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Perioperative management of antithrombotic therapy

Perioperative management of antithrombotic therapy



periprocedural management of anticoagulation

periprocedural management of anticoagulation



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    Perioperative management of antithrombotic therapy Perioperative management of antithrombotic therapy Presentation Transcript

    • Periprocedural AnticoagulationManagementDR GHALEB ALMEKHLAFIMD,SFCCM,EDICPSMMC6/19/2013 1
    • references6/19/2013 2
    • Introduction• OAC therapy during surgery isassociated with increased excessiveoperative bleeding.• Anticoagulation cessation,increases risk of thromboembolism,especially in the postoperativeperiod.6/19/2013 3
    • introduction• Thromboembolic risks:(1)Disease specific thromboembolic risks whendiscontinuing warfarin(2)Hypercoagulability associated with surgery.• Bleeding risks:(1) the patient factors(2) the use of anticoagulant therapy(3) the surgery or procedure6/19/2013 4
    • introductionThromboembolic Risk When Discontinuing WarfarinVenous Thromboembolism (VTE):• In The absence of OAC during the first month of an acuteVTE event-Recurrence 40%/month• During the second and third month- Recurrence10%/2month• After the 3 month treatment-15%/year• Surgery should be deferred following an acute episode ofvenous thromboembolism until patients have received atleast 1 month, and preferably 3 months, of anticoagulation.6/19/2013 5
    • introductionArterial thromboembolism1-Nonvalvular atrial fibrillation (NVAF):• Average risk of systemic embolism -4.5%/yearin the absence of OAC.• The CHADS2 Score(estimate expected stroke rateper 100 patient-years):• Moderate-risk patients have an adjusted strokerate of up to 5.9%• High-risk patients have adjusted stroke ratesof 8.5 to 18.2%.6/19/2013 6
    • CHADS2 scorevalidated for patients with NVAF6/19/2013 7
    • introductionArterial thromboembolism2-MHV• In the absence of anticoagulant therapy- mitral position valves: risk of thrombosis of 22%/y- in aortic position valves: the risk is 10%-12%/y• MHV thrombosis is fatal in 15% of patients• embolic CVA results in death or major disability in 70% ofpatients• case-fatality rates: - VTE =5%-9%,- major bleeding =8%-10%6/19/2013 8
    • 6/19/2013 9
    • introductionprothrombotic effect of procedures• Surgery(major surgery and laparoscopic procedures )• will increase the postoperative• - VTE : risk 100-fold• - ATE :estimates suggesting a 10-fold higher thanexpected risk of stroke in the Periprocedural period inWarfarin-treated patientsTiede DJ, Nishimura RA, Gastineau DA, Mullany CJ,Orszulak TA, Schaff HV. Modernmanagement of prosthetic valve anticoagulation. Mayo Clin Proc.-6/19/2013 10
    • Suggested risk stratification forperioperative Thromboembolism6/19/2013 11
    • Procedural bleeding risksThis table is based on definitions derived from surgical/subspecialty societies inanticoagulant bridging or anticoagulant bridging management studies6/19/2013 12
    • ICU-Procedures With High Bleeding Risk:Interrupting Anticoagulation Advised• serious bleeding in >1.5%.• If high risk for clotting with anticoagulation interruptions should beconsidered for “bridging therapy” with heparin• ICU PROCEDURES:- Lumbar puncture Chest tube plcmt Arterial punctureSpinal/epidural anesthesia Transbronchial bx , Stricture dilationsOrgan biopsies, tracheostomy- OTHERS:- Tunneled catheter plcmt , Cardiac ablations Liver/GB drainsNephrostomy ERCP w sphincterotomy PEG tube plcmt Cardiaccath PCI Pacemaker plcmt• - >1cm polypectomy Major surgery Wide skin excision, Eye surgery(not cataracts) ,Vascular interventions6/19/2013 13
    • Procedural bleeding risksThis table is based on definitions derived from surgical/subspecialty societies inanticoagulant bridging or anticoagulant bridging management studies6/19/2013 14
    • ICU-Procedures Not Necessarily RequiringInterruption of Anticoagulation• risk of serious bleeding < 1.5%,• - VKA may be continued with a target INR of 2.5.• - full-dose antiplatelet therapy (e.g., Plavix) may be continued• ICU PROCEDURES:• Arthrocentesis, Thoracentesis, Paracentesis• Bronchoscopy (Dx) Endotracheal Intubation , Central Lines, Vas-Cath forHD, PICCs, Small abd/pelvis drains• OTHERS MINOR PROCEDURES• EGD (mucosal bx OK), Colposcopy (Dx), PEG• Cardiac cath (Dx)* Some FNAs* Colonoscopy (Dx) IVC filter plcmt .Minorskin surgery ,Dilation & curettage• Root canals, Tooth extraction, nephrostomy tube exchange6/19/2013 15
    • periprocedural antithromboticstrategyFor most patients undergoing low-bleeding-riskprocedures:• Interruption of warfarin is not necessary;• The INR should be adjusted to ~2.5 if possible.• Antiplatelet therapy like Plavix may be continued.For most patients undergoing high-bleeding-riskprocedures:• For those who are at low individual risk for clotting, anticoagulationcan be interrupted without bridging therapy (heparin).• Most patients at high individual risk of blood clots should receivebridging anticoagulation therapy.6/19/2013 16
    • Periprocedural heparin bridging strategies for patientson chronic VKAData from the 9th edition ACCP Guidelines: all grade 2C, except intermediate TE risk.7 *For high-bleed risk procedures: wait a full 48-72 hours beforereinitiating postprocedural heparin (LMWH) bridging (especially treatment dose); stepwise increase in postprocedural heparin (LMWH) dose fromprophylactic dose first 24-48 hours to intermediate/treatmen dose; no postprocedural heparin (LMWH) bridging in very high bleed risk procedures (ie, majorneurosurgical or cardiovascular surgeries) but use of mechanical prophylaxis. **Based on individual patient- and procedural related risk factors for thrombosisand bleeding.6/19/2013 17
    • Bridging therapy• is strongly recommended for people with:• DVT or PE within the past 3 months or severe thrombophilia;• Mechanical mitral valves,• “Old” design mechanical aortic valves (caged-ball or tilting-diskdesign, i.e., non-bileaflet),• Any mechanical valve with a history of stroke or transientischemic attack,• Non-valvular atrial fibrillation with a CHADS2 SCORE 4 orgreater, history of stroke or TIA, or cardiac thrombus6/19/2013 18
    • Perioperative Bridging :General Points1-To eliminate effect of antithrombotic therapybefore surgery, treatment should be stoppedbefore surgery (~5 days for Warfarin, 7-10 daysfor antiplatelet drug) to minimizing bleedingrisk2-Giving bridging after surgery increases risk forbleeding; this risk depends on anticoagulantdose (therapeutic-dose > low-dose) andproximity to surgery (higher risk if given closerto surgery)6/19/2013 19
    • Perioperative Bridging: General Points3-Delaying resumption of therapeutic-dosebridging (for 48-72 h after surgery),decreasing the dose or avoiding its use aftersurgery can mitigate the risk for bleeding4-Low-dose LMWH/UFH is effective to preventpostop VTE, but evidence is lacking thatsuch regimens effective to prevent ATE6/19/2013 20
    • bridging anticoagulation regimensA “high-dose” (therapeutic-dose) regimen involvesgiving a dose similar to that used to treat acute VTEor ACSeg- enoxaparin, 1 mg/kg BID or 1.5 mg/kg QD, -dalteparin 100 IU/kg BID or 200 IU/kg QD- tinzaparin 175 IU/kg QD- IV UFH to attain aPTT 1.5- to 2-times the controlaPTT).A “low-dose” (prophylactic-dose) regimen involvesgiving a dose used, typically, to preventpostoperative VTE (eg, enoxaparin 30 mg BID or 40mg QD, dalteparin 5000 IU QD, UFH 5000-7500 IUBID)6/19/2013 21
    • bridging anticoagulation regimens–An “intermediate-dose” regimen hasbeen recently studied for bridging andis intermediate in anticoagulantintensity between a high-dose andlow-dose regimen (eg, enoxaparin 40mg BID).–Different bridging regimens may havepotential advantages or drawbacksover a “therapeutic-dose” regimen6/19/2013 22
    • Periprocedural anticoagulation and bridging protocol*LMWH regimens include enoxaparin 1.5 mg/kg once daily or 1.0 mg/kg twice daily subcutaneously; dalteparin 200 IU/kgonce daily or 100 IU/kg twice daily subcutaneously; and tinzaparin 175 IU/kg once daily subcutaneously. IntermediatedoseLMWH (ie, nadroparin 2850-5700 U twice daily subcutaneously; enoxaparin 40 mg twice daily subcutaneously) has been lessstudied in this setting†Loading doses (ie, 2 times the daily maintenance dose) of warfarin have also been used.6/19/2013 23
    • Periprocedural anticoagulation andbridging protocol6/19/2013 24
    • Stopping heparin before surgery• To avoid persistence of heparin during surgery,it is suggested that the last therapeutic doseof LMWH be given no less than 12 h beforeoperation with a twice-daily regimen, or 24 hbefore operation with a once-daily regimen.• A recent evidence has shown that a 24-h gapfor LMWH even when given twice daily maybe preferable34. Intravenous• UFH should be stopped 4–6 h before surgeryODonnell MJ, Kearon C, Johnson J, Robinson M, Zondag M, Turpie I et al. Brief communication: preoperativeanticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann InternMed 2007; 146: 184–1876/19/2013 25
    • Neuraxial anesthesia• Most recommend that prophylactic treatment with LMWHshould be stopped at least 12 h before the insertion of anepidural needle.• Patients receiving treatment doses of LMWH require delays ofat least 24 h to assure normal haemostasis at the time ofneedle insertion.• Removal of an epidural catheter should similarly be delayedfor a minimum of 10–12 h after the last dose of LMWH.• Subsequent LMWH dosing should occur a minimum of 2 hafter catheter removal.• If intravenous UFH is used, needle placement and catheterremoval may be done 4 h after discontinuing heparin. Furtherheparin administration should be delayed for 1 h after needleplacement.6/19/2013 26
    • Postoperative Anticoagulation: timeto effect• In resuming treatment after surgery, it takes:- 2-3 days for anticoagulant effect to begin afterstarting warfarin- 3-5 h for peak anticoagulant effect after startingLMWH- minutes for an antiplatelet effect to begin afterstarting ASA- 3-7 days for peak inhibition of platelet aggregationafter starting a maintenance dose of clopidogrel6/19/2013 27
    • Emergency surgery reverse anticoagulation fully before operation. The product of choice is prothrombin complex concentrate(PCC).• The concentration of coagulation factors in FFP is lesspredictable, and many units do not contain sufficient levelsof the four coagulation factors depleted by warfarin• the concentration of these vitamin K-dependent factors inPCC is approximately 25 times higher than in plasma.• The recommended dose of PCC is 25–50 units/kg• Nearly 90 per cent of patients achieve the required INRwithin 15 min of PCC administration. A few INRs do notreach the desired level after a single dose and an additionalsmaller dose may be required.6/19/2013 28
    • Comparison between fresh frozen plasmaand prothrombin complex concentrate6/19/2013 29
    • Emergency surgery• PCC may increase the incidence of thrombosis , mainlyin patients with hemophilia in acute surgical situations,cardiomyopathy, shock and carcinoma.• If PCC is not readily available, FFP may be considered(recommended dose is 10–15 ml/kg)• FFP may cause a lack of correction of factor IX,particularly in situations of over-anticoagulation (INRgreater than 5), which can have implications inoperations with high bleeding risk.6/19/2013 30
    • Emergency surgery• Recombinant activated factor VII (or VIIa) has alsobeen shown to be safe, rapid and effective atreversing bleeding associated with warfarinanticoagulation. However, it does not seem fullyto correct the warfarin-induced coagulopathy• It is imperative to administer intravenous vitaminK (5 mg) with all the products described above asthese agents have a short half-life and the INRcan climb again once their effect has worn off6/19/2013 31
    • Semi-urgent surgery• If more rapid reversal of warfarinanticoagulation is required over one to• two days), warfarin should be withheld and asmall dose of vitamin K administered• either intravenously (eg, 1.0 to 2.5 mg)• or orally (eg, 2.5 to 5.0 mg).6/19/2013 32
    • alternative• Role of inferior vena cava filters• Prophylactic IVC filter may be considered if there is anextremely high risk of recurrent thromboembolicdisease during the perioperative period.• Examples include patients who have had an acute PEor a proximal DVT, and those with recent ICH• A temporary filter is generally preferred as it can beretrieved once the high-risk period is over.• Discussion with both hematologist and interventionalradiologist is recommended in these circumstances6/19/2013 33
    • Other anticoagulants• Periprocedural data with the novel oralanticoagulants,- dabigatran- rivaroxaban- apixaban• their relatively short half-life, rapid onset of action,and predictable pharmacokinetics should simplifyperiprocedural use.Blood.-6/19/2013 34
    • Preoperative interruption of new oral anticoagulants: asuggested management approach*Estimated t1/2 based on renal clearance.†Aiming for mild to moderate residual anticoagulant effect at surgery ( 12%-25%).‡Aiming for no or minimal residual anticoagulant effect ( 3%-6%) at surgery.§Patients receiving rivaroxaban, 15 mg once daily.6/19/2013 35
    • Postoperative resumption of new oral anticoagulants: asuggested management approach*For patients at high risk for thromboembolism, consider administering a reduced dose of dabigatran (eg, 110-150 mg once daily) on the evening after surgery and on the following day (first postoperative day) after surgery.†Consider a reduced dose (ie, rivaroxaban 10 mg once a day or apixaban 2.5 mg twice a day) in patients at highrisk for thromboembolism.6/19/2013 36
    • Perioperative Management ofAntithrombotic Therapy9th ed: American College of ChestPhysicians Evidence-Based ClinicalPractice GuidelinesCopyright: American College of Chest Physicians 2012©6/19/2013 37
    • reference6/19/2013 38
    • Case No. 1• A 68-year-old woman receiving chronicWarfarin for recurrent DVT (most recent was1 year ago) will undergo two dentalextractions that will include local anestheticinjections…6/19/2013 39
    • Case No. 1: Management Options1. Stop warfarin at day -5 before procedure, givetherapeutic-dose bridging with LMWH (eg,enoxaparin, 1 mg/kg bid)2. Continue warfarin without dose reduction andgive prohemostatic mouthwash (cyclokapron)around procedure3. Continue warfarin without dose reduction4. Stop warfarin 2 days before procedure andresume after procedure6/19/2013 40
    • Patients Requiring Minor Procedures• Recommendation: In patients who require minor dentalsurgery and are receiving VKA therapy, either continueVKA with co-administration of an oral prohemostaticagent or stopping VKAs 2-3 days before the procedureinstead of alternative strategies (Grade 2C).• Recommendation: In patients who require minor skinprocedures and are receiving VKA therapy, continue VKAsaround the time of the procedure and optimizing localhemostasis instead of other strategies (Grade 2C).• Recommendation: In patients who require cataractsurgery and are receiving VKA therapy, continue VKAsaround the time of the surgery instead of other strategies(Grade 2C).6/19/2013 41
    • Case No. 2A 54-year-old man with a mechanical mitralvalve replacement on long-term warfarintherapy is scheduled for total hipreplacement…6/19/2013 42
    • Case No. 2: Management Options1. Stop warfarin 5 days preop, administer therapeutic-dose bridging with LMWH (eg, enoxaparin, 1 mg/kgbid) preop and postop2. Stop warfarin 5 days preop, administer low-doseLMWH preop and postop (eg, dalteparin, 5000 IUQD)1. Continue warfarin but reduce dose by 50%starting 5 days preop1. Stop warfarin 5 days preop and resume afterprocedure6/19/2013 43
    • Patients at High Risk for TE havingMajor Surgery• Recommendation: In patients who require temporary interruptionof a VKA before surgery, we recommend stopping VKAsapproximately 5 days before surgery instead of stopping VKAs ashorter time before surgery (Grade 1C).• Recommendation: In patients who require temporary interruptionof a VKA before surgery, we recommend resuming VKAsapproximately 12-24 hrs after surgery (evening of or nextmorning) and when there is adequate hemostasis instead of laterresumption of VKAs (Grade 2C).• Recommendation: In patients with a mechanical heart valve, atrialfibrillation or VTE at high risk for TE, we suggest bridginganticoagulation instead of no bridging during interruption of VKAtherapy (Grade 2C).6/19/2013 44
    • Perioperative Administration ofBridging• Recommendation: In patients who are receivingbridging anticoagulation with therapeutic-dose SCLMWH, we suggest administering the lastpreoperative dose of LMWH approximately 24 hbefore surgery instead of 12 h before surgery (Grade2C).• Recommendation: In patients who are receivingbridging anticoagulation with therapeutic-dose SCLMWH and are undergoing high bleeding-risk surgery,we suggest resuming therapeutic-dose LMWH 48-72 hafter surgery instead of resuming LMWH within 24 hafter surgery (Grade 2C).6/19/2013 45
    • Case No. 3• A 69-year-old man with chronic atrialfibrillation and hypertension (CHADS2 score =1) is undergoing a abdominal surgery forcancer6/19/2013 46
    • Case No. 3: Management Options1. Stop warfarin 5 days preop, administer therapeutic-dose bridging with LMWH (eg, enoxaparin, 1 mg/kgbid) preop and postop2. Stop warfarin 5 days preop, administer low-doseLMWH preop and postop (eg., daltearin, 5000 IUqd)3. Continue warfarin but reduce dose by 50%starting 5 days preop4. Stop warfarin 5 days preop and resume afterprocedure6/19/2013 47
    • Patients at Low Risk for TE HavingMajor Surgery• Recommendation: In patients with a mechanicalheart valve, atrial fibrillation or VTE at low-riskfor TE, we suggest no bridging anticoagulationduring interruption of VKA therapy (Grade 2C).• N.B. In patients at moderate-risk for TE, thebridging or no bridging approach chosen is, as inthe higher and lower risk patients, based on anassessment of individual patient- and surgery-related factors.6/19/2013 48
    • Case No. 466-year-old man with a drug-eluting coronarystent inserted 5 months ago following a non-ST-elevation myocardial infarction…now requires surgery for removal of a parotidadenocarcinomaHe is receiving ASA 81 mg, and clopidogrel 75 mgdailyHis other cardiovascular risk factors are thefollowing: CABG 12 years ago, hypertension, andtype 2 diabetes6/19/2013 49
    • Case No. 4: Management Options1. Stop ASA and clopidogrel 7-10 days preop andresume both drugs 1-2 days postop2. Stop ASA and clopidogrel 7-10 days preop andadminister bridging with SC LMWH3. Continue ASA and stop clopidogrel 7-10 days preop4. Continue both ASA + clopidogrel perioperatively5. Stop ASA and clopidogrel 7-10 days preop and giveGP IIb/IIIa inhibitor before/after surgery6/19/2013 50
    • Patients With Coronary Stents HavingSurgery• Recommendation: In patients with a coronary stentwho are receiving dual antiplatelet therapy andrequire surgery, we recommend deferring surgery forat least 6 weeks after placement of a bare-metal stentand for at least 6 months after placement of a drug-eluting stent (Grade 1C).• Recommendation: In patients who require surgerywithin 6 weeks of placement of a bare-metal stent orwithin 6 months of placement of a drug-eluting stent,we suggest continuing dual antiplatelet therapyaround the time of surgery instead of stopping dualantiplatelet therapy 7-10 days before surgery (Grade2C).6/19/2013 51
    • Case No. 5• 78-year-old obese woman with a non-ST-elevationmyocardial infarction 2 years ago is seenpreoperatively prior to inguinal hernia repair– CAD treated medically, no angiography• Receiving ASA, 81 mg• Other cardiovascular risk factors are the following:hypertension, dyslipidemia, glucose intolerance6/19/2013 52
    • Case No. 5: Management Options1. Stop ASA 7-10 days preop and resume 1-2days postop2. Stop ASA 4-5 days preop and resume 1-2days postop3. Continue ASA without interruption beforesurgery6/19/2013 53
    • Patients With Coronary Stents HavingSurgeryRecommendation: In patients at moderate-to-high risk forcardiovascular events who are receiving ASA therapy andrequire non-cardiac surgery, we suggest continuing ASAaround the time of surgery instead of stopping ASA 7-10days before surgery (Grade 2C).Recommendation: In patients at low risk for cardiovascularevents who are receiving ASA therapy, we suggeststopping ASA 7-10 days before surgery instead ofcontinuation of ASA (Grade 2C).6/19/2013 54
    • Ongoing Studies…Stay Tuned• Randomized controlled trials (RCTs) are ongoing to establishbest practices for patients who are receiving antithrombotictherapy and require surgery.• RCTs are assessing the need for LMWH bridging in warfarin-treated patients who require surgery:– PERIOP-2 (clinicaltrials.gov/NCT00432796) – funded by CIHR– BRIDGE (clinicaltrials.gov/NCT00786474) – funded by NIH– PACEBRIDGE– BRUISECONTROL (clinicaltrials.gov/NCT00800137)• RCTs are assessing the need for perioperative ASA:– POISE-2 (clinicaltrials.gov/ NCT01082874) in patients having noncardiacsurgery– ATACAS in patients undergoing CABG surgery6/19/2013 55