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Cancer-Associated Thrombosis: Improving Patient Adherence to Low-Molecular-Weight Heparin Therapy

Lijun Chen
CJON 2017, 21(4), 502-505 DOI: 10.1188/17.CJON.502-505

Although evidence-based treatment guidelines recommend low-molecular-weight heparin (LMWH) monotherapy for cancer-associated thrombosis (CAT), adherence to outpatient treatment guidelines for CAT still needs improvement. One of the challenges that clinicians face in treating CAT with LMWH is patient preference for oral anticoagulants over daily LMWH injections. This article aims to provide oncology nurses with practical advice on patient education to increase patient acceptance of and adherence to LMWH treatment for CAT.

AT A GLANCE

  • CAT is a major complication that affects patients with cancer throughout the course of their illness.
  • LMWH is effective and safe, and is the preferred treatment for CAT.
  • As patient advocates, oncology nurses can promote treatment acceptance and compliance among patients with CAT.
     

Cancer-associated thrombosis (CAT) refers to all thrombotic events encountered during the cancer journey. The association of cancer and venous thromboembolism, including deep vein thrombosis and pulmonary embolism, has been widely acknowledged since the 19th century and was first described by Armand Trousseau (1865). The risk for venous thromboembolism is four- to sevenfold higher in patients with cancer (Stein et al., 2006), which can be attributed to several factors, including the prothrombotic nature of the malignancy, administration of chemotherapy, suppression of fibrinolytic activity, use of vascular access devices, and surgical interventions used to treat cancer (Grier, 2014). The incidence of CAT has been rising because of greater chemotherapy use and extended survival time related to advances in cancer treatment (Khorana, Francis, Culakova, Kuderer, & Lyman, 2007a). Although CAT is linked to poorer prognoses and is the second leading cause of death in patients with cancer after disease progression, patients, particularly those receiving chemotherapy, usually have little knowledge or warning of their risk for CAT at the time of diagnosis (Noble, Prout, & Nelson, 2015). The support and information they receive on CAT from their medical oncologist or oncology nurse are often inadequate compared to the information they receive on chemotherapy treatment and associated side effects (Noble et al., 2015). The diagnosis of CAT is very physically and emotionally distressing for patients, particularly in the context of the major life event of a recent cancer diagnosis and ongoing cancer treatment. In addition, the management of CAT seems more complicated in the oncology setting because of the lack of ownership of its management among oncologists, primary care physicians, and hematologists. As patient advocates and educators, oncology nurses should proactively learn about newer developments in the management of CAT and apply that knowledge to daily patient care to ensure the best possible outcomes. This article provides an overview of the most recent standard treatment guidelines for CAT, as well as nursing interventions that may improve patient adherence to and satisfaction with recommended treatment.

Low-Molecular-Weight Heparin Therapy and Its Challenges

In the early 2000s, venous thromboembolism was treated with low-molecular-weight heparin (LMWH) or unfractionated heparin, as well as long-term oral anticoagulants, such as vitamin K antagonists like warfarin (Coumadin®) (Barbosa, 2014). Since 2006, more evidence has shown support for long-term LMWH as first-line treatment for CAT (Akl et al., 2008). Noble et al. (2008) published a comprehensive review of 19 publications, including a meta-analysis of four randomized, controlled trials, of anticoagulation treatment in patients with cancer. The data revealed a 50% reduction in relative risk in recurrent venous thromboembolism without increased bleeding rates in favor of LMWH over a vitamin K antagonists. The recommendation of long-term LMWH monotherapy was also considered appropriate in the advanced-cancer setting because 47%–65% of the patients enrolled in those trials had metastatic disease. In addition to improved efficacy, LMWH provides other advantages over vitamin K antagonists, including minimal need for monitoring, limited drug interactions, no food interactions, and consistent absorption of the drug owing to its parenteral administration (Lee & Peterson, 2013).

Three LMWHs are widely used in the United States and Canada: dalteparin (Fragmin®), enoxaparin (Lovenox®), and tinzaparin (Innohep®) (Merli & Groce, 2010). Guidelines recommend LMWH over vitamin K antagonists for the treatment of patients with cancer (Barbosa, 2014; Kearon et al., 2012; Lyman et al., 2007; Mandalà, Falanga, & Roila, 2011; National Comprehensive Cancer Network, 2013) and suggest that LMWH treatment last for three to six months. An indefinite course of treatment should be considered for patients on palliative chemotherapy and for those who are in remission but have a very high risk for recurrence (Barbosa, 2014). Because the treatment journey for CAT is prolonged, providers need to be attentive to patient compliance.

Although evidence-based treatment guidelines recommend LMWH monotherapy for CAT, warfarin-based treatment is used more often (Delate et al., 2012; Imberti et al., 2008; Wittkowsky, 2006). Kleinjan, Hutten, Di Nisio, Büller, and Kamphuisen (2014) presented a similar review and reached similar conclusions: 14% of patients with cancer and pulmonary embolism received LMWH for a prolonged period of time, revealing the need for better adherence to treatment guidelines for venous thromboembolism. The current author observed that clinicians sometimes prescribe oral anticoagulants instead of LMWH based on patient preference. Many patients with cancer prefer to take oral anticoagulants to avoid daily heparin injections, particularly with the emerging use of direct-acting oral anticoagulants to treat venous thromboembolism in patients without cancer. However, the efficacy and safety of direct-acting oral anticoagulants versus LMWH in oncology settings are still unknown (Posch, Königsbrügge, Zielinski, Pabinger, & Ay, 2015).

Seaman, Nelson, and Noble (2014) conducted a qualitative study in a palliative care setting and found that, although LMWH is considered an acceptable intervention, its long-term use is associated with bruising and deterioration at injection sites. Participants favored an oral anticoagulant if it was equivalent to LMWH in efficacy and safety.

Extensive Pretreatment Education

The key to successful implementation of nursing interventions and patient adherence to recommendations is adequate education. Patients and their families are far more likely to adhere to prescribed therapy if they understand the rationale behind it. Also, to effect better patient outcomes, oncology nurses should actively integrate the newest knowledge into daily practice. Clinical research shows that LMWH treatment may have an antineoplastic effect (Kuderer, Ortel, & Francis, 2009). The mechanisms by which LMWHs have this effect still need to be elucidated, but their antitumor action likely involves the inhibition of angiogenesis, inhibition of the release of coagulation proteases, immunomodulatory actions, and apoptosis (Khorana, 2007).

Well-written patient education should include the pathophysiology of and patient risk factors for CAT, benefits of LMWH treatment in oncology settings, and the monitoring and safety of LWMH injections (see Figure 1 for an example).

Improving Patient Experiences of Self-Injection

Patient refusal of self-injection could prompt physicians to prescribe warfarin-based therapy, although they are well aware of the treatment guidelines (Delate et al., 2012). Pain, lumps, and bruising are common side effects of self-injection, making it difficult for patients to locate new areas for injection. As patient educators, nurses play an extremely important role in managing the quality of patient experiences with self-injection of LMWH. Whether their CAT is managed by the oncology team or the primary care provider, patients need face-to-face teaching by nurses. An informative, accurate, easy-to-understand handout is a critical component of patient education on the self-injection of LMWH. Handouts should include detailed step-by-step instructions with illustrations.

The application of adaptive techniques to optimize ongoing injection and reduce patient injury, fear, and anxiety is one of the tasks of oncology nurses. Kuzu and Ucar (2001) investigated the effects of ice application on bruising, hematoma, and pain at the injection site of subcutaneous enoxaparin in patients. Hematoma did not occur at the injection site of any participants, and no significant difference in the incidence or size of bruise among the groups was observed; however, the participants’ perception of pain was significantly less with ice application. Dehghani, Najari, and Dehghani (2014) reported that the duration of enoxaparin injections had no effect on the size of the bruise in patients with acute coronary syndrome. Amaniyan, Varaei, Vaismoradi, Haghani, and Sieloff (2016) found that the local application of cold/hot packs was more effective in reducing bruises following enoxaparin sodium injections compared to local cold-pack application alone. More studies are needed to improve patients’ satisfaction with daily LMWH injections.

Conclusion

As many as 20% of adults with malignancy will develop CAT during the course of their disease (Brose & Lee, 2008). In addition to acute and long-term morbidity, CAT remains the number one cause of death during chemotherapy and the second most common cause of all cancer deaths (Khorana et al., 2007b). Although other cancer complications have clear treatment pathways, CAT does not appear to have been afforded the same treatment priority. Oncology nurses should take on the critical role of improving patient adherence to current recommended LMWH therapy by providing thorough patient education and optimizing patient experiences of LMWH injections, reducing mortality, morbidity, and long-term psychological distress caused by CAT.

About the Author(s)

Lijun Chen, PhD, RN, OCN®, CCRC®, is a clinical research manager at the University of Texas Southwestern Harold C. Simmons Comprehensive Cancer Center in Dallas. The author takes full responsibility for this content and did not receive honoraria or disclose any relevant financial relationships. Mention of specific products and opinions related to those products do not indicate or imply endorsement by the Oncology Nursing Society. Chen can be reached at lijun.chen@utsouthwestern.edu, with copy to CJONEditor@ons.org.

 

References 

Akl, E.A., Barba, M., Rohilla, S., Terrenato, I., Sperati, F., Muti, P., & Schünemann, H.J. (2008). Low-molecular-weight heparins are superior to vitamin K antagonists for the long term treatment of venous thromboembolism in patients with cancer: A cochrane systematic review. Journal of Experimental and Clinical Cancer Research, 27, 21–32. doi:10.1186/1756-9966-27-21

Alifano, M., Benedetti, G., & Trisolini, R. (2004). Can low-molecular-weight heparin improve the outcome of patients with operable non-small cell lung cancer? An urgent call for research. Chest, 126, 601–607. doi:10.1378/chest.126.2.601

Altinbas, M., Coskun, H.S., Er, O., Ozkan, M., Eser, B, Unal, A., . . . & Soyuer, S.A. (2004). A randomized clinical trial of combination chemotherapy with and without low-molecular-weight heparin in small cell lung cancer. Journal of Thrombosis and Haemostasis, 2, 1266–1271. doi:10.1111/j.1538-7836.2004.00871.x

Amaniyan, S., Varaei, S., Vaismoradi, M., Haghani, H., & Sieloff, C. (2016). Effect of local cold and hot pack on the bruising of enoxaparin sodium injection site: A randomized controlled trial. Contemporary Nurse, 52, 30–41. doi:10.1080/10376178.2016.1190289

Babin, J.L., Traylor, K.L., & Witt, D.M. (2017). Laboratory monitoring of low-molecular-weight heparin and fondaparinux. Seminars in Thrombosis and Hemostasis, 43, 261–269. doi:10.1055/s-0036-1581129

Barbosa, M. (2014). What is the best treatment for a cancer patient with thrombosis? Clinical Medicine Insights: Oncology, 8, 49–55. doi:10.4137/CMO.S13386

Brose, K.M.J., & Lee, A.Y.Y. (2008). Cancer-associated thrombosis: Prevention and treatment. Current Oncology, 15(Suppl. 1), S58–S67.

Debergh, I., Van Damme, N., Pattyn, P., Peeters, M., & Ceelen, W.P. (2010). The low-molecular-weight heparin, nadroparin, inhibits tumour angiogenesis in a rodent dorsal skinfold chamber model. British Journal of Cancer, 102, 837–843. doi:10.1038/sj.bjc.6605535

Dehghani, K., Najari, Z., & Dehghani, H. (2014). Effect of subcutaneous enoxaparin injection duration on bruising size in acute coronary syndrome patients. Iranian Journal of Nursing and Midwifery Research, 19, 564–568.

Delate, T., Witt, D.M., Ritzwoller, D., Weeks, J.C., Kushi, L., Hornbrook, M.C., . . . Schrag, D. (2012). Outpatient use of low molecular weight heparin monotherapy for first-line treatment of venous thromboembolism in advanced cancer. Oncologist, 17, 419–427. doi:10.1634/theoncologist.2011-0323

Elyamany, G., Alzahrani, A.M., Bukhary, E. (2014). Cancer-associated thrombosis: An overview. Clinical Medicine Insights: Oncology, 8, 129–137. doi:10.4137/CMO.S18991

Grier, M.A. (2014). Prevention of venous thromboembolism in adult patients with cancer in the acute care setting. Clinical Journal of Oncology Nursing, 18, 290–295. doi:10.1188/14.CJON.18-03AP

Imberti, D., Agnelli, G., Ageno, W., Moia, M., Palareti, G., Pistelli, R., . . . Verso, M. (2008). Clinical characteristics and management of cancer-associated acute venous thromboembolism: Findings from the MASTER Registry. Haematologica, 93, 273–278. doi:10.3324/haematol.11458

Kakkar, A.K., Levine, M.N., Kadziola, Z., Lemoine, N.R., Low, V., Patel, H.K., . . . Williamson, R.C.N. (2004). Low molecular weight heparin, therapy with dalteparin, and survival in advanced cancer: The Fragmin Advanced Malignancy Outcome Study (FAMOUS). Journal of Clinical Oncology, 22, 1944–1948. doi:10.1200/JCO.2004.10.002

Kearon, C., Akl, E.A., Comerota, A.J., Prandoni, P., Bounameaux, H., Goldhaber, S.Z., . . . Kahn, S.R. (2012). Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed.: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 141, 2(Suppl.), e419S–e494S. doi:10.1378/chest.11-2301

Khorana, A.A. (2007). The NCCN clinical practice guidelines on venous thromboembolic disease: Strategies for improving VTE prophylaxis in hospitalized cancer patients. Oncologist, 12, 1361–1370. doi:10.1634/theoncologist.12-11-1361

Khorana, A.A., Francis, C.W., Culakova, E., Kuderer, N.M., & Lyman, G.H. (2007a). Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer, 110, 2339–2346. doi:10.1002/cncr.23062

Khorana, A.A., Francis, C.W., Culakova, E., Kuderer, N.M., & Lyman, G.H. (2007b). Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. Journal of Thrombosis and Haemostasis, 5, 632–634.

Kleinjan, A., Hutten, B.A., Di Nisio, M., Büller, H.R., & Kamphuisen, P.W. (2014). Anticoagulant treatment of cancer patients with pulmonary embolism in the real world: Actual use of low-molecular-weight heparin in cancer. Netherlands Journal of Medicine, 72, 467–72.

Klerk, C.P.W., Smorenburg, S.M., Otten, H.-M., Lensing, A.W.A., Prins, M.H., Piovella, F., . . . Büller, H.R. (2005). The effect of low molecular weight heparin on survival in patients with advanced malignancy. Journal of Clinical Oncology, 23, 2130–2135. doi:10.1200/JCO.2005.03.134

Kuderer, N.M., Ortel, T.L., & Francis, C.W. (2009). Impact of venous thromboembolism and anticoagulation on cancer and cancer survival. Journal of Clinical Oncology, 27, 4902–4911. doi:10.1200/JCO.2009.22.4584

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. International Journal of Nursing Studies, 38, 51–59.

Lee, A.Y.Y., & Peterson, E.A. (2013). Treatment of cancer-associated thrombosis. Blood, 122, 2310–2317. doi:10.1182/blood-2013-04-460162

Lee, A.Y.Y., Rickles, F.R., Julian, J.A., Gent, M., Baker, R.I., Bowden, C., . . . Levine, M.N. (2005). Randomized comparison of low molecular weight heparin and coumarin derivatives on the survival of patients with cancer and venous thromboembolism. Journal of Clinical Oncology, 23, 2123–2129. doi:10.1200/JCO.2005.03.133

Loynes, J.T., Zacharski, L.R., & Rigas, J.R. (2002). Regression of metastatic non-small cell lung cancer with low molecular weight heparin. Thrombosis and Haemostasis, 88, 686.

Lyman, G.H., Khorana, A.A., Falanga, A., Clarke-Pearson, D., Flowers, C., Jahanzeb, M., & Francis, C.W. (2007). American Society of Clinical Oncology guideline: Recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. Journal of Clinical Oncology, 25, 5490–5505. doi:10.1200/JCO.2007.14.1283

Mandalà, M., Falanga, A., & Roila, F. (2011). Management of venous thromboembolism (VTE) in cancer patients: ESMO clinical practice guidelines. Annals of Oncology, 22(Suppl. 6), vi85–vi92. doi:10.1093/annonc/mdr392

Merli, G.J., & Groce, J.B. (2010). Pharmacological and clinical differences between low-molecular-weight heparins: Implications for prescribing practice and therapeutic interchange. Pharmacy and Therapeutics, 35, 95–105.

Mousa, S.A., & Petersen, L.J. (2009). Anti-cancer properties of low-molecular-weight heparin: Preclinical evidence. Thrombosis and Haemostasis, 102, 258–267. doi:10.1160/TH08-12-0832

National Comprehensive Cancer Network. (2013). NCCN Clinical Practice Guidelines in Oncology (NCCN® Guidelines): Venous thromboembolism disease [v.2.2013]. Retrieved from https://www.nccn.org/professionals/physician_gls/f_guidelines.asp#suppor...

Noble, S., Prout, H., & Nelson, A. (2015). Patients’ experiences of living with cancer-associated thrombosis: The PELICAN study. Patient Preference and Adherence, 9, 337–345. doi:10.2147/PPA.S79373

Noble, S.I.R., Shelley, M.D., Coles, B., Williams, S.M., Wilcock, A., & Johnson, M.J. (2008). Management of venous thromboembolism in patients with advanced cancer: A systematic review and meta-analysis. Lancet Oncology, 9, 577–584. doi:10.1016/S1470-2045(08)70149-9

Posch, F., Königsbrügge, O., Zielinski, C., Pabinger, I., & Ay, C. (2015). Treatment of venous thromboembolism in patients with cancer: A network meta-analysis comparing efficacy and safety of anticoagulants. Thrombosis Research, 136, 582–589. doi:10.1016/j.thromres.2015.07.011

Seaman, S., Nelson, A., & Noble, S. (2014). Cancer-associated thrombosis, low-molecular-weight heparin, and the patient experience: A qualitative study. Patient Preference and Adherence, 8, 453–461. doi:10.2147/PPA.S58595

Stein, P.D., Beemath, A., Meyers, F.A., Skaf, E., Sanchez, J., & Olson, R.E. (2006). Incidence of venous thromboembolism in patients hospitalized with cancer. American Journal of Medicine, 119, 60–68. doi:10.1016/j.amjmed.2005.06.058

Trousseau, A. (1865). Phlegmasia alba dolens. In A. Trousseau, Clinique Medicale de l’Hotel Dieu de Paris, vol. 3 (pp. 654–712). London: New Sydenham Society.

Wittkowsky, A.K. (2006). Barriers to the long-term use of low-molecular weight heparins for treatment of cancer-associated thrombosis. Journal of Thrombosis and Haemostasis, 4, 2090–2091. doi:10.1111/j.1538-7836.2006.02073.x