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CME

Cancer-associated Thrombosis

General Information

Description

  • patients with cancer are at increased risk of developing venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE)1,2,4,5
  • other types of thrombosis also occur in patients with cancer, including superficial vein thrombosis, splanchnic vein thrombosis, and catheter-related thrombosis1
  • VTE in patients with cancer
    • patients with cancer reported to be 4-7 times more likely to develop VTE than those without cancer2
    • VTE reported to increase mortality 2-6-fold; second most common cause of death in patients with cancer, after direct effects of cancer1,2
    • cancer is associated with increased risk of bleeding and thrombotic recurrence while on anticoagulation therapy compared with patients without cancer2,4
  • anticoagulation is the mainstay of prevention (low-molecular-weight heparin) and treatment (low-molecular-weight heparin or direct oral anticoagulants such as rivaroxaban, edoxaban, and apixaban) of VTE in patients with cancer

Also Called

  • cancer-related thrombosis
  • cancer-associated venous thromboembolism (VTE)

Types

  • main types of venous thromboembolism observed in patients with cancer include1
    • deep venous thrombosis
      • upper extremity
      • lower extremity
    • pulmonary embolism (PE)
    • superficial vein thrombosis (SVT)
    • Trousseau's syndrome
    • splanchnic vein thrombosis
    • catheter-related thrombosis

References

General References Used

  1. Streiff MB, Hostrom B, Angelini D, et al. Cancer-Associated Venous Thromboembolic Disease. Version 1.2019. In: National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN Guidelines). NCCN 2019 Feb 28 from NCCN website (free registration required)
  2. Farge D, Frere C, Connors JM, et al. International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2019 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. Lancet Oncol. 2019 Oct;20(10):e566-e581
  3. Mandalà M, Falanga A, Roila F, ESMO Guidelines Working Group. Management of venous thromboembolism (VTE) in cancer patients: ESMO Clinical Practice Guidelines. Ann Oncol. 2011 Sep;22 Suppl 6:vi85-92
  4. Watson HG, Keeling DM, Laffan M, Tait RC, Makris M, British Committee for Standards in Haematology. Guideline on aspects of cancer-related venous thrombosis. Br J Haematol. 2015 Sep;170(5):640-8
  5. 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 Feb 10;38(5):496-520

Recommendation Grading Systems Used

  • American College of Chest Physicians (ACCP) grades
    • Grade 1 - strong recommendation based on clear risk/benefit balance
    • Grade 2 - weak recommendation based on unclear or close risk/benefit balance
    • Grade A - high-quality evidence based on consistent evidence from randomized trials without important limitations or exceptionally strong evidence from observational studies
    • Grade B - moderate-quality evidence based on randomized trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise results) or very strong evidence from observational studies
    • Grade C - low- or very low-quality evidence based on evidence for ≥ 1 critical outcome from observational studies, case series, or randomized trials with serious flaws or indirect evidence
    • Reference - ACCP evidence-based clinical practice guideline on methodology for development of antithrombotic therapy and prevention of thrombosis (22315256Chest 2012 Feb;141(2 Suppl):53Sfull-text), commentary can be found in 23546508Chest 2013 Apr;143(4):1190
  • American Society of Clinical Oncology (ASCO) grading system
    • recommendation
      • Evidence based - sufficient evidence from published studies to inform recommendation to guide clinical practice
      • Formal consensus
        • available evidence deemed insufficient to inform recommendation to guide clinical practice
        • expert panel used formal consensus process to reach recommendation, which is considered best current guidance for practice
        • panel may choose to provide strength of recommendation (that is, strong, moderate, or weak)
      • Informal consensus
        • available evidence deemed insufficient to inform recommendation to guide clinical practice
        • recommendation considered best current guidance for practice based on informal consensus of expert panel
        • panel may choose to provide strength of recommendation (that is, strong, moderate, or weak)
      • No recommendation
        • insufficient evidence, confidence, or agreement to provide recommendation to guide clinical practice at this time
        • panel deemed evidence insufficient and concluded formal consensus process unlikely to achieve level of agreement needed for recommendation
    • strength of recommendation
      • Strong - high confidence that recommendation reflects best practice based on
        • strong evidence for true net effect (for example, benefits exceed harms)
        • consistent results, with no or minor exceptions
        • no or minor concerns about study quality
        • extent of panelist agreement
        • other compelling considerations
      • Moderate - moderate confidence that recommendation reflects best practice based on
        • good evidence for true net effect (for example, benefits exceed harms)
        • consistent results, with minor and/or few exceptions
        • minor and/or few concerns about study quality
        • extent of panelist agreement
        • other compelling considerations
      • Weak - some confidence that recommendation offers best current guidance for practice based on
        • limited evidence for true net effect (for example, benefits exceed harms)
        • consistent results, with important exceptions
        • concerns about study quality
        • extent of panelist agreement
        • other considerations
    • strength of evidence
      • Strong
        • high confidence that available evidence reflects true magnitude and direction of net effect (that is, balance of benefits vs. harms)
        • further research very unlikely to change either magnitude or direction of this net effect
      • Moderate
        • moderate confidence that available evidence reflects true magnitude and direction of net effect
        • further research unlikely to alter direction of net effect, although may alter magnitude of net effect
      • Weak
        • low confidence that available evidence reflects true magnitude and direction of net effect
        • further research may change either magnitude and/or direction of net effect
      • Insufficient
        • evidence insufficient to determine true magnitude and direction of net effect
        • further research may better inform topic
        • use of consensus opinion of experts reasonable to inform outcomes related to topic
    • PubMed31381464Journal of clinical oncology : official journal of the American Society of Clinical OncologyJ Clin Oncol20200210385496-520496 Reference - ASCO 2019 guideline on venous thromboembolism prophylaxis and treatment in patients with cancer (J Clin Oncol 2020 Feb 10;38(5):496)
  • European Society of Medical Oncology (ESMO) grades of recommendation
    • grades of recommendation
      • Grade A - strong evidence for efficacy with substantial clinical benefit, strongly recommended
      • Grade B - strong or moderate evidence for efficacy but with a limited clinical benefit, generally recommended
      • Grade C - insufficient evidence for efficacy or benefit does not outweigh the risk or the disadvantages, optional
      • Grade D - moderate evidence against efficacy or for adverse outcomes, generally not recommended
      • Grade E - strong evidence against efficacy or for adverse outcomes, never recommended
    • levels of evidence
      • Level I - evidence from ≥ 1 large, randomized, controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomized trials without heterogeneity
      • Level II - small randomized trials or large randomized trials with a suspicion of bias (lower methodological quality) or meta-analyses of such trials or of trials with demonstrated heterogeneity
      • Level III - prospective cohort studies
      • Level IV - retrospective cohort studies or case-control studies
      • Level V - studies without control group, case reports, expert opinions
    • Reference - ESMO clinical practice guidelines for management of venous thromboembolism (VTE) in cancer patients (21908511Ann Oncol 2011 Sep;22 Suppl 6:vi85)
  • British Society for Haematology (BSH) GRADE system
    • strength of recommendation
      • Grade 1
        • strong recommendations made when there is confidence that benefits do or do not outweigh harm and burden
        • can be applied uniformly to most patients
        • regard as "recommend"
      • Grade 2
        • weak recommendations made where magnitude of benefit or not is less certain
        • require judicious application to individual patients
        • regard as "suggest"
    • quality of evidence
      • A - high
        • further research very unlikely to change confidence in estimate of effect
        • current evidence derived from randomized clinical trials without important limitations
      • B - moderate
        • further research may well have important impact on confidence in estimate of effect and may change estimate
        • current evidence derived from randomized clinical trials with important limitations or very strong evidence from observational studies or case series
      • C - low
        • further research likely to have important impact on confidence in estimate of effect and likely to change estimate
        • current evidence from observational studies, case series, or just opinion
    • Reference - BSH Grading of Recommendations Assessment, Development and Evaluation (GRADE) system PDF
  • International Initiative on Thrombosis and Cancer (ITAC) system for recommendations
    • levels of recommendation
      • Grade 1 - strong recommendation, confidence that desirable effects of adherence outweigh undesirable effects
      • Grade 2 - weak recommendation, desirable effects of adherence probably outweigh the undesirable effects, but not confident
      • Guidance - best clinical practice, absence of clear scientific evidence, based on professional experience and consensus of experts
    • levels of evidence
      • A - high, further research is very unlikely to change confidence in estimate of effect
      • B - moderate, further research is likely to have important impact of confidence in estimate of effect and may change estimate
      • C - low, further research unlikely to have important impact on confidence in estimate of effect and likely to change estimate
      • D - very low, any estimate of effect is very uncertain
    • Reference - ITAC 2019 clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer (Lancet Oncol 2019 Oct;20(10):e566)
  • European Society of Cardiology (ESC) grading system for recommendations
    • classes of recommendations
      • Class I - evidence and/or general agreement that given treatment or procedure is beneficial, useful, and effective
      • Class II - conflicting evidence and/or divergence of opinion about usefulness/efficacy of given treatment or procedure
        • Class IIa - weight of evidence/opinion in favor of usefulness/efficacy
        • Class IIb - usefulness/efficacy less well-established by evidence/opinion
      • Class III - evidence or general agreement that given treatment or procedure is not useful/effective, and in some cases may be harmful
    • levels of evidence
      • Level A - data derived from multiple randomized clinical trials or meta-analyses
      • Level B - data derived from single randomized trial or large nonrandomized studies
      • Level C - consensus of opinion of experts and/or small studies, retrospective studies, registries
    • PubMed31473594The European respiratory journalEur Respir J20191009543 Reference - ESC guideline on diagnosis and management of acute pulmonary embolism (Eur Respir J 2019 Sep;54(3):doi:10.1183/13993003.01647-2019), commentary can be found in Eur Respir J 2020 Jan;55(1):doi:10.1183/13993003.02028-2019
  • National Comprehensive Cancer Network (NCCN) categories of evidence and consensus
    • Category 1 - based on high-level evidence, there is uniform NCCN consensus that intervention is appropriate
    • Category 2A - based on lower-level evidence, there is uniform NCCN consensus that intervention is appropriate
    • Category 2B - based on lower-level evidence, there is NCCN consensus that intervention is appropriate
    • Category 3 - based on any level of evidence, there is major NCCN disagreement that intervention is appropriate
    • Reference - NCCN Categories of Evidence and Consensus

Synthesized Recommendation Grading System for DynaMed Content

  • The DynaMed Team systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based Methodology).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed Team-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

  • DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
  • All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.
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Special Acknowledgements

  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T918731, Cancer-associated Thrombosis; [updated 2018 Nov 30, cited place cited date here]. Available from https://www.dynamed.com/topics/dmp~AN~T918731. Registration and login required.

Published by EBSCO Information Services. Copyright © 2020, EBSCO Information Services. All rights reserved. No part of this may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without permission.

EBSCO Information Services accepts no liability for advice or information given herein or errors/omissions in the text. It is merely intended as a general informational overview of the subject for the healthcare professional.

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