Top

Published in:

Open Access 01-12-2021 | Cancer-Associated Venous Thrombosis | Review

Current status of treatment of cancer-associated venous thromboembolism

Author: Wei Xiong

Published in: Thrombosis Journal | Issue 1/2021

Abstract

Patients with cancer are prone to develop venous thromboembolism (VTE) that is the second leading cause of mortality among them. Cancer patients with VTE may encounter higher rates of VTE recurrence and bleeding complications than patients without cancer. Treatment of established VTE is often complex in patients with cancer. Treatment of cancer-associated VTE basically comprises initial treatment, long-term treatment, treatment within 6 months, treatment beyond 6 months, treatment of recurrent VTE, and treatment in special situations. Decision of antithrombotic therapy, selection of anticoagulants, duration of anticoagulation, decision of adjuvant therapy, and adjustment of regimen in special situations are the major problems in the treatment of cancer-associated VTE. Therapeutic anticoagulation is the key of the key in the treatment of cancer-associated VTE. In addition to the efficacy and safety of low-molecular-weight heparin (LMWH) that has been fully demonstrated, direct oral anticoagulants (DOACs) are increasingly showing its advantages along with the accompanying concern in the treatment of cancer-associated VTE. The latest ASCO, ITAC and NCCN guidelines agree with each other on most aspects with respect to the treatment of cancer-associated VTE, whereas differ on a few issues. Encompassing recent randomized controlled trials, clinical trials, and meta-analyses, as well as the comparison of the latest authoritative guidelines including the NCCN, ASCO, and ITAC guidelines in this field, the objective of this review is to present current overview and recommendations for the treatment of cancer-associated VTE.

Streiff MB, Holmstrom B, Angelini D, Ashrani A, Bockenstedt PL, Chesney C, et al. NCCN guidelines insights: Cancer-associated venous thromboembolic disease, version 2.2018. J Natl Compr Cancer Netw. 2018;16(11):1289–303. https://doi.org/10.6004/jnccn.2018.0084.CrossRef

Farge D, Frere C, Connors JM, Ay C, Khorana AA, Munoz A, et al. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2019;20(10):e566–81. https://doi.org/10.1016/S1470-2045(19)30336-5.CrossRefPubMed

Curigliano G, Cardinale D, Dent S, Criscitiello C, Aseyev O, Lenihan D, et al. Cardiotoxicity of anticancer treatments: epidemiology, detection, and management. CA Cancer J Clin. 2016;66(4):309–25. https://doi.org/10.3322/caac.21341.CrossRefPubMed

Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thromb Res. 2018;164(Suppl 1):S112–8. https://doi.org/10.1016/j.thromres.2018.01.028.CrossRefPubMed

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous thromboembolism prophylaxis and treatment in patients with Cancer: ASCO clinical practice guideline update. J Clin Oncol. 2020;38(5):496–520. https://doi.org/10.1200/JCO.19.01461.CrossRefPubMed

Shimabukuro-Vornhagen A, Böll B, Kochanek M, Azoulay É, von Bergwelt-Baildon MS. Critical care of patients with cancer. CA Cancer J Clin. 2016;66(6):496–517. https://doi.org/10.3322/caac.21351.CrossRefPubMed

Tsoukalas N, Tsapakidis K, Galanopoulos M, Karamitrousis E, Kamposioras K, Tolia M. Real world data regarding the management of cancer-associated thrombosis. Curr Opin Oncol. 2020;32(4):289–94.CrossRef

Guo JD, Hlavacek P, Poretta T, Wygant G, Lane D, Gorritz M, et al. Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States. J Thromb Thrombolysis. 2020;50(2):386–94. https://doi.org/10.1007/s11239-019-02032-3.CrossRefPubMedPubMedCentral

Delate T, Charlu M, Zhu S, Pai A, Clark NP, Witt DM, et al. Temporal trends in first-line outpatient anticoagulation treatment for cancer-associated venous thromboembolism [published online ahead of print, 2020 Sep 10]. Thromb Res. 2020;196:367–70. https://doi.org/10.1016/j.thromres.2020.09.008.CrossRefPubMed

10.

Ueyama H, Miyashita H, Takagi H, et al. Network meta-analysis of anticoagulation strategies for venous thromboembolism in patients with cancer [published online ahead of print, 2020 May 26]. J Thromb Thrombolysis. 2020;51(1):102. https://doi.org/10.1007/s11239-020-02151-2.CrossRef

11.

Sidahmed S, Abdalla A, Kheiri B, Bala A, Salih M, Bachuwa G, et al. Anticoagulants for the treatment of venous thromboembolism in patients with cancer: a comprehensive systematic review, pairwise and network meta-analysis. Crit Rev Oncol Hematol. 2020;152:103005. https://doi.org/10.1016/j.critrevonc.2020.103005.CrossRefPubMed

12.

Hakoum MB, Kahale LA, Tsolakian IG, et al. Anticoagulation for the initial treatment of venous thromboembolism in people with cancer. Cochrane Database Syst Rev. 2018;1(1):CD006649.PubMed

13.

Fuller K, Malecki S, Anselmo L, Borrego ME, Jakeman B, Burnett A. Once-daily versus twice-daily enoxaparin for the treatment of acute venous thromboembolism in Cancer patients. Ann Pharmacother. 2018;52(3):257–62. https://doi.org/10.1177/1060028017737094.CrossRefPubMed

14.

Agnelli G, Becattini C, Meyer G, et al. Apixaban for the treatment of venous thromboembolism associated with Cancer. N Engl J Med. 2020;382(17):1599–607.CrossRef

15.

Brunetti ND, Tricarico L, Correale M, de Gennaro L, Santoro F, Ieva R, et al. Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials. J Thromb Thrombolysis. 2020;50(2):305–10. https://doi.org/10.1007/s11239-019-01974-y.CrossRefPubMed

16.

Giustozzi M, Agnelli G, Del Toro-Cervera J, et al. Direct Oral anticoagulants for the treatment of acute venous thromboembolism associated with Cancer: a systematic review and meta-analysis. Thromb Haemost. 2020;120(7):1128–36. https://doi.org/10.1055/s-0040-1712098.CrossRefPubMed

17.

Balabhadra S, Kuban JD, Lee S, et al. Association of Inferior Vena Cava Filter Placement with Rates of pulmonary embolism in patients with Cancer and acute lower extremity deep venous thrombosis. JAMA Netw Open. 2020;3(7):e2011079.CrossRef

18.

Quezada A, Jiménez D, Bikdeli B, Muriel A, Aramberri M, López-Jiménez L, et al. Outcomes after vena cava filter use in patients with Cancer-associated venous thromboembolism and contraindications to anticoagulation. Thromb Haemost. 2020;120(7):1035–44. https://doi.org/10.1055/s-0040-1710589.CrossRefPubMed

19.

Brailovsky Y, Yeung HM, Lakhter V, Zack CJ, Zhao H, Bashir R. In-hospital outcomes of catheter-directed thrombolysis versus anticoagulation in cancer patients with proximal deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2020;8(4):538–544.e3.CrossRef

20.

Kahale LA, Hakoum MB, Tsolakian IG, et al. Anticoagulation for the long-term treatment of venous thromboembolism in people with cancer. Cochrane Database Syst Rev. 2018;6(6):CD006650.PubMed

21.

Raskob GE, van Es N, Verhamme P, et al. Edoxaban for the treatment of Cancer-associated venous thromboembolism. N Engl J Med. 2018;378(7):615–24.CrossRef

22.

Mulder FI, van Es N, Kraaijpoel N, et al. Edoxaban for treatment of venous thromboembolism in patient groups with different types of cancer: results from the Hokusai VTE Cancer study [published correction appears in Thromb res. 2020 Jul;191:156-159]. Thromb Res. 2020;185:13–9.CrossRef

23.

Marshall A, Levine M, Hill C, et al. Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D trial (SELECT-D: 12m). J Thromb Haemost. 2020;18(4):905–15.CrossRef

24.

Schmidt RA, Al Zaki A, Desilet N, et al. Patient characteristics and long-term outcomes beyond the first 6 months after a diagnosis of cancer-associated venous thromboembolism. Thromb Res. 2020;188:106–14. https://doi.org/10.1016/j.thromres.2020.02.005.CrossRefPubMed

25.

Davies GA, Lazo-Langner A, Gandara E, Rodger M, Tagalakis V, Louzada M, et al. A prospective study of rivaroxaban for central venous catheter associated upper extremity deep vein thrombosis in cancer patients (catheter 2). Thromb Res. 2018;162:88–92. https://doi.org/10.1016/j.thromres.2017.04.003.CrossRefPubMed

26.

Piran S, Schulman S. Management of recurrent venous thromboembolism in patients with cancer: a review. Thromb Res. 2018;164(Suppl 1):S172–7. https://doi.org/10.1016/j.thromres.2017.12.019.CrossRefPubMed

27.

Schulman S, Zondag M, Linkins L, et al. Recurrent venous thromboembolism in anticoagulated patients with cancer: management and short-term prognosis. J Thromb Haemost. 2015;13(6):1010–8.CrossRef

28.

Porfidia A, Giordano M, Sturiale CL, et al. Risk of intracranial bleeding in patients with primary brain cancer receiving therapeutic anticoagulation for venous thromboembolism: a meta-analysis. Brain Behav. 2020;10(6):e01638.CrossRef

29.

Carney BJ, Uhlmann EJ, Puligandla M, et al. Intracranial hemorrhage with direct oral anticoagulants in patients with brain tumors. J Thromb Haemost. 2019;17(1):72–6.CrossRef

30.

Leader A, Gurevich-Shapiro A, Spectre G. Anticoagulant and antiplatelet treatment in cancer patients with thrombocytopenia. Thromb Res. 2020;191(Suppl 1):S68–73. https://doi.org/10.1016/S0049-3848(20)30400-X.CrossRefPubMed

31.

Golightly LK, Simendinger BA, Kiser TH. Cancer-associated thromboembolism: antithrombotic management of hospitalized patients. J Thromb Thrombolysis. 2020;49(1):59–66. https://doi.org/10.1007/s11239-019-01935-5.CrossRefPubMed

32.

Lecumberri R, Ruiz-Artacho P, Trujillo-Santos J, Brenner B, Barillari G, Ruiz-Ruiz J, et al. Management and outcomes of cancer patients with venous thromboembolism presenting with thrombocytopenia. Thromb Res. 2020;195:139–45. https://doi.org/10.1016/j.thromres.2020.07.021.CrossRefPubMed

33.

Bauersachs R, Lee AYY, Kamphuisen PW, Meyer G, Janas MS, Jarner MF, et al. Renal impairment, recurrent venous thromboembolism and bleeding in Cancer patients with acute venous thromboembolism-analysis of the CATCH study. Thromb Haemost. 2018;118(5):914–21. https://doi.org/10.1055/s-0038-1641150.CrossRefPubMed

34.

Woodruff S, Feugère G, Abreu P, Heissler J, Ruiz MT, Jen F. A post hoc analysis of dalteparin versus oral anticoagulant (VKA) therapy for the prevention of recurrent venous thromboembolism (rVTE) in patients with cancer and renal impairment. J Thromb Thrombolysis. 2016;42(4):494–504. https://doi.org/10.1007/s11239-016-1386-8.CrossRefPubMedPubMedCentral

35.

Xu A, Sibai H, Atenafu EG, Japs K, Seki JT. Universal venous thromboembolism policy is effective but may not adequately protect hospitalized cancer patients with larger BMI. J Thromb Thrombolysis. 2020;49(1):113–20. https://doi.org/10.1007/s11239-019-01975-x.CrossRefPubMed

36.

Hase EA, VIPVL B, AMK I, RPV F, Zugaib M. Risk assessment of venous thromboembolism and thromboprophylaxis in pregnant women hospitalized with cancer: Preliminary results from a risk score. Clinics (Sao Paulo). 2018;73:e368.CrossRef

37.

Young AM, Marshall A, Thirlwall J, Chapman O, Lokare A, Hill C, et al. Comparison of an Oral factor Xa inhibitor with low molecular weight heparin in patients with Cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018;36(20):2017–23. https://doi.org/10.1200/JCO.2018.78.8034.CrossRefPubMed

38.

Dong S, Zhang Y, Li Y, et al. Direct Oral Anticoagulant for the Treatment of VTE in Cancer Patients: A Systematic Review and Meta-analysis [published online ahead of print, 2020 Sep 16]. Ann Pharmacother. 2020;173:158.

39.

Desai R, Koipallil GK, Thomas N, et al. Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials. Sci Rep. 2020;10(1):18945.CrossRef

40.

Mulder FI, Bosch FTM, Young AM, et al. Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis. Blood. 2020;136(12):1433–41.CrossRef

41.

Haykal T, Zayed Y, Deliwala S, Kerbage J, Ponnapalli A, Malladi S, et al. Direct oral anticoagulant versus low-molecular-weight heparin for treatment of venous thromboembolism in cancer patients: an updated meta-analysis of randomized controlled trials. Thromb Res. 2020;194:57–65. https://doi.org/10.1016/j.thromres.2020.06.025.CrossRefPubMed

42.

Gu ZC, Yan YD, Yang SY, Shen L, Kong LC, Zhang C, et al. Direct versus conventional anticoagulants for treatment of cancer associated thrombosis: a pooled and interaction analysis between observational studies and randomized clinical trials. Ann Transl Med. 2020;8(4):95. https://doi.org/10.21037/atm.2019.12.152.CrossRefPubMedPubMedCentral

43.

Elbadawi A, Shnoda M, Mahmoud K, Elgendy IY. Efficacy and safety of direct oral anticoagulants versus low molecular weight heparin for cancer related venous thromboembolism: A meta-analysis of randomized trials [published online ahead of print, 2020 Jun 18]. Eur Heart J Cardiovasc Pharmacother. 2020;1:pvaa067.CrossRef

44.

McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: the ADAM VTE trial. J Thromb Haemost. 2020;18(2):411–21. https://doi.org/10.1111/jth.14662.CrossRefPubMed

45.

Mai V, Tanguay VF, Guay CA, et al. DOAC compared to LMWH in the treatment of cancer related-venous thromboembolism: a systematic review and meta-analysis. J Thromb Thrombolysis. 2020;50(3):661–7.CrossRef

46.

Camilli M, Lombardi M, Vescovo GM, del Buono MG, Galli M, Aspromonte N, et al. Efficacy and safety of novel oral anticoagulants versus low molecular weight heparin in cancer patients with venous thromboembolism: a systematic review and meta-analysis. Crit Rev Oncol Hematol. 2020;154:103074. https://doi.org/10.1016/j.critrevonc.2020.103074.CrossRefPubMed

47.

Agnelli G, Buller HR, Cohen A, Gallus AS, Lee TC, Pak R, et al. Oral apixaban for the treatment of venous thromboembolism in cancer patients: results from the AMPLIFY trial. J Thromb Haemost. 2015;13(12):2187–91. https://doi.org/10.1111/jth.13153.CrossRefPubMed

48.

Raskob GE, van Es N, Segers A, et al. Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial. Lancet Haematol. 2016;3(8):e379–87.CrossRef

49.

Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF, et al. Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active Cancer: a randomized clinical trial [published correction appears in JAMA. 2017 Nov 28;318(20):2048]. JAMA. 2015;314(7):677–86. https://doi.org/10.1001/jama.2015.9243.CrossRefPubMed

50.

Lenihan D, Carver J, Porter C, et al. Cardio-oncology care in the era of the coronavirus disease 2019 (COVID-19) pandemic: An International Cardio-Oncology Society (ICOS) statement [published online ahead of print, 2020 Sep 10]. CA Cancer J Clin. 2020;70(6):480. https://doi.org/10.3322/caac.21635.CrossRefPubMedPubMedCentral

51.

Patell R, Bogue T, Bindal P, et al. Incidence of thrombosis and hemorrhage in hospitalized cancer patients with COVID-19 [published online ahead of print, 2020 Jul 21]. J Thromb Haemost. 2020;18(9):2349. https://doi.org/10.1111/jth.15018.CrossRefPubMed

52.

Horowitz NA, Brenner B. Thrombosis and Hemostasis issues in Cancer patients with COVID-19. Semin Thromb Hemost. 2020;46(7):785–8. https://doi.org/10.1055/s-0040-1714275.CrossRefPubMedPubMedCentral

Title: Current status of treatment of cancer-associated venous thromboembolism
Author: Wei Xiong
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Cancer-Associated Venous Thrombosis
Anticoagulant
Direct Oral Anticoagulant
Direct Oral Anticoagulant
Published in: Thrombosis Journal / Issue 1/2021
Electronic ISSN: 1477-9560
DOI: https://doi.org/10.1186/s12959-021-00274-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Current status of treatment of cancer-associated venous thromboembolism

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2021

Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the Total Thrombus-formation Analysis System

Monitoring coagulation-fibrinolysis activation prompted timely diagnosis of hemophagocytic lymphohistiocytosis-related disseminated intravascular coagulation

Successful retrieval of dislocated inferior vena cava filter using double vascular sheaths docking technology: case report

Warfarin versus direct oral anticoagulants for treating left ventricular thrombus: a systematic review and meta-analysis

Superior vena cava syndrome after pacemaker implantation treated with direct oral anticoagulation

Endovascular revascularization strategies using catheter-based thrombectomy versus conventional catheter-directed thrombolysis for acute limb ischemia

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page