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Thromboprophylaxis For The Lung Cancer Patient

Thromboprophylaxis For The Lung Cancer Patient. Prof. Dr. Nil Molinas Mandel Istanbul University Cerrahpaşa Medical Faculty Medical Oncology. Cancer and Thromboembolism. In cancer patients migrant thromboembolic events are common.

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Thromboprophylaxis For The Lung Cancer Patient

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  1. Thromboprophylaxis For The Lung Cancer Patient Prof. Dr. Nil Molinas Mandel Istanbul University Cerrahpaşa Medical Faculty Medical Oncology

  2. Cancer and Thromboembolism In cancer patients migrant thromboembolic events are common. It was first recognized by Armand Trousseau in 1865 as ‘’Phlegmacia alba dolens’’. Dr. Trousseau died because of gastric cancer in 1867. Armand Trousseau (1801-1867)

  3. Thromboembolism in Lung Cancer • The incidence of DVT in lung cancer is about 10-15% • In the patients who developed DVT previously; • The possibility of recurrent DVT increases • The risk of death caused by acute thrombosis increases 4-6 times. • The aspect of survival shortens as compared to the cancer patients without DVT.

  4. Concurrent VTE and cancerincreases the risk ofdeath Probability of death within 183 days of initial hospital admission 1.00 0.80 0.60 0.40 0.20 0.00 DVT/PE and malignant disease Probability of death Malignant disease alone 0 40 80 120 180 Number of days Levitan et al. Medicine 1999; 78(5): 285-291

  5. 100 Cancer at the time of VTE 90 Cancer without VTE 80 70 60 50 Survival (% of patients) 40 30 20 10 0 0 5 10 15 20 Effect of ‘’cancer and VTE’’on survival Years Sorensen et al. 2000 Sorensen et al. NEJM 2000;343:1846-50

  6. Patients with cancer assosiation • 24% have pancreatic cancer • 20% have lung cancer • 13% have prostate cancer • 12% have gastric cancer • 5% have colon cancer • Patients with stage IV disease are more likely to be hypercoagulable and develop clinically relevant thrombosis Winoker S, NOCR Proceedings, 20000

  7. Risk factors for VTE in cancer

  8. Under use of Prophylaxis • 66 % of patients at risk DID NOT receive prophylaxis • 60 % of patients at very high risk with multiple risk factors DID NOT receive prophylaxis Geerts WH, et al. Chest 119; 132S, 2001 Anderson FA, et al. Ann Intern Med 115; 591, 1991 Bratzler DW, et al. Arch Intern Med 158; 1909, 1998 Keene MG, et al. Chest 1994; 106: 13

  9. Thromboprophylaxis for the lung cancer patients • Primary prophylaxis • Secondary prophylaxis ( recurrent VTE )

  10. Common strategies considered for prophylaxis: do they work ? • Ambulation • Mechanical devices • Unfractionated heparin • Low molecular weight heparin • Warfarin

  11. Heparin aPTT measures anti-factor IIa activity anti-factor Xa assay measures anti-factor Xa activity

  12. LMWH aPTT measures anti-factor IIa activity anti-factor Xa assay measures anti-factor Xa activity

  13. Advantages of LMWH over UFH Bioavailability (%) Plasma half-life Effect on platelets Effect on haemostasis Osteoporosis Thrombocytopenia UFH 25–30 Short ++ ++ ++ ++ LMWH 90–95 Long +/– +/– +/– + Weitz JI, N Engl J Med 1997;337:688-98; Hirsh J et al, Chest 1998;114:489S-510S

  14. Prophylaxis for Cancer Surgery When to start? Which dosage? Optimal duration?

  15. Prophylaxis against Fatal Post-operative PE with Low-dose UFH P<0.005 18 16 16 14 12 Number of patientswith fatal PE 10 8 6 4 2 2 0 Control UFH Kakkar VV et al. Lancet 1975;2:45–51

  16. Nadroparin 0.3 ml Placebo Overall mortality Fatal pulmonary Thromboembolic embolism mortality * Nadroparin 0.3 mL shown to reduce mortality in general surgery p<0.05 0.80%(18/2251) 1 p<0.05 NS 0.36%(8/2247) 0.36%(8/2251) Events (%) 0.5 0.18%(4/2251) 0.09%(2/2247) 0.09%(2/2247) 0 No fatal bleeding but postoperative bleeding less frequent (p<0.01) in the placebo group 1/3 of patients in this trial were cancer patients Pezzuoli G et al. Int Surg 1989;74:205–10.

  17. Surgical Prophylaxis 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 Mismetti P et al. Br J Surg 2001;88:913–30.

  18. 7th ACCP Consensus Guidelines Geerts W, et al. Chest 2004; 126: 338S-400S.

  19. Thromboprophylaxis for patients undergoing cancer surgery • Give LDUH or LMWH 2 hours before surgery. • Optimal duration of thromboprophylaxis remains the subject of debate. 7-10 days? 7-8 weeks? • The risk of spinal hematoma with neuroaxial anesthesia may be acceptable. • When pharmacologic prophylaxis is used in conjunction with mechanical prophylaxis the efficacy appears to increase. Leonardii Mj, Ann Surg Oncol 2006 Berqvist D, J Surg Oncol, 2007

  20. Catheter-Related Thrombosis • Low dose warfarin and LMWH prophylaxis have fared to show any reduction in symptomatic catheter-related thrombosis. • Low dose warfarin is associated with an increase in bleeding. • The risk of symptomatic catheter-related thrombosis in adults is low (about 5 %) • Optimal prevention of CRT remains unclear.

  21. 30 Hazard ratio 3.2 20 Cancer Cumulative proportion (%)recurrent thromboembolism 10 No cancer 0 0 181 661 1 160 631 2 3 129 602 4 5 6 92 161 7 8 9 73 120 10 11 12 64 115 Time (months) Cancer No cancer Recurrent VTE during anticoagulant therapy is increased in patients with cancer Prandoni et al. Blood 2002;100:3484-8.

  22. 30 Hazard ratio 2.2 20 Cumulative proportion (%)major bleeding Cancer 10 No cancer 0 0 181 661 1 170 636 2 3 141 615 4 5 6 102 170 7 8 9 81 127 10 11 12 68 124 Time (months) Cancer No cancer Bleeding during anticoagulant therapy is increased in patients with cancer Prandoni et al. Blood 2002;100:3484-8.

  23. Which Anticoagulant?CLOT study design Dalteparin 1 month 200 IU/kg od 5 months 160 IU/kg od Solid tumour malignancy and acute VTE R Oral anticoagulant 6 months All patients received dalteparin 200 IU/kg od 5-7 days Lee et al. N Engl J Med 2003

  24. CLOT study population Inclusion criteria • Objectively documented, symptomatic proximal DVT and/or PE • Active cancer • Cancer diagnosis within past 6 months • Recurrent or metastatic malignancy • Received cancer treatment within past 6 months • 16 years or older Lee et al. N Engl J Med 2003

  25. 25 Risk reduction = 52% p=0.0017 20 15 OAC Probability of recurrent VTE (%) 10 Dalteparin 5 0 0 30 60 90 120 150 180 210 CLOT: dalteparin was more effective and as safe as OAC in long-term treatment of VTE Days post-randomization Lee et al. N Engl J Med 2003

  26. 7th ACCP Consensus Guidelines Buller et al. Chest 2004; 126: 401S-428S.

  27. DVT Prophylaxis • Physical methods: • Intermittent Pneumatic Leg Compression (Venodynes) • Early ambulation • Compression stockings • Pharmacological methods • Unfractionated heparin • LMWH • Warfarin

  28. Prophylaxis Recommendations

  29. 3-6 months: First episode with reversible or time limited RF (i.e. bed rest) – >= 6 months Idiopathic first episode 12 months First recurrent DVT Lifetime First event with Cancer, until resolved Anticardiolipin Ab ATIII deficiency 2 or more recurrent DVTs Long Term Anticoagulation

  30. Conclusion • Most pts who die from PE, die within 2 hours of onset, prior to implementation of treatment • THUS PREVENTION IS KEY

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