Decision-Making in the Management of Venous Thromboembolism

  • Martin H. Ellis
    Requests for reprints should be addressed to Martin Ellis, MD, Hematology Institute, Meir Medical Center, 59 Tchernichovsky St, Kfar Saba 44281, Israel.
    Hematology Institute and Blood Bank, Meir Medical Center, Kfar Saba, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
  • Orly Avnery
    Hematology Institute and Blood Bank, Meir Medical Center, Kfar Saba, Israel

    Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
    Search for articles by this author
Published:October 24, 2020DOI:


      Venous thromboembolism comprising deep venous thrombosis and pulmonary embolus is common. Patients with venous thromboembolism may present to a variety of health care providers, and while a significant proportion of patients begin treatment in the hospital, ambulatory management of both deep venous thrombosis and pulmonary embolus is feasible and becoming more common. Initial anticoagulant management, investigation of venous thromboembolism etiology, and decisions about extended anticoagulation require coordinated care by physicians from multiple specialties. Comprehensive management of venous thromboembolism requires coordinated care from the time of presentation in order to expedite diagnosis, initiate timely anticoagulant treatment, determine the need for extended anticoagulation based on risk of bleeding and recurrent thrombosis, and advise on thromboprophylaxis during future high-risk periods for venous thromboembolism. In this review we use case scenarios to provide an operational framework, based on current evidence-based recommendations, for informed decision-making about a number of clinical practice issues that are frequently encountered in the management of venous thromboembolism patients.


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        • Heit JA
        • Spencer FA
        • White RH
        The epidemiology of venous thromboembolism.
        J Thromb Thrombolysis. 2016; 41: 3-14
        • Wells PS
        • Ihaddadene R
        • Reilly A
        • Forgie MA
        Diagnosis of venous thromboembolism: 20 years of progress.
        Ann Intern Med. 2018; 168: 131-140
        • Kearon C
        • de Wit K
        • Parpia S
        • et al.
        Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability.
        N Engl J Med. 2019; 381: 2125-2134
        • Mausbach LS
        • Avnery O
        • Ellis MH
        Ambulatory versus in-hospital treatment of proximal lower-limb deep vein thrombosis in adults: a retrospective cohort study.
        Clin Appl Thromb Hemost. 2017; 23: 859-864
        • Piran S
        • Le Gal G
        • Wells PS
        • et al.
        Outpatient treatment of symptomatic pulmonary embolism: a systematic review and meta-analysis.
        Thromb Res. 2013; 132: 515-519
        • Tritschler T
        • Kraaijpoel N
        • Le Gal G
        • Wells PS
        Venous thromboembolism: advances in diagnosis and treatment.
        JAMA. 2018; 320: 1583-1594
        • Kearon C
        • Kahn SR
        Long-term treatment of venous thromboembolism.
        Blood. 2020; 135: 317-325
        • Wells PS
        • Anderson DR
        • Rodger M
        • et al.
        Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer.
        Ann Intern Med. 2001; 135: 98-107
        • Le Gal G
        • Righini M
        • Roy P-M
        • et al.
        Prediction of pulmonary embolism in the emergency department: the revised Geneva Score.
        Ann Intern Med. 2006; 144: 165-171
        • Själander A
        • Jansson
        • Bergqvist JH
        • Eriksson D
        • Carlberg H
        • Svensson P B
        Efficacy and safety of anticoagulant prophylaxis to prevent venous hromboembolism in acutely ill medical inpatients: a meta-analysis.
        J Intern Med. 2008; 263: 52-60
        • Mooumneh T
        • Riou J
        • Douillet D
        • et al.
        Validation of risk assessment models predicting venous thromboembolism in acutely ill medical inpatients: a cohort study.
        J Thromb Haemos. 2020; 18: 1398-1407
        • Neumann I
        • Izcovich A
        • Zhang Y
        • et al.
        DOACs vs LMWHs in hospitalized medical patients: a systematic review and meta-analysis that informed 2018 ASH guidelines.
        Blood Adv. 2020; 4: 1512-1517
        • Bhalla V
        • Lamping OF
        • Abdel-Latif A
        • Bhalla M
        • Ziada K
        • Smyth SS
        Contemporary meta-analysis of extended direct-acting oral anticoagulant thromboprophylaxis to prevent venous thromboembolism.
        Am J Med. 2020;; 133: 1074-1081
        • van Es N
        • Coppens M
        • Schulman S
        • Middeldorp S
        • Büller HR
        Direct oral anticoagulants compared with vitamin K antagonists for acute venous thromboembolism: evidence from phase 3 trials.
        Blood. 2014; 124: 1968-1975
        • Pengo V
        • Denas G
        • Zoppellaro G
        • et al.
        Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome.
        Blood. 2018; 132: 1365-1371
        • Tektonidou MG
        • Andreoli L
        • Limper M
        • et al.
        EULAR recommendations for the management of antiphospholipid syndrome in adults.
        Ann Rheum Dis. 2019; 78: 1296-1304
        • Wicki J
        • Perrier A
        • Perneger TV
        • Bounameaux H
        • Junod AF
        Predicting adverse outcome in patients with acute pulmonary embolism: a risk score.
        Thromb Haemost. 2000; 84: 548-552
        • Jiménez D
        • Aujesky D
        • Moores L
        • et al.
        Simplification of the Pulmonary Embolism Severity Index for prognostication in patients with acute symptomatic pulmonary embolism.
        Arch Intern Med. 2010; 170: 1383-1389
        • Stein PD
        • Hughes MJ
        Mounting evidence for safe home treatment of selected patients with acute pulmonary embolism.
        Ann Intern Med. 2018; 169: 881-882
        • Connors JM
        Thrombophilia testing and venous thrombosis.
        N Engl J Med. 2017; 377: 2298
        • Kearon C
        • Ageno W
        • Cannegieter SC
        • et al.
        Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH.
        J Thromb Haemost. 2016; 14: 1480-1483
        • Carrier M
        • Lazo-Langner A
        • Shivakumar S
        • et al.
        Screening for occult cancer in unprovoked venous thromboembolism.
        N Engl J Med. 2015; 373: 697-704
        • Robertson L
        • Yeoh SE
        • Broderick C
        • Stansby G
        • Agarwal R
        Effect of testing for cancer on cancer- or venous thromboembolism (VTE)-related mortality and morbidity in people with unprovoked VTE.
        Cochrane Database Syst Rev. 2018; 11CD010837
        • Stern RM
        • Al-Samkari H
        • Connors JM
        Thrombophilia evaluation in pulmonary embolism.
        Curr Opin Cardiol. 2019; 34: 603-609
        • Stevens SM
        • Woller SC
        • Bauer KA
        • et al.
        Guidance for the evaluation and treatment of hereditary and acquired thrombophilia.
        J Thromb Thrombolysis. 2016; 41: 154-164
        • Speed V
        • Roberts LN
        • Patel JP
        • Arya R
        Venous thromboembolism and women's health.
        Br J Haematol. 2018; 183: 346-363
        • Bouvier S
        • Cochery-Nouvellon E
        • Lavigne-Lissalde G
        • et al.
        Comparative incidence of pregnancy outcomes in thrombophilia-positive women from the NOH-APS observational study.
        Blood. 2014; 123: 414-421
        • Baglin T
        • Luddington R
        • Brown K
        • Baglin C
        Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study.
        Lancet. 2003; 362: 523-526
        • Kearon C
        • Parpia S
        • Spencer FA
        • et al.
        Long-term risk of recurrence in patients with a first unprovoked venous thromboembolism managed according to D-dimer results: a cohort study.
        J Thromb Haemost. 2019; 17: 1144-1152
        • Rodger MA
        • Kahn SR
        • Wells PS
        • et al.
        Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.
        CMAJ. 2008; 179: 417-426
        • Tosetto A
        • Iorio A
        • Marcucci M
        • et al.
        Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH).
        J Thromb Haemost. 2012; 10: 1019-1025
        • Eichinger S
        • Heinze G
        • Jandeck LM
        • Kyrle PA
        Risk assessment of recurrence in patients with unprovoked deep vein thrombosis or pulmonary embolism: the Vienna prediction model.
        Circulation. 2010; 121: 1630-1636
        • Rodger MA
        • Le Gal G
        • Anderson DR
        • et al.
        Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: multinational prospective cohort management study.
        BMJ. 2017; 356: j1065
        • Palareti G
        • Cosmi B
        • Legnani C
        • et al.
        D‐dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study.
        Blood. 2014; 124: 196-203
        • Schulman S
        • Kearon C
        • Kakkar AK
        • et al.
        Extended use of dabigatran, warfarin, or placebo in venous thromboembolism.
        N Engl J Med. 2013; 368: 709-718
        • Agnelli G
        • Buller HR
        • Cohen A
        • et al.
        Apixaban for extended treatment of venous thromboembolism.
        N Engl J Med. 2013; 368: 699-708
        • Weitz JI
        • Lensing AWA
        • Prins MH
        • et al.
        Rivaroxaban or aspirin for extended treatment of venous thromboembolism.
        N Engl J Med. 2017; 376: 1211-1222
        • Mai V
        • Guay CA
        • Perreault L
        • et al.
        Extended anticoagulation for VTE: a systematic review and meta-analysis.
        Chest. 2019; 155: 1199-1216
        • Kearon C
        • Akl EA
        • Ornelas J
        • et al.
        Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.
        Chest. 2016; 149: 315-352
        • Farge D
        • Bounameaux H
        • Brenner B
        • et al.
        International clinical practice guidelines including guidance for direct oral anticoagulants in the treatment and prophylaxis of venous thromboembolism in patients with cancer.
        Lancet Oncol. 2016; 17: e452-e466
        • Raskob G
        • van Es N
        • Verhamme P
        • et al.
        Edoxaban for the treatment of cancer-associated venous thromboembolism.
        N Engl J Med. 2018; 378: 615-624
        • Young A
        • Marshall A
        • Thirlwall J
        • et al.
        Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D).
        J Clin Oncol. 2018; 36: 2017-2023
        • McBane RDII
        • Wysokinski WE
        • Le-Rademacher JG
        • et al.
        Apixaban and dalteparin in active malignancy-associated venous thromboembolism: the ADAM-VTE trial.
        J Thromb Haemost. 2020; 18: 411-421
        • Agnelli G
        • Becattini C
        • Meyer G
        • et al.
        Apixaban for the treatment of venous thromboembolism associated with cancer.
        N Engl J Med. 2020; 382: 1599-1607
        • Schaefer JK
        • Li Y
        • Kong X
        • et al.
        Impact of adding aspirin to direct oral anticoagulant therapy without an apparent indication.
        Blood. 2019; (Supplement. Abstract 787)
        • Konstantinides SV
        • Meyer G
        • Becattini C
        • et al.
        2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS).
        Eur Heart J. 2020; 41: 543-603
        • Prins MH
        • Lensing AWA
        • Prandoni P
        • et al.
        Risk of recurrent venous thromboembolism according to baseline risk factor profiles.
        Blood Adv. 2018; 2: 788-796
        • Arabi YM
        • Khedr M
        • Dara SI
        • et al.
        Use of intermittent pneumatic compression and not graduated compression stockings is associated with lower incident VTE in critically ill patients: a multiple propensity scores adjusted analysis.
        Chest. 2013; 144: 152-159
        • Nemeth B
        • van Adrichem RA
        • van Hylckama Vlieg A
        • et al.
        Venous thrombosis risk after arthroscopy of the knee: derivation and validation of the L-TRiP(ascopy) score.
        Thromb Haemost. 2018; 118: 1823-1831
        • Berger RE
        • Pai M
        • Rajasekhar A
        Thromboprophylaxis after knee arthroscopy.
        N Engl J Med. 2017; 376: 580-583