procedure and held 24 hours preoperatively, and resumed 24-72 hours post-procedure till reaching therapeutic INR with warfarin


How to bridgeDays prior or

post procedureManagement of Warfarin/ LMWH

-7 to -10 Assess need for bridging. Check baseline labs ( INR; Hgb, platelets, Cr.Cl)

-6 to -5 Begin to hold warfarin. No LMWH

-3 to -4 Start LMWH

-1 Last dose of LMWH (24hr prior to procedure). Recheck INR

0 Continue to hold warfarin or resume in the evening. No LMWH

+1 Resume LMWH (or wait for 48-72hrs if at bleeding risk)

+4 to +7 Discontinue LMWH if INR is ≥ 1.9


• Therapeutic dose:– Enoxaparin: 1mg/Kg SC Q12hrs or 1.5mg/Kg SC Q24hrs

• Reduce the dose to 1mg/Kg SC Q24hrs if Cr.Cl<30 ml/min

– Dalteparin: 100 IU/Kg SC Q12hrs or 200 IU/Kg SC Q24hrs (Only if Cr.Cl≥30ml/min)

• Prophylactic dose:– Enoxaparin: 40mg SC Q24hrs or 30mg SC Q12hrs

• Reduce the dose to 30mg SC Q24hrs if Cr.Cl<30 ml/min

– Dalteparin: 5000 IU SC Q24hrs (Only if Cr.Cl≥30ml/min)

• Intermediate dose:– Dose between prophylactic and therapeutic

Dosing regimen of LMWH

Siegal et al. Circulation. 2012;126:1630-1639

• To evaluate the safety and efficacy of periprocedural bridging anticoagulation

• There was no reduction in the risk of TE events with the use of heparin bridging (OR, 0.80; 95% CI, 0.42–1.54)

• There was an increased risk of overall bleeding (OR, 5.40; 95% CI, 3.00 –9.74) in bridged Vs.non-bridged

Review of bridging studies


Risk of TE events in bridged Vs non-bridged patients


Risk of bleeding events in bridged Vs. non-bridged patients


• 20 studies (57%) reported use of therapeutic dose LMWH

• 13 studies (37%) reported use of prophylactic/ intermediate dose LMWH for bridging

• There was no difference in TE events but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27– 4.08) with therapeutic versus prophylactic/intermediate dose LMWH bridging



• Majority of the studies included were observational (only 1 RCT)

• Significant heterogeneity for the analyses of bleeding events

• Lack of systematic report of bleeding events according to the type of procedure



Possibly, majority of bridged patients were at high TE risk whereas non-bridged patients were at low TE risk which explains the lack of difference in TE events between groups

The BRIDGE study

The bridge study investigators. Circulation. 2012;125:e496-e498www.clinicaltrials.gov/ct2/show/NCT00432796

Includes only AF patients with at least 1 risk factor

Dalteparin daily 3 days prior to the procedure to be stopped 24hrs prior to the procedure and resumed the day after

Matching placebo with the same regimen

TE and bleeding events

http://www.clinicaltrials.gov/ct2/show/NCT00432796

PERIOP 2 study

www.clinicaltrials.gov/ct2/show/NCT00432796

Include AF or mechanical heart valveStop warfarin 5 days before and start

dalteparin(200 IU/Kg/day) 3 days before

Surgery

Dalteparin daily the day after the procedure

If low risk of bleeding 200 IU/Kg daily

Matching placebo the day after the procedure

If high risk of bleeding 5000 IU daily

http://www.clinicaltrials.gov/ct2/show/NCT00432796

Periprocedural management with NOACs

Clinical case

• An 71 year-old female on chronic warfarin therapy for a mitral valve replacement is having a dental extraction in 10 days.

• Which of the following is the best approach:

– A) Interrupt warfarin for the procedure with no bridging– B) Bridge using prophylactic LMWH before and after the

procedure– C) Bridge using therapeutic LMWH before and after the procedure– D) Continue warfarin with co-administration of local

prohemostatic agent

• Periprocedural management of patients on long-term anticoagulation remains a common but difficult problem

• Decision to interrupt, bridge and resume anticoagulants MUST BE CLEARLY COMMUNICATED among providers and patients

• American College of Chest Physicians (ACCP) recommendations in regards to periprocedural management have weak grade (2C), reflecting the lack of high-quality evidence

• There may be an overuse of bridging which can lead to increase in bleeding risk with theoretical benefit

Conclusion

to bridge or not to bridge: guide to clinicians hazem elewa, rph, phd, bcps assistant professor,...

Documents

patients risk

risk of thromboembolism5

underlying thrombosis

bleeding complications

surgery bridging

optimal bridging

bridging recommendation

bladder resection