Perioperative Management of Oral Anticoagulation

1. Perioperative Management of Oral Anticoagulation Ri 陳信宏

2. References • Perioperative Management of Oral Anticoagulation Clinics Geriatric Medicine 22 (2006) 199– 213 • Perioperative bridging therapy for the at-risk patient on chronic anticoagulation Disease-A-Month 01-FEB-2005; 51(2-3): 183-93

3. Introduction(1) • OAC therapy during surgery is associated with increased excessive operative bleeding. • Patients receiving long-term oral anticoagulant (OAC) therapy that requires temporary discontinuation for an elective surgical or invasive procedure. • Anticoagulation cessation, －increased risk of thromboembolism, especially in the postoperative period.

4. Introduction(2) • A management strategy for the at-risk patient on chronic OAC requiring temporary discontinuation for an elective surgical or invasive procedure. • Emphasis on the indications for use of perioperativebridging therapy. • The use of parenteral, short-acting anticoagulants such as unfractionated heparin (UFH) or low-molecular-weight-heparin (LMWH) in the perioperative period.

5. Thromboembolic and Bleeding Risks in the Perioperative Period • Thromboembolic risks: (1)Disease specific thromboembolic risks when discontinuing warfarin (2)Hypercoagulability associated with surgery. • Bleeding risks: (1) the patient (2) the use of anticoagulant therapy (3) the surgery or procedure

6. Thromboembolic Risk When Discontinuing Warfarin Venous thromboembolism (VTE): • 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.

7. Venous thromboembolism • Surgery is performed within 1 month of an acute event, bridging therapy should be used while the INR is less than 2. • Within 1 and 3 months previously, patients are immobilized－bridging therapy • Treated with 3 or more months of anticoagulation－not use bridging therapy.

8. Arterial thromboembolism 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%.

9. Arterial thromboembolism Mechanical prosthetic cardiac valves (MHV) • In the absence of OAC, mitral position valve prostheses have an annualized thrombosis risk of 22% compared with an annualized risk of approximately 10 to 12% for aortic position valves. • The average rate of major thromboembolism in non-anticoagulated patients with mechanical heart valves is estimated to be 8%.

10. Previous thromboembolism • The single most important risk factor for ischemic stroke in patients with atrial fibrillation • Also an important risk factor in patients with prosthetic heart valve.

11. Hypercoagulability associated with surgery • Prothrombotic effect of major surgery and laparoscopic procedures－theoretically increase the postoperative VTE risk 100-fold. • A recent systematic review revealed a 10-fold greater risk of stroke than expected in patients not receiving perioperative anticoagulation.

14. Bleeding Risks Patient: • Previous history of bleeding, especially with invasive procedures or trauma • Use of concomitant antiplatelet and nonsteroidal antiinflammatory medications. Procedure: • High :include major operations and procedures (lasting >45 minutes) • Low : include non-major operations and procedures (lasting <45 minutes) Perioperative anticoagulants: • 2-day period : 2 to 4% for major surgery 0 to 2% for non-major surgery.

16. Thromboembolic risk when discontinuing OAC

17. Procedural Bleeding Risks

19. Clinical consequences • MHV thrombosis is fatal in 15% of patients • ATE: mortality －about 40% of events major disability －about 20% of events • VTE : mortality －approximately 6% major disability －approximately 5% or less in treated patients. • Postoperative major bleeding has a fatality rate of approximately 3%.

20. Perioperative Management Recommendations The Seventh American College of Chest Physician Consensus Conference: • Intermediate risk of thromboembolism－prophylactic (or higher) dose UFH or LMWH as perioperative bridging therapy • High risk of thromboembolism－ full-dose UFH or LMWH • Low risk of bleeding－ Continue warfarin therapy at a lower dose to maintain an INR of 1.3 to 1.5.

22. Perioperative bridging algorithm • Low risk of ATE or VTE: No heparin bridging preoperatively and only prophylactic doses of LMWH or UFH postoperatively in conjunction with resumption of warfarin.

23. Warfarin • INR starts to fall at approximately 29 hours after the last dose of warfarin • A half-life of approximately 22 hours • It is reasonable to start bridging therapy approximately 60 hours after the last dose of warfarin.

24. Unfractionated heparin (UFH) Advantage: • A short half-life(60 minutes) • easily reversed (by protamine sulfate) Disadvantage: • Intravenous administration necessitates hospitalization before surgery, • Inconvenient and expensive.

25. Low-molecular-weight-heparin (LMWH) • Allowed bridging therapy to be administered to outpatients. • Doses of LMWH that are recommended for treatment of venous thromboembolism are administered once or twice daily, generally for 3 days before surgery. • Required to determine whether the benefit of bridging therapy outweighs the associated risks of bleeding.

26. Perioperative bridging protocol Instructions regarding warfarin use: • 1. Stop warfarin at least 4 days prior to surgery • 2. Check INR 1 day prior to surgery If 1.5, proceed with surgery If 1.5 to 1.8, consider low-level reversal with Vitamin K If 1.8, recommend reversal with Vitamin K (either 1 mg SC or 2.5 mg PO) • 3. Recheck INR day of surgery • 4. Restart maintenance dose of warfarin the evening of surgery • 5. Daily INR until in therapeutic range (1.9)

27. Perioperative bridging protocol Instructions regarding IV UFH use • 1. Should start at least 2 days prior to surgery at therapeutic dose using a validated, aPTT-adjusted, weight-based nomogram (ie, 80 U/kg bolus dose IV followed by a maintenance dose of 18 U/kg/h IV) • 2. Discontinue 6 hours prior to surgery • 3. Restart no less than 12 hours postoperatively at the previous maintenance dose once hemostasis is achieved • 4. Discontinue IV UFH when INR is in therapeutic range (1.9)

28. Perioperative bridging protocol Instructions regarding LMWH use: • 1. Should start at least 2 days prior to surgery at BID therapeutic dose (ie, enoxaparin 1 mg/kg SC BID or dalteparin 100 IU/kg SQ BID) • 2. Discontinue at least 12 hours prior to surgery (if surgery is in early A.M. consider holding previous evening dose) • 3. Restart usual therapeutic dose within 12–24 hours after surgery once hemostasis is achieved • 4. Discontinue LMWH when INR in therapeutic range (1.9)

29. Summary • OAC should be discontinued at least 4 days prior to the surgical intervention or procedure • Heparin (either UFH or LMWH) initiated at least 2 days prior to the intervention. • Many experts-advocate preoperative therapeutic-dose UFH or LMWH for intermediate- to high-risk patients • Considerable disagreement －prophylactic dose, treatment dose, or no heparin bridging therapy should be initiated postoperatively in conjunction with resumption of OAC

30. Summary • OAC should be resumed at the usual maintenance dose within 24 hours of the procedure, preferably the same evening. • Heparin should be reinitiated within 24 hours of the procedure, provided that adequate hemostasis is achieved, and discontinued once the INR is in therapeutic range (1.9).

31. Thanks for your attentions !