NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer-Associated Venous Thromboembolic Disease focus on the prevention, diagnosis, and treatment of patients with cancer who have developed or who are at risk for developing venous thromboembolism (VTE). VTE is a significant concern among cancer patients, who are at heightened risks for developing as well as dying from the disease. The management of patients with cancer with VTE often requires multidisciplinary efforts at treating institutions. The NCCN panel comprises specialists from various fields: cardiology, hematology/hematologic oncology, internal medicine, interventional radiology, medical oncology, pharmacology/pharmacy, and surgery/surgical oncology. This article focuses on VTE prophylaxis for medical and surgical oncology inpatients and outpatients, and discusses risk factors for VTE development, risk assessment tools, as well as management methods, including pharmacological and mechanical prophylactics. Contraindications to therapeutic interventions and special dosing, when required, are also discussed.
Individual Disclosures for the NCCN Cancer-Associated Venous Thromboembolic Disease Panel
Blom JW, Doggen CJM, Osanto S, et al. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005;293:715–722.
Mulder FI, Horváth-Puhó E, van Es N, et al. Venous thromboembolism in cancer patients: a population-based cohort study. Blood 2021;137:1959–1969.
Khorana AA, Dalal M, Lin J, et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory high-risk cancer patients undergoing chemotherapy in the United States. Cancer 2013;119:648–655.
Khorana AA, Francis CW, Culakova E, et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007;5:632–634.
Khorana AA, Francis CW, Culakova E, et al. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007;110:2339–2346.
Khorana AA, Francis CW, Culakova E, et al. Thromboembolism in hospitalized neutropenic cancer patients. J Clin Oncol 2006;24:484–490.
Fotopoulou C, duBois A, Karavas AN, et al. Incidence of venous thromboembolism in patients with ovarian cancer undergoing platinum/paclitaxel-containing first-line chemotherapy: an exploratory analysis by the Arbeitsgemeinschaft Gynaekologische Onkologie Ovarian Cancer Study Group. J Clin Oncol 2008;26:2683–2689.
Chew HK, Wun T, Harvey D, et al. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458–464.
Chew HK, Wun T, Harvey DJ, et al. Incidence of venous thromboembolism and the impact on survival in breast cancer patients. J Clin Oncol 2007;25:70–76.
Sørensen HT, Mellemkjaer L, Olsen JH, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000;343:1846–1850.
Kuderer NM, Francis CW, Culakova E, et al. Venous thromboembolism and all-cause mortality in cancer patients receiving chemotherapy (abstract). J Clin Oncol 2008;26(Supple 15):Abstract 9521.
Martino MA, Williamson E, Siegfried S, et al. Diagnosing pulmonary embolism: experience with spiral CT pulmonary angiography in gynecologic oncology. Gynecol Oncol 2005;98:289–293.
Agnelli G, Bolis G, Capussotti L, et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006;243:89–95.
Ohashi Y, Ikeda M, Kunitoh H, et al. Venous thromboembolism in cancer patients: report of baseline data from the multicentre, prospective Cancer-VTE Registry. Jpn J Clin Oncol 2020;50:1246–1253.
Rickles FR, Levine MN. Epidemiology of thrombosis in cancer. Acta Haematol 2001;106:6–12.
Key NS, Khorana AA, Kuderer NM, et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol 2020;38:496–520.
Farge D, Bounameaux H, Brenner B, et al. International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol 2016;17:e452–e466.
Heit JA, Silverstein MD, Mohr DN, et al. Predictors of survival after deep vein thrombosis and pulmonary embolism: a population-based, cohort study. Arch Intern Med 1999;159:445–453.
Aggarwal A, Fullam L, Brownstein AP, et al. Deep vein thrombosis (DVT) and pulmonary embolism (PE): awareness and prophylaxis practices reported by patients with cancer. Cancer Invest 2015;33:405–410.
Secin FP, Jiborn T, Bjartell AS, et al. 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 2008;53:134–145.
Girard P, Decousus M, Laporte S, et al. Diagnosis of pulmonary embolism in patients with proximal deep vein thrombosis: specificity of symptoms and perfusion defects at baseline and during anticoagulant therapy. Am J Respir Crit Care Med 2001;164:1033–1037.
Anderson FA, Jr., Wheeler HB, Goldberg RJ, et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991;151:933–938.
Wells PS, Forgie MA, Rodger MA. Treatment of venous thromboembolism. JAMA 2014;311:717–728.
Ageno W, Squizzato A, Garcia D, et al. Epidemiology and risk factors of venous thromboembolism. Semin Thromb Hemost 2006;32:651–658.
Connolly GC, Khorana AA. Emerging risk stratification approaches to cancer-associated thrombosis: risk factors, biomarkers and a risk score. Thromb Res 2010;125(Suppl 2):S1–S7.
Khorana AA, Kuderer NM, Culakova E, et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008;111:4902–4907.
Stein PD, Beemath A, Olson RE. Obesity as a risk factor in venous thromboembolism. Am J Med 2005;118:978–980.
Borch KH, Hansen-Krone I, Braekkan SK, et al. Physical activity and risk of venous thromboembolism: the Tromso study. Haematologica 2010;95:2088–2094.
Cheng YJ, Liu ZH, Yao FJ, et al. Current and former smoking and risk for venous thromboembolism: a systematic review and meta-analysis. PLoS Med 2013;10:e1001515.
Enga KF, Braekkan SK, Hansen-Krone IJ, et al. Cigarette smoking and the risk of venous thromboembolism: the Tromsø Study. J Thromb Haemost 2012;10:2068–2074.
Hansson PO, Eriksson H, Welin L, et al. Smoking and abdominal obesity: risk factors for venous thromboembolism among middle-aged men: “the study of men born in 1913”. Arch Intern Med 1999;159:1886–1890.
Danin-Mankowitz H, Ugarph-Morawski A, Braunschweig F, et al. The risk of venous thromboembolism and physical activity level, especially high level: a systematic review. J Thromb Thrombolysis 2021.
van Stralen KJ, Doggen CJ, Lumley T, et al. The relationship between exercise and risk of venous thrombosis in elderly people. J Am Geriatr Soc 2008;56:517–522.
Mahmoodi BK, Brouwer JL, Ten Kate MK, et al. A prospective cohort study on the absolute risks of venous thromboembolism and predictive value of screening asymptomatic relatives of patients with hereditary deficiencies of protein S, protein C or antithrombin. J Thromb Haemost 2010;8:1193–1200.
Poort SR, Rosendaal FR, Reitsma PH, et al. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996;88:3698–3703.
Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002;46:1019–1027.
Ginsburg KS, Liang MH, Newcomer L, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992;117:997–1002.
Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018;2:3360–3392.
Segal JB, Streiff MB, Hofmann LV, et al. Management of venous thromboembolism: a systematic review for a practice guideline. Ann Intern Med 2007;146:211–222.
Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related mortality surveillance--United States, 1991--1999. MMWR Surveill Summ 2003;52:1–8.
Rogers MA, Levine DA, Blumberg N, et al. Triggers of hospitalization for venous thromboembolism. Circulation 2012;125:2092–2099.
Schmidt M, Horvath-Puho E, Thomsen RW, et al. Acute infections and venous thromboembolism. J Intern Med 2012;271:608–618.
Mandalà M, Barni S, Prins M, et al. Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial. Ann Oncol 2010;21:871–876.
Lu HY, Liao KM. Increased risk of deep vein thrombosis in end-stage renal disease patients. BMC Nephrol 2018;19:204.
Monreal M, Falgá C, Valle R, et al. Venous thromboembolism in patients with renal insufficiency: findings from the RIETE Registry. Am J Med 2006;119:1073–1079.
Wattanakit K, Cushman M, Stehman-Breen C, et al. Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol 2008;19:135–140.
Børvik T, Brækkan SK, Enga K, et al. COPD and risk of venous thromboembolism and mortality in a general population. Eur Respir J 2016;47:473–481.
Kim V, Goel N, Gangar J, et al. Risk factors for venous thromboembolism in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis (Miami) 2014;1:239–249.
Piazza G, Goldhaber SZ, Kroll A, et al. Venous thromboembolism in patients with chronic obstructive pulmonary disease. Am J Med 2012;125:1010–1018.
Bertoletti L, Quenet S, Laporte S, et al. Pulmonary embolism and 3-month outcomes in 4036 patients with venous thromboembolism and chronic obstructive pulmonary disease: data from the RIETE registry. Respir Res 2013;14:75.
Tang L, Wu YY, Lip GY, et al. Heart failure and risk of venous thromboembolism: a systematic review and meta-analysis. Lancet Haematol 2016;3:e30–e44.
Leizorovicz A, Turpie AG, Cohen AT, et al. Epidemiology of venous thromboembolism in Asian patients undergoing major orthopedic surgery without thromboprophylaxis. The SMART study. J Thromb Haemost 2005;3:28–34.
Eliasson A, Bergqvist D, Björck M, et al. Incidence and risk of venous thromboembolism in patients with verified arterial thrombosis: a population study based on 23,796 consecutive autopsies. J Thromb Haemost 2006;4:1897–1902.
Hong C, Zhu F, Du D, et al. Coronary artery calcification and risk factors for atherosclerosis in patients with venous thromboembolism. Atherosclerosis 2005;183:169–174.
Prandoni P, Bilora F, Marchiori A, et al. An association between atherosclerosis and venous thrombosis. N Engl J Med 2003;348:1435–1441.
Darze ES, Latado AL, Guimarães AG, et al. Incidence and clinical predictors of pulmonary embolism in severe heart failure patients admitted to a coronary care unit. Chest 2005;128:2576–2580.
Kröger K, Weiland D, Ose C, et al. Risk factors for venous thromboembolic events in cancer patients. Ann Oncol 2006;17:297–303.
Prandoni P, Lensing AWA, Prins MH, et al. Residual venous thrombosis as a predictive factor of recurrent venous thromboembolism. Ann Intern Med 2002;137:955–960.
Prandoni P, Lensing AWA, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002;100:3484–3488.
Heit JA, O’Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002;162:1245–1248.
Beam DM, Courtney DM, Kabrhel C, et al. Risk of thromboembolism varies, depending on category of immobility in outpatients. Ann Emerg Med 2009;54:147–152.
Flinterman LE, van Hylckama Vlieg A, Rosendaal FR, et al. Body height, mobility, and risk of first and recurrent venous thrombosis. J Thromb Haemost 2015;13:548–554.
Centers for Disease Control and Prevention (CDC). Venous thromboembolism in adult hospitalizations - United States, 2007-2009. MMWR Morb Mortal Wkly Rep 2012;61:401–404.
Levitan N, Dowlati A, Remick SC, et al. Rates of initial and recurrent thromboembolic disease among patients with malignancy versus those without malignancy. Risk analysis using Medicare claims data. Medicine (Baltimore) 1999;78:285–291.
Ogren M, Bergqvist D, Wåhlander K, et al. Trousseau’s syndrome - what is the evidence? A population-based autopsy study. Thromb Haemost 2006;95:541–545.
Sallah S, Wan JY, Nguyen NP. Venous thrombosis in patients with solid tumors: determination of frequency and characteristics. Thromb Haemost 2002;87:575–579.
Hall IE, Andersen MS, Krumholz HM, et al. Predictors of venous thromboembolism in patients with advanced common solid cancers. J Cancer Epidemiol 2009;2009:182521–182521.
Marras LC, Geerts WH, Perry JR. The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review. Cancer 2000;89:640–646.
Khorana AA, Francis CW, Menzies KE, et al. Plasma tissue factor may be predictive of venous thromboembolism in pancreatic cancer. J Thromb Haemost 2008;6:1983–1985.
Khorana AA, Ahrendt SA, Ryan CK, et al. Tissue factor expression, angiogenesis, and thrombosis in pancreatic cancer. Clin Cancer Res 2007;13:2870–2875.
Andtbacka RHI, Babiera G, Singletary SE, et al. Incidence and prevention of venous thromboembolism in patients undergoing breast cancer surgery and treated according to clinical pathways. Ann Surg 2006;243:96–101.
Carrier M, Le Gal G, Tay J, et al. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 2011;9:653–663.
De Stefano V, Sorà F, Rossi E, et al. The risk of thrombosis in patients with acute leukemia: occurrence of thrombosis at diagnosis and during treatment. J Thromb Haemost 2005;3:1985–1992.
Mohren M, Markmann I, Jentsch-Ullrich K, et al. Increased risk of thromboembolism in patients with malignant lymphoma: a single-centre analysis. Br J Cancer 2005;92:1349–1351.
Ottinger H, Belka C, Kozole G, et al. Deep venous thrombosis and pulmonary artery embolism in high-grade non Hodgkin’s lymphoma: incidence, causes and prognostic relevance. Eur J Haematol 1995;54:186–194.
Hicks LK, Cheung MC, Ding K, et al. Venous thromboembolism and nonsmall cell lung cancer: a pooled analysis of National Cancer Institute of Canada Clinical Trials Group trials. Cancer 2009;115:5516–5525.
Sandhu R, Pan C-X, Wun T, et al. The incidence of venous thromboembolism and its effect on survival among patients with primary bladder cancer. Cancer 2010;116:2596–2603.
Gade IL, Braekkan SK, Naess IA, et al. The impact of initial cancer stage on the incidence of venous thromboembolism: the Scandinavian Thrombosis and Cancer (STAC) Cohort. J Thromb Haemost 2017;15:1567–1575.
Hammond J, Kozma C, Hart JC, et al. Rates of venous thromboembolism among patients with major surgery for cancer. Ann Surg Oncol 2011;18:3240–3247.
Toledano TH, Kondal D, Kahn SR, et al. The occurrence of venous thromboembolism in cancer patients following major surgery. Thromb Res 2013;131:e1–e5.
Baarslag HJ, Koopman MMW, Hutten BA, et al. Long-term follow-up of patients with suspected deep vein thrombosis of the upper extremity: survival, risk factors and post-thrombotic syndrome. Eur J Intern Med 2004;15:503–507.
Heit JA, Silverstein MD, Mohr DN, et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000;160:809–815.
Prandoni P, Polistena P, Bernardi E, et al. Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med 1997;157:57–62.
Lee AY, Levine MN, Butler G, et al. Incidence, risk factors, and outcomes of catheter-related thrombosis in adult patients with cancer. J Clin Oncol 2006;24:1404–1408.
Gerber DE, Segal JB, Levy MY, et al. The incidence of and risk factors for venous thromboembolism (VTE) and bleeding among 1514 patients undergoing hematopoietic stem cell transplantation: implications for VTE prevention. Blood 2008;112:504–510.
Joffe HV, Goldhaber SZ. Upper-extremity deep vein thrombosis. Circulation 2002;106:1874–1880.
Verso M, Agnelli G. Venous thromboembolism associated with long-term use of central venous catheters in cancer patients. J Clin Oncol 2003;21:3665–3675.
van Rooden CJ, Schippers EF, Barge RMY, et al. Infectious complications of central venous catheters increase the risk of catheter-related thrombosis in hematology patients: a prospective study. J Clin Oncol 2005;23:2655–2660.
Lordick F, Hentrich M, Decker T, et al. Ultrasound screening for internal jugular vein thrombosis aids the detection of central venous catheter-related infections in patients with haemato-oncological diseases: a prospective observational study. Br J Haematol 2003;120:1073–1078.
Khorana AA, Francis CW, Culakova E, et al. Risk factors for chemotherapy-associated venous thromboembolism in a prospective observational study. Cancer 2005;104:2822–2829.
Otten HM, Mathijssen J, ten Cate H, et al. Symptomatic venous thromboembolism in cancer patients treated with chemotherapy: an underestimated phenomenon. Arch Intern Med 2004;164:190–194.
Cummings SR, Eckert S, Krueger KA, et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 1999;281:2189–2197.
Decensi A, Maisonneuve P, Rotmensz N, et al. Effect of tamoxifen on venous thromboembolic events in a breast cancer prevention trial. Circulation 2005;111:650–656.
Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005;97:1652–1662.
Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998;90:1371–1388.
Vogel VG, Costantino JP, Wickerham DL, et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: preventing breast cancer. Cancer Prev Res (Phila) 2010;3:696–706.
Leaf AN, Propert K, Corcoran C, et al. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. Med Oncol 2003;20:137–146.
Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291:1701–1712.
Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333.
Blanco-Molina A, Trujillo-Santos J, Tirado R, et al. Venous thromboembolism in women using hormonal contraceptives. Findings from the RIETE Registry. Thromb Haemost 2009;101:478–482.
Lidegaard Ø, Nielsen LH, Skovlund CW, et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011;343(oct25 4):d6423.
Manzoli L, De Vito C, Marzuillo C, et al. Oral contraceptives and venous thromboembolism: a systematic review and meta-analysis. Drug Saf 2012;35:191–205.
Jick SS, Hernandez RK. Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data. BMJ 2011;342(apr21 2):d2151.
Parkin L, Sharples K, Hernandez RK, et al. Risk of venous thromboembolism in users of oral contraceptives containing drospirenone or levonorgestrel: nested case-control study based on UK General Practice Research Database. BMJ 2011;342(apr21 2):d2139.
Tepper NK, Dragoman MV, Gaffield ME, et al. Nonoral combined hormonal contraceptives and thromboembolism: a systematic review. Contraception 2017;95:130–139.
El Accaoui RN, Shamseddeen WA, Taher AT. Thalidomide and thrombosis: a meta-analysis. Thromb Haemost 2007;97:1031–1036.
Weber DM, Chen C, Niesvizky R, et al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 2007;357:2133–2142.
Zangari M, Siegel E, Barlogie B, et al. Thrombogenic activity of doxorubicin in myeloma patients receiving thalidomide: implications for therapy. Blood 2002;100:1168–1171.
Bennett CL, Silver SM, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA 2008;299:914–924.
Connolly GC, Dalal M, Lin J, et al. Incidence and predictors of venous thromboembolism (VTE) among ambulatory patients with lung cancer. Lung Cancer 2012;78:253–258.
Ay C, Dunkler D, Marosi C, et al. Prediction of venous thromboembolism in cancer patients. Blood 2010;116:5377–5382.
Mandala M, Clerici M, Corradino I, et al. Incidence, risk factors and clinical implications of venous thromboembolism in cancer patients treated within the context of phase I studies: the ‘SENDO experience’. Ann Oncol 2012;23:1416–1421.
Moore RA, Adel N, Riedel E, et al. High incidence of thromboembolic events in patients treated with cisplatin-based chemotherapy: a large retrospective analysis. J Clin Oncol 2011;29:3466–3473.
Kearney JC, Rossi S, Glinert K, et al. Venous thromboembolism (VTE) and survival in a cancer chemotherapy outpatient clinic: a retrospective chart review validation of a VTE predictive model. [abstract] Blood 2009;114:114. (Abstract 2503)
Price LH, Nguyen MB, Picozzi VJ, et al. Portal vein thrombosis in pancreatic cancer: Natural history, risk factors, and implications for patient management [abstract]. Proceedings of the Gastrointestinal Cancers Symposium 2010:Abstract 143.
Pabinger I, van Es N, Heinze G, et al. A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts. Lancet Haematol 2018;5:e289–e298.
Verso M, Agnelli G, Barni S, et al. A modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012;7:291–292.
Pelzer U, Sinn M, Stieler J, et al. [Primary pharmacological prevention of thromboembolic events in ambulatory patients with advanced pancreatic cancer treated with chemotherapy?]. Dtsch Med Wochenschr 2013;138:2084–2088.
Cella CA, Di Minno G, Carlomagno C, et al. Preventing venous thromboembolism in ambulatory cancer patients: the ONKOTEV Study. Oncologist 2017;22:601–608.
Muñoz Martín AJ, Ortega I, Font C, et al. Multivariable clinical-genetic risk model for predicting venous thromboembolic events in patients with cancer. Br J Cancer 2018;118:1056–1061.
Gerotziafas GT, Taher A, Abdel-Razeq H, et al. A predictive score for thrombosis associated with breast, colorectal, lung, or ovarian cancer: the Prospective COMPASS-Cancer-Associated Thrombosis study. Oncologist 2017;22:1222–1231.
van Es N, Di Nisio M, Cesarman G, et al. Comparison of risk prediction scores for venous thromboembolism in cancer patients: a prospective cohort study. Haematologica 2017;102:1494–1501.
Khorana AA, Soff GA, Kakkar AK, et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019;380:720–728.
Carrier M, Abou-Nassar K, Mallick R, et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019;380:711–719.
Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:381S-453S.
Kahn SR, Morrison DR, Diendéré G, et al. Interventions for implementation of thromboprophylaxis in hospitalized patients at risk for venous thromboembolism. Cochrane Database Syst Rev 2018;4:CD008201.
Kakkar VV, Corrigan TP, Fossard DP, et al. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. Reappraisal of results of international multicentre trial. Lancet 1977;1:567–569.
Mismetti P, Laporte S, Darmon JY, et al. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 2001;88:913–930.
Agnelli G, Bergqvist D, Cohen AT, et al. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005;92:1212–1220.
Kakkar AK, Levine M, Pinedo HM, et al. Venous thrombosis in cancer patients: insights from the FRONTLINE survey. Oncologist 2003;8:381–388.
Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008;371:387–394.
Tapson VF, Decousus H, Pini M, et al. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007;132:936–945.
Couban S, Goodyear M, Burnell M, et al. Randomized placebo-controlled study of low-dose warfarin for the prevention of central venous catheter-associated thrombosis in patients with cancer. J Clin Oncol 2005;23:4063–4069.
Karthaus M, Kretzschmar A, Kröning H, et al. Dalteparin for prevention of catheter-related complications in cancer patients with central venous catheters: final results of a double-blind, placebo-controlled phase III trial. Ann Oncol 2006;17:289–296.
Verso M, Agnelli G, Bertoglio S, et al. Enoxaparin for the prevention of venous thromboembolism associated with central vein catheter: a double-blind, placebo-controlled, randomized study in cancer patients. J Clin Oncol 2005;23:4057–4062.
Young AM, Billingham LJ, Begum G, et al. Warfarin thromboprophylaxis in cancer patients with central venous catheters (WARP): an open-label randomised trial. Lancet 2009;373:567–574.
Spyropoulos AC, Anderson FA, Jr., FitzGerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011;140:706–714.
Grant PJ, Greene MT, Chopra V, et al. Assessing the Caprini score for risk assessment of venous thromboembolism in hospitalized medical patients. Am J Med 2016;129:528–535.
Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010;8:2450–2457.
Greene MT, Spyropoulos AC, Chopra V, et al. Validation of risk assessment models of venous thromboembolism in hospitalized medical patients. Am J Med 2016;129:1001.e1009–1001.e1018.
Prescribing information. Dalteparin sodium injection, for subcutaneous use; 2020. Available at: .
Kucher N, Leizorovicz A, Vaitkus PT, et al. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med 2005;165:341–345.
Leizorovicz A, Cohen AT, Turpie AG, et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874–879.
Prescribing information. Enoxaparin sodium injection, for subcutaneous use; 2018. Available at: .
Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999;341:793–800.
Lederle FA, Sacks JM, Fiore L, et al. The prophylaxis of medical patients for thromboembolism pilot study. Am J Med 2006;119:54–59.
Kakkar AK, Cimminiello C, Goldhaber SZ, et al. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463–2472.
Prescribing information. Fondaparinux sodium solution for subcutaneous injection; 2020. Available at: .
Kahn SR, Lim W, Dunn AS, et al. 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 2012;141:e195S–226S.
Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325–329.
Belch JJ, Lowe GD, Ward AG, et al. Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J 1981;26:115–117.
Dentali F, Douketis JD, Gianni M, et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007;146:278–288.
Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg 1988;208:227–240.
King CS, Holley AB, Jackson JL, et al. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis. Chest 2007;131:507–516.
Prevention of fatal postoperative pulmonary embolism by low doses of heparin: an international multicentre trial. Lancet 1975;2:45–51.
Gruber UF, Duckert F, Fridrich R, et al. Prevention of postoperative thromboembolism by dextran 40, low doses of heparin, or xantinol nicotinate. Lancet 1977;1:207–210.
Rasmussen MS, Jorgensen LN, Wille-Jørgensen P, et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 2006;4:2384–2390.
Bergqvist D, Agnelli G, Cohen AT, et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002;346:975–980.
Turpie AG, Bauer KA, Caprini JA, et al. Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. J Thromb Haemost 2007;5:1854–1861.
Kakkar VV, Boeckl O, Boneu B, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 1997;21:2–8., discussion 8–9.
Koppenhagen K, Adolf J, Matthes M, et al. Low molecular weight heparin and prevention of postoperative thrombosis in abdominal surgery. Thromb Haemost 1992;67:627–630.
McLeod RS, Geerts WH, Sniderman KW, et al. Subcutaneous heparin versus low-molecular-weight heparin as thromboprophylaxis in patients undergoing colorectal surgery: results of the Canadian colorectal DVT prophylaxis trial: a randomized, double-blind trial. Ann Surg 2001;233:438–444.
ENOXACAN Study Group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg 1997;84:1099–1103.
Guntupalli SR, Brennecke A, Behbakht K, et al. Safety and efficacy of apixaban vs enoxaparin for preventing postoperative venous thromboembolism in women undergoing surgery for gynecologic malignant neoplasm: a randomized clinical trial. JAMA Netw Open 2020;3:e207410.
McGowan KE, Makari J, Diamantouros A, et al. Reducing the hospital burden of heparin-induced thrombocytopenia: impact of an avoid-heparin program. Blood 2016;127:1954–1959.
Akl EA, Terrenato I, Barba M, et al. Low-molecular-weight heparin vs unfractionated heparin for perioperative thromboprophylaxis in patients with cancer: a systematic review and meta-analysis. Arch Intern Med 2008;168:1261–1269.
DeBernardo RL, Jr., Perkins RB, Littell RD, et al. Low-molecular-weight heparin (dalteparin) in women with gynecologic malignancy. Obstet Gynecol 2005;105:1006–1011.
Nutescu EA, Spinler SA, Wittkowsky A, et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother 2009;43:1064–1083.
Becker RC, Spencer FA, Gibson M, et al. Influence of patient characteristics and renal function on factor Xa inhibition pharmacokinetics and pharmacodynamics after enoxaparin administration in non-ST-segment elevation acute coronary syndromes. Am Heart J 2002;143:753–759.
Bazinet A, Almanric K, Brunet C, et al. Dosage of enoxaparin among obese and renal impairment patients. Thromb Res 2005;116:41–50.
Chow SL, Zammit K, West K, et al. Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin. J Clin Pharmacol 2003;43:586–590.
Shprecher AR, Cheng-Lai A, Madsen EM, et al. Peak antifactor xa activity produced by dalteparin treatment in patients with renal impairment compared with controls. Pharmacotherapy 2005;25:817–822.
Polkinghorne KR, McMahon LP, Becker GJ. Pharmacokinetic studies of dalteparin (Fragmin), enoxaparin (Clexane), and danaparoid sodium (Orgaran) in stable chronic hemodialysis patients. Am J Kidney Dis 2002;40:990–995.
Lim W, Dentali F, Eikelboom JW, et al. Meta-analysis: low-molecular-weight heparin and bleeding in patients with severe renal insufficiency. Ann Intern Med 2006;144:673–684.
Spinler SA, Inverso SM, Cohen M, et al. Safety and efficacy of unfractionated heparin versus enoxaparin in patients who are obese and patients with severe renal impairment: analysis from the ESSENCE and TIMI 11B studies. Am Heart J 2003;146:33–41.
Thorevska N, Amoateng-Adjepong Y, Sabahi R, et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004;125:856–863.
Collet JP, Montalescot G, Agnelli G, et al. Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events. Eur Heart J 2005;26:2285–2293.
Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern Med 2007;147:304–310.
Scholten DJ, Hoedema RM, Scholten SE. A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg 2002;12:19–24.
Borkgren-Okonek MJ, Hart RW, Pantano JE, et al. Enoxaparin thromboprophylaxis in gastric bypass patients: extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008;4:625–631.
Simone EP, Madan AK, Tichansky DS, et al. Comparison of two low-molecular-weight heparin dosing regimens for patients undergoing laparoscopic bariatric surgery. Surg Endosc 2008;22:2392–2395.
Frederiksen SG, Hedenbro JL, Norgren L. Enoxaparin effect depends on body-weight and current doses may be inadequate in obese patients. Br J Surg 2003;90:547–548.
Martinez L, Burnett A, Borrego M, et al. Effect of fondaparinux prophylaxis on anti-factor Xa concentrations in patients with morbid obesity. Am J Health Syst Pharm 2011;68:1716–1722.
Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease: fragmin in unstable coronary artery disease study (FRIC). Circulation 1997;96:61–68.
Gaborit B, Moulin PA, Bege T, et al. Lean body weight is the best scale for venous thromboprophylaxis algorithm in severely obese patients undergoing bariatric surgery. Pharmacol Res 2018;131:211–217.
Freeman AL, Pendleton RC, Rondina MT. Prevention of venous thromboembolism in obesity. Expert Rev Cardiovasc Ther 2010;8:1711–1721.
Escalante-Tattersfield T, Tucker O, Fajnwaks P, et al. Incidence of deep vein thrombosis in morbidly obese patients undergoing laparoscopic Roux-en-Y gastric bypass. Surg Obes Relat Dis 2008;4:126–130.
Kardys CM, Stoner MC, Manwaring ML, et al. Safety and efficacy of intravascular ultrasound-guided inferior vena cava filter in super obese bariatric patients. Surg Obes Relat Dis 2008;4:50–54.
Rowan BO, Kuhl DA, Lee MD, et al. Anti-Xa levels in bariatric surgery patients receiving prophylactic enoxaparin. Obes Surg 2008;18:162–166.
Steib A, Degirmenci SE, Junke E, et al. Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study. Surg Obes Relat Dis 2016;12:613–621.
Brunetti L, Wassef A, Sadek R, et al. Anticoagulant activity of enoxaparin and unfractionated heparin for venous thromboembolism prophylaxis in obese patients undergoing sleeve gastrectomy. Surg Obes Relat Dis 2019;15:363–373.
Celik F, Huitema AD, Hooijberg JH, et al. Fixed-dose enoxaparin after bariatric surgery: the influence of body weight on peak anti-Xa levels. Obes Surg 2015;25:628–634.
Ojo P, Asiyanbola B, Valin E, et al. Post discharge prophylactic anticoagulation in gastric bypass patient-how safe? Obes Surg 2008;18:791–796.
Singh K, Podolsky ER, Um S, et al. Evaluating the safety and efficacy of BMI-based preoperative administration of low-molecular-weight heparin in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg 2012;22:47–51.
Rondina MT, Wheeler M, Rodgers GM, et al. Weight-based dosing of enoxaparin for VTE prophylaxis in morbidly obese, medically-Ill patients. Thromb Res 2010;125:220–223.
Al Otaib N, Bootah Z, Al Ammari MA, et al. Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients. Ann Thorac Med 2017;12:199–203.
Freeman A, Horner T, Pendleton RC, et al. Prospective comparison of three enoxaparin dosing regimens to achieve target anti-factor Xa levels in hospitalized, medically ill patients with extreme obesity. Am J Hematol 2012;87:740–743.
Steele KE, Canner J, Prokopowicz G, et al. The EFFORT trial: Preoperative enoxaparin versus postoperative fondaparinux for thromboprophylaxis in bariatric surgical patients: a randomized double-blind pilot trial. Surg Obes Relat Dis 2015;11:672–683.
Clarke-Pearson DL, Synan IS, Dodge R, et al. A randomized trial of low-dose heparin and intermittent pneumatic calf compression for the prevention of deep venous thrombosis after gynecologic oncology surgery. Am J Obstet Gynecol 1993;168:1146–1153., discussion 1153–1154.
Ramirez JI, Vassiliu P, Gonzalez-Ruiz C, et al. Sequential compression devices as prophylaxis for venous thromboembolism in high-risk colorectal surgery patients: reconsidering American Society of Colorectal Surgeons parameters. Am Surg 2003;69:941–945.
Dennis M, Sandercock P, Reid J, et al. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013;382:516–524.
Dennis M, Sandercock PA, Reid J, et al. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet 2009;373:1958–1965.
Martino MA, Borges E, Williamson E, et al. Pulmonary embolism after major abdominal surgery in gynecologic oncology. Obstet Gynecol 2006;107:666–671.
Arabi YM, Al-Hameed F, Burns KEA, et al. Adjunctive intermittent pneumatic compression for venous thromboprophylaxis. N Engl J Med 2019;380:1305–1315.
Amaragiri SV, Lees TA. Elastic compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev 2000; (3):CD001484.
Sachdeva A, Dalton M, Lees T. Graduated compression stockings for prevention of deep vein thrombosis. Cochrane Database Syst Rev 2018;11:CD001484.
Cohen AT, Skinner JA, Warwick D, et al. The use of graduated compression stockings in association with fondaparinux in surgery of the hip. A multicentre, multinational, randomised, open-label, parallel-group comparative study. J Bone Joint Surg Br 2007;89:887–892.
Shalhoub J, Lawton R, Hudson J, et al. Graduated compression stockings as adjuvant to pharmaco-thromboprophylaxis in elective surgical patients (GAPS study): randomised controlled trial. BMJ 2020;369:m1309.
Spencer FA, Lessard D, Emery C, et al. Venous thromboembolism in the outpatient setting. Arch Intern Med 2007;167:1471–1475.
Maraveyas A, Waters J, Roy R, et al. Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer. Eur J Cancer 2012;48:1283–1292.
Pelzer U, Opitz B, Deutschinoff G, et al. Efficacy of prophylactic low-molecular weight heparin for ambulatory patients with advanced pancreatic cancer: outcomes from the CONKO-004 trial. J Clin Oncol 2015;33:2028–2034.
Gould MK, Garcia DA, Wren SM, et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e227S–277S.
Felder S, Rasmussen MS, King R, et al. Prolonged thromboprophylaxis with low molecular weight heparin for abdominal or pelvic surgery. Cochrane Database Syst Rev 2019;8:CD004318.
Prescribing information. Rivaroxaban tablets, for oral use; 2018. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022406s028lbl.pdf.
Prescribing information. Heparin sodium injection. USP 2020.
Napolitano M, Saccullo G, Marietta M, et al. Platelet cut-off for anticoagulant therapy in thrombocytopenic patients with blood cancer and venous thromboembolism: an expert consensus. Blood Transfus 2019;17:171–180.
Khanal N, Bociek RG, Chen B