Fatal P.E. Historic 1-2% Current %

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1 Dr. (Prof.) Anil Arora MS (Ortho) DNB (Ortho) Dip SIROT (USA) FAPOA (Korea), FIGOF (Germany), FJOA (Japan) Commonwealth Fellow Joint Replacement (Royal National Orthopaedic Hospital, London, UK) Senior Knee and Hip Replacement Surgeon Associate Director Department of Orthopaedics and Joint Replacement Max Superspeciality Hospital, Patparganj, Delhi (India) anilarora@delhiorthojournal.com

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3 Fatal P.E. Historic 1-2% Current %

4 In many cases the complication is preventable Only surgeons are responsible for choosing and administering prophylaxis

5 Pubmed; MesH heading DVT and THA 29,714 articles

6 Warwick, JBJS, Br, THA No chemical prophylaxis Fatal PE 0.34% Murray et al, JBJS Br, 1996 Meta-analysis 130,000 THA Reported fatal PE %

7 Effective prophylaxis is necessary in these patients [THA, TKA]... NIH consensus panel, 1986 European consensus conference 1992

8 No of n Prevalence trials % (95%Cl) RRR % Placebo/control (50-58) - Elastic stockings (36-48) 23 Aspirin (35-45) 26 Low-dose UFH (27-33) 45 Warfarin (20-24) 59 IPC (17-24) 63 LMWH (15-17) 70 R-hirudin (14-19) 70 Geerts WH et al. Chest 2001;119:132S 175S

9 When to start What agent How long

10 In Europe, the first dose of LMWH is commonly administered the evening (10-12 hours) before surgery

11 In North America the initial dose of warfarin, or less common, LMWH is not administered until hours after surgery

12 Odds ratio 1.4 Quadratic fit for study odds ratio for DVT vs. the number of hours from surgery for the first dose of LMWH Hours from surgery Upper and lower dashed lines indicate the 95% confidence interval for the estimated odds ratio Hull R et al. Arch Intern Med 2001;160:

13 When to start What agent How long

14 Unfractionated heparin LMWH Aspirin Mechanical prophylaxis

15 Advantages: Predictable dose response Proven efficacy Disadvantages: Bleeding complications Injection required

16 LMWH BID 194 THA DVT rate 5% 8 major bleeding episodes Colwell et al, JBJS Am, 1994

17 Randomized, double blind 1472 THA Dalteparin before or early after vs warfarin Venogram detected DVT Symptomatic thrombi less frequent in preop dalteparin group (p<0.02) Increased bleeding at surgical site for preop dalteparin group Modified regimen (postoperative) Hull R et al: Arch Intern Med. 2000

18 Prospective, randomized Venography endpoint LMWH started 2 hrs postop Proximal DVT 5% (LMWH) vs 8% (Warfarin), p = 0.19 More bleeding in LMWH group (p=0.001) Francis, et al: JBJS (A), 1995

19 434 surgeons representing 48 states and three countries (Canada, Egypt, Pakistan) Surgeons have been in practice an average of 19 years >96% prophylax for DVT in their THA and TKA patients

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21 Certoparin (18 mg), dalteparin 30 mg, enoxaparin (24 mg) 188 patients undergoing TJA, or spine sx Changes in venous flow pre and postop doppler DVT= 1.1% Bleeding = 11.2% (13 in certoparin, 4 in each) No difference in APTT, TCT, blood count All as efficacious Janni W, et al.zentralbl Chir. 2001

22 Bottom Line: Effective Probably increased bleed risk esp. if given too early

23 Control vs LDUH Control vs IPC LDUH vs LMWH 50% reduction in DVT (20 sudies) 52% reduction in DVT (4 studies) 54% further red. in DVT (10 studies) LMWH vs Fondaparinux 24% further red. In DVT (2 studies) 50% further red. In PE (2 studies) LMWH vs LMWH+IPC 28% vs 0% DVT (1 study)

24 Fondaparinux better Enoxaparin better 95% CI Hip replacement n=3,411 (2 studies) -45.3% [-58.9; -27.4] Hip fracture n=1, % [-73.4; -45.0] Knee replacement n= % [-75.5; -44.8] Overall odds reduction -55.2% p=10-17 [-63.1; -45.8] Homogeneity test: ns Odds reduction (%) Turpie et al. Arch Intern Med 2002;162:

25 New Oral Anticoagulants

26 Figure 1: Site Site of of Actions for for Conventional and and Newer Oral Oral Anticoagulants Factor IX Factor VII FIXa Factor X FVIIa VKA drugs Anti-Xa drugs Apixaban Betrixaban Edoxaban Rivaroxaban Factor Xa Antithrombin Warfarin Factor II (Prothrombin) Factor IIa (Thrombin) Anti-IIa drugs Dabigatran Fibrinogen Fibrin

27 Fondaparinux LMWH IPC + GEC IPC+GEC+LMWH Rivaroxaban, Dabigatran LE: high (Most effective) LE: high LE: high (Equivalent to LMWH) LE: high (More effective than either) LE: high Initiation LMWH: before or after operation LE: high Fondaparinux: at least 6 hours after operation

28 Coumadin and LMWH equally effective at preventing DVT after THA A slightly higher bleeding rate with LMWH Coumadin is harder to use (outpatient monitoring)

29 When to start What agent How long

30 Thromboprophylaxis for at least 10 days [Grade 1A] with: LMWH (high-risk dose) Fondaparinux (2.5 mg daily) Vitamin K antagonist (VKA, target INR 2.5 [INR range 2 3]) For TKR, intermittent pneumatic compression is an alternative [Grade 2B] Geerts WH et al. Chest 2004;126:338S 400S

31 7 th ACCP recommendations Total hip, knee replacement or hip fracture surgery Prophylaxis should be extended until days after surgery THR: LMWH, VKA or fondaparinux [all Grade 1A)] HFS: Fondaparinux (Grade 1A), LMWH or VKA [both Grade 1C+] TKR: Benefits remain unclear Geerts WH et al. Chest 2004; 126:338S 400S

32 LMWH Conflicting data Warfarin Amstutz: 15 days Colwell: 7 days

33 Patients with no specific risk factors (1-3 weeks) Patients with specific risk factor (6 weeks) (like previous DVT)

34 Total hip replacement patients (Hull et al) 4-5 weeks vs 1-2 weeks LMWH 64% RRR for symptomatic VTE Hull RD, et al. Ann Intern Med. 2001; 135:

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