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A K Kakkar

Prevention of Venous Thromboembolism in t he Medical and Surgical Oncology Patient. A K Kakkar Barts and the London School of Medicine and Thrombosis Research Institute, London UK.

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A K Kakkar

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  1. Prevention of Venous Thromboembolism in the Medical and Surgical Oncology Patient A K Kakkar Barts and the London School of Medicine and Thrombosis Research Institute, London UK

  2. Opportunities for intervention with antithrombotic therapy

  3. ACCP Consensus conference on antithrombotic therapy Major surgery in cancer patients ACCP=American College of Chest Physicians; PE=pulmonary embolism Geerts WH, et al. Chest. 2004;126 Suppl 3:338S-400S.

  4. Thromboprophylaxis in the cancer surgical patient LMWH better UFH better Asymptomatic DVT Clinical PE Clinical thromboembolism Cancer Death Non-cancer Major hemorrhage Total hemorrhage Wound hematoma Transfusion 0 1.0 2.0 3.0 4.0 DVT=deep vein thrombosis; LMWH=low molecular weight heparin; PE=pulmonary embolism; UFH=unfractionated heparin Mismetti P et al. Br J Surg. 2001;88:913–930.

  5. Guidelines ACCP=American College of Chest Physicians; ASCO=American Society of Clinical Oncology; LMWH=low molecular weight heparin; UFH=unfractionated heparin

  6. PE occurs after hospital discharge Days PE=pulmonary embolism Huber O et al. Arch Surg. 1992;127:310-3.

  7. Extended thromboprophylaxis: meta analysis • 4 studies: 2 double-blind and 2 open • 1,037 patients • Bilateral venography 7–10 days 4–5 weeks p DVT 15% 6.5% < 0.0005 Proximal DVT 5% 1% < 0.01 Symptomatic DVT 1% 0.3% 0.27 DVT=deep vein thrombosis Rasmussen MS et al. J Thromb Haemost. 2005; 3 Suppl 1:P2213.

  8. Guidelines ACCP=American College of Chest Physicians; ASCO=American Society of Clinical Oncology

  9. Effects of compression methods of thromboprophylaxis on DVT Compression (monotherapy)Graduated 9 57/665 133/627 –39.7 37.2 66% (10) compression stockings (8.6%) (21.2%)Intermittent 19 112/1108 268/1147 –76.3 71.0 66% (7) pneumatic compression (10.1%) (23.4%)Footpump 2 11/61 34/65 –10.7 7.3 77% (19) (18.0%) (52.3%) 30 180/1834 435/1839 –126.7 115.5 67% (6) (9.8%) (23.7%) 2p < 0.00001 No. of Deep venous Stratified Odds ratio and % odds trials thrombosis statistics confidence interval reduction Category with data Compression Control O–E Variance (compression : control) (SE) 99% or 95% confidence intervals 0.0 0.5 1.0 1.5 2.0 Compression Compression better worse Treatment effect 2p < 0.00001 Roderick P et al. Health Technology Assessment 2005; Vol. 9: No. 49.

  10. Effects of compression methods of thromboprophylaxis on PE (a) Compression (monotherapy)Graduated 3 0/123 4/90 –1.8 0.9 compression stockings (0.0%) (4.4%)Intermittent 8 14/590 18/618 –1.6 7.6 pneumatic compression (2.4%) (2.9%)Footpump 1 0/28 0/32 (0.0%) (0.0%) 12 14/741 22/740 –3.4 8.5 33% (28) (1.9%) (3.0%) 2p > 0.1; NS No. of Deep venous Stratified Odds ratio and % odds trials thrombosis statistics confidence interval reduction Category with data Compression Control O–E Variance (compression : control) (SE) 99% or 95% confidence intervals 0.0 0.5 1.0 1.5 2.0 Compression Compression better worse Treatment effect 2p = 0.006 Roderick P, et al. Health Technology Assessment 2005; Vol. 9: No. 49.

  11. Combined mechanical and pharmacological prophylaxis Intervention LDH (n=451) LDH+GCS (n=439) RR (95%CI) 6 studies DVT n (%) 83 (18) 35 (%) 0.47 0.33-0.69 DVT=deep vein thrombosis; GCS=graduated compression stockings; LDH=low dose heparin; RR=risk reduction IUA Consensus statement Int Angiol 2006 .

  12. Guidelines

  13. Guidelines

  14. VTE in hospitalised cancer patients

  15. Relative risk for VTE by cancer type 1Levitan et al. 1999; 2Thodiyil and Kakkar. 2001

  16. Clear benefits of thromboprophylaxis over placebo Study RRR Thromboprophylaxis Patients with VTE (%) MEDENOX1 63% Placebo Enoxaparin PREVENT2 49% Placebo Dalteparin ARTEMIS3 47% Placebo Fondaparinux 14.9* p< 0.001 5.5 5.0* p = 0.0015 2.8 10.5† 5.6 p = 0.029 *VTE at day 14; †VTE at day 15. 1Samama MM, et al. N Engl J Med. 1999;341:793-800.2Leizorovicz A, et al. Circulation. 2004;110:874-9. 3Cohen AT, et al. J Thromb Haemost. 2003;1 (Suppl 1):P2046. RRR = relative risk reduction

  17. Major bleeding Study or subcategory Cohen 2006 Leizorovicz 2004 Fraisse 2000 Samama 1999 Total (95% CI) Total events: 28 (Anticoagulant), 14 (Placebo) Test for heterogeneity: Chi2 = 0.72, df = 3 (P=0.87), I2 = 0% Test for overall effect: Z = 2.12 (P=0.03) Anticoagulant n/N 1 / 429 9 / 1856 6 / 109 12 / 367 2761 Placebo n/N 1 / 420 3 / 1850 3 / 114 7 / 371 2755 RR (random) 95% CI Weight % 5.35 24.10 22.16 48.39 100.00 RR (random) 95% CI 0.98 [0.06, 15.60] 2.99 [0.81, 11.03] 2.09 [0.54, 8.16] 1.73 [0.69, 4.35] 2.00 [1.05, 3.79] 0.1 0.2 0.5 1 2 5 10 Favors Anticoagulant Favors Placebo Lloyd NS et al. J Thromb Haemost. 2008;6:405–414.

  18. Guidelines

  19. Guidelines

  20. Risk of VTE: chemotherapy population 7.1% 6.7% Development cohort Validation cohort 2.0% 1.8% 0.8% 0.3% n=374 n=842 n=149 n=734 n=1627 n=340 8% 7% 6% 5% Rate of VTE (%) 4% 3% 2% 1% 0% RiskLow (0) Intermediate(1-2) High(>3) Khorana AA et al. Blood .2008.

  21. Guidelines

  22. Randomised Controlled Clinical Trials of Prophylaxis of CVC - Related Thrombosis * Symptomatic events ° Routine venography at 6 weeks

  23. Guidelines

  24. Parenteral anticoagulation and survival Favours heparin Favours control Akl EA et al. Cochrane Database of Systemic Reviews 2007;3:1-28.

  25. Guidelines

  26. Conclusions • Consistent guidelines between Thrombosis and Oncology communities • Evidence base still limited for some guidance • Many areas still lack guidelines

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