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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
Douketis et al. Chest 2012;141;e326S-e350S
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
Douketis et al. Chest 2012;141;e326S-e350S
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
Bridging with LMWH: Yes/No
Warfarin interruption: Yes/No
Bridging with LMWH: Yes/No
Warfarin interruption: No
Bridging with LMWH: No
Warfarin interruption: Yes
Bridging with LMWH: No
Warfarin interruption: Yes
Bridging with LMWH: No
Warfarin interruption: No
Bridging with LMWH: 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
Douketis et al. Chest 2012;141;e326S-e350S
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
Douketis et al. Chest 2012;141;e326S-e350S
• 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
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
Siegal et al. Circulation. 2012;126:1630-1639
Risk of TE events in bridged Vs non-bridged patients
Siegal et al. Circulation. 2012;126:1630-1639
Risk of bleeding events in bridged Vs. non-bridged patients
Siegal et al. Circulation. 2012;126:1630-1639
• 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
Review of bridging studies
Siegal et al. Circulation. 2012;126:1630-1639
• 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
Review of bridging studies
Siegal et al. Circulation. 2012;126:1630-1639
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
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
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
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