Venous Thromboembolism Treatment and Prevention in Cancer Patients: Can We Use Pills Yet? - Beyond the Abstract

Active cancer alone is a risk for venous thromboembolism (VTE). However, many cancer patients have additional risk factors for VTE including older age, poor performance status, tobacco use, obesity, physical inactivity, familial hypercoagulability, or presence of bulky lymphadenopathy resulting in venous compression.1 Furthermore, patients receiving chemotherapy have an increased risk for VTE if their hemoglobin is < 10g/dL, body mass index (BMI) is greater than or equal to 35 kg/m2, have a history of VTE, or if pre-treatment labs show platelets > 350,00mcL or white blood cell count > 11,000/mcL.2,3 Additionally, treatment-related events can increase VTE risk including major surgery, placement of a central venous catheter, or use of exogenous hormonal therapies.1 Given the prevalence of these risk factors, it is not surprising that cancer patients have a 7-fold increased risk of VTE compared to the general population.4 Therefore, guidelines for the prevention and treatment of venous thromboembolism in cancer patients are essential.

The National Comprehensive Cancer Network (NCCN) recommends prophylactic anticoagulation for all hospitalized patients with known or suspected cancer.1 Following major abdominal surgery, this prophylaxis should be continued for four weeks, which has resulted in a 50% reduction in venous thromboembolism.5,6 Patients who develop a VTE can be treated either with single-agent therapy or combination therapy.1 Anticoagulation should be continued for at least three months (six months for hepatic, portal, mesenteric, or splenic vein thrombosis), as long as the patient has active cancer, is receiving treatment, or if the inciting risk factor remains persistent.1 Catheter-related VTEs should be treated as long as the catheter is in place.1

Selection of an anticoagulant can be challenging given the number of agents available as well as patient-related factors including bleeding risk, ability to administer the anticoagulation, options for drug reversal, drug cost, adequate hepatic or renal function, and patient preference.1 NCCN guidelines favor the use of single-agent low molecular weight heparin, edoxaban, or rivaroxaban,7 but practice patterns vary. Our full article provides a discussion of the data surrounding anticoagulation selection and the increasing utilization of direct oral anticoagulants (DOACs). Use of DOACs for treatment of VTE in cancer patients and prevention of VTE in cancer patients undergoing surgery has become more common in recent years, fueled by increased provider experience with these agents in other clinical settings, ease of administration, and patient preference. Although existing data remains somewhat limited for patients with cancer, the full article reviews recent studies and meta-analyses that demonstrate the potential effectiveness and safety of this new class of drugs in cancer patients. There are also several on-going clinical trials that will continue to add to our knowledge of the role of DOACs in patients with cancer. 

Although this was not formally covered in the review article, healthcare providers should be mindful of modifications or contraindications to pharmacologic anticoagulation. Obesity is a common indication for anti-coagulation dose adjustments. Specifically, patients with a BMI of greater than or equal to 40kg/m2 often require higher or more frequent dosing to reach efficacious levels.1 Agent-specific contraindications are beyond the scope of this commentary. However, the following are general contraindications to prophylactic anticoagulation: active bleeding, thrombocytopenia (platelets < 30,000 - 50,000/mcL), underlying coagulopathy or bleeding disorder, presence of indwelling neuraxial catheters (specifically apixaban, dabigatran, edoxaban, fondaparinux, rivaroxaban, or enoxaparin dose >40mg/day), interventional spine or pain procedures, or neuraxial anesthesia/lumbar punctures.1 Similarly, the absolute contraindications for therapeutic anticoagulation are active bleeding, neuraxial catheters, neuraxial anesthesia/ lumbar puncture, or interventional spine and pain procedures. Relative contraindications to therapeutic anticoagulation are thrombocytopenia, underlying coagulopathy or bleeding disorders, severe platelet dysfunction, recent operation with high bleeding risk, high fall risk, CNS metastases, or long-term antiplatelet therapy.1

Patients are sometimes eligible for anticoagulation based on the previously listed criteria; however, anticoagulation is not always administered. Healthcare providers should discuss risks and benefits with patients, allowing for patient refusal. The use of prophylactic peri and post-operative anticoagulation for minimally invasive cancer surgeries in low-risk patients has been questioned given the low risk of VTE compared to historical cohorts undergoing laparotomy that were the basis for many of the risk calculators.8,9 However, given the excellent safety profile, even in higher-risk patients,6 usage in relatively lower risk surgical cancer patients is certainly reasonable. Additionally, anticoagulation may be withheld if there is no therapeutic advantage (high-risk in a patient with limited survival), no palliative benefit, or decreased quality of life associated with receipt of treatment/monitoring plan.1 

Written by: Shannon Armbruster MD, Twitter: @SArmbrusterMD, Erin Saks MD, and David A. Iglesias MD, Division of Gynecologic Oncology, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia


  1. Streiff MB HB, Angelini D et al. NCCN Guidelines Version 1.2020 Cancer-Associated Venous Thromboembolic Disease: National Comprehensive Cancer Network; 2020
  2. Khorana, Alok A., Nicole M. Kuderer, Eva Culakova, Gary H. Lyman, and Charles W. Francis. "Development and validation of a predictive model for chemotherapy-associated thrombosis." Blood 111, no. 10 (2008): 4902-4907.
  3. Mandala, M., S. Barni, M. Prins, R. Labianca, C. Tondini, L. Russo, A. Milesi et al. "Acquired and inherited risk factors for developing venous thromboembolism in cancer patients receiving adjuvant chemotherapy: a prospective trial." Annals of oncology 21, no. 4 (2010): 871-876.
  4. Blom, Jeanet W., Carine JM Doggen, Susanne Osanto, and Frits R. Rosendaal. "Malignancies, prothrombotic mutations, and the risk of venous thrombosis." Jama 293, no. 6 (2005): 715-722.
  5. Bergqvist, David, Giancarlo Agnelli, Alexander T. Cohen, Amiram Eldor, Paul E. Nilsson, Anne Le Moigne-Amrani, and Flavia Dietrich-Neto. "Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer." New England Journal of Medicine 346, no. 13 (2002): 975-980.
  6. RASMUSSEN, Morten Schnack, L. N. Jorgensen, P. Wille‐Jørgensen, J. D. Nielsen, A. Horn, A. C. Mohn, L. Sømod, B. Olsen, and FAME INVESTIGATORS. "Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open‐label study." Journal of Thrombosis and Haemostasis 4, no. 11 (2006): 2384-2390.
  7. Streiff, Michael B., Bjorn Holmstrom, Dana Angelini, Aneel Ashrani, Paula L. Bockenstedt, Carolyn Chesney, John Fanikos et al. "NCCN guidelines insights: cancer-associated venous thromboembolic disease, version 2.2018." Journal of the National Comprehensive Cancer Network 16, no. 11 (2018): 1289-1303.
  8. Freeman, Alexandra H., Allison Barrie, Liisa Lyon, Ramey D. Littell, Christine Garcia, Carol Conell, and C. Bethan Powell. "Venous thromboembolism following minimally invasive surgery among women with endometrial cancer." Gynecologic oncology 142, no. 2 (2016): 267-272.
  9. Kim, Josephine S., Kathryn A. Mills, Julia Fehniger, Chuanhong Liao, Jean A. Hurteau, Carolyn V. Kirschner, Nita K. Lee et al. "Venous thromboembolism in patients receiving extended pharmacologic prophylaxis after robotic surgery for endometrial cancer." International Journal of Gynecologic Cancer 27, no. 8 (2017): 1774-1782.
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