Peri Operative Management of Anti Coagulation

Dr Nihar Pandit September 14th, 2013

Consultant, General Medicine Tan Tock Seng Hospital

Objectives

To understand the characteristics of the patient population requiring peri-operative anti coagulation

To help decide between the perioperative risk of thrombosis Versus the risk of bleeding

To familiarize with the available protocols

‘Bridging Anticoagulation’

Substitution of another anti coagulant (typically Heparin derivative) when Warfarin is interrupted for an

invasive procedure.

Bridging Therapy

Cross Coverage to Therapeutic INR

Requiring AC but have not achieved

Therapeutic INR Peri-procedural:

RATIONALE FOR BRIDGING

Already Rxed w chronic AC and

now documented drop in INR

mechanical heart valves

A Fib w risk factors for emboli

recent VTE (< 3 months)

hypercoaguable states

BENEFITS Supporting Need for

Bridge Therapy

high risk for thrombosis when patients remain unprotected for several days peri-procedure

Subtherapeutic INR offers little or no protection

Possible rebound hypercoaguable state, especially when warfarin reinitiated leading to thrombosis

Bleeding complications can be controlled while stroke or PE may have lasting effect

New drugs and new data offer increased ease of therapy

Expert Opinion on Bridge Therapy

British Society of Hematology

American College of Chest Physicians (ACCP)

Does the surgery matter ?

Warfarin need not be stopped before every procedure (low bleeding risk)

For surgeries in which the bleeding Risk is not low …

Common indications for anti coagulation

1. Atrial Fibrillation 2. Deep Vein Thrombosis and Pulmonary Embolism (VTE) 3. Mechanical Heart Valves (MHV)

Atrial Fibrillation

A 77 year old man having a history of Hypertension, Atrial fibrillation and Diabetes Mellitus is scheduled to undergo TURP for BPH. He has no history of CVA or CCF

What would you advise: 1. Stop Warfarin 5 days before the procedure, give therapeutic

dose LMWH pre and post op 2. Continue Warfarin without dose reduction 3. Stop Warfarin 2 days before the procedure and resume 2

days later 4. Stop Warfarin 5 days before and resume 1 week post op

Stroke rate according to CHADS2 score in the Non Perioperative and Perioperative setting

Kaatz S, Douketis JD, White RH, Zhou H. Can the CHADS2 score predict postoperative stroke risk in patients with chronic atrial fibrilation who are having elective non-cardiac surgery? J ThrombHaemost 2011

Bridging Therapy for A fib

Risk Characteristics Bridging Therapy High Any of the following:

CHADS2 3-6 Previous CVA or TIA Intra Cardiac thrombus

Rheumatic Afib

Yes

Low CHADS2 0-2 And no CVA or TIA

No

Wysokinski et al Mayo Clinic Proc, June 2008; 83(6), 639- 645 Chest June 2008 133:6 suppl 299S- 339S

VTE 72 year old woman has been taking Warfarin for DVT and PE

five years ago. She has no known Cancer or thrombophilia. She is scheduled for THR for Degenerative Joint disease. What would you advise this patient ? 1. Stop Warfarin 5 days pre-op and administer therapeutic dose

LMWH pre-op and post-op 2. Stop Warfarin 5 days pre-op and administer low dose

LMWH pre and post-op 3. Continue Warfarin but reduce the dose 50% pre-op 4. Stop Warfarin 5 days pre-op and resume post-op with

Warfarin and LMWH.

Bridging Therapy for VTE

Risk Level

Characteristics Bridging Therapy

High One of the following: Severe thrombophilia

Active Cancer or cancer treatment Recurrent VTE

Recent VTE within 3 months

Yes

Low Last VTE > 3 months ago and no additional risk factors

No

McBane et al, Arterioscler Thromb Vasc Bio, June 2010, 30: 442- 448 Chest June 2008 133:6 suppl 299S- 339S

What is severe Thrombophilia?

Protein C or Protein S deficiency

Antithrombin III deficiency

Antiphospholipid antibodies Multiple defects, homozygous Factor V Leiden or

Prothrombin gene 20210 mutation

Mechanical Heart Valve

62 year old gentleman with a St Jude (Bileaflet) Mechanical AV and Afib but no prior thromboembolism, Rheumatic heart disease or CCF.

He is scheduled for partial colectomy for colon cancer.

Would you give this patient bridging ? Yes ? No ?

Thrombosis risk of Mechanical Heart Valves (MHV) without Anti coagulation

Characteristic Low Risk High Risk Number of Valves Single Multiple

Position of valve Aortic Mitral

Type of valve Bi leaflet Tilting disc and Caged ball

Other A fib, low EF,

prior embolism

Cannegleter et al, Circulation; 1994, 89: 635- 641

Bridging Therapy for MHV

Risk level Characteristics Bridging Therapy

High Any mitral MHV Older (caged ball or tilting disc) Aortic MHV

h/o TIA or cardioembolic CVA Aortic bileaflet and CHF or A fib

Yes

Low Aortic bileaflet MHV without A fib, CHF or intracardiac thrombus

No

Daniels et al, Thrombosis Research; 124: 300- 305

Pre procedure management for those requiring interruption of Warfarin

Stop Warfarin 5 days before the procedure

Check INR One day prior to the procedure, ensuring <1.3

Pre procedure LMWH/ UFH dosing for Bridging (if given)

Start LMWH when INR below the therapeutic range

- Enoxaparin: 1 mg/kg SC q 12 hours - Enoxaparin 1.5 mg/kg SC q 24 hour

Last dose of LMWH given

24 hours before the procedure

- Enoxaparin 1 mg/kg 24 hours before the procedure

UFH: Start Heparin when INR below the therapeutic range

- Discontinue UFH 4-6 hours before the procedure

Day -7 -5 -3 -1 +1 +2 +3 +5

Surgery

√ INR √ CBC

√ INR

Hold Coumadin

J.D. Douketis, Thrombosis Research; 108 (2003) 3-13

√ INR

Coumadin

‘BRIDGING’ STRATEGY

# Days pre-op # Days post-op

Resume Coumadin

Start full Dose LMWH

Resume full dose LMWH

Prophylactic Dose LMWH

How and when do we restart Anticoagulation after a procedure?

Depends on the risk of post procedure bleeding Consider the procedure: Is it a major surgery Is the operative site observable or compressible? Is it neuraxial anaesthesia? Consider the patient: Does the patient have any issues with hemostasis? Does the patient have a history of bleeding ?

Classifying Bleeding Risk of procedures:

High risk Cardiovascular surgery- Valve replacement, CABG, AAA repair Cancer surgery, Neuro surgery Intra abdominal surgery Others: TKA, laminectomy, TURP, Kidney biopsy

Non High Risk

All others

Douketic et al, Arch Internal Med. 2004; 164: 1319- 1326

Possible strategies for post procedure management

High Bleeding risk:

Resume Warfarin when safe

No bridging Low Dose bridging (prophylaxis dose) Full dose bridging

Starting 24 hours after procedure

Wait for 48- 72 hours before starting

Low dose versus Full dose bridging Heparin

Low dose Thromboprophylaxis dosing of LMWH or UFH Not specifically studied- could reduce thrombosis yet mitigate

post procedure bleeding Full dose Therapeutic bridging – treatment doses Enoxaparin 1.5mg/kg every 24 hours

Which is to be used ? LMWH or UFH ?

REGIMEN REGISTRY

Multicenter Observational Study Compared safety and efficacy of UFH Versus LMWH as

bridging anticoagulants

REGIMEN REGISTRY Outcome % with outcome in each group

UFH (N= 164) LMWH (N= 668)

ATE 2.4 0.6

VTE 0 0.3

Major bleed 5.5 3.3

Minor bleed 9.1 12

Death 1.2 0.6

LoS 10.3 4.6

Days of heparin 6.8 8.6

Spyropoulos et al, Journ Throm and Hemostasis, 2006; 4: 1246: 1252

LMWH according to Renal function

Calculated Cr Cl (ml/min) Dose adjustment

>30 None

20-30 Decrease by 50%

<20 Avoid LMWH (use UFH)

Nutescu et al: Ann Pharmacotherapy; 2009: 43: 1064- 1083

Post procedure Warfarin dosing

Resume at the dose the patient was stable pre- procedure

CAUTION: More senstitive to Warfarin after a procedure due to NBM,

Antibiotics, so may require a lower dose at re-initiation and a closer monitoring of the INR

Emergency Surgery in a patient on Warfarin

Surgery in a patient on Newer Anticoagulants

No studies, Opinion from Manufacturers

Dabigatran (BD) Stop for 2 days if Cr Cl >

50ml/min Stop 3-5 days if Cr Cl < 50

ml/min

Rivaroxaban (OD) Stop for: 1 day if Cr Cl normal 2 days if Cr Cl 60-90ml/min 3 days if Cr Cl 30- 50ml/min 4 days if Cr Cl 15- 29ml/min

Putting it together

Patients at low risk of thrombosis do not require Bridging therapy

A fib CHADS2 0-2 And no CVA, TIA,

Intra cardiac thrombus, RHD

VTE Last event >3 months ago and no Cancer or severe

thrombophilia MHV Aortic position only,

bileaflet valve And no AFib, ATE, CHF,

intra cardiac thrombus

Putting it together

LMWH is advised for bridging therapy – need to be aware of

Renal function

Last dose of LMWH is 24 hours before the procedure, this dose is half the usual full daily dose

Timing of Post Procedure Anti coagulation (assuming adequate Hemostasis)

Thrombosis Risk level Warfarin Heparin

Low 12-24 hrs post procedure

NA

High 12-24 hrs post procedure

Low bleeding risk: 24 hrs post procedure

High Bleeding Risk: 1. no bridging or

2. low dose bridging or 3. Full bridging 48- 72 hrs

post procedure

Atrial Fibrillation

A 77 year old man having a history of Hypertension, Atrial fibrillation and Diabetes Mellitus is scheduled to undergo TURP for BPH. He has no history of CVA or CCF

What would you advise: 1. Stop Warfarin 5 days before the procedure, give therapeutic

dose LMWH pre and post op 2. Continue Warfarin without dose reduction 3. Stop Warfarin 2 days before the procedure and resume 2

days later 4. Stop Warfarin 5 days before and resume 1 week post op

CHADS2 score is 3 Risk for perioperative ATE is high

He would be a candidate for bridging LMWH (provided Cr Cl >20 mls/min) Anticoagulation could be resumed: Warfarin 12- 24 hours post procedure Heparin 48-72 hrs post procedure prophylactic dose 24 hrs post procedure (?benefit)

VTE 72 year old woman has been taking Warfarin for DVT and PE

five years ago. She has no known Cancer or thrombophilia. She is scheduled for THR for Degenerative Joint disease. What would you advise this patient ? 1. Stop Warfarin 5 days pre-op and administer therapeutic dose

LMWH pre-op and post-op 2. Stop Warfarin 5 days pre-op and administer low dose

LMWH pre and post-op 3. Continue Warfarin but reduce the dose 50% pre-op 4. Stop Warfarin 5 days pre-op and resume post-op with

Warfarin and LMWH.

No known thrombophilia or Cancer Last VTE was >3 months ago

Low risk of Perioperative VTE Not a candidate for pre-operative bridging Post operative Anti coagualtion with Warfarin 12- 24 hours

after the procedure and LMWH

Mechanical Heart Valve

62 year old gentleman with a St Jude Bileaflet Mechanical AV and Afib but no prior thromboembolism, Rheumatic heart disease or CCF.

He is scheduled for partial colectomy for colon cancer.

Would you give this patient bridging ? Yes ? No ?

Single (Aortic) MHV Bileaflet (low risk)

However he has Afib which places him in a high risk category

and hence would be a candidate for Bridging.

Thank you