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Central Virginia Center. for Coagulation Disorders. Management of Anticoagulation Therapy in the Peri-operative Period . J. Christian Barrett, MD Assistant Professor, Division of Hematology-Oncology Virginia Commonwealth University. Management of Anticoagulation Therapy Peri-operatively.
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Central Virginia Center for Coagulation Disorders Management of Anticoagulation Therapy in the Peri-operative Period J. Christian Barrett, MD Assistant Professor, Division of Hematology-Oncology Virginia Commonwealth University
Management of Anticoagulation Therapy Peri-operatively • What are the issues? • Risk ofthrombosis vs. bleeding • Variable indications for the therapy • Variable procedural risks • Reversal of Therapy • Lack of conclusive evidence
Weighing the Risks THROMBOSIS HEMORRHAGE • Venous • 5-10% fatal • <5% disabling • Arterial • 20-40% fatal • 20-50% disabling • Major bleeding • 9-13% fatal • Rarely disabling
Case #1 • 70 year old male with a history of atrial fibrillation and CHF (EF 30%) on chronic warfarin therapy with a therapeutic INR of 2.4 • Going for a routine screening colonoscopy • Asks what he should do with his warfarin for the procedure.
Thrombotic Risk: Non-Valvular Heart Disease • Non-valvular Atrial Fibrillation • 4.5% per year risk of arterial thromboembolism (range 1-20% based on individual risk factors) • Warfarin reduces risk by 66% • Left Ventricular Dysfunction • 18% increase stroke risk for every 5% decrease in LV EF • Warfarin reduces risk by 81% • Aspirin reduces risk by 56% Archives Internal Medicine 1994;154:1449
Colonoscopy Risk? • American Society for Gastrointestinal Endoscopy Guidelines… • Low-risk procedures • EGD, Flex sig, and colonoscopy with/without biopsy • EUS and push enteroscopy • ERCP and biliary stent placement without sphincterotomy • High-risk procedures • Gastric (4%) or colonoscopic (1%-2.5%) polypectomy • Laser ablation and coagulation (<6%) • Endoscopic sphincterotomy (2.5%-5%) • EUS-guided biopsy • Percutaneous gastrostomy • Stricture dilation
ASGE Guideline • Recommendation for low risk procedure: No adjustments in anticoagulation need be made irrespective of the underlying condition. • Recommendation for high risk procedure: Warfarin should be discontinued 3-5 days before the scheduled procedure. • In patients, with high risk conditions, bridging with heparin or LMWH may be individualized. • If to resume after procedure, heparin may resume 2-6 hours after procedure and warfarin that night.* *extra caution if s/p sphincterotomy where major hemorrhage risk is 10%-15% if reinstituted within first 3 days (or if s/p large sessile polyp removal where caution in order up to 2 weeks.)
Polypectomy Risk • Retrospective review of 6617 colorectal polypectomies in 3138 consecutive patients • Delayed hemorrhage defined as bloody feces reported on >2 occasions • 37 patients (1.2%) or 38 polypectomies (0.57%) • At second endoscopy, 15 patients had stopped and 22 patients required endoscopic hemostasis. • Only 1 patient required blood transfusion • Anticoagulation use was prohibited for 7 days post-procedure per the protocol Watabe H et al. Gastointest Edosc 2006;64:73-78
Polypectomy Risk • Multivariate analysis • Polyp-related factors • Polyp size >1 cm (OR 4.5 with 95% CI 2.0-10.3) • Patient-related factors • Hypertension control (OR 5.6 with 95% CI 1.8-17.2) • Associated with a longer interval of recognition of bleeding
Polypectomy on Anticoagulation • Retrospective review of 1657 consecutive patients with colonoscopic polypectomy • Immediate hemorrhage defined as bleeding sufficient to require endoscopic interventions judged by the endoscopist • 32 patients (1.9%) • 31/32 were classified as MILD (drop<4 g/dL and no blood) • Delayed hemorrhage defined as rectal bleeding within 30 days of procedure of sufficient severity to require hospitalization for management • 5 patients (0.3%)—all transfused • Did not report warfarin use specifically among this subgroup Hui AJ et. Gastrointest Endosc 2004;59:44-48
Polypectomy on Anticoagulation • Among those with bleeding … • No difference seen related to anti-platelet agent use • Warfarin use was significantly associated with risk of hemorrhage (p<0.001) • 4 patients (10.8%) among the 37 with hemorrhage • Median INR 1.41 [range 1.09-2.86] • 13 patients (0.8%) among the 1620 without hemorrhage • Median INR 1.38 [range 1.08-1.84]
Polypectomy on Anticoagulation • Retrospective review of 21 patients undergoing 41 colonoscopic polypectomies • Held warfarin evening before procedure only • Median INR 2.0 [range 1.4-4.9] • Polypectomy with prophylactic clips if <1 cm • No concomitant anti-platelet agent use • No immediate hemorrhage (all <10 mL) • No delayed hemorrhage reported at follow-up (3-8 weeks) Friedland and Soetikno. Gastrointest Endosc 2006;64:98-100
Cataract Surgery on Anticoagulation • Reviewed medication use among 19,282 cataract surgeries on a RCT • 4588 patients used aspirin (23.8%) • 13.8% advised to stop use before the procedure • 22.5% actually did so • 752 patients used warfarin (3.9%) • 10.5% advised to stop use before the procedure • 28.3% actually did so Katz J et al. Ophthalmology 2003;110:1784-1788
Cataract Surgery on Anticoagulation • Among the aspirin users … • No difference seen in ocular hemorrhage events • 0.56% among those with no routine use • 0.59% among those who continued aspirin • Increased incidence of medical events seen … • Myocardial Infarction • 0.84% among those with no routine use • 4.16% among those who continued aspirin • TIA • 0% among those with no routine use • 1.19% among those who continued aspirin
Cataract Surgery on Anticoagulation • Among the warfarin users … • No difference seen in ocular hemorrhage events • 0.55% among those with no routine use • 0% among those who continued warfarin • Increased incidence of medical events seen … • Myocardial Infarction • 1.43% among those with no routine use • 5.7% among those who continued aspirin
Recommendation • Minor procedure: Should be able to proceed without any adjustments in anticoagulation perioperatively • If endoscopist unwilling, hold warfarin for 3-4 days before procedure and resume warfarin same day without use of heparin • If polyp found, second procedure could be scheduled off warfarin • Though some data suggests may be safe to proceed at initial procedure if <1cm, small numbers and unconfirmed.
Case #2 • 44 year old female with a St Jude (bileaflet) mitral valve on warfarin with an INR of 2.9 (goal 2.5-3.5) • Is scheduled to have a laparoscopic cholecystectomy • Asks what she should do with her anticoagulation therapy for the surgery.
Thrombotic Risk: Valvular Heart Disease • 4% per year risk of major* arterial thromboembolism with a mechanical valve • plus 1.8% per year risk of valve thrombosis • 2.2% per year with antiplatelet therapy • plus 1.6% per year risk of valve thrombosis • 1% per year with warfarin • 0.8% per year with an aortic valve • 1.3% per year with a mitral valve • plus 0.2% per year risk of valve thrombosis *major=death, neurologic deficit or requiring surgery Cannegieter SC et al. Circulation 1994;89(2):635-41
ESC Guidelines • Recommendation for low risk procedure: No adjustments in anticoagulation need be made. • Recommendation for high risk procedure: Warfarin should be discontinued 3-4 days before the scheduled procedure. • In patients, with high risk factors for thrombosis, bridging with heparin* is recommended stopping 4 hours before the procedure. • After procedure, heparin* may resume within 6-12 hours after procedure and warfarin as soon as possible. *LMWH is not included in the ESC guidelines
High Risk Factors • Mechanical valve in the mitral position • High risk prostheses • Starr Edward, Lillehei Kaster, Omniscience • Atrial fibrillation • LVEF < 30% • Prior thromboembolism • Hypercoagulable state • Surgery for malignancy or infection
Bridging with Heparin • Refers to the use of therapeutic doses of UFH or LMWH to cover the interval when warfarin dosing is subtherapeutic • LMWH has been demonstrated to be cost-effective in cost models compared with UFH • Data is limited
UFH Start 36-60 hours after last warfarin dose Stop 6 hours before surgery LMWH Once or twice daily dosing starting 36 hours after last warfarin dose Stop before surgery… >18 hours with twice daily dosing >30 hours with once daily dosing Bridging Heparin:Preoperative Planning
UFH No load and not greater than 18 u/kg/hr starting ~12 hours post-op 1st PTT 12hours after start infusion LMWH Start ~24 hours after surgery If thrombosis risk is high can consider starting prophylactic dosing within 12 hours and “step up” the next day Heparin BridgingPostoperative Planning • Additional factors to consider … • Post-operative risk of thrombosis (venous not arterial risk increased) • Post-operative bleeding risk* *If the operative bleeding risk is moderate or high, consider prophylactic dosing instead of full bridging doses.
Recommendation • High risk of arterial thrombosis with a minor surgical bleeding risk • Stop the warfarin 5 days before the surgery • Start therapeutic dose LMWH with the AM dose 3 days before surgery • Stop LMWH after the AM dose day before surgery • Resume therapeutic dose LMWH the next day along with the warfarin at prior steady state dose • Stop LMWH once INR >2 on 2 consecutive days
Case #3 • 59 year-old female with a history of … • DVT following her 2nd pregnancy at age 35 treated • DVT with PTE at age 55 years at which time noted to be heterozygous for FVL • On chronic anticoagulation since the 2nd event with an INR 2.6 • Scheduled for a right-sided hemicolectomy (non-malignant indication)
Thrombotic Risk: Venous Thomboembolism • Risk reduces with longer duration of warfarin • 50% risk of recurrence within three months without anticoagulation • 40% risk during the first month • 10% risk during the next two months • 5% after three months of anticoagulation • 10-15% per year risk of recurrence among those with history of recurrent venous thrombosis without continued anticoagulation
Venous Thrombosis • Pre-operatively • Time from prior venous event • Time of surgery • Mobility of the patient • Post-operatively • Time from prior venous event • Operative risk of thrombosis • Operative risk of hemorrhage
Venous Thrombosis • Pre-operative recommendation • Stop warfarin 4-5 days before the surgery with no bridging or prophylactic dosing of heparin • Post-operatively recommendation • Prophylactic dose LMWH and steady state dose of warfarin starting 12-24 hours after surgery if hemostasis achieved and continued until warfarin is therapeutic
Case #4 • 38 year-old male discharged 8 days ago following a DVT returns off LMWH on warfarin with an INR of 3.2 with a gun shot wound requiring emergent exploratory surgery of the abdomen. Surgeons are lining up the OR and asking for recommendations.
Warfarin Reversal • Warfarin Discontinuation • Vitamin K • Fresh Frozen Plasma • Recombinant VIIa
Warfarin Discontinuation • Wide variability—especially among elderly • Generalizations to achieve INR <1.2 at surgery if steady state … • INR 2-3 hold 4 doses preoperatively • INR 3-4 hold 5 doses preoperatively White RH et al. Annals of Internal Medicine 1995;122:40-42
Vitamin K • Subcutaneous administration inferior to oral or IV which appear equivalent • IV associated with a risk of hypotension and/or anaphylaxis • Effects seen starting 12-24 hours after administration
Fresh Frozen Plasma • Can be infused rapidly if patient can tolerate volume • Cheaper and more widely/rapidly available at many centers than rVIIa • Calculate dose to achieve prothrombin complex level of 40% normal plasma • If subtherapeutic INR, 10mL/kg (3 units in 70 kg pt) • If therapeutic INR, 25mL/kg (7 units in 70 kg pt) • If supratherapeutic INR, 35mL/kg (10 units in 70 kg pt)
Recombinant Factor VIIa • Warfarin reversal—not approved indication • Candidates for consideration • Life-threatening bleed with INR > 2.0 (+ INR >1.5 though Vit K / FFP preferable) • Emergent surgery unable to be delayed 24+ hours • Other factors to consider • Fibrinogen > 120 mg/dL • MI/angina/stroke ongoing or within prior 4 weeks • Active DVT or other thrombotic disorder • Optimal dose is uncertain
Recommendations • Because of the emergent nature of surgery • Hold warfarin • Give dose of vitamin K (5-10mg orally or slow IV) • Fresh frozen plasma 25-35 mL/kg or Recombinant factor VIIa 10-20 mcg/kg (rounded to nearest full vial dose) • IVC filter placed intraoperatively