静脉血栓防治指南
Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer:American Society of Clinical Oncology Clinical Practice Guideline Update
Gary H.Lyman,Alok A.Khorana,Nicole M.Kuderer,Agnes Y.Lee,Juan Ignacio Arcelus,Edward P.Balaban,
Jeffrey M.Clarke,Christopher R.Flowers,Charles W.Francis,Leigh E.Gates,Ajay K.Kakkar,Nigel S.Key,Mark N.Levine,Howard A.Liebman,Margaret A.Tempero,Sandra L.Wong,Ann Alexis Prestrud,and Anna Falanga
Gary H.Lyman,Nicole M.Kuderer,and Jeffrey M.Clarke,Duke University and Duke Cancer Institute,Durham;Nigel S.Key,Lineberger Comprehensive Cancer Center,University of North Carolina,Chapel Hill,NC;Alok A.Khorana,Taussig Cancer Institute,Cleveland Clinic,Cleveland,OH;Agnes Y.Lee,University of British Colum-bia,Vancouver,British Columbia;Mark N.Levine,McMaster University,Hamilton,Ontario,Canada;Juan Ignacio Arcelus,Hospital Universitario Virgen de las Nieves,University of Granada,Granada,Spain;
Edward P.Balaban,University of Pittsburgh Cancer Centers Network,Pittsburgh,PA;Christopher R.Flowers,Emory University School of Medicine and Winship Cancer Institute,Atlanta,GA;Charles W.Francis,James P.Wilmot Cancer Center and University of Rochester,Rochester,NY;Leigh E.Gates,patient representative,Denver,CO;Ajay K.Kakkar,Thrombosis Research Institute,London,United King-dom;Howard A.Liebman,Keck School of Medicine,University of Southern California,Los Angeles;Margaret A.Tempero,University of California–San Francisco Pancreas Center,San Francisco,CA;Sandra L.Wong,University of Michigan,Ann Arbor,MI;Ann Alexis Prestrud,Ameri-can Society of Clinical Oncology,Alexan-dria,VA;and Anna Falanga,Hospital Papa Giovanni XXIII,Bergamo,Italy.Published online ahead of print at https://www.360docs.net/doc/761351916.html, on May 13,2013.Clinical Practice Guidelines Committee Approval:Pending
Editor’s note:This American Society of Clinical Oncology Clinical Practice Guideline Update provides recommendations with comprehensive discussion of the relevant literature for each recommendation.The Data Supplement,including evidence
tables,is available at https://www.360docs.net/doc/761351916.html,/guidelines/vte.
Authors’disclosures of potential con?icts of interest and author contributions are found at the end of this article.
Corresponding author:American Society of Clinical Oncology,2318Mill Rd,Suite 800,Alexandria,VA 22314;e-mail:guidelines@https://www.360docs.net/doc/761351916.html,.
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0732-183X/13/3199-1/$20.00DOI:10.1200/JCO.2013.49.1118
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Purpose
To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE)in patients with cancer.Prophylaxis in the outpatient,inpatient,and perioperative settings was considered,as were treatment and use of anticoagulation as a cancer-directed therapy.Methods
A systematic review of the literature published from December 2007to December 2012was completed in MEDLINE and the Cochrane Collaboration Library.An Update Committee reviewed evidence to determine which recommendations required revision.
Results
Forty-two publications met eligibility criteria,including 16systematic reviews and 24randomized controlled trials.
Recommendations
Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization.Thrombopro-phylaxis is not routinely recommended for outpatients with cancer.It may be considered for selected high-risk patients.Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low–molecular weight heparin (LMWH)or low-dose aspirin.Patients undergoing major cancer surgery should receive prophylaxis,starting before surgery and continuing for at least 7to 10days.Extending prophylaxis up to 4weeks should be considered in those with high-risk features.LMWH is recommended for the initial 5to 10days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term (6months)secondary https://www.360docs.net/doc/761351916.html,e of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE.Anticoagulation should not be used for cancer treatment in the absence of other indications.Patients with cancer should be periodically assessed for VTE risk.Oncology professionals should provide patient education about the signs and symptoms of VTE.
J Clin Oncol 31.?2013by American Society of Clinical Oncology
INTRODUCTION
The American Society of Clinical Oncology (ASCO)?rst published an evidence-based clinical practice guideline on prophylaxis and treatment of venous thromboembolism (VTE)in 2007.1ASCO guide-lines are updated at intervals determined by an Up-date Committee;this is a full guideline update.Table 1provides a summary of the 2007and 2012guide-line recommendations.
GUIDELINE QUESTIONS
1.Should hospitalized patients with cancer re-ceive anticoagulation for VTE prophylaxis?
2.Should ambulatory patients with cancer re-ceive anticoagulation for VTE prophylaxis during systemic chemotherapy?
3.Should patients with cancer undergoing sur-gery receive perioperative VTE prophylaxis?
4.What is the best method for treatment of pa-tients with cancer with established VTE to pre-vent recurrence?
5.Should patients with cancer receive anticoagu-lants in the absence of established VTE to im-prove survival?
6.What is known about risk prediction and awareness of VTE among patients with cancer?
METHODS
Panel Composition
An Update Committee was formed (Appendix Table A1,online only)to review data published since the initial
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https://www.360docs.net/doc/761351916.html,/cgi/doi/10.1200/JCO.2013.49.1118The latest version is at Published Ahead of Print on May 13, 2013 as 10.1200/JCO.2013.49.1118
guideline and update recommendations,as warranted,considering evidence identi?ed by the systematic review.
Guideline Development Process
The Update Committee met in July2012and had a second meeting via teleconference.During those meetings,the Update Committee reviewed evi-dence identi?ed by the systematic review and revised guideline recommenda-tions.Additional work on the guideline was completed electronically.The steering committee and lead ASCO staff person prepared an updated guideline to share with the Update Committee members for review.As per standard practice,the guideline was submitted to Journal of Clinical Oncology for review. The VTE Update Committee and the ASCO Clinical Practice Guideline Com-mittee reviewed and approved this guideline document before publication. Guideline Policy
The practice guideline is not intended to substitute for the independent professional judgment of the treating physician.Practice guidelines do not account for individual variation among patients and may not re?ect the most recent evidence.This guideline does not recommend any particular product or course of medical https://www.360docs.net/doc/761351916.html,e of the practice guideline is voluntary.The Additional information is available at https://www.360docs.net/doc/761351916.html,/guidelines/vte.
ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the oppor-tunity to participate.
Update Methodology
The goal of this update was to review evidence available since publication of the original guideline and to revise recommendations,as needed,about the prevention and treatment of VTE among patients with cancer.One new clinical question,regarding risk,was added,and a separate systematic review was completed to address this issue.
Literature Review and Analysis
Literature search strategy.The effectiveness search included the MED-LINE,Cochrane Database of Systematic Reviews,and Cochrane Central Reg-ister of Controlled Trials databases.Conference proceedings from annual meetings of ASCO,the American Society of Hematology,the European Soci-ety of Medical Oncology,and the International Society of Thrombosis and Hemostasis were searched through2012or the most recent year available.The risk assessment search was completed in MEDLINE.
Reference lists from seminal articles,guidelines from other organiza-tions,and recent review articles were hand searched for additional citations.
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The Update Committee reviewed the list of included reports for completeness. Subject headings and keywords used in the ef?cacy literature search included four major categories:VTE,anticoagulation,malignancy,and randomized controlled trials(RCTs).The full search string is available in the Data Supple-ment.The risk literature search also included four major categories:risk assessment,VTE,cancer,and cohort studies.
Inclusion and exclusion criteria.Articles for the ef?cacy systematic review were selected for inclusion if they were RCTs or systematic reviews of RCTs that assessed the ef?cacy and safety of anticoagulation in patients with cancer and included at least50patients per arm.Only data from conference proceedings available as full presentations or posters were included.
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For the risk systematic review,studies from the ambulatory setting that either developed or validated risk models were included.Only reports that included multivariate analyses were eligible.Risk assessment models limited to single cancer types were excluded.
Data extraction.Eligible reports for both reviews were preliminarily identi?ed after the literature search.Full-text copies were obtained to further assess eligibility.Articles that met eligibility for the ef?cacy search underwent data extraction by ASCO staff for study design and quality,patient character-istics,outcomes,and adverse events.Outcomes of interest included symptom-atic and asymptomatic thrombotic events found on screening,major and minor bleeding,early and overall mortality,sudden death,and adverse events. For the risk review,data extraction included study characteristics,quality,and risk assessment model development and evaluation.Outcomes of interest included factors incorporated into the risk assessment model,model equation, and outcomes according to risk.
Evidence summary tables(Data Supplement)were reviewed for accu-racy and completeness by an ASCO staff member who was not involved in data extraction.Disagreements were resolved through discussion;the Steering Committee was consulted if necessary.
Study quality.Trial characteristics from the RCTs were extracted to evaluate the potential for bias.Study quality was also assessed for the reports in the risk systematic review.
Guideline and Con?icts of Interest
The Update Committee was assembled in accordance with ASCO’s Con-?ict of Interest Management Procedures for Clinical Practice Guidelines (“Procedures,”summarized at https://www.360docs.net/doc/761351916.html,/guidelinescoi).Members of the Update Committee completed ASCO’s disclosure form,which requires disclosure of?nancial and other interests that are relevant to the subject matter of the guideline,including relationships with commercial entities that are reasonably likely to experience direct regulatory or commercial impact as the result of promulgation of the guideline.Categories for disclosure include employment relationships,consulting arrangements,stock ownership,hono-raria,research funding,and expert testimony.In accordance with the Proce-dures,the majority of the members of the Update Committee did not disclose any such relationships.
Revision Dates
At intervals,the Update Committee co-chairs and two Update Commit-tee members designated by the co-chairs will determine the need for guideline revisions based on the available literature.If necessary,the Update Committee will be reconvened.When appropriate,the Update Committee will suggest revised recommendations to the Clinical Practice Guideline Committee.
RESULTS
Literature Search
The ef?cacy literature search yielded a total of380citations from MEDLINE,531citations from conference proceedings,and 18from hand searching.Forty-two reports provisionally met in-clusion and exclusion criteria and were selected for full-text review. Of those,reports from30trials and systematic reviews were se-lected for data extraction.The QUOROM diagram is available in the Data Supplement.
For the risk systematic review,the MEDLINE literature search yielded664citations.Of those,54provisionally met eligibility criteria and were selected for full-text review.Six articles were identi?ed for data extraction.
Study Quality and Limitations of the Literature Publications identi?ed by the systematic review varied with re-spect to potential for bias,ranging from low to high.A majority of the trials were of moderate quality.Speci?c quality issues are discussed within the section for the relevant clinical question.
GUIDELINE RECOMMENDATIONS:CLINICAL QUESTION1 Should hospitalized patients with cancer receive anticoagulation for VTE prophylaxis?
Recommendation1.1
Hospitalized patients who have active malignancy with acute medical illness or reduced mobility should receive phar-macologic thromboprophylaxis in the absence of bleeding or other contraindications.
Recommendation1.2
Hospitalized patients who have active malignancy without addi-tional risk factors may be considered for pharmacologic thrombopro-phylaxis in the absence of bleeding or other contraindications. Recommendation1.3
Data are inadequate to support or oppose thromboprophy-laxis in patients admitted for minor procedures or short chemo-therapy infusion or in patients undergoing stem-cell/bone marrow transplantation.
Literature Update and Analysis1
Three randomized trials were identi?ed by the systematic review: CERTIFY(Certoparin for Thromboprophylaxis in Medical Patients), CERTAIN(Certoparin Versus Unfractionated Heparin for the Pre-vention of Thromboembolic Complications in Acutely Ill Medical Patients),and EXCLAIM(Extended Prophylaxis for Venous Throm-boEmbolism in Acutely Ill Medical Patients with Prolonged Immobilization).2-4EXCLAIM evaluated extended prophylaxis.2One systematic review and meta-analysis of inpatient thromboprophylaxis was also identi?ed.5Dosing information is provided in Table2. Primary Prophylaxis
Both new primary prophylaxis trials in medically ill patients, CERTAIN and CERTIFY,compared a low molecular–weight heparin (LMWH),certoparin,with unfractionated heparin(UFH).The primary outcome for both trials was the composite of symptomatic or asymptomatic deep vein thrombosis(DVT),symptomatic pul-monary embolism(PE),or VTE-related death.Among the172 patients randomly assigned in the CERTAIN trial,8.0%and9.2% in the UFH and LMWH groups,respectively,had active or previ-ous cancer(not signi?cant).3The primary end point was reported in18%of patients receiving UFH and10.7%of patients receiving certoparin(not signi?cant).
Patients with cancer were eligible to participate in CERTIFY,but the percentage was not reported.4Among the3,244patients randomly assigned in this trial,the primary outcome of DVT or PE occurred in 3.9%in the certoparin arm compared with4.5%receiving UFH(not signi?cant).Both trials included an older patient population;the mean age in CERTIFY was?78years,4and in CERTAIN,it was?70 years.3Neither trial reported data for cancer subgroups.Bleeding rates were higher with UFH compared with LMWH.Sudden death was not reported for either trial.
The systematic review examined pharmacologic thrombopro-phylaxis with LMWH,UFH,fondaparinux,and placebo.5DVT rates were lower with LMWH/fondaparinux compared with placebo(odds
VTE Prophylaxis and Treatment:ASCO Guideline Update
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ratio[OR],0.60;95%CI,0.47to0.75)but similar between LMWH and UFH(OR,0.92;95%CI,0.56to1.52).No differences in the rate of death or PE were noted between patients who were treated with LMWH/fondaparinux,UFH,or placebo.Major bleeding rates were similar across all treatment arms considered.Minor bleeding rates were similar with LMWH and UFH and greater than in placebo-treated patients.Cancer-speci?c rates were not provided for either VTE or bleeding.
Extended Prophylaxis
In an RCT,6,085acutely ill medical patients were assigned to extended prophylaxis with enoxaparin or placebo for28days(?4 days)after receiving open-label enoxaparin for an initial10days(?4 days).2Of the patients in the LMWH arm,14.1%had cancer,as did 16.0%intheplaceboarm.TheprimaryoutcomeswereVTEde?nedas
a composite of symptomatic or asymptomatic proximal DVT,symp-tomatic PE,and fatal PE,and major bleeding.The proportion of VTE events was greater with placebo:4.0%versus2.5%for an absolute risk difference of?1.53%(95%CI,?2.54%to?0.52%).Major bleeding was uncommon but signi?cantly greater with active therapy:0.8% versus0.3%.The early mortality rate was similar across trial arms (hazard ratio[HR],0.93;95%CI,0.65to1.32).2Cancer-speci?c data were not reported.
Trial Considerations
The inpatient trials enrolled mixed populations including pa-tients with cancer as well as general medical patients.To date,no trials
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have evaluated inpatient thromboprophylaxis in a cancer-only popu-lation.These recommendations were formulated by extrapolating the best available data.All RCTs included reduced mobility as an eligibility criterion,but the de?nitions of immobility were not explicit or con-sistent.This limits generalizability of these data to all hospitalized patients with cancer and tempered the willingness of the Update Committee to recommend thromboprophylaxis for all inpatients with malignancy.
The extended thromboprophylaxis trial,CERTAIN,indicates that prolonging anticoagulation reduces VTE event rates but increases the risk of bleeding.Importantly,a midstudy amendment narrowed the eligible patient population after interim analysis noted limited ef?cacy in patients without reduced mobility.2Findings from this trial must be interpreted with this narrow patient population in mind. Risk Among Inpatients
A vast majority of hospitalized patients with cancer are at moderate to high risk for thromboembolic events,because active cancer is a strong risk factor.7-13Most patients have additional risk factors,including comorbid conditions such as infection,immo-bility,or advanced age.14The bene?t of prophylaxis increases with the risk of VTE.Table3includes a list of risk factors that can be used to evaluate risk in oncology inpatients.Risk is further ad-dressed in Clinical Question6.
CLINICAL QUESTION2
Should ambulatory patients with cancer receive anticoagulation for VTE prophylaxis during systemic chemotherapy? Recommendation2.1
Routine pharmacologic thromboprophylaxis is not recom-mended in cancer outpatients.
Recommendation2.2
Based on limited RCT data,clinicians may consider LMWH prophylaxis on a case-by-case basis in highly selected outpatients with solid tumors receiving chemotherapy.Consideration of such therapy should be accompanied by a discussion with the patient about the uncertainty concerning bene?ts and harms as well as dose and dura-tion of prophylaxis in this setting.
Recommendation2.3
Patients with multiple myeloma receiving thalidomide-or lenalidomide-based regimens with chemotherapy and/or dexameth-asone should receive pharmacologic thromboprophylaxis with either aspirin or LMWH for lower-risk patients and LMWH for higher-risk patients.
Literature Update and Analysis2
The updated systematic review identi?ed three systematic reviews15-17considering the ambulatory setting and nine RCTs.18-25 Two RCTs,SAVE-ONCO(Evaluation of AVE5026in the Prevention of Venous Thromboembolism in Cancer Patients Undergoing Chem-otherapy),18and PROTECHT(Prophylaxis of Thromboembolism During Chemotherapy)19included patients with a variety of solid tumors.Two others,FRAGEM(Gemcitabine With or Without Dalte-parin in Treating Patients With Locally Advanced or Metastatic Pan-creatic Cancer)21and PROSPECT-CONKO004(Chemotherapy With or Without Enoxaparin in Pancreatic Cancer)24,25included only patients with pancreatic cancer.The PRODIGE(Dalteparin Low Molecular Weight Heparin for Primary Prophylaxis of Venous Thromboembolism in Brain Tumour Patients)trial examined antico-agulation for patients with glioma.23Two recent trials evaluated thromboprophylaxis in multiple myeloma.20,22Final publications of two trials discussed in the previous guideline are also discussed.26 Systematic Reviews
Two systematic reviews identi?ed RCTs comparing LMWH pro-phylaxis in the outpatient setting with placebo or no prophylaxis. Estimated risk ratios(RRs)across trials indicated decreases in symp-tomatic VTE events with LMWH thromboprophylaxis of0.53(95% CI,0.39to0.72)and0.54(95%CI,0.31to0.95),respectively.16,17 Neither meta-analysis noted a statistically signi?cant increase in bleed-ing with LMWH.Of note,the second report included only trials of patients with advanced lung cancer from two RCTs.16The relative risk for symptomatic VTE was0.58(95%CI,0.28to1.06).
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A recent Cochrane review compared the ef?cacy and safety of LMWHs,vitamin K antagonists(VKAs),and direct thrombin inhib-itors with no intervention or placebo in ambulatory patients with cancer.15Fewer symptomatic VTEs occurred with LMWH throm-boprophylaxis in the pooled analysis of?2,400patients(RR,0.62; 95%CI,0.41to0.99).Rates of major and minor bleeding were not consistently increased with anticoagulation compared with placebo. Four trials speci?cally considered the LMWH dalteparin,allowing a subgroup analysis of that agent.No difference in VTE event rates was noted between dalteparin and placebo(RR,0.75;95%CI,0.42 to1.32).
The absolute differences in symptomatic VTE event rates be-tween treated and control patients were?5%in most trials.Among the three systematic reviews,the absolute risk differences in VTE were 1.5%,2.8%,and1.7%with estimates of the number needed to treat (NNT)of67,36,and59,respectively,to prevent one symptomatic VTE event across the included trials.Importantly,individual patient data were not evaluated,limiting the assessment of patients with different cancers,often receiving different cancer therapies and anti-coagulants,and with varying degrees of VTE risk.
Recent Clinical Trials
Mixed solid tumors.The PROTECHT and SAVE-ONCO trials evaluated thromboprophylaxis in ambulatory patients with cancer receiving chemotherapy for locally advanced or metastatic solid tu-mors.18,19These double-blind trials compared anticoagulation with either the LMWH nadroparin or the ultra-LMWH semuloparin with placebo.Semuloparin is not available and has been withdrawn from marketing worldwide.The primary end point for PROTECHT was a composite of symptomatic VTEs and arterial thromboembolic events during treatment and follow-up.19In PROTECHT,3.9%of patients in the control arm experienced events compared with2.0%of patients treated with nadroparin for an NNT of53(one-tailed P?.02).Major bleeding rates were not different between the arms.In an exploratory subgroup analysis,thromboembolic event rates were greater in pa-tients who received thromboprophylaxis compared with controls: 8.3%versus5.9%.In SAVE-ONCO,fewer symptomatic VTE events occurred in patients who received semuloparin(1.2%)compared with placebo(3.4%;HR,0.36;95%CI,0.21to0.60;P?.001).18The absolute risk difference for VTE events was2.2%for an NNT of45. Major bleeding was similar across arms(HR,1.05;95%CI,0.55to 1.99).
Two double-blind RCTs of ambulatory patients with metastatic breast carcinoma(TOPIC-1)or stage III/IV non–small-cell lung car-cinoma(TOPIC-2)compared certoparin3,000IU subcutaneously once daily with placebo for6months.26The primary outcome was symptomatic or asymptomatic VTE.TOPIC-1randomly assigned 353patients but was stopped after an interim analysis revealed no difference between treatment arms.VTE occurred in4%from both studyarms,resultinginanORof1.02(95%CI,0.30to3.48).TOPIC-2 randomly assigned547patients,4.5%of whom experienced VTE in the certoparin arm and8.3%in the placebo arm(OR,0.52;95%CI,
0.23to1.12).Major bleeding in the certoparin and control arms was
1.7%and0%in TOPIC-1and3.7%and
2.2%in TOPIC-2,respec-tively,neither of which was statistically signi?cant.A post hoc explor-atory analysis demonstrated a reduction in VTE in stage IV lung carcinoma in the certoparin arm(
3.5%v10.2%;P?.032).
Pancreatic cancer.The FRAGEM and PROSPECT-CONKO 004trials enrolled patients with advanced pancreatic neoplasms.21,25 The FRAGEM trial was a phase IIb RCT of123patients with advanced pancreatic cancer receiving gemcitabine-based chemotherapy com-paring thromboprophylaxis with therapeutic doses of dalteparin up to 12weeks,following a schedule similar to that of the CLOT(Random-ized Comparison of Low Molecular–Weight Heparin Versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer)trial,with no throm-boprophylaxis.21VTE over the course of the study was reduced from 28%to12%,with a relative risk of0.42(95%CI,0.19to0.94;P?.039).No differences in rates of major bleeding or mortality between study arms were observed.
The PROSPECT-CONKO004trial was presented as an oral presentation but has not yet been published.25In this trial,312patients with stage IV pancreatic cancer being treated with gemcitabine-based chemotherapy were randomly assigned to enoxaparin at half the therapeutic dose for3months or no thromboprophylaxis.VTE was reduced from15%to5%,with a relative risk of0.35(95% CI,0.16to0.75;P?.007).Again,no signi?cant difference in rates of major bleeding was reported.
Glioma.The PRODIGE trial included186patients with newly diagnosed grade3or4glioma and was terminated early.23Patients were randomly assigned to dalteparin or placebo for6months,and therapy could continue for an additional6months.VTE events oc-curred in nine patients(9%)in the dalteparin arm compared with13 patients(15%)in the placebo arm(HR,0.51;95%CI,0.19to1.40;P?.29).Five patients in the dalteparin arm experienced intracranial bleeding by12months compared with one in the control arm(HR, 4.2;95%CI,0.48to36;P?.22).
Overall,the Panel concluded that offering all patients with solid malignancies anticoagulation for thromboprophylaxis in the ambula-tory setting is not justi?ed based on the available clinical trial data and the heterogeneity of this patient population.
Multiple myeloma.Two RCT substudies assessed different thromboprophylaxis strategies in patients with newly diagnosed mul-tiple myeloma receiving lenalidomide-or thalidomide-based treat-ment.20,22Palumbo et al22strati?ed patients on the basis of age and transplantation eligibility and then randomly assigned them to one of two chemotherapy regimens.Patients who received thalidomide-based regimens were eligible for random assignment to warfarin, low-dose aspirin,or enoxaparin.Of659analyzed patients,serious thromboembolic events,acute cardiovascular events,or sudden death during the?rst6months occurred in6.4%in the aspirin group,8.2% in the warfarin group,and5.0%in the LMWH https://www.360docs.net/doc/761351916.html,pared with LMWH,the absolute differences were1.3%(95%CI,3.0%to5.7%; P?.544)with aspirin and3.2%(95%CI,1.5%to7.8%;P?.183) with warfarin.Three major bleeding episodes occurred with aspirin (1.4%)compared with none in the other arms.22No difference in the risk of VTE was found when comparing aspirin with LMWH(HR, 1.13;95%CI,0.59to2.17).
In the other study from the same group,342patients with newly diagnosed multiple myeloma treated with lenalidomide-based chem-otherapy were randomly assigned to either prophylactic low-dose aspirin(100mg per day)or enoxaparin during induction and consol-idation chemotherapy.20Symptomatic VTE was reported in2.3%of patients receiving aspirin and1.2%receiving LMWH for an absolute difference of1.07%(95%CI,?1.69to3.83;P?.452).No major
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bleeding was reported in either arm,and minor bleeding was noted in one patient receiving enoxaparin.
CLINICAL QUESTION3
Should patients with cancer undergoing surgery receive perioperative VTE prophylaxis?
Recommendation3.1
All patients with malignant disease undergoing major surgical intervention should be considered for pharmacologic thrombopro-phylaxis with either UFH or LMWH unless contraindicated because of active bleeding or high bleeding risk.
Recommendation3.2
Prophylaxis should be commenced preoperatively. Recommendation3.3
Mechanical methods may be added to pharmacologic throm-boprophylaxis but should not be used as monotherapy for VTE pre-vention unless pharmacologic methods are contraindicated because of active bleeding or high bleeding risk.
Recommendation3.4
A combined regimen of pharmacologic and mechanical prophy-laxis may improve ef?cacy,especially in the highest-risk patients. Recommendation3.5
Pharmacologic thromboprophylaxis for patients undergoing major surgery for cancer should be continued for at least7to10days. Extended prophylaxis with LMWH for up to4weeks postoperatively should be considered for patients undergoing major abdominal or pelvic surgery for cancer who have high-risk features such as restricted mobility,obesity,history of VTE,or with additional risk factors as listed in Table3.In lower-risk surgical settings,the decision on appro-priate duration of thromboprophylaxis should be made on a case-by-case basis considering the individual patient.
Literature Update and Analysis3
Six meta-analyses27-32and three RCTs33-35of perioperative pro-phylaxis in patients with cancer were identi?ed by the updated system-atic review.Three of the meta-analyses28,30,31and one of the RCTs considered extended perioperative thromboprophylaxis.33 Primary Prophylaxis
A Cochrane meta-analysis comparing prophylactic LMWH with UFH in the cancer perioperative setting found little difference in rates of PE and DVT.32Major bleeding was also similar with the two anticoagulants(RR,0.84;95%CI,0.52to1.36).A systematic review limited to patients undergoing surgery for gynecologic cancer com-pared UFH,LMWH,or sequential compression devices with either untreated controls or one another.29A reduction in DVT with UFH compared with untreated controls was observed(RR,0.58;95%CI, 0.35to0.95),but there was no difference between UFH and LMWH (RR,0.91;95%CI,0.38to2.17).Bleeding rates were not reported.
The three RCTs that assessed primary perioperative prophylaxis included patients undergoing abdominal or pelvic surgery.In the Sakon et al34trial,164patients with cancer undergoing abdominal laparotomy were randomly assigned to enoxaparin or intermittent pneumatic compression(IPC).The incidence of symptomatic VTE was1.2%(95%CI,0.03to6.53%)in the enoxaparin group and19.4% (95%CI,7.45to37.47%)in the IPC group.Major bleeding was reported in4.6%(95%CI,1.5%to10.4%)in the enoxaparin group and2.6%(95%CI,0.1%to13.8%)in the IPC group.The SAVE-ABDO(Evaluation of AVE5026as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery)33and Simonneau et al35trials compared two different LMWH regimens.SAVE-ABDO was a randomized, double-blind,phase III trial of4,414patients undergoing major ab-dominal surgery,of whom81%underwent surgery for malignant disease.Patients were randomly assigned to either ultra-LMWH semuloparin starting before surgery or enoxaparin starting after sur-gery.The primary outcome of any VTE and all-cause mortality oc-curred in5.5%of those receiving enoxaparin and6.3%receiving semuloparin(OR,1.16;95%CI,0.84to1.59).There were fewer events of major bleeding with semuloparin(OR,0.63;95%CI,0.46to0.87). In the double-blind Simonneau et al study,patients with colorectal cancer were randomly assigned to nadroparin or enoxaparin,both starting before surgery.35Of1,288patients randomly assigned,only 950(73.8%)were analyzed,with symptomatic and asymptomatic VTE rates of15.9%with nadroparin and12.6%with enoxaparin for a relative risk of1.27(95%CI,0.93to1.74;not signi?cant).Major bleeding was reported in11.5%of patients receiving enoxaparin and 7.3%receiving nadroparin(RR,0.64;95%CI,0.45to0.91;P?.012).
These surgical studies were conducted in patients with GI,gyne-cologic,or urologic malignancies undergoing major cancer surgeries and examined thromboprophylaxis administered for approximately7 to10days.This duration was established in historical trials of primary prophylaxis in the surgical setting.36-44There are no studies assessing shorter durations or limiting thromboprophylaxis during the hospi-talization for lower risk cancer surgery.
Extended Prophylaxis
Three systematic reviews of extended prophylaxis,for4weeks postoperatively with LMWH in mixed cancer and noncancer popula-tions,were reported.28,30,31The meta-analysis by Bottaro et al28in-cluded three trials involving1,104patients,70.6%of whom had cancer.A decrease in asymptomatic and symptomatic VTE among patients with cancer was noted in a subgroup analysis(RR,0.46;95% CI,0.28to0.77).Major bleeding was not signi?cantly different in the treatment groups overall(RR,0.83;95%CI,0.22to3.12),although no cancer-speci?c rates were reported.Akl et al31included three trials or subgroups of trials representing patients with cancer and reported a decrease in the risk of asymptomatic DVT with extended LMWH prophylaxis versus untreated control or placebo(RR,0.21;95%CI, 0.05to0.94).No signi?cant difference in the risk of major bleeding was reported(RR,2.94;95%CI,0.12to71.85).Rasmussen et al30 included one additional trial in their meta-analysis but did not present results speci?cally among patients with cancer undergoing surgery. The incidence of asymptomatic and symptomatic VTE after major abdominal or pelvic surgery was14.3%among controls and6.1% among those receiving extended prophylaxis with LMWH(OR,0.41; 95%CI,0.26to0.63;P?.001).Although major bleeding events were notpresentedseparately,allbleedingeventsinthecontrolandLMWH
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groups were3.7%(95%CI,2.4%to5.5%)and4.1%(95%CI,2.7%to 6.0%),respectively(OR,1.11;95%CI,0.62to1.97;P?.73).
The more recent CANBESURE(Cancer,Bemiparin,and Surgery Evaluation)study randomly assigned626patients undergoing ab-dominal or pelvic cancer surgery to either extended thromboprophy-laxis with bemiparin(28days)or bemiparin(8days)in a double-blind fashion.45The primary outcome of asymptomatic or symptomatic DVT,nonfatal PE,or all-cause mortality during the double-blind period occurred in10.1%of patients receiving bemiparin and13.3% of those in the placebo group,and the primary end point was not met (RR,0.75;95%CI;0.46to1.24;P?.26).Major bleeding was reported in two patients(0.6%)receiving bemiparin and one(0.3%)in the placebo arm(not signi?cant).While the study was underway,but before unblinding,a secondary outcome of major VTE was de?ned as asymptomatic proximal or symptomatic proximal DVT,nonfatal PE, and VTE-related death.At the end of the double-blind period,major VTE was reported in two(0.8%)and11(4.6%)patients,respectively (RR,0.18;95%CI;0.04to0.78;P?.010).
CLINICAL QUESTION4
What is the best method for treatment of patients with cancer with established VTE to prevent recurrence?
Recommendation4.1
LMWH is preferred over UFH for the initial5to10days of anticoagulation for the patient with cancer with newly diagnosed VTE who does not have severe renal impairment(de?ned as creatinine clearance?30mL/min).
Recommendation4.2
For long-term anticoagulation,LMWH for at least6months is preferred because of improved ef?cacy over VKAs.VKAs are an ac-ceptable alternative for long-term therapy if LMWH is not available.
Recommendation4.3
Anticoagulation with LMWH or VKAs beyond the initial6 months may be considered for select patients with active cancer,such as those with metastatic disease or those receiving chemotherapy. Recommendation4.4
The insertion of a vena cava?lter is only indicated for patients with contraindications to anticoagulant therapy(Table4).It may be considered as an adjunct to anticoagulation in patients with progres-sion of thrombosis(recurrent VTE or extension of existing thrombus) despite optimal therapy with LMWH.
Recommendation4.5
For patients with primary CNS malignancies,anticoagulation is recommended for established VTE as described for other patients with cancer.Careful monitoring is necessary to limit the risk of hemor-rhagic complications.
Recommendation4.6
Use of novel oral anticoagulants for either prevention or treat-ment of VTE in patients with cancer is not recommended at this time.Recommendation4.7
Based on consensus,incidental PE and DVT should be treated in the same manner as symptomatic VTE.Treatment of splanchnic or visceral vein thrombi diagnosed incidentally should be consid-ered on a case-by-case basis,considering potential bene?ts and risks of anticoagulation.
Literature Update and Analysis4
Three systematic reviews relevant to VTE treatment and second-ary prophylaxis were identi?ed.46-48No new RCTs that met inclusion criteria were identi?ed.
Systematic Reviews
Data on the relative ef?cacy and safety of LMWH and UFH for initial treatment in patients with cancer come from post hoc subgroup analysis of large RCTs.48Differences in recurrent thrombosis and bleeding were not observed.However,a reduction in mortality with LMWH compared with UFH at3months of follow-up was estimated (RR,0.71;95%CI,0.52to0.98).A systematic review and meta-analysis comparing LMWH and VKAs for long-term anticoagulation was reported by the Cochrane Collaboration.47The rate of recurrent
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thromboembolism was lower with LMWH(RR,0.49;95%CI,0.34to 0.70),but the rates of mortality and bleeding were similar.
Romera-Villegas et al46assessed LMWH dose(full,intermediate, or prophylactic)compared with VKAs for long-term VTE treatment. LMWH at full(RR,0.37;95%CI,0.19to0.74)or intermediate(RR, 0.52;95%CI,0.35to0.79)dose was superior to a VKA.No difference between prophylactic doses of LMWH and VKA was found based on small numbers of patients.Indirect comparison revealed no differ-ences in major bleeding between the LMWH doses.
Initial and Long-Term Treatment Up to6Months For initial therapy in patients with established VTE without renal impairment(creatinine clearance?30mL/min),a Cochrane meta-analysis found improved survival with LMWH over UFH in patients with cancer.48However,a small RCT in elderly patients with renal insuf?ciency(only6%with cancer)reported higher mortality with tinzaparin compared with UFH(see Special Populations).49For treat-ment up to6months,meta-analyses and RCTs validate superiority of LMWH over VKAs.47,50-52
Data on other anticoagulants for patients with cancer are limited. Fondaparinux has been used for initial53and extended therapy for VTE54in patients with cancer.The numbers of patients in these reports were small.Nonetheless,although fondaparinux may be an alternative for patients with heparin-induced thrombocytopenia,it does not have a US Food and Drug Administration indication in this setting.
Treatment Beyond6Months
No published studies address optimal anticoagulation beyond the?rst6months in patients with cancer.However,it is the consensus of the Panel,based on extrapolation from patients with idiopathic VTE,that continuing anticoagulation beyond6months should be considered for selected patients because of the persistent high risk of recurrence in those with active cancer.The decision to continue anti-coagulation must be balanced against the risk of bleeding,cost of therapy,quality of life,life expectancy,and patient preference. Novel Oral Anticoagulants
Novel anticoagulants that target thrombin(direct thrombin in-hibitor dabigatran)or activated factor X(antifactor Xa inhibitors rivaroxaban,apixaban,and edoxaban)are now approved for selected indications in VTE prevention and treatment.However,RCTs evalu-ating these drugs for VTE treatment included few patients with malig-nant disease:RECOVER(Dabigatran Versus Warfarin in the Treatment of Acute Venous Thromboembolism)study of dabigatran, 5%55;EINSTEIN trials of rivaroxaban,6.8%(DVT;Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep Vein Thrombosis),4.7%(PE;Oral Direct Factor Xa Inhibitor Rivar-oxaban in Patients With Acute Symptomatic Pulmonary Embolism), and4.7%(Extended Treatment;Once-Daily Oral Direct Factor Xa Inhibitor Rivaroxaban in the Long-Term Prevention of Recurrent Symptomatic Venous Thromboembolism in Patients With Symp-tomatic Deep-Vein Thrombosis or Pulmonary Embolism)56,57;and AMPLIFY-EXT(Apixaban After Initial Management of PE and VTE With First-Line Therapy–Extended Treatment)trial of apixaban, 1.8%(2.5mg)and1.1%(5mg).58Additional concerns with using these agents in patients with cancer include:unpredictable absorption and higher risk of GI bleeding in those with mucositis or other GI complications,altered metabolism in those with liver or renal impair-ment,drug interaction with hormonal and chemotherapeutic agents, inability to measure the anticoagulant activity using standard assays, and lack of an antidote.In a placebo-controlled pilot study of primary prophylaxis with apixabain for3months in patients with advanced or metastatic cancer,Levine et al59reported major bleeding in only2.2% of patients.Nonetheless,adequately powered RCTs are needed to examine the ef?cacy and safety of these drugs in patients with cancer. Recurrent VTE
Patients with recurrent VTE despite standard doses of anti-coagulant therapy should be assessed for treatment compliance, heparin-induced thrombocytopenia,or any evidence of mechanical compression resulting from malignancy.Otherwise,management op-tions include treatment with an alternate anticoagulant regimen,in-creasing the dose of LMWH,or adding a vena cava?lter to LMWH.In patients for whom standard doses of LMWH fail,higher doses should be considered and are generally well tolerated in those without an increased risk of bleeding.In a retrospective study of patients with cancer and recurrent thrombosis,increasing the LMWH dose by20% to25%was effective in preventing further recurrence.60
Incidental VTE
Incidental?ndings of PE and/or DVT during routine staging with computed tomography scans of abdomen and pelvis as well as splanchnic or visceral vein thrombi are frequently reported.In a recent large systematic review and meta-analysis of12studies including?10,000patients,those had a weighted mean prevalence of incidental PE of3.1%(95%CI,2.2to4.1%).61In a retrospective cohort analysis by Moore et al,6244%of all thromboembolic events were incidental. In a cohort study by Singh,6350%of DVTs and?35%of PEs were incidentally discovered.The pulmonary distribution of incidental em-boli is no different from that of symptomatic emboli,with nearly half occurring in major pulmonary vessels.64,65Importantly,rates of VTE recurrence,bleeding,and mortality seem to be similar in patients with cancer and incidental VTE compared with those with symptom-atic VTE.64-68
Vena Cava Filter
The role of inferior vena cava(IVC)?lters remains uncertain and controversial because of the paucity of trials.In an8-year follow-up report from the only RCT of permanent IVC?lters,the addition of IVC?lters to standard anticoagulation for at least3months compared with anticoagulation alone reduced the risk of PE but increased the incidence of DVT and had no effect on survival.69Patients with cancer constituted16%and12%of those with and without?lters,respec-tively.In a small RCT comparing fondaparinux alone for90days with fondaparinux and IVC?lter placement,no difference in recurrent VTE,bleeding,or mortality was found.54Cohort studies in patients with cancer suggest much higher rates of recurrent VTE and no sur-vival advantage with?lters.70It remains unclear whether permanent or retrievable?lters are preferable in the cancer setting.It is reasonable to select a retrievable?lter when the contraindication to anticoagula-tion is expected to be transient.The safety,however,of retrievable ?lters has raised serious concerns.In2010,the US Food and Drug Administration released a safety alert for optional recovery?lters in response to the high number of adverse events reported.71
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Intracranial Malignancy
Patients with intracranial tumors are at increased risk for throm-botic complications and intracranial hemorrhage.However,presence of an intracranial tumor or brain metastasis is not an absolute contra-indication to anticoagulation.Limited data support use of antithrom-botic therapy in patients with primary or metastatic brain tumors who develop concurrent venous thrombosis.72-77A high failure rate has been reported with IVC?lters,without improved overall survival or reduced intracranial hemorrhage in small retrospective series.74,75,77 Special Populations
Evidence on LMWH and other anticoagulants in special patient populations comes largely from patients without cancer.Most studies were retrospective,had small samples,and did not include appropri-ate control groups.Although increasing age is a risk factor for bleed-ing,anticoagulant therapy should be offered to elderly patients who have no contraindications.Caution and close monitoring are neces-sary in those with renal impairment,cognitive decline,and without family or nearby support.
The elderly.The IRIS(Innohep in Renal Insuf?ciency Study) trial comparing tinzaparin with UFH for initial therapy in patients age?70years with renal impairment was terminated early because of an excess number of deaths in the tinzaparin group.49Poor prognosis factors,including cancer,were over-represented in the tinzaparin arm.Because of early termination,the study was underpowered to detect differences in clinically relevant bleeding and recurrent VTE.
Renal impairment.Bleeding risk is high in patients with renal impairment and likely even higher in those with concurrent cancer. Limited data suggest that LMWH can accumulate when therapeutic doses are administered to patients with creatinine clearance?30 mL/min and that the risk of bleeding in these patients is at least two-fold higher than in patients with normal creatinine clearance.78 Studies indicate that enoxaparin requires dose reduction,but tinza-parin does not.79-81Data on dalteparin at therapeutic doses in patients with renal impairment are lacking.Anti-Xa monitoring is recom-mended if LMWH is used in patients with moderate to severe renal impairment.If this is not available,UFH and VKAs are safer options for initial and long-term treatment,respectively.
Obesity.In obese patients,LMWH dosing has not been well studied.Cohort studies using enoxaparin and dalteparin suggest that LMWH dose should be based on a patient’s actual body weight.82,83 Bleeding risk does not seem to be higher in obese patients.
CLINICAL QUESTION5
Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?
Recommendation5.1
Anticoagulants are not recommended to improve survival in patients with cancer without VTE.
Recommendation5.2
Patients with cancer should be encouraged to participate in clin-ical trials designed to evaluate anticoagulant therapy as an adjunct to standard anticancer therapies.Literature Update and Analysis5
The updated systematic review identi?ed three systematic reviews84-86and one RCT.87All included patients who did not have any indication for anticoagulation.
The systematic review and meta-analysis from Kuderer et al84 evaluated the impact of anticoagulation on survival.The general com-parison of any anticoagulation with no therapy—as well as the more speci?c LMWH or warfarin versus no therapy—demonstrated a lower mortality risk at1year with anticoagulation.Bleeding rates were higher with any anticoagulation(RR,2.31;95%CI,1.93to2.76).
Two Cochrane reviews were published on this topic;one evalu-ated survival with oral anticoagulation and the other with parenteral agents.85,86Comparisons of warfarin with no therapy showed no signi?cant differences in mortality or the incidence of VTE.As ex-pected,warfarin was associated with increased bleeding.In the com-parisons of UFH or LMWH versus placebo,a decrease in mortality was noted at2years(RR,0.92;95%CI,0.88to0.97).This decrease was also noted in the small subgroup of patients with small-cell lung cancer(RR,0.86;95%CI,0.75to0.98).
One RCT included patients with advanced lung,hormone-refractory prostate,or pancreatic cancer and life expectancy?6 months.87Patients were randomly assigned to6weeks of LMWH or no treatment.No bene?t in overall survival was noted(HR,0.94;95% CI,0.75to1.18).This trend was consistent in the subgroup analysis by cancer type.
CLINICAL QUESTION6
What is known about risk prediction and awareness of VTE among patients with cancer?
Recommendation6.1
Based on consensus,the Panel recommends that patients with cancer be assessed for VTE risk at the time of chemotherapy initiation and periodically thereafter.Individual risk factors,including biomark-ers and cancer site,do not reliably identify patients with cancer at high risk of VTE.In the outpatient setting,risk assessment can be con-ducted based on a validated risk assessment tool(Table5). Recommendation6.2
Based on consensus,the Panel recommends that oncologists educate patients regarding VTE,particularly in settings that increase risk such as major surgery,hospitalization,and while receiving sys-temic antineoplastic therapy.
Literature Update and Analysis6
The risk systematic review identi?ed?ve cohort studies.62,88-91 Two reported development of new risk assessment models,88,89and three evaluated existing models.62,90,91The International Myeloma Working Group proposed a consensus-based risk assessment algo-rithm to categorize risk among patients with myeloma;validation is awaited.92Several VTE risk assessment tools have been developed and validated in the perioperative setting,but none has speci?cally focused on patients with cancer.93
Multiple cancer-,treatment-,and patient-related risk factors for VTE relevant to various cancer populations are summarized in Table 3.91,94-96Although patients with brain,pancreatic,stomach,kidney,
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ovarian,or lung cancer are commonly considered at high risk for VTE,patients with hematologic malignancies are also at elevated risk.97,98Hospitalization or major surgery can lead to a transient increase in risk.2,3,27-32,34,35,45,99Speci?c therapeutic agents such as thalidomide,22lenalidomide,20and cisplatin 62,100can also increase VTE risk.Al-though a number of biomarkers have been evaluated,neither solitary risk factors nor individual biomarkers reliably identify high-risk patients.101-103
A multivariable clinical risk assessment model for VTE was de-veloped and internally validated in a cohort of ambulatory patients with cancer receiving systemic chemotherapy (Table 5).88This model has now been externally validated for predicting risk of VTE by several investigators.90,91The balance of bene?t and harm with thrombopro-phylaxis for high-risk patients identi?ed by the model is under study.Therefore,routine thromboprophylaxis in this setting is not cur-rently recommended.
PATIENT AND CLINICIAN COMMUNICATION
Despite the well-known association of VTE and cancer,patients are woefully unaware of that risk and of warning signs and symptoms.Two patient surveys found that fewer than half of patients were aware of the increased risk of VTE associated with malignancy.105,106In a survey of hospitalized patients receiving thromboprophylaxis,re-sponders reported hearing about VTE more frequently from friends,family,or the media than from health care providers.107A different survey indicates that inpatients knew more about VTE than outpa-tients:36%versus 15%.106
The need for increased patient education and awareness is https://www.360docs.net/doc/761351916.html,cated patients are more likely to report symptoms that could lead to early intervention.107In addition,aware and educated patients are more likely to accept efforts such as anticoagulation or early mobility after surgery.In fact,a qualitative survey of patients with cancer noted that increased awareness of VTE led to increased acceptance of pro-
reported improved quality of life and reassurance.108
patients about the signs,symptoms,and along with other health care pro-team,should assure,at minimum,that of VTE warning signs.Nurses are in patients.109Resources,including informa-checklists,are available to facilitate such to the qualitative survey who were given to such (15%of the sample)found 106
help patients distinguish between symp-disease,treatment,and other not report new symptoms,unless que-assume symptoms are manifes-effects of therapy.A good patient communication with the health care communication as well as facilitate HEALTH DISPARITIES
Rates of VTE are higher among African Americans than in the general population overall.110,111Rates are lower in the Asian population than in other ethnicities.111A nationwide analysis of nearly 500,000patients with cancer in Taiwan recently described risk factors and a scoring system for this population.112Applicability of these ?ndings to North American and European patients is unknown.
Although ASCO clinical practice guidelines represent expert rec-ommendations on best practices to provide the highest level of cancer care,it is important to note that many patients have limited access to medical care.Racial and ethnic disparities in health care contribute signi?cantly to this problem in the United States.Minority racial/ethnic patients with cancer suffer disproportionately from comorbidi-ties,experience more substantial obstacles to receiving care,are more likely to be uninsured,and are at greater risk of receiving care of poor quality than other Americans.113-116Many other patients lack access to care because of geography or distance from appropriate treatment facilities.Awareness of these disparities in access to care should be considered in the context of this clinical practice guideline,and health care providers should strive to deliver the highest level of cancer care to these vulnerable populations.
LIMITATIONS
These recommendations are based on data identi?ed by a systematic review of the literature.Some key questions are,as yet,unanswered.The potential bene?ts and harms of thromboprophylaxis in patients with cancer receiving chemotherapy in the outpatient setting and the utility of risk assessment require additional research.Future throm-boprophylaxis trials in outpatients receiving chemotherapy may ben-e?t from the identi?cation of high-risk groups in whom the balance of bene?ts and harms favors prophylaxis.
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?2013by American Society of Clinical Oncology
13
ADDITIONAL RESOURCES
The Data Supplement,including evidence tables,and clinical tools and resources can be found at https://www.360docs.net/doc/761351916.html,/guidelines/vte.Patient information is also available there and at https://www.360docs.net/doc/761351916.html,.
AUTHORS’DISCLOSURES OF POTENTIAL CONFLICTS
OF INTEREST
Although all authors completed the disclosure declaration,the following author(s)and/or an author’s immediate family member(s)indicated a
?nancial or other interest that is relevant to the subject matter under consideration in this article.Certain relationships marked with a“U”are those for which no compensation was received;those relationships marked with a“C”were compensated.For a detailed description of the disclosure categories,or for more information about ASCO’s con?ict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Con?icts of Interest section in Information for Contributors. Authors marked with an asterisk(*)are participants in ASCO’s Disclosure Management System Pilot;their disclosure is not limited to subject matter under consideration in this article and includes payments to themselves,an immediate family member(I),and/or their institutions(INST).For information on the pilot program,or to provide feedback,please visit https://www.360docs.net/doc/761351916.html,.Employment or Leadership Position:None Consultant or Advisory Role:Alok Khorana,Daiichi Sankyo(C),Johnson&Johnson(C),Eisai (C),sano?-aventis(C),LEO Pharma(C),Bristol-Myers Squibb(C), Genentech(C),Eli Lilly(C);Agnes Lee,Bristol-Myers Squibb(C); Charles W.Francis,Eisai(C);Ajay K.Kakkar,Bayer HealthCare Pharmaceuticals(C),Boehringer Ingelheim(C),Eisai(C), GlaxoSmithKline(C),P?zer(C),sano?-aventis(C);Howard A. Liebman,Eisai(C),GlaxoSmithKline(C),Johnson&Johnson(C), sano?-aventis(C)Stock Ownership:None Honoraria:Alok Khorana, Eli Lilly,sano?-aventis,Daiichi Sankyo,Johnson&Johnson,Eisai,LEO Pharma,Bristol-Myers Squibb,Genentech;Agnes Lee,Bayer HealthCare Pharmaceuticals,Boehringer Ingelheim,LEO Pharma,P?zer,
sano?-aventis;Juan Ignacio Arcelus,Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb,P?zer,sano?-aventis Research Funding:*Gary H. Lyman,Amgen;Alok Khorana,LEO Pharma,sano?-aventis;Agnes Lee, LEO Pharma;Charles W.Francis,Eisai;Ajay K.Kakkar,Bayer HealthCare Pharmaceuticals,Boehringer Ingelheim,Eisai, GlaxoSmithKline,P?zer,sano?-aventis Expert Testimony:None Other Remuneration:None
AUTHOR CONTRIBUTIONS
Administrative support:Ann Alexis Prestrud
Manuscript writing:All authors
Final approval of manuscript:All authors
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VTE Prophylaxis and Treatment:ASCO Guideline Update
Acknowledgment
The Update Committee wishes to thank Rose Z.Morrison,Kaitlin Einhaus,Nancy K.Thomasson,Nicholas J.Petrelli MD,Ken Carson,MD, the Journal of Clinical Oncology editorial board and staff,the Clinical Practice Guidelines Committee for its thoughtful reviews of earlier drafts,
and the American Society of Clinical Oncology Board of Directors.
Appendix
https://www.360docs.net/doc/761351916.html,?2013by American Society of Clinical Oncology17
深静脉血栓指南(中华医学会骨科)邱贵兴
中国骨科大手术静脉血栓栓塞症预防指南 中华医学会骨科学分会 通信作者：邱贵兴E-mail: qguixing@https://www.360docs.net/doc/761351916.html, 骨科大手术后静脉血栓栓塞症（venous thromboembolism，VTE）发生率较高，是患者围手术期死亡的主要原因之一，也是医院内非预期死亡的重要原因。对骨科大手术患者施以有效的预防方法，不仅可以降低发生静脉血栓栓塞症的风险，减轻患者痛苦，大量的医药经济学研究证实还可降低医疗费用[1]。为提高与骨科相关的静脉血栓栓塞症的预防水平、规范预防方法，特制订“中国骨科大手术静脉血栓栓塞症预防指南”。本指南中的“骨科大手术”特指人工全髋关节置换术（total hip replacement，THR）、人工全膝关节置换术（total knee replacement，TKR）和髋部周围骨折手术（hip fractures surgery，HFS）[2]。本指南仅为学术性指导意见，具体实施时必须依据患者的医疗情况而定。 一、概述 1. 静脉血栓栓塞症：指血液在静脉内不正常地凝结，使血管完全或不完全阻塞，属静脉回流障碍性疾病[3]。包括两种类型：深静脉血栓形成（deep vein thrombosis，DVT）和肺动脉血栓栓塞症（pulmonary thromboembolism，PTE），即静脉血栓栓塞症在不同部位和不同阶段的两种临床表现形式。 2. 深静脉血栓形成：可发生于全身各部位静脉，以下肢深静脉为多，常见于骨科大手术后。下肢近端（腘静脉或其近侧部位）深静脉血栓形成是肺栓塞血栓栓子的主要来源，预防深静脉血栓形成可降低发生肺动脉血栓栓塞症的风险。 3. 肺动脉血栓栓塞症：指来自静脉系统或右心的血栓阻塞肺动脉或其分支导致的肺循环和呼吸功能障碍疾病[4,5]，是骨科围手术期死亡的重要原因之一。 4. 骨科大手术后静脉血栓栓塞症的流行病学：国外骨科大手术后静脉血栓栓塞症的发生率如表1所示[2]。一项亚洲7个国家19个骨科中心407例人工全髋、人工全膝关节置换及髋关节周围骨折手术后深静脉血栓形成发生率调查研究[6]表明，经静脉造影证实深静脉血栓形成发生率为43.2%（120/278）。国内邱贵兴等[7]的一项多中心研究结果显示，关节置换术后深静脉血栓形成的发生率在未预防组为30.8%（16/52）、预防组为11.8%（8/68）。余楠生等[8]报告髋关节置换术后深静脉血栓形成的发生率为20.6%（83/402），膝关节置换术后为58.2%（109/187）。吕厚山等[9]报告髋关节和膝关节置换术后深静脉血栓形成发生率为47.1%（24/51）。陆芸等[10]报告股骨干骨折术后深静脉血栓形成的发生率为30.6%，髋部骨折术后为1 5.7%。 二、静脉血栓栓塞症的危险因素 任何引起静脉损伤、静脉血流停滞及血液高凝状态的原因都是静脉血栓栓塞症的危险因素，其中骨科大手术是静脉血栓栓塞症的极高危因素[11,12]其他常见的继发性危险因素包括老龄、创伤、既往静脉血栓栓塞症病史、肥胖、瘫痪、制动、术中应用止血带、全身麻醉、恶性肿瘤、中心静脉插管、慢性静脉瓣功能不全等。少见的原发性危险因素有抗凝血酶缺乏症等。危险因素越多，发生静脉血栓栓塞症的风险就越大，当骨科大手术伴有其他危险因素时，危险性更大。骨科手术的静脉血栓栓塞症危险分度如表2所示[13,14]。 三、预防骨科大手术深静脉血栓形成的措施 对接受骨科大手术患者需常规进行静脉血栓预防。预防方法包括基本预防、物理预防和药物预防。 1. 基本预防措施[15,16]：（1）手术操作尽量轻柔、精细，避免静脉内膜损伤；（2）规范使用止血带；（3）术后抬高患肢，防止深静脉回流障碍；（4）常规进行静脉血栓知识宣教，鼓励患者勤翻身、早期功能锻炼、下床活动、做深呼吸及咳嗽动作；（5）术中和术后适度
11 ICU患者深静脉血栓形成预防指南
ICU患者深静脉血栓形成预防指南 中华医学会重症医学分会 ICU患者是深静脉血栓形成(deep vein thrombosis，DVT)的高发人群，在DVT的发生、预防和治疗等方面有着明显的特殊性。DVT的预防国内外已有多个共识或指南，但目前尚缺乏针对ICU患者DVT预防的指南。为此，中华医学会重症医学分会组织有关专家，经广泛征求意见，采用循证医学的方法制定了本指南，旨在进一步提高临床医生对ICU患者DVT的认识，并重视其预防。 一、概念 1．DVT：指血液在深静脉内异常凝结所致的一种静脉回流障碍性疾病。好发部位为下肢深静脉，可发生在下肢近端和远端，前者位于胭静脉或以上部位，后者位于胭静脉以下。下肢近端DVT是肺血栓栓塞症栓子的主要来源。 2．肺血栓栓塞症(pulmonary thromboembolism，PTE)：指来自静脉系统或右心的血栓阻塞肺动脉或其分支所致的肺循环功能障碍性疾病。 3．静脉血栓栓塞症(venous thromboembolism，VTE)：DVT和PTE统称为VTE。因在发病机制上互相关联，DVT和PTE可作为同一疾病表现为VTE在不同部位和不同阶段的临床两种重要形式。 二、流行病学 由于存在长期卧床、制动、血管损伤和(或)血液高凝状态等因素，ICU患者是发生DVT的高危人群。因病情、血栓预防方法和检查手段的不同，DVT在ICU患者中的发生率差异很大(5％一90％)。有研究显示，脓毒症患者早期(6 d)为DVT的高发期，尽管接受了抗凝药物预防，DVT的发生率仍可达5％左右；由于ICU患者的DVT多是无症状，故实际发生率可能更高。在ICU中即使进行预防，DVT 仍有较高的发生率。近期的另一项单中心回顾性研究发现，重症患者转出ICU后仍属发生DVT的高危人群，究其原因可能与患者转出ICU后接受DVT预防的比率下降、住院和制动时间较长有关。故
围术期深静脉血栓肺动脉血栓栓塞症的诊断、预防与治疗专家共识(2014)
围术期深静脉血栓/肺动脉血栓栓塞症的诊断、预防与治疗专家共识(2014) 王秀丽（共同执笔人），王庚，冯泽国，江伟，张兰，张英泽（共同执笔人），陈绍辉，金善良，姚尚龙（共同执笔人），徐懋，郭向阳（负责人） 一、前言 围术期深静脉血栓（deep venous thrombosis, DVT)/肺动脉血栓栓塞症（pulmonary thrombo-embolism，PTE）是围手术期患者的常见并发症和重要死亡原因之一，多见于骨科、妇产科、血管外科和胸外科手术病人，以骨科手术最为常见。我国每年接受全髋关节置换术、全膝关节置换术和髋部周围骨折手术等骨科大手术的数百万病例中，有近50%患者形成DVT，其中20%出现有症状的肺栓塞（pulmonary embolism，PE）。美国1988年调查结果提示大约17％的孕产妇死亡是由于静脉血栓栓塞所致；另外，大面积烧伤等也是诱发DVT的高危因素。因此，对手术患者围术期静脉血栓栓塞症(venous thrombo-embolism，VTE)及早诊断，并进行有效的预防和治疗不仅可以降低发生PE的风险，降低患者死亡率，还可有效地减少医疗费用。 二、深静脉血栓/肺动脉血栓栓塞症的定义/诊断 （一）定义 静脉血栓栓塞症（VTE）：是指血液在静脉内不正常地凝结，使血管完全或不完全阻塞，属静脉回流障碍性疾病。 深静脉血栓形成（DVT）：是指血液在深静脉腔内不正常凝结，阻塞静脉腔，导致静脉回流障碍。可发生于全身各部位静脉，以下肢深静脉为多，常见于骨科大手术后。下肢近端（腘静脉或其近侧部位）DVT是肺栓塞血栓栓子的主要来源，预防DVT可降低发生PTE的风险。 肺动脉血栓栓塞症（PTE）：指内源性或外源性栓子堵塞肺动脉主干或其分枝引起肺循环障碍和呼吸障碍的临床综合征。包括PTE、脂肪栓塞、羊水栓塞和空气栓塞等。其中PTE为PE的最常见类型，通常所说的PE即指PTE。围术期的PTE多见于静脉系统的栓子脱落，偶见心房纤颤者心房栓子脱落，是围手术期患者死亡的主要原因之一。 （二）诊断：可根据其临床表现，结合物理、化验检查，做出较明确诊断。 1. 临床表现 下肢DVT主要表现为下肢肿胀、疼痛、患侧肢体皮肤颜色变紫变暗。腓静脉型DVT多无临床症状，约40%～50%有症状者血栓向近端延展。近端DVT患者出现患肢疼痛、肿胀等症状，其中近一半发生无明显临床症状的肺栓塞。 PE的临床表现取决于栓子的大小和肺循环状态，清醒病人的主要症状为突发呼吸困难、胸痛、晕厥。呼吸困难多为靠近肺门中心部的PE引起，胸痛一般是远端栓子刺激胸膜所致，晕厥是因脑动脉供血减少、心律失常、迷走反射等因素引起。全身麻醉状态下，PE主要表现为突发、无诱因的低氧血症，大面积肺栓塞可致呼气末二氧化碳骤降、高碳酸血症和循环衰竭（临床上以休克和低血压为主要表现，即体循环动脉收缩压<90mmHg或较基础值下降幅度>40mmHg,持续15分钟以上。需除外新发生的心律失常，低血容量或感染中毒症所致血压下降）。 有下列情况可考虑PE：①下肢无力，静脉曲张，不对称下肢浮肿，血栓性静脉炎；②外伤后呼吸困难，胸痛、咯血；③原因不明的呼吸困难，或原有的呼
深静脉血栓预防流程
深静脉血栓预防路径流程图 1、深静脉血栓危险因素评估量表(Autar 评分表)
注:总分28分,低风险≤10分;中风险 11-14分; 高风险≥15分 体质指数=体重/身高2 贫血症包括镰状细胞性贫血、红细胞增多症、溶血性贫血 强制性评估对象:长期卧床、肢体制动、晚期肿瘤、大手术或创伤后。 2、预防下肢深静脉血栓干预方法: ①用小枕垫高患者得脚后跟,使患者小腿悬空,与床面形成20-30度角为宜,防止 深静脉回流障碍。 ②帮助患者进行双侧足踝运动,即踝关节得被动背伸、趾屈与内外翻得“环转” 运动,频率15-20次|min,每个动作重复20次。 ③为患者按摩腓肠肌、股二头肌、股四头肌等,按摩方向由肢体远端向近端,每 侧肢体按摩5min。 ④膝关节伸屈运动频率15-20次|min,重复活动20-30次。 ⑤麻醉作用完全消失后,由护士帮助患者进行第一次翻身,此后间隔2h翻身一 次。 ⑥清醒患者鼓励主动运动,包括进行深呼吸运动及踝关节主动背屈与跖屈运动, 踝关节内翻与外翻运动,腓肠肌、股二头肌、股四头肌与臀大肌得等长收缩训练。指导患者先呼吸10次,然后由肢体远端向近端依次进行踝关节主动背屈与跖屈运动,踝关节主动内翻与外翻运动,频率15-20次|min,腓肠肌、股二头肌、股四头肌与臀大肌得等长收缩训练,每次动作保持收缩状态5s,放松5s,所有动作各重复20-30次。 ⑦物理预防措施:间歇充气加压装置应用。 ⑧对患者及家属进行预防静脉血栓知识教育,鼓励卧床患者进行早期功能锻炼 包括足趾屈伸、踝关节转动、膝关节伸缩锻炼等,鼓励患者及早帮扶下地行走。
术后2h内开始进行第1-3项活动,术后2-4h内进行第4-5项,术后当日执行两次。术后1-7d若患者意识朦胧或昏迷时,继续进行1-5项,但要求增加活动量;意识清醒者,鼓励进行第6项活动,高危患者常规使用第7项措施。以上训练每天4次,分别在晨起、上午、下午及睡前指导患者进行;患者活动均在接受过统一培训得护士协助与指导下完成。 3、观察及评估: [1]瞧:肢体有无肿胀与浅静脉扩张得程度、远端动脉搏动情况 [2]问:肢体有无疼痛,皮肤发绀、潮红、皮肤温度升高提示可能发生静脉血栓。 [3]触:每日做1次小腿腓肠肌得扪诊检查,如有腓肠肌局部压痛,提示腓肠肌静脉 丛有血栓形成。 [4]量:进行双下肢得周胫测量评价差别。大小腿得测量点为髌骨上缘以上15cm 及髌骨下缘以下10cm,双侧相差大于1cm要进一步超声、血浆D-二聚体检查。 4、具体流程: [1]接诊医生及护士共同评估患者深静脉栓塞风险评估(根据深静脉栓塞风险评 估表); [2]予以告知(把此项作为入院常规):评估后,凡有高危因素者,应告知,使其认 识了解深静脉栓塞得原因、危险因素及后果,认真告知深静脉栓塞得早期症状,使患者及家属认识并重视,如有下肢肿痛、呼吸困难、胸闷胸痛等不适,及时向医护人员汇报; [3]凡有高危因素者,进行基本预防措施:鼓励多饮水;多做深呼吸;抬高肢体;鼓 励早期肢体活动、下床活动;不能下地行走或需要卧床休息者,鼓励家属给予被动运动及机械压迫;下肢运动以足踝关节主动及被动活动为最佳活动;被动按摩下肢肌肉;严重高危可借助机械间歇充气加压装置; [4]对于高危因素患者,根据患者情况选择下列药物治疗:低分子肝素皮下注射; 华法林口服;拜阿司匹林片0、1 qd;氯吡格雷75mg qd; [5]密切观察患者病情变化,观察下肢肿胀出现情况及呼吸情况,如出现明显疼 痛、肿胀、患肢皮肤青紫、足背动脉搏动减弱,Homans征(+),或胸痛、胸闷、呼吸困难时,应及时做患肢动静脉彩超、血气分析及肺CTA等检查; [6]明确有深静脉血栓形成者,如有早期血栓形成应及时应用尿激酶 8万u溶于
《中国骨科大手术静脉血栓预防指南》
中国骨科大手术静脉血栓预防指南 中华医学会骨科学分会 静脉血栓栓塞症在骨科大手术中发生率较高，是围手术期最主要的死因之一，也是医院内非预期死亡的重要原因。对骨科大手术患者采用各种方法预防VTE不仅可明显降低其发生，如方法得当也是安全的。为提高中国骨科VTE预防水平、规范预防方法，特制订中国骨科大手术静脉血栓预防指南。本指南中提到的“骨科大手术”特指人工髋关节置换术、人工膝关节置换术和髋部周围骨折手术[1]。本指南仅为学术性指导意见，实施时仍须根据患者以及具体的医疗情况而定。 一、概述 （一）静脉血栓栓塞症（venous thromboemlolism, VTE）血液在静脉内不正常地凝结，使血管完全或不完全阻塞，属静脉回流障碍性疾病[2]包括两种临床类型，即DVT 和PTE （二）深静脉血栓形成（deep vein thrombosis, DVT）：可发生于全身各部位的静脉，以下肢深静脉多见，常见于骨科大手术后，下肢近端（腘静脉或以上部位）DVT是肺栓塞血栓栓子的主要来源。 （三）肺动脉血栓栓塞症（pulmonary thromboembolism, PTE）：指来自静脉系统或右心的血栓阻塞肺动脉或其分支所致肺循环和呼吸功能障碍疾病[2-4]，是骨科围手术期的重要死亡原因。 （四）骨科大手术后VTE流行病学：骨科大手术患者容易发生VTE[1]（表1）。 我国等亚洲国家的骨科大手术后DVT的发生率（经静脉造影证实）也很高，在一项亚洲7个国家19个骨科中心的407例全髋、全膝关节置换及髋关节骨折手术AIDA研究[6]表明，在完成静脉造影的278例患者中，发生DVT 120例，占43.2%。邱贵兴等[7]报告，关节置换术后DVT 的发生率增高，未预防组为30.8 %（16/52），预防组为11.8 %（8/68）（P＜0.05）。余楠生等[8]报道，2001至2005年间髋关节置换术后DVT 发生率为20.6%（83 / 402），膝关节置的术后为58.2%（109 / 187）。吕厚山等[9]报告，1997至1998年间髋关节和膝关节置换术后DVT发生率为47.1%(24/51)。陆芸等[10]报告，股骨干骨折的患者DVT发生率为30.6%，髋部骨折的发生率为15.7%。 二、VTE危险因素 任何可引起静脉损伤、静脉血流停滞及血液高凝状态的原因都是VTE的危险因素，其中骨科大手术是VTE的高危因素[11,12] ，其他常见继发性危险因素包括：老年、创伤、既往VTE 病史、肥胖、瘫痪、制动、术中应用止血带、全身麻醉、恶性肿瘤、中心静脉插管、慢性静脉机能不全等。其他少见的原发性危险因素有如抗凝血酶缺乏症等，危险因素越多，发生VTE 的风险就越大，当骨科大手术患者伴有其他危险因素时发生VTE危险性更大。骨科手术患者发生VTE的危险分度情况见表2[13]。 表2 骨科手术患者VTE 的危险分度
深静脉血栓预防流程
深静脉血栓预防路径流程图
天台人民医院深静脉血栓预防管理流程 1、深静脉血栓危险因素评估量表（Autar评分表） 注：总分28分，低风险≤10分；中风险 11-14分；高风险≥15分体质指数=体重/身高2 贫血症包括镰状细胞性贫血、红细胞增多症、溶血性贫血 强制性评估对象：长期卧床、肢体制动、晚期肿瘤、大手术或创伤后。 2、预防下肢深静脉血栓干预方法： ①用小枕垫高患者的脚后跟，使患者小腿悬空，与床面形成20-30度角为宜， 防止深静脉回流障碍。 ②帮助患者进行双侧足踝运动，即踝关节的被动背伸、趾屈和内外翻的“环转” 运动，频率15-20次|min，每个动作重复20次。 ③为患者按摩腓肠肌、股二头肌、股四头肌等，按摩方向由肢体远端向近端，
每侧肢体按摩5min。 ④膝关节伸屈运动频率15-20次|min，重复活动20-30次。 ⑤麻醉作用完全消失后，由护士帮助患者进行第一次翻身，此后间隔2h翻身 一次。 ⑥清醒患者鼓励主动运动，包括进行深呼吸运动及踝关节主动背屈和跖屈运 动，踝关节内翻和外翻运动，腓肠肌、股二头肌、股四头肌和臀大肌的等长收缩训练。指导患者先呼吸10次，然后由肢体远端向近端依次进行踝关节主动背屈和跖屈运动，踝关节主动内翻和外翻运动，频率15-20次|min，腓肠肌、股二头肌、股四头肌和臀大肌的等长收缩训练，每次动作保持收缩状态5s，放松5s，所有动作各重复20-30次。 ⑦物理预防措施：间歇充气加压装置应用。 ⑧对患者及家属进行预防静脉血栓知识教育，鼓励卧床患者进行早期功能锻炼 包括足趾屈伸、踝关节转动、膝关节伸缩锻炼等，鼓励患者及早帮扶下地行走。 术后2h内开始进行第1-3项活动，术后2-4h内进行第4-5项，术后当日执行两次。术后1-7d若患者意识朦胧或昏迷时，继续进行1-5项，但要求增加活动量；意识清醒者，鼓励进行第6项活动，高危患者常规使用第7项措施。以上训练每天4次，分别在晨起、上午、下午及睡前指导患者进行；患者活动均在接受过统一培训的护士协助和指导下完成。 3、观察及评估： [1]看：肢体有无肿胀和浅静脉扩张的程度、远端动脉搏动情况 [2]问：肢体有无疼痛，皮肤发绀、潮红、皮肤温度升高提示可能发生静脉血栓。 [3]触：每日做1次小腿腓肠肌的扪诊检查，如有腓肠肌局部压痛，提示腓肠肌 静脉丛有血栓形成。 [4]量：进行双下肢的周胫测量评价差别。大小腿的测量点为髌骨上缘以上15cm
预防骨科大手术深静脉血栓形成指南
预防骨科大手术深静脉血栓形成指南 一、概述 1.骨科大手术：特指人工髋关节置换术、人工膝关节置换术和髋部周围骨折手术。 2.深静脉血栓（deep vein thrombosis,DVT）：指血液在深静脉内不正常地凝结，属静脉回流障碍性疾病。好发部位下肢深静脉，常见于骨科大手术后，可分为下肢近端和远端DVT，前者位于腘静脉或以上部位，后者位于腘静脉以下。肢近端DVT是肺栓塞栓子的主要来源。 3.肺血栓栓塞症（pulmonary thomboembolism,PTE）：来自静脉系统或右心的血栓堵塞肺动脉或其分支所致肺循环和呼吸功能障碍疾病，是骨科围手术期的重要死亡原因。 4.静脉血栓栓塞症（venos thomboembolism,VTE）：VT和PTE统称为VTE,因在发病机制上相互关联，两者为同一疾病为VTE在不同部位和不同阶段的两种重要临床表现形式。 5.骨科大手术后VTE流行病学：骨科大手术可造成静脉损伤、静脉血流停滞及血液高凝状态，如不采取有效的预防措施，术后患者容易发生VTE。 二、VTE的危险因素 1.继发性危险因素：手术、创伤、既往VTE病史、老年瘫痪、制动、术中应用止血带、全身麻醉、恶性肿瘤、中心静脉插管、慢性静脉机能不全等，其中骨科大手术是VTE的高危因素。 2.原发性危险因素：抗凝血酶缺乏症、因子vleiden突变、因子XII缺乏症、凝血酶原基因G20210A突变、高半胱氨酸血症、蛋白C缺乏症、蛋白S缺乏症等。当行骨科大手术患者伴有其他危险因素时发生VTE的危险性更大。 三、预防骨科大手术DVT形成的措施 骨科大手术患者需常规进行静脉血栓预防。 1.基本预防措施：（1）手术操作轻巧、精细、避免损伤静脉内膜；（2）规范使用止血带；（3）术后抬高患肢，防止深静脉回流障碍；（4）对患者进行预防静脉血栓知识教育，鼓励患者勤翻身、早期功能锻炼、下床活动以及做深呼吸及咳嗽动作；（5）术中和术后适度补液，避免脱水而增加血液粘度。 2.物理预防措施：足底静脉泵（VFP）、间歇充气加压装置（IPC）及梯度弹力袜（GCS），均利用机械性原理促使下肢静脉血流加速，避免血液滞留，降低术后下肢DVT发病率，与药物预防联合应用疗效更佳。单独使用物理预防适用于合并凝血异常疾病、有高危出血风险的患者。对于患侧肢无法或不宜采取物理预防的患者，可在对侧肢实施预防。建议应用前筛查禁忌。 以下情况禁用物理预防措施：（1）充血性心力衰竭，肺水肿或腿部严重水肿；（2）下肢深静脉血栓症、血栓性静脉炎或肺栓塞；（3）间歇充气加压装置和梯度压力弹力袜不适用于腿部局部情况异常（如皮炎、坏疽、近期接受皮肤移植手术）、下肢血管严重的动脉硬化或其他缺血性血管病、腿部严重畸形。 3.药物预防措施：有出血风险患者应权衡降低DVT的发生率与增加出血危险的关系。 3.1低剂量普通肝素
深静脉血栓形成的诊断和预防指南_(试行)
深静脉血栓形成的诊断和预防指南 深静脉血栓形成(deep venous thrombosis，DVT)是血液在深静脉内不正常凝结引起的病症，多发生于下肢，血栓脱落可引起肺栓塞(pulmonary embolism，PE)，合称为静脉血栓栓塞症(venous throboembolism，VTE)。DVT是常见的一种病症，后果主要是肺栓塞和DVT后综合征，严重者可导致死亡和显著影响生活质量。为提高我院对DVT的诊断和预防水平，特制订了DVT诊断和预防指南。本指南的内容用于协助我院临床医生在工作中处理相应的临床问题。本指南并非唯一的临床处理流程。在具体临床实施过程中，应根据患者的个体情况及家庭经济情况，对本指南内容进行相应的调整。
二、下肢深静脉血栓形成（LEDVT）与妇产科手术的关系：
血液流速缓慢、高凝状态及血管壁损伤是DVT形成的三大因素。 妇产科手术与以上三大因素关系密切。 1.手术因素:盆腔内静脉丰富,膀胱、生殖器官、直肠三个系统静脉彼此相通,形成盆底静脉丛,手术过程中容易出现血管损伤、出血,一方面引起继发性凝血功能增强,另一方面血管损伤引起炎性细胞分泌的白介素-1和肿瘤坏死因子增加,损伤血管内皮,激活外源性凝血系统;麻醉作用下肌肉处于松弛状态,失去“泵”的功能,术后患者卧床,活动减少,下肢血液回流缓慢,尤其是比目鱼肌内静脉窦的血流,完全靠肌肉的收缩作用才能向心回流。因此,LEDVT多见于小腿深静脉;术前肠道准备、术中失血失液、术后禁食、补液量不足导致围手术期体内脱水,血液浓缩,血黏度增加。 2.肿瘤性因素：许多研究表明妇科恶性肿瘤术后是并发DVT的高危人群,约有5%-20%的恶性肿瘤患者可发生血栓。原因为肿瘤细胞自身可以生成并释放促凝因子,或者刺激血管内皮细胞、单核-巨噬细胞系统等释放促凝因子,导致血液高凝状态。 3.妊娠因素:妊娠期妇女体内雌激素总量明显增加，促进肝脏产生多种凝血因子,同时妊娠末期体内纤维蛋白原大量增加,血液处于高凝状态;此外,妊娠期子宫增大压迫下腔静脉,盆腔血管扩张、血流缓慢。因此,孕妇LEDVT的发病率高于非孕妇女,剖宫产LEDVT的发病率明显高于经阴道分娩者。妊娠合并VTE是造成孕妇死亡的主要原因，妊娠发生VTE是正常妇女的四倍。 4.腹腔镜因素:腹腔镜手术形成CO2气腹压力通常为12-15mmHg,
深静脉血栓指南 ACCP指南解读
深静脉血栓指南 ACCP指南解读 推荐总则 1.4.3 我们推荐,机械性预防血栓方法主要应用于出血高风险的患者(1C级)或作为抗凝剂预防血栓的辅助方法(2A级)。我们推荐使用机械性装置必须谨慎,以确保正确和最佳的使用(1C 级)。 1.4.4 我们推荐,对于任何患者,都反对单独使用阿司匹林来预防血栓(1A级)。 1.4.5.1 对于每一种抗血栓药物,我们推荐,临床医师必须考虑生产厂家的剂量使用指南(1C 级)。 1.4.5.2 我们推荐,在决定低分子量肝素、合成戊糖(fondaparinux)、凝血酶直接抑制剂和其他抗血栓药物等由肾脏清除的药物剂量时,特别是对老年患者和有出血高风险的患者,应考虑其对肾功能的损害(1C级)。 1.5.1 我们推荐,对于接受神经轴麻醉或镇痛患者,使用抗凝剂预防时要特别小心(1C 级)。 2.0 普通外科手术、血管外科手术、妇产科手术和泌尿外科手术 2.1 普通外科手术 2.1.1 接受小手术、年龄小于40岁和无其他危险因素的低危普通外科患者,我们推荐,除早期和坚持活动外,不需特殊的预防(1C级)。 2.1.2 对于中度危险的普通外科患者,即年龄在40~60岁,而且接受非大型手术,或者有其他危险因素的患者,以及对于年龄在40岁以下、接受大手术而且无其他危险因素的患者,我们推荐,低剂量普通肝素5000 U,每天2次,或低分子量肝素≤3400 U,每天1次(1A级)。 2.1.3 对于接受非大型手术而且年龄大于60岁或者有其他危险因素,以及对于接受大型手术而且年龄大于40岁或有其他危险因素的更高危险普外科患者,我们推荐,低剂量普通肝素5000 U,每日3次,或低分子量肝素≥3400 U,每天1次(1A级)。
静脉血栓预防手册
静脉血栓预防手册 导读：我根据大家的需要整理了一份关于《静脉血栓预防手册》的内容，具体内容：静脉血栓被称为"最隐秘的危险杀手"，想要做好预防，首先要从饮食下手，那么预防静脉血栓吃什么?下面是我精心为你们整理的预防静脉血栓的相关内容，希望你们会喜欢!... 静脉血栓被称为"最隐秘的危险杀手"，想要做好预防，首先要从饮食下手，那么预防静脉血栓吃什么?下面是我精心为你们整理的预防静脉血栓的相关内容，希望你们会喜欢! 预防静脉血栓吃什么? 一般认为，血栓性疾病包括动脉血栓和静脉血栓病变。近些年的研究发现，静脉血栓隐秘性强，不易诊断，发病和死亡率高，被医学界誉为"最隐秘的危险杀手"。生活中所有人都要有"防栓意识"。首先在饮食方面多吃新鲜果蔬，减少肉类和油脂的摄入。 预防静脉血栓吃什么?今天，我就给大家介绍有助于预防静脉血栓的食物。 洋葱：洋葱含有一种较强血管扩张作用的前列腺素A，它能舒张血管，降低血液熟度，减少血管的压力，同时洋葱还含有二烯丙基二硫化物和含硫氨基酸，可增强纤维蛋白溶解的活性，具有降血脂、抗动脉硬化的功能。红薯：红薯含有胶原与黏多糖，能抑制胆固醇在动脉壁沉积，保持血管弹性，使血流畅通，从而减少心血管疾病的发生。 黑巧克力：美国最新研究结果表明，可可浓度高的黑巧克力有阿司匹林
的功效，每天吃上一点儿，可以预防血栓和心脏病。 豆豉：日本老年病研究所的专家发现，常吃豆豉可预防脑血栓。豆豉中钴的含量是小麦的40倍，有良好的预防冠心病的作用;豆豉中还含有大量能溶解血栓的尿激酶，对改善大脑的血流量和防治老年性痴呆有一定作用。 生姜：生姜中所含的姜油酮、姜烯酚等物质具有抗凝血功能。平时吃一些生姜末或姜粉，血液会保持良好状态，不易出现血栓。 玉米：玉米含脂肪中不饱和脂肪酸，特别是亚油酸的含量高达60%以上。有助于人体脂肪及胆固醇的正常代谢，可以减少胆固醇在血管中的沉积，从而软化动脉血管。 西红柿：西红柿不仅各种维生素含量比苹果、梨高2至4倍，而且还含维生素——芦丁，它可提高机体氧化能力，消除自由基等体内垃圾，保持血管弹性，有预防血栓形成的作用。 海带：海带中含有丰富的岩藻多糖、昆布素，这类物质均有类似肝素的活性，既能防止血拴，又有降胆固醇和脂蛋白、抑制动脉粥样硬化的作用。红葡萄酒：红葡萄酒中所含的白藜芦醇，能降低血小板的凝聚力，对抗血栓形成。饮用紫葡萄汁也具有对抗血栓形成的作用。 茶叶：含有茶多酚，能提高机体抗氧化能力，降低血脂，缓解血液高凝状态，强红细胞弹性，缓解或延缓动脉粥样硬化。经常饮茶可以软化动脉血管。 大蒜：大蒜富含锗和硒等元素，这些有效成分具有明显的降血脂及预防冠心病和动脉硬化的作用，并可防止血栓的形成。
下肢静脉血栓诊疗指南(修订版).doc
一、病因和危险因素 DVT的主要原因是静脉壁损伤、血流缓慢和血液高凝状态。危险因素包括原发性因素和继发性因素(表1)。DVT多见于长期卧床、肢体制动、大手术或创伤后、晚期肿瘤或有明显家族史的患者。 二、临床表现 DVT主要表现为患肢的突然肿胀、疼痛、软组织张力增高;活动后加重，抬高患肢可减轻，静脉血栓部位常有压痛。发病1～2周后，患肢可出现浅静脉显露或扩张。血栓位于小腿肌肉静脉丛时，Homans征和Neuhof征呈阳性(患肢伸直，足突然背屈时，引起小腿深部肌肉疼痛，为Homans征阳性;压迫小腿后方，引起局部疼痛，为Neuhof征阳性)。 严重的下肢DVT患者可出现股白肿甚至股青肿。股白肿为全下肢明显肿胀、剧痛，股三角区、腘窝、小腿后方均有压痛，皮肤苍白，伴体温升高和心率加快。股青肿是下肢DVT 最严重的情况，由于髂股静脉及其侧支全部被血栓堵塞，静脉回流严重受阻，组织张力极高，导致下肢动脉痉挛，肢体缺血;临床表现为患肢剧痛，皮肤发亮呈青紫色、皮温低伴有水疱，足背动脉搏动消失，全身反应强烈，体温升高;如不及时处理，可发生休克和静脉性坏疽。静脉血栓一旦脱落，可随血流进入并堵塞肺动脉，引起PE的临床表现。 DVT慢性期可发生PTS。主要症状是下肢肿胀、疼痛(严重程度随时间的延长而变化)，体征包括下肢水肿、色素沉着、湿疹、静脉曲张，严重者出现足靴区的脂性硬皮病和溃疡。PTS 发生率为20%～50%。 三、诊断 DVT不能仅凭临床表现作出诊断，还需要辅助检查加以证实。 (一)辅助检查 1.血浆D-二聚体测定：D-二聚体是反映凝血激活及继发性纤溶的特异性分子标志物，诊断急性DVT的灵敏度较高(>99%)，>500 μg/L(ELISA法)有重要参考价值。可用于急性VTE 的筛查、特殊情况下DVT的诊断、疗效评估、VTE复发的危险程度评估。 2.多普勒超声检查：灵敏度、准确性均较高，是DVT诊断的首选方法，适用于对患者的筛查和监测。在超声检查前，按照DVT诊断的临床特征评分，可将患有DVT的临床可能性分为高、中、低度(表2)。如连续两次超声检查均为阴性，对于低度可能的患者可以排除诊断，对于高、中度可能的患者，建议行血管造影等影像学检查。 3.螺旋CT静脉成像：准确性较高，可同时检查腹部、盆腔和下肢深静脉情况。 4.MRI静脉成像：能准确显示髂、股、腘静脉血栓，但不能满意地显示小腿静脉血栓。无需使用造影剂。 5.静脉造影：准确性高，不仅可以有效判断有无血栓、血栓部位、范围、形成时间和侧支循环情况，而且常被用来鉴定其他方法的诊断价值。 (二)临床可能性评估和诊断流程 DVT的临床可能性评估参考Wells临床评分(表2)，DVT诊断流程见图1。 四、治疗 (一)早期治疗 1.抗凝：抗凝是DVT的基本治疗，可抑制血栓蔓延、有利于血栓自溶和管腔再通，从而减轻症状、降低PE发生率和病死率。但是单纯抗凝不能有效消除血栓、降低PTS发生率。药物包括普通肝素、图1深静脉血栓形成诊断流程 低分子肝素、维生素K拮抗剂、直接Ⅱa因子抑制剂、Ⅹa因子抑制剂等。 (1)普通肝素：治疗剂量个体差异较大，使用时必须监测凝血功能，一般采用静脉持续给药。起始剂量为80～100 U/kg静脉推注，之后以10～20 U·kg-1·h-1静脉泵入，以后每4～6小时根据活化部分凝血活酶时间(APTT)再作调整，使APTT的国际标准化比值(INR)保持在
静脉血栓防治指南
Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer:American Society of Clinical Oncology Clinical Practice Guideline Update Gary H.Lyman,Alok A.Khorana,Nicole M.Kuderer,Agnes Y.Lee,Juan Ignacio Arcelus,Edward P.Balaban, Jeffrey M.Clarke,Christopher R.Flowers,Charles W.Francis,Leigh E.Gates,Ajay K.Kakkar,Nigel S.Key,Mark N.Levine,Howard A.Liebman,Margaret A.Tempero,Sandra L.Wong,Ann Alexis Prestrud,and Anna Falanga Gary H.Lyman,Nicole M.Kuderer,and Jeffrey M.Clarke,Duke University and Duke Cancer Institute,Durham;Nigel S.Key,Lineberger Comprehensive Cancer Center,University of North Carolina,Chapel Hill,NC;Alok A.Khorana,Taussig Cancer Institute,Cleveland Clinic,Cleveland,OH;Agnes Y.Lee,University of British Colum-bia,Vancouver,British Columbia;Mark N.Levine,McMaster University,Hamilton,Ontario,Canada;Juan Ignacio Arcelus,Hospital Universitario Virgen de las Nieves,University of Granada,Granada,Spain; Edward P.Balaban,University of Pittsburgh Cancer Centers Network,Pittsburgh,PA;Christopher R.Flowers,Emory University School of Medicine and Winship Cancer Institute,Atlanta,GA;Charles W.Francis,James P.Wilmot Cancer Center and University of Rochester,Rochester,NY;Leigh E.Gates,patient representative,Denver,CO;Ajay K.Kakkar,Thrombosis Research Institute,London,United King-dom;Howard A.Liebman,Keck School of Medicine,University of Southern California,Los Angeles;Margaret A.Tempero,University of California–San Francisco Pancreas Center,San Francisco,CA;Sandra L.Wong,University of Michigan,Ann Arbor,MI;Ann Alexis Prestrud,Ameri-can Society of Clinical Oncology,Alexan-dria,VA;and Anna Falanga,Hospital Papa Giovanni XXIII,Bergamo,Italy.Published online ahead of print at https://www.360docs.net/doc/761351916.html, on May 13,2013.Clinical Practice Guidelines Committee Approval:Pending Editor’s note:This American Society of Clinical Oncology Clinical Practice Guideline Update provides recommendations with comprehensive discussion of the relevant literature for each recommendation.The Data Supplement,including evidence tables,is available at https://www.360docs.net/doc/761351916.html,/guidelines/vte. Authors’disclosures of potential con?icts of interest and author contributions are found at the end of this article. Corresponding author:American Society of Clinical Oncology,2318Mill Rd,Suite 800,Alexandria,VA 22314;e-mail:guidelines@https://www.360docs.net/doc/761351916.html,. ?2013by American Society of Clinical Oncology 0732-183X/13/3199-1/$20.00DOI:10.1200/JCO.2013.49.1118 A B S T R A C T Purpose To provide recommendations about prophylaxis and treatment of venous thromboembolism (VTE)in patients with cancer.Prophylaxis in the outpatient,inpatient,and perioperative settings was considered,as were treatment and use of anticoagulation as a cancer-directed therapy.Methods A systematic review of the literature published from December 2007to December 2012was completed in MEDLINE and the Cochrane Collaboration Library.An Update Committee reviewed evidence to determine which recommendations required revision. Results Forty-two publications met eligibility criteria,including 16systematic reviews and 24randomized controlled trials. Recommendations Most hospitalized patients with cancer require thromboprophylaxis throughout hospitalization.Thrombopro-phylaxis is not routinely recommended for outpatients with cancer.It may be considered for selected high-risk patients.Patients with multiple myeloma receiving antiangiogenesis agents with chemotherapy and/or dexamethasone should receive prophylaxis with either low–molecular weight heparin (LMWH)or low-dose aspirin.Patients undergoing major cancer surgery should receive prophylaxis,starting before surgery and continuing for at least 7to 10days.Extending prophylaxis up to 4weeks should be considered in those with high-risk features.LMWH is recommended for the initial 5to 10days of treatment for deep vein thrombosis and pulmonary embolism as well as for long-term (6months)secondary https://www.360docs.net/doc/761351916.html,e of novel oral anticoagulants is not currently recommended for patients with malignancy and VTE.Anticoagulation should not be used for cancer treatment in the absence of other indications.Patients with cancer should be periodically assessed for VTE risk.Oncology professionals should provide patient education about the signs and symptoms of VTE. J Clin Oncol 31.?2013by American Society of Clinical Oncology INTRODUCTION The American Society of Clinical Oncology (ASCO)?rst published an evidence-based clinical practice guideline on prophylaxis and treatment of venous thromboembolism (VTE)in 2007.1ASCO guide-lines are updated at intervals determined by an Up-date Committee;this is a full guideline update.Table 1provides a summary of the 2007and 2012guide-line recommendations. GUIDELINE QUESTIONS 1.Should hospitalized patients with cancer re-ceive anticoagulation for VTE prophylaxis? 2.Should ambulatory patients with cancer re-ceive anticoagulation for VTE prophylaxis during systemic chemotherapy? 3.Should patients with cancer undergoing sur-gery receive perioperative VTE prophylaxis? 4.What is the best method for treatment of pa-tients with cancer with established VTE to pre-vent recurrence? 5.Should patients with cancer receive anticoagu-lants in the absence of established VTE to im-prove survival? 6.What is known about risk prediction and awareness of VTE among patients with cancer? METHODS Panel Composition An Update Committee was formed (Appendix Table A1,online only)to review data published since the initial J OURNAL OF C LINICAL O NCOLOGY A S C O S P E C I A L A R T I C L E ?2013by American Society of Clinical Oncology 1 https://www.360docs.net/doc/761351916.html,/cgi/doi/10.1200/JCO.2013.49.1118The latest version is at Published Ahead of Print on May 13, 2013 as 10.1200/JCO.2013.49.1118