Sử dụng dài hạn heparin trọng lượng phân tử thấp tiêm dưới da hàng ngày ở bệnh nhân ung thư với hiện tượng huyết khối tĩnh mạch: Tại sao còn chần chừ?

Springer Science and Business Media LLC - Tập 16 - Trang 1333-1341 - 2008
Philippe Debourdeau1, Ismail Elalamy2, Axelle de Raignac3, Paul Meria4, Jean Marc Gornet5, Yahovi Amah6, Wolfang Korte7,8, Michel Marty9, Dominique Farge3,10,11
1Internal Medicine and Oncology Department, Desgenettes Military Hospital, Lyon cedex 3, France
2Haemobiology Department, Assistance Publique Hôpitaux de Paris, Tenon Hospital, Paris, France
3Department of Internal Medicine and Vascular Pathology, and INSERM U 697, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Paris, France
4Department of Urology, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Paris, France
5Department of Gatroenterology, Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Paris, France
6Internal Médicine Department, University Hospital, Lomé, Togo
7Institute for Clinical Chemistry and Hematology, Kantonsspital, St. Gallen, Switzerland
8University of Bern, Bern, Switzerland
9Assistance Publique Hôpitaux de Paris, Saint-Louis Hospital, Service de Greffe de Moelle, Paris, France
10INSERM U 697 Paris, France Saint-Louis Hospital, Paris, France
11Service de Médecine Interne et Pathologie Vasculaire, Hôpital Saint-Louis, INSERM U697, Paris, France

Tóm tắt

Bệnh ung thư gây ra trạng thái đông máu kháng nguyên đã được chứng minh là một đặc điểm rõ ràng. Huyết khối tĩnh mạch (VTE) xảy ra ở 4% đến 20% bệnh nhân và là nguyên nhân thứ hai gây tử vong ở bệnh nhân ung thư; tỷ lệ VTE cao hơn từ bốn đến sáu lần ở bệnh nhân ung thư so với bệnh nhân khác. Trong 10 năm qua, các thử nghiệm lâm sàng ngẫu nhiên quan trọng đã chứng minh rõ ràng rằng việc sử dụng lâu dài heparin trọng lượng phân tử thấp (LMWH) tiêm dưới da hàng ngày hiệu quả hơn so với các thuốc đối kháng vitamin K trong điều trị VTE ở bệnh nhân ung thư. Đầu tiên là các hướng dẫn quốc gia của Ý, sau đó là của Mỹ và gần đây là của Pháp khuyến nghị sử dụng LMWH trong 3 đến 6 tháng cho điều trị nhằm chữa khỏi VTE ở những bệnh nhân ung thư có mức chứng cứ rõ ràng (A). Mặc dù có dữ liệu thuyết phục, nhiều bác sĩ vẫn chưa thay đổi thực hành lâm sàng của họ, nghi ngờ khả năng dung nạp của việc tiêm dưới da trong khoảng thời gian dài như vậy. Trên thực tế, việc sử dụng lâu dài LMWH cho thấy khả năng dung nạp tốt và có thể tăng thời gian sống cho bệnh nhân ung thư. Mục tiêu của bài viết này là trình bày lý do khoa học cho việc sử dụng LMWH tiêm dưới da hàng ngày trong thời gian dài ở bệnh nhân ung thư và nhấn mạnh tỷ lệ lợi ích/độ dung nạp cải thiện với chiến lược kháng thrombo này.

Từ khóa

#huyết khối tĩnh mạch #ung thư #heparin trọng lượng phân tử thấp #điều trị #dung nạp #sống sót

Tài liệu tham khảo

Agnelli G, Bolis G, Capussotti L, Scarpa RM, Tonelli F, Bonizzoni E et al (2006) A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 243(1):89–95 doi:10.1097/01.sla.0000193959.44677.48 Akl EA, van Doormaal FF, Barba M, Kamath G, Kim SY, Kuipers S et al (2007) Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. Cochrane Database Syst Rev 3:CD006652 Balci Akpinar R, Celebioglu A (2008) Effect of injection duration on bruising associated with subcutaneous heparin: a quasi-experimental within-subject design. Int J Nurs Stud 45(6):812–817, Jun Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, Zhou H et al (2006) Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 24(7):1112–1118 doi:10.1200/JCO.2005.04.2150 Alikhan R, Cohen AT, Combe S, Samama MM, Desjardins L, Eldor A et al (2004) Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med 164(9):963–968 doi:10.1001/archinte.164.9.963 Altinbas M, Coskun HS, Er O, Ozkan M, Eser B, Unal A et al (2004) A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. J Thromb Haemost 2(8):1266–1271 doi:10.1111/j.1538-7836.2004.00871.x Andtbacka RH, Babiera G, Singletary SE, Hunt KK, Meric-Bernstam F, Feig BW et al (2006) Incidence and prevention of venous thromboembolism in patients undergoing breast cancer surgery and treated according to clinical pathways. Ann Surg 243(1):96–101 doi:10.1097/01.sla.0000193832.40178.0a Baron JA, Gridley G, Weiderpass E, Nyren O, Linet M (1998) Venous thromboembolism and cancer. Lancet 351(9109):1077–1080 doi:10.1016/S0140-6736(97)10018-6 Blom JW, Doggen CJ, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293(6):715–722 doi:10.1001/jama.293.6.715 Bona RD, Hickey AD, Wallace DM (2000) Warfarin is safe as secondary prophylaxis in patients with cancer and a previous episode of venous thrombosis. Am J Clin Oncol 23(1):71–73 doi:10.1097/00000421-200002000-00020 Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE (2004) Antithrombotic therapy for venous thromboembolic disease: the Seventh ACCP Conference on antithrombotic and thrombolytic therapy. Chest 126(Suppl 3):401S–428S doi:10.1378/chest.126.3_suppl.401S Calligaro KD, Bergen WS, Haut MJ, Savarese RP, DeLaurentis DA (1991) Thromboembolic complications in patients with advanced cancer: anticoagulation versus Greenfield filter placement. Ann Vasc Surg 5(2):186–189 doi:10.1007/BF02016754 Chan A, Woodruff RK (1992) Complications and failure of anticoagulation therapy in the treatment of venous thromboembolism in patients with disseminated malignancy. Aust N Z J Med 22(2):119–122 Chan H (2001) Effects of injection duration on site-pain intensity and bruising associated with subcutaneous heparin. J Adv Nurs 35(6):882–892 doi:10.1046/j.1365-2648.2001.01925.x Chew HK, Wun T, Harvey D, Zhou H, White RH (2006) Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 166(4):458–464 doi:10.1001/.458 Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W et al (2006) Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 332(7537):325–329 doi:10.1136/bmj.38733.466748.7C Debourdeau P, Meyer G, Sayeg H, Marjanovic Z, Bastit L, Cabane J et al (1996) Classical anticoagulant treatment of venous thromboembolic disease in cancer patients. Apropos of a retrospective study of 71 patients. Rev Med Intern 17(3):207–212 doi:10.1016/0248-8663(96)81247-1 Deitcher SR, Kessler CM, Merli G, Rigas JR, Lyons RM, Fareed J (2006) Secondary prevention of venous thromboembolic events in patients with active cancer: enoxaparin alone versus initial enoxaparin followed by warfarin for a 180-day period. Clin Appl Thromb Hemost 12(4):389–396 doi:10.1177/1076029606293692 Dolovich LR, Ginsberg JS, Douketis JD, Holbrook AM, Cheah G (2000) A meta-analysis comparing low-molecular-weight heparins with unfractionated heparin in the treatment of venous thromboembolism: examining some unanswered questions regarding location of treatment, product type, and dosing frequency. Arch Intern Med 160(2):181–188 doi:10.1001/archinte.160.2.181 Dranitsaris G, Vincent M, Crowther M (2006) Dalteparin versus warfarin for the prevention of recurrent venous thromboembolic events in cancer patients: a pharmacoeconomic analysis. Pharmacoeconomics 24(6):593–607 doi:10.2165/00019053-200624060-00006 Ferretti G, Bria E, Giannarelli D, Carlini P, Felici A, Mandala M et al (2006) Is recurrent venous thromboembolism after therapy reduced by low-molecular-weight heparin compared with oral anticoagulants? Chest 130(6):1808–1816 doi:10.1378/chest.130.6.1808 Gould MK, Dembitzer AD, Doyle RL, Hastie TJ, Garber AM (1999) Low-molecular-weight heparins compared with unfractionated heparin for treatment of acute deep venous thrombosis. A meta-analysis of randomized, controlled trials. Ann Intern Med 130(10):800–809 Hadley SA, Chang M, Rogers K (1996) Effect of syringe size on bruising following subcutaneous heparin injection. Am J Crit Care 5(4):271–276 Heit JA (2005) Cancer and venous thromboembolism: scope of the problem. Cancer Control 12(Suppl 1):5–10 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O’Fallon WM, Melton LJ 3rd (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 160(6):809–815 doi:10.1001/archinte.160.6.809 Hettiarachchi RJ, Smorenburg SM, Ginsberg J, Levine M, Prins MH, Buller HR (1999) Do heparins do more than just treat thrombosis? The influence of heparins on cancer spread. Thromb Haemost 82(2):947–952 Hettiarachchi RJ, Prins MH, Lensing AW, Buller HR (1998) Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism. Curr Opin Pulm Med 4(4):220–225 doi:10.1097/00063198-199807000-00007 Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R et al (2006) Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med 119(12):1062–1072 doi:10.1016/j.amjmed.2006.02.022 Hutten BA, Prins MH, Gent M, Ginsberg J, Tijssen JG, Buller HR (2000) Incidence of recurrent thromboembolic and bleeding complications among patients with venous thromboembolism in relation to both malignancy and achieved international normalized ratio: a retrospective analysis. J Clin Oncol 18(17):3078–3083 Ihnat DM, Mills JL, Hughes JD, Gentile AT, Berman SS, Westerband A (1998) Treatment of patients with venous thromboembolism and malignant disease: should vena cava filter placement be routine? J Vasc Surg 28(5):800–807 doi:10.1016/S0741-5214(98)70054-0 Kakkar AK, Levine MN, Kadziola Z, Lemoine NR, Low V, Patel HK et al (2004) Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: the fragmin advanced malignancy outcome study (FAMOUS). J Clin Oncol 22(10):1944–1948 doi:10.1200/JCO.2004.10.002 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH (2007) Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 110(10):2339–2346 doi:10.1002/cncr.23062 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW (2008) Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 111:4902–4907 Klerk CP, Smorenburg SM, Otten HM, Lensing AW, Prins MH, Piovella F et al (2005) The effect of low molecular weight heparin on survival in patients with advanced malignancy. J Clin Oncol 23(10):2130–2135 doi:10.1200/JCO.2005.03.134 Kuderer NM, Khorana AA, Lyman GH, Francis CW (2007) A meta-analysis and systematic review of the efficacy and safety of anticoagulants as cancer treatment: impact on survival and bleeding complications. Cancer 110(5):1149–1161 doi:10.1002/cncr.22892 Kuzu N, Ucar H (2001) The effect of cold on the occurrence of bruising, haematoma and pain at the injection site in subcutaneous low molecular weight heparin. Int J Nurs Stud 38(1):51–59 doi:10.1016/S0020-7489(00)00061-4 Laupacis A, Feeny D, Detsky AS, Tugwell PX (1992) How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ 146(4):473–481 Lazo-Langner A, Goss GD, Spaans JN, Rodger MA (2007) The effect of low-molecular-weight heparin on cancer survival. A systematic review and meta-analysis of randomized trials. J Thromb Haemost 4:729–737 doi:10.1111/j.1538-7836.2007.02427.x Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M et al (2003) Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med 349(2):146–153 doi:10.1056/NEJMoa025313 Lee AY, Rickles FR, Julian JA, Gent M, Baker RI, Bowden C et al (2005) Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. J Clin Oncol 23(10):2123–2129 doi:10.1200/JCO.2005.03.133 Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ (2004) Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 110(7):874–879 doi:10.1161/01.CIR.0000138928.83266.24 Lensing AW, Prins MH, Davidson BL, Hirsh J (1995) Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis. Arch Intern Med 155(6):601–607 doi:10.1001/archinte.155.6.601 Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, Beyth R et al (1999) Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 78(5):285–291 doi:10.1097/00005792-199909000-00001 Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, Jahanzeb M et al (2007) American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25(34):5490–5505 doi:10.1200/JCO.2007.14.1283 Mandala M, Falanga A, Piccioli A, Prandoni P, Pogliani EM, Labianca R et al (2006) Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM). Crit Rev Oncol Hematol 59(3):194–204 doi:10.1016/j.critrevonc.2006.05.001 Marchetti M, Pistorio A, Barone M, Serafini S, Barosi G (2001) Low-molecular-weight heparin versus warfarin for secondary prophylaxis of venous thromboembolism: a cost-effectiveness analysis. Am J Med 111(2):130–139 doi:10.1016/S0002-9343(01)00793-8 Mason DP, Quader MA, Blackstone EH, Rajeswaran J, DeCamp MM, Murthy SC et al (2006) Thromboembolism after pneumonectomy for malignancy: an independent marker of poor outcome. J Thorac Cardiovasc Surg 131(3):711–718 doi:10.1016/j.jtcvs.2005.10.027 Martino MA, Borges E, Williamson E, Siegfried S, Cantor AB, Lancaster J et al (2006) Pulmonary embolism after major abdominal surgery in gynecologic oncology. Obstet Gynecol 107(3):666–671 Meyer G, Farge D, Sauvaget F, Diehl JL, Herve R, Rouffy J et al (1994) Thromboembolic disease and cancer. Presse Med 23(38):1767–1771 Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, Solal-Celigny P et al (2002) Comparison of low-molecular-weight heparin and warfarin for the secondary prevention of venous thromboembolism in patients with cancer: a randomized controlled study. Arch Intern Med 162(15):1729–1735 doi:10.1001/archinte.162.15.1729 Mismetti P, Quenet S, Levine M, Merli G, Decousus H, Derobert E et al (2005) Enoxaparin in the treatment of deep vein thrombosis with or without pulmonary embolism: an individual patient data meta-analysis. Chest 128(4):2203–2210 doi:10.1378/chest.128.4.2203 Noble SI, Finlay IG (2005) Is long-term low-molecular-weight heparin acceptable to palliative care patients in the treatment of cancer related venous thromboembolism? A qualitative study. Palliat Med 19(3):197–201 doi:10.1191/0269216305pm1008oa Noble SI, Nelson A, Turner C, Finlay IG (2006) Acceptability of low molecular weight heparin thromboprophylaxis for inpatients receiving palliative care: qualitative study. BMJ 332(7541):577–580 doi:10.1136/bmj.38733.616065.802 Noboa S, Mottier D, Oger E (2006) Estimation of a potentially preventable fraction of venous thromboembolism: a community-based prospective study. J Thromb Haemost 4(12):2720–2722 doi:10.1111/j.1538-7836.2006.02196.x Opatrny L, Warner MN (2004) Risk of thrombosis in patients with malignancy and heparin-induced thrombocytopenia. Am J Hematol 76(3):240–244 doi:10.1002/ajh.20098 Otten HM, Mathijssen J, ten Cate H, Soesan M, Inghels M, Richel DJ et al (2004) Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 164(2):190–194 doi:10.1001/archinte.164.2.190 Palareti G, Legnani C, Lee A, Manotti C, Hirsh J, D’Angelo A et al (2000) A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy. Thromb Haemost 84(5):805–810 Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B et al (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100(10):3484–3488 doi:10.1182/blood-2002-01-0108 Prandoni P, Falanga A, Piccioli A (2007) Cancer, thrombosis and heparin-induced thrombocytopenia. Thromb Res 120(Suppl 2):S137–S140 doi:10.1016/S0049-3848(07)70143-3 Quinlan DJ, McQuillan A, Eikelboom JW (2004) Low-molecular-weight heparin compared with intravenous unfractionated heparin for treatment of pulmonary embolism: a meta-analysis of randomized, controlled trials. Ann Intern Med 140(3):175–183 Rocha E, Martinez-Gonzalez MA, Montes R, Panizo C (2000) Do the low molecular weight heparins improve efficacy and safety of the treatment of deep venous thrombosis? A meta-analysis. Haematologica 85(9):935–942 Ross S, Soltes D (1995) Heparin and haematoma: does ice make a difference? J Adv Nurs 21(3):434–439 doi:10.1111/j.1365-2648.1995.tb02724.x Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C et al (1999) A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 341(11):793–800 doi:10.1056/NEJM199909093411103 Sideras K, Schaefer PL, Okuno SH, Sloan JA, Kutteh L, Fitch TR et al (2006) Low-molecular-weight heparin in patients with advanced cancer: a phase 3 clinical trial. Mayo Clin Proc 81(6):758–767 Siragusa S, Cosmi B, Piovella F, Hirsh J, Ginsberg JS (1996) Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 100(3):269–277 doi:10.1016/S0002-9343(97)89484-3 Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343(25):1846–1850 doi:10.1056/NEJM200012213432504 Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, Olson RE (2006) Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119(1):60–68 doi:10.1016/j.amjmed.2005.06.058 Ten Cate-Hoek AJ, Prins MH (2008) Low molecular weight heparins in cancer. Management and prevention of venous thromboembolism in patients with malignancies. Thromb Res (in press) doi:10.1016/j.thromres.2006.12.026 Tetsche MS, Norgaard M, Pedersen L, Lash TL, Sorensen HT (2006) Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study. BMC Cancer 6:189 doi:10.1186/1471-2407-6-189 Vucic N, Ostojic R, Svircic T (2002) Treatment of deep vein thrombosis with oral anticoagulants in patients with malignancy: prospective cohort study. Croat Med J 43(3):296–300 Warkentin TE (2004) Heparin-induced thrombocytopenia: diagnosis and management. Circulation 110(18):e454–e458 doi:10.1161/01.CIR.0000147537.72829.1B Weijl NI, Rutten MF, Zwinderman AH, Keizer HJ, Nooy MA, Rosendaal FR et al (2000) Thromboembolic events during chemotherapy for germ cell cancer: a cohort study and review of the literature. J Clin Oncol 18(10):2169–2178 Zaybak A, Khorshid L (2008) A study on the effect of the duration of subcutaneous heparin injection on bruising and pain. J Clin Nurs 17(3):378–385