Risk of venous thromboembolism in patients with cancer: a systematic review and meta-analysis

Freesia Horsted, Joe West, Matthew J Grainge, Freesia Horsted, Joe West, Matthew J Grainge

Abstract

Background: People with cancer are known to be at increased risk of venous thromboembolism (VTE), and this risk is believed to vary according to cancer type, stage of disease, and treatment modality. Our purpose was to summarise the existing literature to determine precisely and accurately the absolute risk of VTE in cancer patients, stratified by malignancy site and background risk of VTE.

Methods and findings: We searched the Medline and Embase databases from 1 January 1966 to 14 July 2011 to identify cohort studies comprising people diagnosed with one of eight specified cancer types or where participants were judged to be representative of all people with cancer. For each included study, the number of patients who developed clinically apparent VTE, and the total person-years of follow-up were extracted. Incidence rates of VTE were pooled across studies using the generic inverse variance method. In total, data from 38 individual studies were included. Among average-risk patients, the overall risk of VTE was estimated to be 13 per 1,000 person-years (95% CI, 7 to 23), with the highest risk among patients with cancers of the pancreas, brain, and lung. Among patients judged to be at high risk (due to metastatic disease or receipt of high-risk treatments), the risk of VTE was 68 per 1,000 person-years (95% CI, 48 to 96), with the highest risk among patients with brain cancer (200 per 1,000 person-years; 95% CI, 162 to 247). Our results need to be considered in light of high levels of heterogeneity, which exist due to differences in study population, outcome definition, and average duration of follow-up between studies.

Conclusions: VTE occurs in greater than 1% of cancer patients each year, but this varies widely by cancer type and time since diagnosis. The absolute VTE risks obtained from this review can aid in clinical decision-making about which people with cancer should receive anticoagulant prophylaxis and at what times.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram for study selection.
Figure 1. Flow diagram for study selection.
Figure 2. Pooled incidence of venous thromboembolism…
Figure 2. Pooled incidence of venous thromboembolism for overall cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Black diamonds indicate the point estimate (VTE incidence) for each individual study. Horizontal lines indicate the 95% confidence interval surrounding this estimate. Open blue diamonds describe both the point estimate (centre of the diamond) for the pooled VTE incidence for average-risk, high-risk, and all studies (average- and high-risk together), and the 95% confidence interval for this pooled estimate (width of the diamond). Blom (2006) indicates data from .
Figure 3. Pooled incidence of venous thromboembolism…
Figure 3. Pooled incidence of venous thromboembolism for breast cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 4. Pooled incidence of venous thromboembolism…
Figure 4. Pooled incidence of venous thromboembolism for lung cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 5. Pooled incidence of venous thromboembolism…
Figure 5. Pooled incidence of venous thromboembolism for colorectal cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 6. Pooled incidence of venous thromboembolism…
Figure 6. Pooled incidence of venous thromboembolism for prostate cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 7. Pooled incidence of venous thromboembolism…
Figure 7. Pooled incidence of venous thromboembolism for brain cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 8. Pooled incidence of venous thromboembolism…
Figure 8. Pooled incidence of venous thromboembolism for bone cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 9. Pooled incidence of venous thromboembolism…
Figure 9. Pooled incidence of venous thromboembolism for haematological cancer.
Natural logarithms of the incidence rate are presented on the x-axis. The studies reported by Chew et al. (non-Hodgkin lymphoma) and Ku et al. (leukaemia) were both from the California Cancer Registry cohort. However, because they included different subsets of patients and were conducted over different time intervals (Chew, 1993–1995, and Ku, 1993–1999), a decision was made to pool these as separate studies. Symbols as in Figure 2. Blom (2006) indicates data from .
Figure 10. Pooled incidence of venous thromboembolism…
Figure 10. Pooled incidence of venous thromboembolism for pancreatic cancer.
Natural logarithms of the incidence rate are presented on the x-axis. Blom (2006) indicates data from . Blom (2006a) indicates data from .
Figure 11. Relative risks of venous thromboembolism…
Figure 11. Relative risks of venous thromboembolism in cancer patients compared with in the general population.
Results for selected cancer types obtained from Cronin-Fenton et al. . IRR, incidence rate ratio.

References

    1. Heit JA, Cohen AT, Anderson FA Jr (2005) on behalf of the VTE Impact Assessment Group (2005) Estimated annual number of incident and recurrent, non-fatal and fatal venous thromboembolism (VTE) events in the US. ASH Annual Meeting Abstracts 106: 910.
    1. Heit JA, O'Fallon WM, Petterson TM, Lohse CM, Silverstein MD, et al. (2002) Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 162: 1245–1248.
    1. Sorensen HT, Mellemkjaer L, Olsen JH, Baron JA (2000) Prognosis of cancers associated with venous thromboembolism. N Engl J Med 343: 1846–1850.
    1. Kohler BA, Ward E, McCarthy BJ, Schymura MJ, Ries LAG, et al. (2011) Annual report to the nation on the status of cancer, 1975–2007, featuring tumors of the brain and other nervous system. J Natl Canc Inst 103: 714–736.
    1. Vincent GK, Velkoff VA (2010) The next four decades—the older population in the United States: 2010 to 2050. Population estimates and projections. Washington (District of Columbia): US Census Bureau.
    1. Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, et al. (2000) Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 160: 809–815.
    1. White RH, Zhou H, Romano PS (2003) Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 90: 446–455.
    1. Khorana AA, Connolly GC (2009) Assessing risk of venous thromboembolism in the patient with cancer. J Clin Oncol 27: 4839–4847.
    1. Lyman GH, Khorana AA, Falanga A, Clarke-Pearson D, Flowers C, et al. (2007) American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25: 5490–5505.
    1. Mandalà M, Falanga A, Piccioli A, Prandoni P, Pogliani EM, et al. (2006) Venous thromboembolism and cancer: guidelines of the Italian Association of Medical Oncology (AIOM). Crit Rev Oncol Hemat 59: 194–204.
    1. Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, et al. (2012) Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed. American College of Chest Physicians evidence-based clinical practice guidelines. Chest 141: e195S–e226S.
    1. Streiff MB, Bockenstedt PL, Cataland SR, Chesney C, Eby C, et al. (2011) Venous thromboembolic disease. J Natl Compr Canc Netw 9: 714–777.
    1. 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: 2339–2346.
    1. Levitan N, Dowlati A, Remick SC, Tahsildar HI, Sivinski LD, 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: 285–291.
    1. Stein PD, Beemath A, Meyers FA, Skaf E, Sanchez J, et al. (2006) Incidence of venous thromboembolism in patients hospitalized with cancer. Am J Med 119: 60–68.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG, The PG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6: e1000097 doi:.
    1. Satariano WA, Silliman RA (2003) Comorbidity: implications for research and practice in geriatric oncology. Crit Rev Oncol Hemat 48: 239–248.
    1. Cancer Research UK (2012) January 27 Cancer incidence—UK statistics [database]. Available: . Accessed 28 March 2012.
    1. Khorana AA, Francis CW, Culakova E, Lyman GH (2005) Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 104: 2822–2829.
    1. Ay C, Vormittag R, Dunkler D, Simanek R, Chiriac A-L, et al. (2009) D-dimer and prothrombin fragment 1+2 predict venous thromboembolism in patients with cancer: results from the Vienna Cancer and Thrombosis Study. J Clin Oncol 27: 4124–4129.
    1. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for meta-analysis in medical research. Chichester (United Kingdom): Wiley.
    1. Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327: 557–560.
    1. Abdel-Razeq HN, Hijjawi SB, Jallad SG, Ababneh BA (2010) Venous thromboembolism risk stratification in medically-ill hospitalized cancer patients. A comprehensive cancer center experience. J Thromb Thrombolysis 30: 286–293.
    1. Alcalay A, Wun T, Khatri V, Chew HK, Harvey D, et al. (2006) Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 24: 1112–1118.
    1. Andtbacka RHI, Babiera G, Singletary SE, Hunt KK, Meric-Bernstam F, et al. (2006) Incidence and prevention of venous thromboembolism in patients undergoing breast cancer surgery and treated according to clinical pathways. Ann Surg 243: 96–101.
    1. Arai Y, Egawa S, Tobisu K, Sagiyama K, Sumiyoshi Y, et al. (2000) Radical retropubic prostatectomy: time trends, morbidity and mortality in Japan. BJU Int 85: 287–294.
    1. Auguste KI, Quinones-Hinojosa A, Gadkary C, Zada G, Lamborn KR, et al. (2003) Incidence of venous thromboembolism in patients undergoing craniotomy and motor mapping for glioma without intraoperative mechanical prophylaxis to the contralateral leg. J Neurosurg 99: 680–684.
    1. Blom JW, Osanto S, Rosendaal FR (2004) The risk of a venous thrombotic event in lung cancer patients: higher risk for adenocarcinoma than squamous cell carcinoma. J Thromb Haemost 2: 1760–1765.
    1. Blom JW, Osanto S, Rosendaal FR (2006) High risk of venous thrombosis in patients with pancreatic cancer: a cohort study of 202 patients. Eur J Cancer 42: 410–414.
    1. Blom JW, Vanderschoot JPM, Oostindier MJ, Osanto S, van der Meer FJM, et al. (2006) Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 4: 529–535.
    1. Brandes AA, Scelzi E, Salmistraro G, Ermani M, Carollo C, et al. (1997) Incidence of risk of thromboembolism during treatment of high-grade gliomas: a prospective study. Eur J Cancer 33: 1592–1596.
    1. Chew HK, Davies AM, Wun T, Harvey D, Zhou H, et al. (2008) The incidence of venous thromboembolism among patients with primary lung cancer. J Thromb Haemost 6: 601–608.
    1. 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: 458–464.
    1. Chew HK, Wun T, Harvey DJ, Zhou H, White RH (2007) Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol 25: 70–76.
    1. Connolly GC, Khorana AA, Kuderer NM, Culakova E, Francis CW, et al. (2010) Leukocytosis, thrombosis and early mortality in cancer patients initiating chemotherapy. Thromb Res 126: 113–118.
    1. Cronin-Fenton DP, Sondergaard F, Pedersen LA, Fryzek JP, Cetin K, et al. (2010) Hospitalisation for venous thromboembolism in cancer patients and the general population: a population-based cohort study in Denmark, 1997–2006. Br J Cancer 103: 947–953.
    1. De Stefano V, Sora F, Rossi E, Chiusolo P, Laurenti L, et al. (2005) The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 3: 1985–1992.
    1. Di Nisio M, Ferrante N, De Tursi M, Iacobelli S, Cuccurullo F, et al. (2010) Incidental venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Thromb Haemost 104: 1049–1054.
    1. Hall IE, Andersen MS, Krumholz HM, Gross CP (2009) Predictors of venous thromboembolism in patients with advanced common solid cancers. J Cancer Epidemiol 2009: 182521 doi:.
    1. Hernandez RK, Sorensen HT, Pedersen L, Jacobsen J, Lash TL (2009) Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer 115: 4442–4449.
    1. Kanz R, Vukovich T, Vormittag R, Dunkler D, Ay C, et al. (2011) Thrombosis risk and survival in cancer patients with elevated C-reactive protein. J Thromb Haemost 9: 57–63.
    1. Kaufman JL, Nooka A, Vrana M, Gleason C, Heffner LT, et al. (2010) Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer 116: 3143–3151.
    1. Kirwan CC, McDowell G, McCollum CN, Kumar S, Byrne GJ (2008) Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer. Br J Cancer 99: 1000–1006.
    1. Komrokji RS, Uppal NP, Khorana AA, Lyman GH, Kaplan KL, et al. (2006) Venous thromboembolism in patients with diffuse large B-cell lymphoma. Leuk Lymphoma 47: 1029–1033.
    1. Ku GH, White RH, Chew HK, Harvey DJ, Zhou H, et al. (2009) Venous thromboembolism in patients with acute leukemia: incidence, risk factors, and effect on survival. Blood 113: 3911–3917.
    1. Mandala M, Barni S, Prins M, Labianca R, Tondini C, et al. (2010) Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial. Ann Oncol 21: 871–876.
    1. Mason DP, Quader MA, Blackstone EH, Rajeswaran J, DeCamp MM, et al. (2006) Thromboembolism after pneumonectomy for malignancy: an independent marker of poor outcome. J Thorac Cardiovasc Surg 131: 711–718.
    1. Negaard HFS, Iversen PO, Ostenstad B, Iversen N, Holme PA, et al. (2008) Hypercoagulability in patients with haematological neoplasia: no apparent initiation by tissue factor. Thromb Haemost 99: 1040–1048.
    1. Numico G, Garrone O, Dongiovanni V, Silvestris N, Colantonio I, et al. (2005) Prospective evaluation of major vascular events in patients with nonsmall cell lung carcinoma treated with cisplatin and gemcitabine. Cancer 103: 994–999.
    1. Oh SY, Kim JH, Lee K-W, Bang S-M, Hwang J-H, et al. (2008) Venous thromboembolism in patients with pancreatic adenocarcinoma: lower incidence in Asian ethnicity. Thromb Res 122: 485–490.
    1. Otten H-MMB, Mathijssen J, ten Cate H, Soesan M, Inghels M, et al. (2004) Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 164: 190–194.
    1. Poruk KE, Firpo MA, Huerter LM, Scaife CL, Emerson LL, et al. (2010) Serum platelet factor 4 is an independent predictor of survival and venous thromboembolism in patients with pancreatic adenocarcinoma. Cancer Epidemiol Biomarkers Prev 19: 2605–2610.
    1. Reeves D, Liu CY (2010) Retrospective evaluation of venous thromboembolism prophylaxis in the adult cancer population. J Oncol Pharm Pract 16: 27–31.
    1. Sallah S, Wan JY, Nguyen NP (2002) Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 87: 575–579.
    1. Secin FP, Jiborn T, Bjartell AS, Fournier G, Salomon L, et al. (2008) Multi-institutional study of symptomatic deep venous thrombosis and pulmonary embolism in prostate cancer patients undergoing laparoscopic or robot-assisted laparoscopic radical prostatectomy. Eur Urol 53: 134–145.
    1. Semrad TJ, O'Donnell R, Wun T, Chew H, Harvey D, et al. (2007) Epidemiology of venous thromboembolism in 9489 patients with malignant glioma. J Neurosurg 106: 601–608.
    1. Sgarabotto D, Prandoni P, Stefani PM, Scano F, Vianello F, et al. (1998) Prevalence and patterns of symptomatic thromboembolism in oncohematology. Haematologica 83: 442–446.
    1. Simanek R, Vormittag R, Hassler M, Roessler K, Schwarz M, et al. (2007) Venous thromboembolism and survival in patients with high-grade glioma. Neuro Oncol 9: 89–95.
    1. Streiff MB, Segal J, Grossman SA, Kickler TS, Weir EG (2004) ABO blood group is a potent risk factor for venous thromboembolism in patients with malignant gliomas. Cancer 100: 1717–1723.
    1. Tagalakis V, Levi D, Agulnik JS, Cohen V, Kasymjanova G, et al. (2007) High risk of deep vein thrombosis in patients with non-small cell lung cancer: a cohort study of 493 patients. J Thorac Oncol 2: 729–734.
    1. Van Hemelrijck M, Adolfsson J, Garmo H, Bill-Axelson A, Bratt O, et al. (2010) Risk of thromboembolic diseases in men with prostate cancer: results from the population-based PCBaSe Sweden. Lancet Oncol 11: 450–458.
    1. Vormittag R, Simanek R, Ay C, Dunkler D, Quehenberger P, et al. (2009) High factor VIII levels independently predict venous thromboembolism in cancer patients: the cancer and thrombosis study. Arterioscler Thromb Vasc Biol 29: 2176–2181.
    1. Weder W, Collaud S, Eberhardt WEE, Hillinger S, Welter S, et al. (2010) Pneumonectomy is a valuable treatment option after neoadjuvant therapy for stage III non-small-cell lung cancer. J Thorac Cardiovasc Surg 139: 1424–1430.
    1. Whittle AM, Allsup DJ, Bailey JR (2011) Chronic lymphocytic leukaemia is a risk factor for venous thromboembolism. Leuk Res 35: 419–421.
    1. Zecchina G, Ghio P, Bosio S, Cravino M, Camaschella C, et al. (2007) Reactive thrombocytosis might contribute to chemotherapy-related thrombophilia in patients with lung cancer. Clin Lung Cancer 8: 264–267.
    1. Zhou X, Teegala S, Huen A, Ji Y, Fayad L, et al. (2010) Incidence and risk factors of venous thromboembolic events in lymphoma. Am J Med 123: 935–941.
    1. Cheruku R, Tapazoglou E, Ensley J, Kish JA, Cummings GD, et al. (1991) The incidence and significance of thromboembolic complications in patients with high-grade gliomas. Cancer 68: 2621–2624.
    1. Clarke CS, Otridge BW, Carney DN (1990) Thromboembolism. A complication of weekly chemotherapy in the treatment of non-Hodgkin's lymphoma. Cancer 66: 2027–2030.
    1. Dentali F, Malato A, Ageno W, Imperatori A, Cajozzo M, et al. (2008) Incidence of venous thromboembolism in patients undergoing thoracotomy for lung cancer. J Thorac Cardiovasc Surg 135: 705–706.
    1. Dhami MS, Bona RD, Calogero JA, Hellman RM (1993) Venous thromboembolism and high grade gliomas. Thromb Haemost 70: 393–396.
    1. Hershman DL, Buono DL, Malin J, McBride R, Tsai WY, et al. (2009) Patterns of use and risks associated with erythropoiesis-stimulating agents among Medicare patients with cancer. J Natl Cancer Inst 101: 1633–1641.
    1. Hoy J, Neeman T, Stuart-Harris R, Davis A (2009) Risk of venous thromboembolism in patients receiving adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide for early breast cancer. Asia Pac J Clin Oncol 5: 129–136.
    1. Imberti D, Vallisa D, Anselmi E, Moroni CF, Berte R, et al. (2004) Safety and efficacy of enoxaparin treatment in venous thromboembolic disease during acute leukemia. Tumori 90: 390–393.
    1. Iversen LH, Okholm M, Thorlacius-Ussing O (1996) Pre- and postoperative state of coagulation and fibrinolysis in plasma of patients with benign and malignant colorectal disease—a preliminary study. Thromb Haemost 76: 523–528.
    1. Lerner SE, Blute ML, Lieber MM, Zincke H (1995) Morbidity of contemporary radical retropubic prostatectomy for localized prostate cancer. Oncology (Williston) 9: 379–389.
    1. Mandala M, Falanga A, Cremonesi M, Zaccanelli M, Floriani I, et al. (2006) The extension of disease is associated to an increased risk of venous thromboembolism (VTE) in patients with gastrointestinal (GI) carcinoma. Thromb Haemost 95: 752–754.
    1. Mitchell SY, Lingard EA, Kesteven P, McCaskie AW, Gerrand CH (2007) Venous thromboembolism in patients with primary bone or soft-tissue sarcomas. J Bone Joint Surg Am 89: 2433–2439.
    1. Roddy JVF, Partridge SM, Rockey ML, Pruemer JM, Guo JJ, et al. (2010) Thromboembolic events in patients with colorectal cancer receiving the combination of bevacizumab-based chemotherapy and erythropoietin stimulating agents. Am J Clin Oncol 33: 36–42.
    1. Ruggieri P, Montalti M, Pala E, Angelini A, Calabro T, et al. (2010) Clinically significant thromboembolic disease in orthopedic oncology: an analysis of 986 patients treated with low-molecular-weight heparin. J Surg Oncol 102: 375–379.
    1. Santos FPS, Alvarado Y, Kantarjian H, Verma D, O'Brien S, et al. (2011) Long-term prognostic impact of the use of erythropoietic-stimulating agents in patients with chronic myeloid leukemia in chronic phase treated with imatinib. Cancer 117: 982–991.
    1. Seifter EJ, Young RC, Longo DL (1985) Deep venous thrombosis during therapy for Hodgkin's disease. Cancer Treat Rep 69: 1011–1013.
    1. Silvani A, Salmaggi A, Eoli M, Lamperti E, Boiardi A (2003) Venous thromboembolism in malignant glioma patients treated by chemoradiotherapy. Neurol Sci 24: 272.
    1. Zincke H, Oesterling JE, Blute ML, Bergstralh EJ, Myers RP, et al. (1994) Long-term (15 years) results after radical prostatectomy for clinically localized (stage T2c or lower) prostate cancer. J Urol 152: 1850–1857.
    1. Rodrigues C, Ferrarotto R, Filho R, Novis Y, Hoff P (2010) Venous thromboembolism and cancer: a systematic review. J Thromb Thrombolysis 30: 67–78.
    1. Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 48: 526–535.
    1. Thomas T, Abrams KA, Robinson RJ, Mayberry JF (2007) Meta-analysis: cancer risk of low-grade dysplasia in chronic ulcerative colitis. Alimen Pharm Ther 25: 657–668.
    1. Blom JW, Doggen CJM, Osanto S, Rosendaal FR (2005) Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 293: 715–722.
    1. Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, 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: 325–329.
    1. Mismetti P, Laporte-Simitsidis S, Tardy B, Cucherat M, Buchmuller A, et al. (2000) Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 83: 14–19.
    1. Levine M, Hirsh J, Gent M, Arnold A, Warr D, et al. (1994) Double-blind randomized trial of very-low-dose warfarin for prevention of thromboembolism in stage-IV breast-cancer. Lancet 343: 886–889.
    1. Meyer G, Marjanovic Z, Valcke J, Lorcerie B, Gruel Y, 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: 1729–1735.
    1. Prandoni P, Lensing AWA, Piccioli A, Bernardi E, Simioni P, et al. (2002) Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 100: 3484–3488.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa