1. Oral anticoagulants and regional anesthesia for joint replacement surgery Reported by R1 康庭瑞 2002/11/5

2. Case present Identifying data Identifying data  Name: 王 X 傭  Age: 73 years old  Gender: male  Chart number: 2000625  Bed number: 11B11-1  Operative day: 2002.10.28

3. Brief history Chief complaint: Chief complaint: Right knee walking pain for more than 1 month Right knee walking pain for more than 1 month Present illness: Present illness: 1) Falling down and right knee was injured years ago. 2) Intermittent right knee pain and soreness, poor weight bearing 3) Severe varus deformity and osteoarthritis with joint space narrowing

4. Brief history Past history: Past history: 1) Heart disease with 3VD s/p CABG 2 years ago at 振興 hospital 2) Denied of DM, liver, renal, lung diseases 3) Drug and food allergy: denied 4) Previous operation history: (1) CABG 2 years ago. (2) Gall bladder stone s/p. (3) Cataract s/p 5) Smoking (+) – 1~2 PPD, alcohol comsumption – denied

5. Brief history Current drugs: Current drugs: 1) Bokey (Aspirin): 100 ㎎ 2) Lipitor (Atorvastatin) 3) Mirobect (Atenolol) 4) Imdur (Isosorbride 5-mononitrate) 5) Lasix, spironolactone 6) Narcaricin (Benzbromarone)

6. Brief history Physical examination Physical examination 1) Consciousness: clear 2) Vital sign: T/P/R — 36.5/60/15 BP — 100/60 ㎜ Hg 3) BW:55.2 ㎏, BH: 152 ㎝ 4) HEENT: conjunctiva — pink, JVE — nil 5) Chest: symmetric expansion, breathing sound — clear 6) Heart: NSR, no murmur 7) Extremities: no pitting edema

7. Brief history Laboratory data: (2002.10.27) Laboratory data: (2002.10.27) Blood type: O, Rh(+) Blood type: O, Rh(+) WBC: 6310 WBC: 6310 RBC: 344 RBC: 344 Hb: 11.1 Hb: 11.1 PLT:205 PLT:205 Bilirubin T: 0.31 Bilirubin T: 0.31 GOT: 16 GOT: 16 BUN: 42.5 BUN: 42.5 Creatinine: 2.34 Creatinine: 2.34 Na: 139 Na: 139 K: 4.89 K: 4.89 Cl: 102 Cl: 102 Sugar AC: 136 Sugar AC: 136

10. Discussion Regional anesthesia and anticoagulation – Journal of clinical anesthesia, February 2001 Regional anesthesia and anticoagulation – Journal of clinical anesthesia, February 2001 Update on spinal anesthesia – Anesthesiology, May 2001 Update on spinal anesthesia – Anesthesiology, May 2001 Spinal-epidural hematoma following epidural anesthesia in the presence of antiplatelet and heparin therapy – Anesthesiology, October 2001 Spinal-epidural hematoma following epidural anesthesia in the presence of antiplatelet and heparin therapy – Anesthesiology, October 2001

11. Discussion Oral anticoagulants and regional anesthesia for joint – regional anesthesia and pain medicine, January-February 2002 Oral anticoagulants and regional anesthesia for joint – regional anesthesia and pain medicine, January-February 2002 Epidural anesthesia prevents hyper- coagulation in patients undergoing major orthopedic surgery – regional anesthesia and pain medicine, May-June 2002 Epidural anesthesia prevents hyper- coagulation in patients undergoing major orthopedic surgery – regional anesthesia and pain medicine, May-June 2002

12. The use of regional anesthesia and analgesia in the presence of anticoagulation has always been a controversial issue The use of regional anesthesia and analgesia in the presence of anticoagulation has always been a controversial issue Incidence of spinal hematoma with spinal anesthesia without anticoagulation is estimated at 1:220,000  small surveys, anecdotal reports, and expert opinion Incidence of spinal hematoma with spinal anesthesia without anticoagulation is estimated at 1:220,000  small surveys, anecdotal reports, and expert opinion Anticoagulants used in the surgical population as prophylaxis and treatment for thrombotic condition Anticoagulants used in the surgical population as prophylaxis and treatment for thrombotic condition

13. Review of commonly used anticoagulants Antiplatelet drugs – inhibit platelet function Antiplatelet drugs – inhibit platelet function 1) Aspirin(ASA): irreversible inactivates COX, even low-dose aspirin (40~81 ㎎ ) may suppress TXA2 synthesis & PLT aggregation, inhibiting 1 hr after ingestion, entire lifespan ≒ 10 days 2) Newer generations: inhibiting ADP- induced PLT aggregation (entire lifespan) or PLT GPIIb/IIIa receptor (48 hrs) 3) NSAIDs: reversibly and competitively inhibit COX, duration is dose-dependent and half-life of the NSAID

15. Review of commonly used anticoagulants Oral anticoagulants (Warfarin) Oral anticoagulants (Warfarin)  Interfering with the Vit. K-dependent coagulation protein, factors II (thrombin), VII, IX, and X  Inhibiting Vit. K reductases, depletes Vit. KH 2, and limits carboxylation  PT and INR may not accurately measure true antithrombotic activity  A decrease in factors II and X (longer half- life) is more important for the antithrombotic efficacy of warfarin

16. Review of commonly used anticoagulants Heparin Heparin  Binding with antithrombin III, which accelerates inactivation of factors II, IX, X, XI and XI  Mixture of polysaccharide chains, MW ranging from 5,000 to 30,000; the length of the heparin chain determines which factor will be inhibited  Extensive binding to plasma proteins complicated the pharmacokineyics of heparin

17. Review of commonly used anticoagulants  LMWH has relatively greater anti-Xa activity, more predictable bioavailability and longer half-life  PTT doesn ’ t accurately reflect the degree of anticoagulation, factor X levels don ’ t correlated with potential for bleeding

18. Regional anesthesia and anticoagulants Concurrent use of other anticoagulants increasing the risk of bleeding complication without influencing standard laboratory test Concurrent use of other anticoagulants increasing the risk of bleeding complication without influencing standard laboratory test Minimize the degree of sensory and motor deficit of the analgesic regimen Minimize the degree of sensory and motor deficit of the analgesic regimen Epidural catheters should be removed at the nadir of anticoagulant therapy Epidural catheters should be removed at the nadir of anticoagulant therapy Routine continued neurologic monitoring for at least 24 hours Routine continued neurologic monitoring for at least 24 hours

19. Regional anesthesia and antiplatelet medications 1,000 patients undergoing orthopedic procedures while taking anti-PLT drugs and 1,800 obstetric patients with low-dose aspirin(60 ㎎ ) received neuraxial anesthetic and no hematoma were noted 1,000 patients undergoing orthopedic procedures while taking anti-PLT drugs and 1,800 obstetric patients with low-dose aspirin(60 ㎎ ) received neuraxial anesthetic and no hematoma were noted Review of all reported cases of neuraxial hematoma from 1906 to 1994, only 4 of 61 cases were associated with the use of anti-PLT drugs, and 3 use of another anticoagulant Review of all reported cases of neuraxial hematoma from 1906 to 1994, only 4 of 61 cases were associated with the use of anti-PLT drugs, and 3 use of another anticoagulant

21. A case report 63-yr-old woman(165 ㎝ ;75 ㎏ ), ASA class III, for reimplantation of a prosthesis of the right knee 63-yr-old woman(165 ㎝ ;75 ㎏ ), ASA class III, for reimplantation of a prosthesis of the right knee One subcutaneous injection of LMWH (nadroparin,3800IU/day) as a prophylactic antithrombotic treatment (12hrs before surgery) One subcutaneous injection of LMWH (nadroparin,3800IU/day) as a prophylactic antithrombotic treatment (12hrs before surgery) Pre-OP, PTT:33s(30~40s), PT:84% (70~120%), INR:1.01 (therapeutic level 2~4.5), PLT count:151*109/L (150~400) Pre-OP, PTT:33s(30~40s), PT:84% (70~120%), INR:1.01 (therapeutic level 2~4.5), PLT count:151*109/L (150~400)

22. Epidural puncture and insertion of the catheter were uneventful Epidural puncture and insertion of the catheter were uneventful Combined regional and general anesthesia was induced Combined regional and general anesthesia was induced At the end of surgery, continuous epidural infusion of 0.25% marcaine (8ml/h) was initiated. LMWH was reestablished 6h after the end of surgery At the end of surgery, continuous epidural infusion of 0.25% marcaine (8ml/h) was initiated. LMWH was reestablished 6h after the end of surgery 18hrs later, epidural infusion rate ↑ to 12ml/h and 2 boluses of 12ml marcaine given for surgical and back pain 18hrs later, epidural infusion rate ↑ to 12ml/h and 2 boluses of 12ml marcaine given for surgical and back pain 400 ㎎ ibuprofen rectally for back pain 400 ㎎ ibuprofen rectally for back pain Painful during injection → remove catheter ≒ 7h after 2 nd post-OP LMWH given Painful during injection → remove catheter ≒ 7h after 2 nd post-OP LMWH given

23. At that time, the coagulation parameters were within normal range, PLT count was 118*109/L At that time, the coagulation parameters were within normal range, PLT count was 118*109/L After removal, she received PCA After removal, she received PCA 10hrs after removal, back pain ↑ and voiding difficulty, ↓ muscle strength and sensation in both lower limbs 10hrs after removal, back pain ↑ and voiding difficulty, ↓ muscle strength and sensation in both lower limbs MRI revealed a spinal-epidural hematoma from T10 to L4 MRI revealed a spinal-epidural hematoma from T10 to L4 Emergency decompressive surgery → partially organized and fresh Emergency decompressive surgery → partially organized and fresh No neoplastic changes or vascular malformations No neoplastic changes or vascular malformations Specific drugs taken per-OP:500 ㎎ QID ibuprofen on her own for arthritic pain and the last dose ≒ 10h before surgery Specific drugs taken per-OP:500 ㎎ QID ibuprofen on her own for arthritic pain and the last dose ≒ 10h before surgery

24. High dose ibuprofen and a single dose High dose ibuprofen and a single dose Lower limit of normal range PLT count, and decreased after surgery Lower limit of normal range PLT count, and decreased after surgery 2 subcutaneous injection of LMWH before catheter removal 2 subcutaneous injection of LMWH before catheter removal Back pain as an early symptom can be absent with continuous epidural analgesia. Insufficient analgesia was probably the first clinical sign Back pain as an early symptom can be absent with continuous epidural analgesia. Insufficient analgesia was probably the first clinical sign German society of anesthesiology and intensive care medicine: free interval of 1~2 days after NSAID, and at least 3 days without ASA-containing medication for central neuraxial manipulation German society of anesthesiology and intensive care medicine: free interval of 1~2 days after NSAID, and at least 3 days without ASA-containing medication for central neuraxial manipulation

25. Epidural anesthesia prevents hyper-coagulation in patients undergoing major orthopedic surgery

26. methods Clot signature analysis(CSA) to assess PLT and clotting function Clot signature analysis(CSA) to assess PLT and clotting function Pre- and post-OP venous blood were collected from 41 P ’ t of major orthopedic surgery Pre- and post-OP venous blood were collected from 41 P ’ t of major orthopedic surgery