perioperative management of antithrombotic therapy

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Periprocedural Anticoagulation Management

DR GHALEB ALMEKHLAFIMD,SFCCM,EDIC

PSMMC

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references

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Introduction

• OAC therapy during surgery is associated with increased excessive operative bleeding.• Anticoagulation cessation,

increases risk of thromboembolism, especially in the postoperative period.

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introduction

• Thromboembolic risks: (1)Disease specific thromboembolic risks when

discontinuing warfarin(2)Hypercoagulability associated with surgery.• Bleeding risks:(1) the patient factors(2) the use of anticoagulant therapy(3) the surgery or procedure

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introduction

Thromboembolic Risk When Discontinuing WarfarinVenous Thromboembolism (VTE):• In The absence of OAC during the first month of an acute

VTE event － Recurrence 40%/month• During the second and third month － Recurrence

10%/2month• After the 3 month treatment － 15%/year• Surgery should be deferred following an acute episode of

venous thromboembolism until patients have received at least 1 month, and preferably 3 months, of anticoagulation.

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introduction

Arterial thromboembolism1-Nonvalvular atrial fibrillation (NVAF): • Average risk of systemic embolism － 4.5%/year

in the absence of OAC.• The CHADS2 Score(estimate expected stroke rate

per 100 patient-years):• Moderate-risk patients have an adjusted stroke

rate of up to 5.9%• High-risk patients have adjusted stroke rates of 8.5 to 18.2%.6/19/2013

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CHADS2 score validated for patients with NVAF

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introductionArterial 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% of

patients• case-fatality rates: - VTE =5%-9%, - major bleeding =8%-10%

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introduction

prothrombotic effect of procedures• Surgery(major surgery and laparoscopic procedures )• will increase the postoperative• - VTE : risk 100-fold• - ATE :estimates suggesting a 10-fold higher than

expected risk of stroke in the Periprocedural period in Warfarin-treated patients

Tiede DJ, Nishimura RA, Gastineau DA, Mullany CJ,Orszulak TA, Schaff HV. Modern management of prosthetic valve anticoagulation. Mayo Clin Proc.1998;73(7):665-680.6/19/2013

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Suggested risk stratification for perioperative Thromboembolism

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Procedural bleeding risks

This table is based on definitions derived from surgical/subspecialty societies in anticoagulant bridging or anticoagulant bridging management studies6/19/2013

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ICU-Procedures With High Bleeding Risk: Interrupting Anticoagulation Advised

• serious bleeding in >1.5%.• If high risk for clotting with anticoagulation interruptions should be

considered for “bridging therapy” with heparin• ICU PROCEDURES:- Lumbar puncture Chest tube plcmt Arterial puncture Spinal/epidural

anesthesia Transbronchial bx , Stricture dilations Organ biopsies, tracheostomy

- OTHERS:- Tunneled catheter plcmt , Cardiac ablations Liver/GB drains

Nephrostomy ERCP w sphincterotomy PEG tube plcmt Cardiac cath PCI Pacemaker plcmt

• - >1cm polypectomy Major surgery Wide skin excision, Eye surgery (not cataracts) ,Vascular interventions

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Procedural bleeding risks

This table is based on definitions derived from surgical/subspecialty societies in anticoagulant bridging or anticoagulant bridging management studies6/19/2013

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ICU-Procedures Not Necessarily Requiring Interruption 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 for

HD, 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 .Minor

skin surgery ,Dilation & curettage • Root canals, Tooth extraction, nephrostomy tube exchange

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periprocedural antithromboticstrategy

For most patients undergoing low-bleeding-risk

procedures:• 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-risk procedures:

• For those who are at low individual risk for clotting, anticoagulation can be interrupted without bridging therapy (heparin).

• Most patients at high individual risk of blood clots should receive bridging anticoagulation therapy.

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Periprocedural heparin bridging strategies for patients on chronic VKA

Data 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 before reinitiating postprocedural heparin (LMWH) bridging (especially treatment dose); stepwise increase in postprocedural heparin (LMWH) dose from prophylactic dose first 24-48 hours to intermediate/treatmen dose; no postprocedural heparin (LMWH) bridging in very high bleed risk procedures (ie, major neurosurgical or cardiovascular surgeries) but use of mechanical prophylaxis. **Based on individual patient- and procedural related risk factors for thrombosis

and bleeding.6/19/2013

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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-disk

design, i.e., non-bileaflet),• Any mechanical valve with a history of stroke or transient

ischemic attack,• Non-valvular atrial fibrillation with a CHADS2 SCORE 4 or

greater, history of stroke or TIA, or cardiac thrombus

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Perioperative Bridging :General Points

1-To eliminate effect of antithrombotic therapy before surgery, treatment should be stopped before surgery (~5 days for Warfarin, 7-10 days for antiplatelet drug) to minimizing bleeding risk

2-Giving bridging after surgery increases risk for bleeding; this risk depends on anticoagulant dose (therapeutic-dose > low-dose) and proximity to surgery (higher risk if given closer to surgery)

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Perioperative Bridging: General Points

3-Delaying resumption of therapeutic-dose bridging (for 48-72 h after surgery), decreasing the dose or avoiding its use after surgery can mitigate the risk for bleeding

4-Low-dose LMWH/UFH is effective to prevent postop VTE, but evidence is lacking that such regimens effective to prevent ATE

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bridging anticoagulation regimens

A “high-dose” (therapeutic-dose) regimen involves giving a dose similar to that used to treat acute VTE or 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 control aPTT). A “low-dose” (prophylactic-dose) regimen involves

giving a dose used, typically, to prevent postoperative VTE (eg, enoxaparin 30 mg BID or 40 mg QD, dalteparin 5000 IU QD, UFH 5000-7500 IU BID)

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bridging anticoagulation regimens

–An “intermediate-dose” regimen has been recently studied for bridging and is intermediate in anticoagulant intensity between a high-dose and low-dose regimen (eg, enoxaparin 40 mg BID).

–Different bridging regimens may have potential advantages or drawbacks over a “therapeutic-dose” regimen

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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/kg once daily or 100 IU/kg twice daily subcutaneously; and tinzaparin 175 IU/kg once daily subcutaneously. Intermediatedose LMWH (ie, nadroparin 2850-5700 U twice daily subcutaneously; enoxaparin 40 mg twice daily subcutaneously) has been less studied in this setting †Loading doses (ie, 2 times the daily maintenance dose) of warfarin have also been used.6/19/2013

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Periprocedural anticoagulation and bridging protocol

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Stopping heparin before surgery

• To avoid persistence of heparin during surgery, it is suggested that the last therapeutic dose of LMWH be given no less than 12 h before operation with a twice-daily regimen, or 24 h before operation with a once-daily regimen.

• A recent evidence has shown that a 24-h gap for LMWH even when given twice daily may be preferable34. Intravenous

• UFH should be stopped 4–6 h before surgeryO'Donnell MJ, Kearon C, Johnson J, Robinson M, Zondag M, Turpie I et al. Brief communication: preoperative anticoagulant activity after bridging low-molecular-weight heparin for temporary interruption of warfarin. Ann Intern Med 2007; 146: 184–1876/19/2013

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Neuraxial anesthesia

• Most recommend that prophylactic treatment with LMWH should be stopped at least 12 h before the insertion of an epidural needle.

• Patients receiving treatment doses of LMWH require delays of at least 24 h to assure normal haemostasis at the time of needle insertion.

• Removal of an epidural catheter should similarly be delayed for a minimum of 10–12 h after the last dose of LMWH.

• Subsequent LMWH dosing should occur a minimum of 2 h after catheter removal.

• If intravenous UFH is used, needle placement and catheter removal may be done 4 h after discontinuing heparin. Further heparin administration should be delayed for 1 h after needle placement.

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Postoperative Anticoagulation: time to effect

• In resuming treatment after surgery, it takes: - 2-3 days for anticoagulant effect to begin after starting warfarin- 3-5 h for peak anticoagulant effect after starting LMWH

- minutes for an antiplatelet effect to begin after starting ASA

- 3-7 days for peak inhibition of platelet aggregation after starting a maintenance dose of clopidogrel

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Emergency surgery reverse anticoagulation fully before operation. The product of choice is prothrombin complex concentrate (PCC). • The concentration of coagulation factors in FFP is less predictable,

and many units do not contain sufficient levels of the four coagulation factors depleted by warfarin

• the concentration of these vitamin K-dependent factors in PCC 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 INR within 15

min of PCC administration. A few INRs do not reach the desired level after a single dose and an additional smaller dose may be required.

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Comparison between fresh frozen plasma and prothrombin complex concentrate

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Emergency surgery

• PCC may increase the incidence of thrombosis , mainly in 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 (INR greater than 5), which can have implications in operations with high bleeding risk.

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Emergency surgery

• Recombinant activated factor VII (or VIIa) has also been shown to be safe, rapid and effective at reversing bleeding associated with warfarin anticoagulation. However, it does not seem fully to correct the warfarin-induced coagulopathy

• It is imperative to administer intravenous vitamin K (5 mg) with all the products described above as these agents have a short half-life and the INR can climb again once their effect has worn off

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Semi-urgent surgery

• If more rapid reversal of warfarin anticoagulation is required over one to

• two days), warfarin should be withheld and a small dose of vitamin K administered

• either intravenously (eg, 1.0 to 2.5 mg) • or orally (eg, 2.5 to 5.0 mg).

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alternative

• Role of inferior vena cava filters• Prophylactic IVC filter may be considered if there is an

extremely high risk of recurrent thromboembolic disease during the perioperative period.

• Examples include patients who have had an acute PE or a proximal DVT, and those with recent ICH

• A temporary filter is generally preferred as it can be retrieved once the high-risk period is over.

• Discussion with both hematologist and interventional radiologist is recommended in these circumstances

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Other anticoagulants

• Periprocedural data with the novel oral anticoagulants,

- dabigatran - rivaroxaban - apixaban• their relatively short half-life, rapid onset of action,

and predictable pharmacokinetics should simplify periprocedural use.

Blood.2012;120(15):2954-2962)6/19/2013

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Preoperative interruption of new oral anticoagulants: a suggested 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.

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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 high risk for thromboembolism.6/19/2013

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Perioperative Management of Antithrombotic Therapy

9th ed: American College of Chest Physicians Evidence-Based Clinical

Practice Guidelines

Copyright: American College of Chest Physicians 2012©

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reference

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Case No. 1

• A 68-year-old woman receiving chronic Warfarin for recurrent DVT (most recent was 1 year ago) will undergo two dental extractions that will include local anesthetic injections…

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Case No. 1: Management Options

1. Stop warfarin at day -5 before procedure, give therapeutic-dose bridging with LMWH (eg, enoxaparin, 1 mg/kg bid)

2. Continue warfarin without dose reduction and give prohemostatic mouthwash (cyclokapron) around procedure

3. Continue warfarin without dose reduction

4. Stop warfarin 2 days before procedure and resume after procedure

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Patients Requiring Minor Procedures

• Recommendation: In patients who require minor dental surgery and are receiving VKA therapy, either continue VKA with co-administration of an oral prohemostatic agent or stopping VKAs 2-3 days before the procedure instead of alternative strategies (Grade 2C).

• Recommendation: In patients who require minor skin procedures and are receiving VKA therapy, continue VKAs around the time of the procedure and optimizing local hemostasis instead of other strategies (Grade 2C).

• Recommendation: In patients who require cataract surgery and are receiving VKA therapy, continue VKAs around the time of the surgery instead of other strategies (Grade 2C).

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Case No. 2

A 54-year-old man with a mechanical mitral valve replacement on long-term warfarin therapy is scheduled for total hip replacement…

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1. Stop warfarin 5 days preop, administer therapeutic-dose bridging with LMWH (eg, enoxaparin, 1 mg/kg bid) preop and postop

2. Stop warfarin 5 days preop, administer low-dose LMWH preop and postop (eg, dalteparin, 5000 IU QD)

3. Continue warfarin but reduce dose by 50% starting 5 days preop

4. Stop warfarin 5 days preop and resume after procedure

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Patients at High Risk for TE having Major Surgery

• Recommendation: In patients who require temporary interruption of a VKA before surgery, we recommend stopping VKAs approximately 5 days before surgery instead of stopping VKAs a shorter time before surgery (Grade 1C).

• Recommendation: In patients who require temporary interruption of a VKA before surgery, we recommend resuming VKAs approximately 12-24 hrs after surgery (evening of or next morning) and when there is adequate hemostasis instead of later resumption of VKAs (Grade 2C).

• Recommendation: In patients with a mechanical heart valve, atrial fibrillation or VTE at high risk for TE, we suggest bridging anticoagulation instead of no bridging during interruption of VKA therapy (Grade 2C).

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Perioperative Administration of Bridging

• Recommendation: In patients who are receiving bridging anticoagulation with therapeutic-dose SC LMWH, we suggest administering the last preoperative dose of LMWH approximately 24 h before surgery instead of 12 h before surgery (Grade 2C).

• Recommendation: In patients who are receiving bridging anticoagulation with therapeutic-dose SC LMWH and are undergoing high bleeding-risk surgery, we suggest resuming therapeutic-dose LMWH 48-72 h after surgery instead of resuming LMWH within 24 h after surgery (Grade 2C).

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Case No. 3

• A 69-year-old man with chronic atrial fibrillation and hypertension (CHADS2 score = 1) is undergoing a abdominal surgery for cancer

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1. Stop warfarin 5 days preop, administer therapeutic-dose bridging with LMWH (eg, enoxaparin, 1 mg/kg bid) preop and postop

2. Stop warfarin 5 days preop, administer low-dose LMWH preop and postop (eg., daltearin, 5000 IU qd)

3. Continue warfarin but reduce dose by 50% starting 5 days preop

4. Stop warfarin 5 days preop and resume after procedure

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Patients at Low Risk for TE Having Major Surgery

• Recommendation: In patients with a mechanical heart valve, atrial fibrillation or VTE at low-risk for TE, we suggest no bridging anticoagulation during interruption of VKA therapy (Grade 2C).

• N.B. In patients at moderate-risk for TE, the bridging or no bridging approach chosen is, as in the higher and lower risk patients, based on an assessment of individual patient- and surgery-related factors.

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Case No. 466-year-old man with a drug-eluting coronary stent inserted 5 months ago following a non-ST-elevation myocardial infarction

…now requires surgery for removal of a parotid adenocarcinoma

He is receiving ASA 81 mg, and clopidogrel 75 mg daily

His other cardiovascular risk factors are the following: CABG 12 years ago, hypertension, and type 2 diabetes

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1. Stop ASA and clopidogrel 7-10 days preop and resume both drugs 1-2 days postop

2. Stop ASA and clopidogrel 7-10 days preop and administer bridging with SC LMWH

3. Continue ASA and stop clopidogrel 7-10 days preop 4. Continue both ASA + clopidogrel perioperatively

5. Stop ASA and clopidogrel 7-10 days preop and give GP IIb/IIIa inhibitor before/after surgery

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Patients With Coronary Stents Having Surgery

• Recommendation: In patients with a coronary stent who are receiving dual antiplatelet therapy and require surgery, we recommend deferring surgery for at least 6 weeks after placement of a bare-metal stent and for at least 6 months after placement of a drug-eluting stent (Grade 1C).

• Recommendation: In patients who require surgery within 6 weeks of placement of a bare-metal stent or within 6 months of placement of a drug-eluting stent, we suggest continuing dual antiplatelet therapy around the time of surgery instead of stopping dual antiplatelet therapy 7-10 days before surgery (Grade 2C).

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Case No. 5

• 78-year-old obese woman with a non-ST-elevation myocardial infarction 2 years ago is seen preoperatively prior to inguinal hernia repair– CAD treated medically, no angiography

• Receiving ASA, 81 mg

• Other cardiovascular risk factors are the following: hypertension, dyslipidemia, glucose intolerance

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1. Stop ASA 7-10 days preop and resume 1-2 days postop

2. Stop ASA 4-5 days preop and resume 1-2 days postop

3. Continue ASA without interruption before surgery

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Patients With Coronary Stents Having Surgery

Recommendation: In patients at moderate-to-high risk for cardiovascular events who are receiving ASA therapy and require non-cardiac surgery, we suggest continuing ASA around the time of surgery instead of stopping ASA 7-10 days before surgery (Grade 2C).

Recommendation: In patients at low risk for cardiovascular events who are receiving ASA therapy, we suggest stopping ASA 7-10 days before surgery instead of continuation of ASA (Grade 2C).

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Ongoing Studies…Stay Tuned • Randomized controlled trials (RCTs) are ongoing to establish

best practices for patients who are receiving antithrombotic therapy 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 noncardiac

surgery– ATACAS in patients undergoing CABG surgery

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