Last updated April 19, 2023

Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer

Treatment

Hospitalized patients who have active malignancy and acute medical illness or reduced mobility should be offered pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications. ( EB , I , M )
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Hospitalized patients who have active malignancy without additional risk factors may be offered pharmacologic thromboprophylaxis in the absence of bleeding or other contraindications. ( EB , L , M )
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Routine pharmacologic thromboprophylaxis should not be offered to patients admitted for the sole purpose of minor procedures or chemotherapy infusion, nor to patients undergoing stem-cell/bone marrow transplantation. ( IC , Ins , M )
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Routine pharmacologic thromboprophylaxis should not be offered to all outpatients with cancer. ( EB , H , S )
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High-risk outpatients with cancer (Khorana score [Table 2] ≥2 prior to starting a new systemic chemotherapy regimen) may be offered thromboprophylaxis with apixaban, rivaroxaban or low-molecular-weight heparin (LMWH) provided there are no significant risk factors for bleeding and no drug interactions. Consideration of such therapy should be accompanied by a discussion with the patient about the relative benefits and harms, drug cost, and duration of prophylaxis in this setting. ( EB , I , M )
(Moderate Recommendation; EB-I/H for apixaban and rivaroxaban; EB-I for LMWH)
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Patients with multiple myeloma receiving thalidomide- or lenalidomide-based regimens with chemotherapy and/or dexamethasone should be offered pharmacologic thromboprophylaxis with either aspirin or LMWH for lower-risk patients and LMWH for higher-risk patients. ( EB , I , S )
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All patients with malignant disease undergoing major surgical intervention should be offered pharmacologic thromboprophylaxis with either unfractionated heparin (UFH) or LMWH unless contraindicated because of active bleeding, or high bleeding risk, or other contraindications. ( EB , H , S )
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Prophylaxis with UFH or LMWH should be commenced preoperatively. ( EB , I , M )
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Mechanical methods may be added to pharmacologic thromboprophylaxis but should not be used as monotherapy for VTE prevention unless pharmacologic methods are contraindicated because of active bleeding or high bleeding risk. ( EB , I , S )
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A combined regimen of pharmacologic and mechanical prophylaxis may improve efficacy, especially in the highest-risk patients. ( EB , I , M )
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Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least 7–10 days. ( EB , H , S )
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Extended pharmacologic thromboprophylaxis for up to 4 weeks postoperatively should be offered to patients undergoing major open or laparoscopic abdominal or pelvic surgery for cancer who have high-risk features such as restricted mobility, obesity, history of VTE, or with additional risk factors. In lower-risk surgical settings, the decision on appropriate duration of thromboprophylaxis should be made on a case-by-case basis. ( EB , H , S )
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(Updated) Patients who are candidates for extended pharmacologic thromboprophylaxis after surgery may be offered prophylactic doses of LMWH. ( EB , H , S )
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(Updated) Alternatively, patients may be offered prophylactic doses of rivaroxaban or apixaban after an initial period of LMWH or UFH. ( EB , L , W )
Qualifying statement: Evidence for rivaroxaban and apixaban in this setting remains limited. The two available trials differed with respect to type of cancer, type of surgery, and timing of rivaroxaban or apixaban initiation after surgery.
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(Updated) Initial anticoagulation may involve LMWH, UFH, fondaparinux, rivaroxaban, or apixaban. For patients initiating treatment with parenteral anticoagulation, LMWH is preferred over UFH for the initial 5 to 10 days of anticoagulation for the patient with cancer with newly diagnosed VTE who does not have severe renal impairment (defined as creatinine clearance less than 30 mL/min). ( EB , H , S )
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(Updated) For long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months are preferred over vitamin K antagonists (VKAs) because of improved efficacy. VKAs may be used if LMWH or direct factor Xa inhibitors are not accessible. There is reduction in recurrent thrombosis but an increase in clinically relevant nonmajor bleeding risk with direct factor Xa inhibitors compared with LMWH. Caution with direct factor Xa inhibitors is warranted in gastrointestinal and genitourinary malignancies, and other settings with high risk for mucosal bleeding. Drug–drug interaction should be checked prior to using a direct factor Xa inhibitor. ( EB , H , S )
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Anticoagulation with LMWH, direct factor Xa inhibitors, or VKAs beyond the initial 6 months should be offered to select patients with active cancer, such as those with metastatic disease or those receiving chemotherapy. Anticoagulation beyond 6 months needs to be assessed on an intermittent basis to ensure a continued favorable risk-benefit profile ( IC , L , W )
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Based on expert opinion in the absence of randomized trial data, uncertain short-term benefit, and mounting evidence of long-term harm from filters, the insertion of a vena cava filter should not be offered to patients with established or chronic thrombosis (VTE diagnosis more than 4 weeks ago) nor to patients with temporary contraindications to anticoagulant therapy (e.g., surgery). There also is no role for filter insertion for primary prevention or prophylaxis of PE or DVT due to its long-term harm concerns. It may be offered to patients with absolute contraindications to anticoagulant therapy in the acute treatment setting (VTE diagnosis within the past 4 weeks) if the thrombus burden was considered life-threatening. Further research is needed. ( IC , L , M )
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The insertion of a vena cava filter may be offered as an adjunct to anticoagulation in patients with progression of thrombosis (recurrent VTE or extension of existing thrombus) despite optimal anticoagulant therapy. ( IC , L , W )
This is based on the panel’s expert opinion, given the absence of a survival improvement, a limited short-term benefit, but mounting evidence of the long-term increased risk for VTE.
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For patients with primary or metastatic central nervous system malignancies and established VTE, anticoagulation as described for other patients with cancer should be offered, although uncertainties remain about choice of agents and selection of patients most likely to benefit. ( IC , L , M )
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Incidental PE and deep vein thrombosis should be treated in the same manner as symptomatic VTE, given their similar clinical outcomes compared patients with cancer with symptomatic events. ( IC , L , M )
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Treatment of isolated subsegmental PE or splanchnic or visceral vein thrombi diagnosed incidentally should be offered on a case-by-case basis, considering potential benefits and risks of anticoagulation. ( IC , Ins , M )
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Anticoagulant use is not recommended to improve survival in patients with cancer without VTE. ( EB , H , S )
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There is substantial variation in risk of VTE between individual cancer patients and cancer settings. Patients with cancer should be assessed for VTE risk initially and periodically thereafter, particularly when starting systemic antineoplastic therapy or at the time of hospitalization. Individual risk factors, including biomarkers or cancer site, do not reliably identify patients with cancer at high risk of VTE. In the ambulatory setting among patients with solid tumors treated with systemic therapy, risk assessment can be conducted based on a validated risk assessment tool (Khorana score, Table 2). ( EB , I , S )
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Oncologists and members of the oncology team should educate patients regarding VTE, particularly in settings that increase risk such as major surgery, hospitalization, and while receiving systemic antineoplastic therapy. ( IC , Ins , S )
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Notes regarding off-label use in guideline recommendations: LMWH and direct factor Xa inhibitors have not been FDA approved for thromboprophylaxis in outpatients with cancer. Outside of LMWH approval for thromboprophylaxis in patients undergoing abdominal surgery, anticoagulants have not been FDA approved for thromboprophylaxis in patients undergoing cancer surgery. Dalteparin is the only LMWH with FDA approval for extended therapy to prevent recurrent venous thromboembolism in patients with cancer.

Recommendation Grading

Disclaimer

The information in this patient summary should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.

Overview

Title

Venous Thromboembolism Prophylaxis and Treatment in Patients with Cancer

Authoring Organization

Publication Month/Year

April 19, 2023

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Target Patient Population

Adults with cancer

Target Provider Population

Oncologists, surgeons, oncology nurses, oncology pharmacists, other health care professionals

Inclusion Criteria

Female, Male, Adult, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Prevention, Treatment

Diseases/Conditions (MeSH)

D054556 - Venous Thromboembolism

Keywords

VTE, Venous Thromboembolism, VTE Prophylaxis, VTE in Cancer, deep vein thrombosis, pulmonary embolism

Source Citation

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Gates LE, Kakkar AK, Tempero MA, Gupta S, Lyman GH, Falanga A. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Guideline Update. J Clin Oncol. 2023 Jun 1;41(16):3063-3071. doi: 10.1200/JCO.23.00294. Epub 2023 Apr 19. PMID: 37075273.

Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, Wong SL, Balaban EP, Flowers CR, Francis CW, Gates LE, Kakkar AK, Levine MN, Liebman HA, Tempero MA, Lyman GH, Falanga A. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2020 Feb 10;38(5):496-520. doi: 10.1200/JCO.19.01461. Epub 2019 Aug 5. PMID: 31381464.

Supplemental Methodology Resources

Data Supplement, Evidence Tables

Methodology

Number of Source Documents
53
Literature Search Start Date
August 14, 2014
Literature Search End Date
December 5, 2018
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 to 3‐week period. Guideline recommendations available for open comment are posted on asco.org/open‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Hematology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
See full-text.
Description of Study Criteria
See supplement.
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI
100