Guideline and Protocols

Warfarin Therapy – Management During Invasive Procedure and Surgery

Effective Date: October 1, 2010.

Advisory committeeBritish Columbia Medical Association

Dr. Tarek MahmoodFCPS(medicine),

MD, Rheumatology ( phase – B)BSMMU

Glimpses of warfarin

• Coumarin derivatives• Inhibit Vit-K dependent carboxylation• Effective deficiency of factor II, VII, IX, X• Monitored by INR• >3 days to be effective• Narrow therapeutic window• Metabolism affected by many factor• Major bleeding - 1%/year• Fatal haemorrhage 0.25%/year

Indications • INR 2.5

– Prevention and treatment of VTE– Arterial embolism– AF with specific stroke risk factors– Mobile mural thrombus/ post MI– Extensive anterior MI– DCM– Cardioversion– Ischemic stroke in APS– MS/MR with AF

• INR 3.5– Recurrent venous thrombosis whilst on warfarin– Mechanical prosthetic cardiac valve

Treatment Recommendation for Persistently APA-positive Individuals

Clinical circumstances Recommendation

Asymptomatic No treatment

Venous thrombosis Warfarin INR 2.5 - indefinitely

Arterial thrombosis Warfarin INR 2.5 - indefinitely

Recurrent thrombosis Warfarin INR 3-4 +/- aspirin

Pregnancy:

First pregnancy No treatment

Single pregnancy loss <10wk No treatment

1 Fetal/3 embryonic losses/ no thrombosis

Prophylactic heparin + low dose aspirin discontinue 6-12 wk postpartum

Thrombosis regardless of pregnancy history

Therapeutic heparin or low dose aspirin warfarin postpartum

Thrombocytopenia:

>50,000/cc No treatment

<50,000/cc Prednisolone, IVIG

Catastrophic APS Anticoagulation + corticosteroids + IVIG or plasmapheresis

Contraindications • Recent surgery, specially eye or CNS• Pre-existing haemorrhagic state - liver disease - haemophilia - thrombocytopenia• Pre-existing structural lesions - peptic ulcer• Recent cerebral haemorrhage• Uncontrolled HTN• Cognitive impairment• Frequent falls in old age

Bleeding risk score • Age >65 yrs – 1• Previous GI bleed – 1• Previous stroke – 1• Medical illness – 1 - recent MI - renal failure - anemia - DM• Score: 0 = 3% 1-2 = 12% 3- 4 = 40%

Therapeutic Measures for Reversal of Warfarin Therapy

• Vitamin K

• Virally inactivated plasma-derived concentrate

• Frozen plasma

Vitamin K

• IV – fastest/most reliable• IM/SC - should be avoided• Procedure >24hrs – IV=PO• Useful post-operatively• Excessive dose – difficulty with re-anticoagulation• Effect on INR 8-12hrs• Doses: - oral 1-2 mg - IV 5mg/50cc NS/30 mins

Virally inactivated plasma-derived concentrate

• Rapid reversal• One dose – duration 6 hrs• Factors II, VII, IX, X, protein C, protein S• Must with IV vit K• Indications - active serious bleeding - surgery next 6 hrs• Contra indication - heparin induced thrombocytopenia - hepatic insufficiency

Frozen plasma

• Short duration – 4 hrs

• Rapid reversal

• Slight risk of infectious agent transmission

• Available in large center

Consideration for Perioperative Anticoagulation

• Acceptable INR for surgery

• Risk of bleeding

• Risk of thrombosis and need for peri-procedural bridging therapy

• Management based on risk of thrombosis

• Timing of procedure

• Type of anesthesia

Acceptable INR for Surgery

• Always discuss surgeon/anesthesiologist

• INR <1.5 generally acceptable, except:

- neurosurgery

- ocular surgery

- spinal anesthesia

- epidural analgesia

Risk of bleeding

• Type of procedure• Discontinuation of warfarin/ high risk of bleeding• - body cavity ( thoracic/abdominal/pelvic)• - percutaneous needle procedure in non-compressible sites, organ • - prostatic surgery• - surgery sites/minor bleeding/significant morbidity• CNS• Intraocular• - major arthroplasty• Discontinuation of warfarin not necessary/ low risk of bleeding• - percutaneous needle procedure in compressible sites• - many skin procedure• - routine dental procedure• - endoscopy without biopsy

Risk of thrombosis and need for peri-procedural bridging therapy

• Risk of thrombosis• from pre-existing condition• -lower risk• newer model mechanical aortic valve/ tissue valve• AF• DVT/PE >3 months• hypercoagulable state (no recent/recurrent/life threatening)• - higher risk• mechanical mitral valve/ old model aortic prosthesis• AF + H/O stroke/TIA, > 2 risk factors for cardio embolic events• DVT/PE < 3 months• DVT/PE in active cancer• Hypercoagulable state (recent/recurrent/life threatening)• from the procedure• - surgeon/ Anesthesiologist

Management based on risk of thrombosis

• Low risk• - discontinue warfarin 5 days prior to surgery (-6)• - INR day before procedure (1.5)• - restart warfarin at pre-op dose (hemostasis/ epidural catheter)• - recheck INR – one week• High risk• - discontinue warfarin at least 5 days prior to surgery (-6/-7)• - start LMWH on day -3• - last dose of LMWH <24hrs• - INR day before procedure (1.5)• - post-op LMWH (12-24hrs)• - restart warfarin at pre-op dose (hemostasis/ epidural catheter)• - continue LMWH until INR therapeutic range – 2 days

Timing of procedure

• Surgery should be elective if possible• If fixed duration anticoagulation – consider delaying invasive procedure• Urgent or emergency surgery/procedure• - <24 hours• discontinue warfarin• IV vit K• within 6 hours – virally inactivated plasma-derived concentrate• check INR before procedure – if not corrected – repeat• - 24-96 hours• discontinue warfarin• IV/PO vit K• check INR 24 hours – if not corrected – IV vit K – INR in 12 hours• if not corrected – consider – DIC/liver disease• check INR prior to surgery•

Timing of procedure – contd.

• Elective surgery with planned anticoagulant reversal• 5-6 days warfarin free• consider LMWH bridging therapy• check INR one day prior to/on day of surgery

Type of anesthesia

• LA/GA safe to a patient on warfarin• Neuraxial blocks should not be performed• - epidural• - spinal• - retrobulbar• If central venous access is needed, a compressible site is preferred• In patient with epidural catheters• - prophylactic LMWH• - not therapeutic LMWH• - catheter should not be removed <12 hrs after LMWH dose• - no warfarin until epidural catheter is removed• - do not give LMWH until after 2 hours of catheter removal

intervention Timing of surgery

elective Urgent >24hrs Urgent 6-24hrs

Urgent < 6 hrs

Discontinue warfarin

5days prior surgery (-6)

immediately immediately immediately

LMWH +/- thrombotic risk

+/- thrombotic risk

NO NO

Vitamin K NO PO/IV IV IV

Octaplex NO NO NO Preferred

Frozen plasma NO NO NO If octaplex not available

Recheck INR 24hrs prior surgery

12hrs > vit K 12 hrs > vit K After FP/Octaplex

INR >1.5 Postpone if necessary

Repeat vit K Repeat vit K, Octaplex/FP if surgery < 6hrs

Repeat vit K, Octaplex/FP if surgery < 6hrs

Risk of thrombosisLow risk High risk

Pre operative Proceed to surgery <1.5 Elective- LMWH on day -3Discontinue 24hrs

postoperative Restart warfarin at pre-op dose/ hemostasis ensured / epidural catheter removed

LMWH 12-24hrs/ hemostasis ensured/ >2hrs of epidural catheter removal

Stop LMWH / INR therapeutic range 2 consecutive days

“The darkest places in hell are reserved for those, who maintain their neutrality in times of moral crisis.” -Dante

Thank You