Phlebologie 2018; 47(06): 319-328
DOI: 10.12687/phleb2449-6-2018
Übersichtsarbeiten
Georg Thieme Verlag KG Stuttgart · New York

The lower leg vein thrombosis – a disease for specialists

Artikel in mehreren Sprachen: deutsch | English
J. Herold
1   Klinik für Gefäßmedizin – Angiologie, Gefäßzentrum, Klinikum Darmstadt GmbH, Darmstadt
,
R. Bauersachs
1   Klinik für Gefäßmedizin – Angiologie, Gefäßzentrum, Klinikum Darmstadt GmbH, Darmstadt
› Institutsangaben
Weitere Informationen

Korrespondenzadresse

Prof. Dr. med. Rupert Bauersachs
Grafenstraße 9
64283 Darmstadt
Telefon: 06151 – 107 4401   
Fax: 06151 – 107 4429   

Publikationsverlauf

Eingegangen: 30. Juni 2018

Angenommen: 02. Juli 2018

Publikationsdatum:
03. Januar 2019 (online)

 

Summary

For patients with proximal deep vein thrombosis or pulmonary embolism, the initial treatment is well defined. However, there are conflicting recommendations from current guidelines when distal (calf) veins are thrombosed, ranging from surveillance without anticoagulation to full therapeutic anticoagulation for three months or even longer, as the dose and duration of the anticoagulant is not yet established due to sparse and contradicting evidence. This article is intended to critically review the available evidence and facilitate patient-specific treatment recommendations based on current studies, guidelines and expert opinion.


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  • Literatur

  • 1 Schellong SM. [Ultrasound investigation of vessels supplying the extremities]. Der Radiologe 2009; Nov; 49 (11) 1005-15 PubMed PMID: 19859687. Ultraschalluntersuchung der extremitatenversorgenden Gefäße.
  • 2 Hach-Wunderle V, Gerlach H, Konstantinides S, Noppeney T, Riess H, Schellong S. et al. Interdisziplinäre S2k: Leitlinie: Diagnostik und Therapie der Bein- und Beckenvenenthrombose und der Lungenembolie; Registernummer 065 – 002. VASA 2016; 45 (Suppl. 90) 1-48.
  • 3 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; Feb; 149 (02) 315-52 PubMed PMID: 26867832. Epub 2016/02/13. eng.
  • 4 Schellong S, Gerlach H, Hach-Wunderle V, Rabe E, Riess H, Carnarius H. et al. Diagnostic Work-Up And Diagnostic Safety In Patients With Suspected Deep Vein Thrombosis – Data From The German Tulipa Registry. Journal of Thrombosis and Hemostasis. 2007 05. 02.
  • 5 Galanaud JP, Sevestre MA, Genty C, Kahn SR, Pernod G, Rolland C. et al. Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis. Journal of thrombosis and haemostasis : JTH 2014; Apr; 12 (04) 436-443 PubMed PMID: 24450376.
  • 6 Schellong SM, Schwarz T, Halbritter K, Beyer J, Siegert G, Oettler W. et al. Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis. Thromb Haemost 2003; Feb; 89 (02) 228-234 PubMed PMID: 12574800. Epub 2003/02/08. eng.
  • 7 Schellong SM, Gerlach H, Hach-Wunderle V, Rabe E, Riess H, Carnarius H. et al. Diagnosis of deepvein thrombosis: adherence to guidelines and outcomes in real-world health care. Thromb Haemost 2009; Dec; 102 (06) 1234-40 PubMed PMID: 19967156. Epub 2009/12/08. eng.
  • 8 Gibson NS, Schellong SM, Kheir DY, Beyer-Westendorf J, Gallus AS, McRae S. et al. Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. Journal of thrombosis and haemostasis. JTH 2009; Dec; 07 (12) 2035-2041 PubMed PMID: 19817986. Epub 2009/10/13. eng.
  • 9 Robert-Ebadi H, Righini M. Management of distal deep vein thrombosis. Thrombosis research 2017; Jan; 149: 48-55 PubMed PMID: 27889688. Epub 2016/11/28. eng.
  • 10 Schellong SM, Schwarz T, Pudollek T, Schmidt B, Schroeder HE. Complete compression ultrasound for the diagnosis of proximal and distal deep venous thrombosis--a retrospective outcome study. VASA Zeitschrift fur Gefasskrankheiten 2001; Nov; 30 (04) 253-257 PubMed PMID: 11771208.
  • 11 Geersing GJ, Janssen KJ, Oudega R, Bax L, Hoes AW, Reitsma JB. et al. Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis. Bmj 2009; Aug 14; 339: b2990 PubMed PMID: 19684102. Pubmed Central PMCID: 2727580.
  • 12 Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venous thromboembolism. Seminars in thrombosis and hemostasis 2009; Feb; 35 (01) 50-9 PubMed PMID: 19308893.
  • 13 Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R. et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Annals of internal medicine 2004; Apr 20; 140 (08) 589-602 PubMed PMID: 15096330.
  • 14 Wu AR, Garry J, Labropoulos N. Incidence of pulmonary embolism in patients with isolated calf deep vein thrombosis. Journal of vascular surgery Venous and lymphatic disorders 2017; Mar; 05 (02) 274-279 PubMed PMID: 28214497. Epub 2017/02/20. eng.
  • 15 Kearon C. Extended anticoagulation for unprovoked venous thromboembolism: a majority of patients should be treated. J Thromb Thrombolysis 2011; Apr; 31 (03) 295-300 PubMed PMID: 21331558. Epub 2011/02/19. eng.
  • 16 Schulman S, Lindmarker P, Holmstrom M, Larfars G, Carlsson A, Nicol P. et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. Journal of thrombosis and haemostasis JTH 2006; Apr; 04 (04) 734-42 PubMed PMID: 16634738.
  • 17 Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. Jama 1998; Feb 11; 279 (06) 458-462 PubMed PMID: 9466640.
  • 18 Mazzolai L, Aboyans V, Ageno W, Agnelli G, Alatri A, Bauersachs R. et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European society of cardiology working groups of aorta and peripheral circulation and pulmonary circulation and right ventricular function. European heart journal. 2017 Feb 17. PubMed PMID: 28329262.
  • 19 Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D. et al. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thrombosis and haemostasis 2009; Sep; 102 (03) 493-500 PubMed PMID: 19718469.
  • 20 Barco S, Corti M, Trinchero A, Picchi C, Ambaglio C, Konstantinides SV. et al. Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism. Journal of thrombosis and haemostasis JTH 2017; Jul; 15 (07) 1436-1442 PubMed PMID: 28439954. Epub 2017/04/26. eng.
  • 21 Galanaud JP, Sevestre MA, Pernod G, Genty C, Richelet S, Kahn SR. et al. Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. Journal of thrombosis and haemostasis JTH 2017; May; 15 (05) 907-16 PubMed PMID: 28266773. Epub 2017/03/08. eng.
  • 22 Lagerstedt C, Olsson CG, Fagher B, Oqvist B, Albrechtsson U. Oral anticoagulants in calf-vein thrombosis. Lancet 1985; Dec 7; 02 (8467): 1311-2 PubMed PMID: 2866380.
  • 23 Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 1985; Sep 7; 02 (8454): 515-8 PubMed PMID: 2863541.
  • 24 Schwarz T, Buschmann L, Beyer J, Halbritter K, Rastan A, Schellong S. Therapy of isolated calf muscle vein thrombosis: a randomized, controlled study. J Vasc Surg 2010; Nov; 52 (05) 1246-50 PubMed PMID: 20630682. Epub 2010/07/16. eng.
  • 25 Righini M, Galanaud JP, Guenneguez H, Brisot D, Diard A, Faisse P. et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol 2016; Dec; 03 (12) e556-e62 PubMed PMID: 27836513. Epub 2016/11/12. eng.
  • 26 Franco L, Giustozzi M, Agnelli G, Becattini C. Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis. Journal of thrombosis and haemostasis : JTH 2017; Jun; 15 (06) 1142-54 PubMed PMID: 28316124. Epub 2017/03/21. eng.
  • 27 Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I. et al. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation 2001; May 22; 103 (20) 2453-2460 PubMed PMID: 11369685.
  • 28 Ferrara F, Meli F, Amato C, Cospite V, Raimondi F, Novo G. et al. Optimal duration of treatment in surgical patients with calf venous thrombosis involving one or more veins. Angiology 2006; Aug-Sep; 57 (04) 418-423 PubMed PMID: 17022376.
  • 29 Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Larfars G, Nicol P. et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. The New England journal of medicine 1995; Jun 22; 332 (25) 1661-1665 PubMed PMID: 7760866.
  • 30 Li AY, Woulfe T, Rolfe-Vyson V, Rowland V, Simpson D, Merriman E. Management and outcomes of axial isolated distal deep vein thrombosis at North Shore Hospital, New Zealand: a retrospective audit. Intern Med J 2015; Feb; 45 (02) 177-182 PubMed PMID: 25521797. Epub 2014/12/19. eng.
  • 31 VASA Zeitschrift fur Gefasskrankheiten. 2016; Nov; 45 (Suppl. 95) 1-100 PubMed PMID: 27855568. S3-Leitlinie PAVK – Diagnostik, Therapie und Nachsorge der peripheren arteriellen Verschlusskrankheit.
  • 32 Kamphuisen PW, Lee AYY, Meyer G, Bauersachs R, Janas MS, Jarner MF. et al. Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study. Journal of thrombosis and haemostasis JTH 2018; Mar 24 PubMed PMID: 29573330.
  • 33 Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF. et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. Jama 2015; Aug 18; 314 (07) 677-686 PubMed PMID: 26284719.
  • 34 Decousus H, Prandoni P, Mismetti P, Bauersachs RM, Boda Z, Brenner B. et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. The New England journal of medicine 2010; Sep 23; 363 (13) 1222-1232 PubMed PMID: 20860504.
  • 35 Beyer-Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K. et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, noninferiority SURPRISE phase 3b trial. The Lancet Haematology 2017; Mar; 04 (03) e105-e13 PubMed PMID: 28219692.
  • 36 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; Feb; 149 (02) 315-352 PubMed PMID: 26867832.

Korrespondenzadresse

Prof. Dr. med. Rupert Bauersachs
Grafenstraße 9
64283 Darmstadt
Telefon: 06151 – 107 4401   
Fax: 06151 – 107 4429   

  • Literatur

  • 1 Schellong SM. [Ultrasound investigation of vessels supplying the extremities]. Der Radiologe 2009; Nov; 49 (11) 1005-15 PubMed PMID: 19859687. Ultraschalluntersuchung der extremitatenversorgenden Gefäße.
  • 2 Hach-Wunderle V, Gerlach H, Konstantinides S, Noppeney T, Riess H, Schellong S. et al. Interdisziplinäre S2k: Leitlinie: Diagnostik und Therapie der Bein- und Beckenvenenthrombose und der Lungenembolie; Registernummer 065 – 002. VASA 2016; 45 (Suppl. 90) 1-48.
  • 3 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; Feb; 149 (02) 315-52 PubMed PMID: 26867832. Epub 2016/02/13. eng.
  • 4 Schellong S, Gerlach H, Hach-Wunderle V, Rabe E, Riess H, Carnarius H. et al. Diagnostic Work-Up And Diagnostic Safety In Patients With Suspected Deep Vein Thrombosis – Data From The German Tulipa Registry. Journal of Thrombosis and Hemostasis. 2007 05. 02.
  • 5 Galanaud JP, Sevestre MA, Genty C, Kahn SR, Pernod G, Rolland C. et al. Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis. Journal of thrombosis and haemostasis : JTH 2014; Apr; 12 (04) 436-443 PubMed PMID: 24450376.
  • 6 Schellong SM, Schwarz T, Halbritter K, Beyer J, Siegert G, Oettler W. et al. Complete compression ultrasonography of the leg veins as a single test for the diagnosis of deep vein thrombosis. Thromb Haemost 2003; Feb; 89 (02) 228-234 PubMed PMID: 12574800. Epub 2003/02/08. eng.
  • 7 Schellong SM, Gerlach H, Hach-Wunderle V, Rabe E, Riess H, Carnarius H. et al. Diagnosis of deepvein thrombosis: adherence to guidelines and outcomes in real-world health care. Thromb Haemost 2009; Dec; 102 (06) 1234-40 PubMed PMID: 19967156. Epub 2009/12/08. eng.
  • 8 Gibson NS, Schellong SM, Kheir DY, Beyer-Westendorf J, Gallus AS, McRae S. et al. Safety and sensitivity of two ultrasound strategies in patients with clinically suspected deep venous thrombosis: a prospective management study. Journal of thrombosis and haemostasis. JTH 2009; Dec; 07 (12) 2035-2041 PubMed PMID: 19817986. Epub 2009/10/13. eng.
  • 9 Robert-Ebadi H, Righini M. Management of distal deep vein thrombosis. Thrombosis research 2017; Jan; 149: 48-55 PubMed PMID: 27889688. Epub 2016/11/28. eng.
  • 10 Schellong SM, Schwarz T, Pudollek T, Schmidt B, Schroeder HE. Complete compression ultrasound for the diagnosis of proximal and distal deep venous thrombosis--a retrospective outcome study. VASA Zeitschrift fur Gefasskrankheiten 2001; Nov; 30 (04) 253-257 PubMed PMID: 11771208.
  • 11 Geersing GJ, Janssen KJ, Oudega R, Bax L, Hoes AW, Reitsma JB. et al. Excluding venous thromboembolism using point of care D-dimer tests in outpatients: a diagnostic meta-analysis. Bmj 2009; Aug 14; 339: b2990 PubMed PMID: 19684102. Pubmed Central PMCID: 2727580.
  • 12 Prisco D, Grifoni E. The role of D-dimer testing in patients with suspected venous thromboembolism. Seminars in thrombosis and hemostasis 2009; Feb; 35 (01) 50-9 PubMed PMID: 19308893.
  • 13 Stein PD, Hull RD, Patel KC, Olson RE, Ghali WA, Brant R. et al. D-dimer for the exclusion of acute venous thrombosis and pulmonary embolism: a systematic review. Annals of internal medicine 2004; Apr 20; 140 (08) 589-602 PubMed PMID: 15096330.
  • 14 Wu AR, Garry J, Labropoulos N. Incidence of pulmonary embolism in patients with isolated calf deep vein thrombosis. Journal of vascular surgery Venous and lymphatic disorders 2017; Mar; 05 (02) 274-279 PubMed PMID: 28214497. Epub 2017/02/20. eng.
  • 15 Kearon C. Extended anticoagulation for unprovoked venous thromboembolism: a majority of patients should be treated. J Thromb Thrombolysis 2011; Apr; 31 (03) 295-300 PubMed PMID: 21331558. Epub 2011/02/19. eng.
  • 16 Schulman S, Lindmarker P, Holmstrom M, Larfars G, Carlsson A, Nicol P. et al. Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months. Journal of thrombosis and haemostasis JTH 2006; Apr; 04 (04) 734-42 PubMed PMID: 16634738.
  • 17 Douketis JD, Kearon C, Bates S, Duku EK, Ginsberg JS. Risk of fatal pulmonary embolism in patients with treated venous thromboembolism. Jama 1998; Feb 11; 279 (06) 458-462 PubMed PMID: 9466640.
  • 18 Mazzolai L, Aboyans V, Ageno W, Agnelli G, Alatri A, Bauersachs R. et al. Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European society of cardiology working groups of aorta and peripheral circulation and pulmonary circulation and right ventricular function. European heart journal. 2017 Feb 17. PubMed PMID: 28329262.
  • 19 Galanaud JP, Sevestre-Pietri MA, Bosson JL, Laroche JP, Righini M, Brisot D. et al. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thrombosis and haemostasis 2009; Sep; 102 (03) 493-500 PubMed PMID: 19718469.
  • 20 Barco S, Corti M, Trinchero A, Picchi C, Ambaglio C, Konstantinides SV. et al. Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism. Journal of thrombosis and haemostasis JTH 2017; Jul; 15 (07) 1436-1442 PubMed PMID: 28439954. Epub 2017/04/26. eng.
  • 21 Galanaud JP, Sevestre MA, Pernod G, Genty C, Richelet S, Kahn SR. et al. Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. Journal of thrombosis and haemostasis JTH 2017; May; 15 (05) 907-16 PubMed PMID: 28266773. Epub 2017/03/08. eng.
  • 22 Lagerstedt C, Olsson CG, Fagher B, Oqvist B, Albrechtsson U. Oral anticoagulants in calf-vein thrombosis. Lancet 1985; Dec 7; 02 (8467): 1311-2 PubMed PMID: 2866380.
  • 23 Lagerstedt CI, Olsson CG, Fagher BO, Oqvist BW, Albrechtsson U. Need for long-term anticoagulant treatment in symptomatic calf-vein thrombosis. Lancet 1985; Sep 7; 02 (8454): 515-8 PubMed PMID: 2863541.
  • 24 Schwarz T, Buschmann L, Beyer J, Halbritter K, Rastan A, Schellong S. Therapy of isolated calf muscle vein thrombosis: a randomized, controlled study. J Vasc Surg 2010; Nov; 52 (05) 1246-50 PubMed PMID: 20630682. Epub 2010/07/16. eng.
  • 25 Righini M, Galanaud JP, Guenneguez H, Brisot D, Diard A, Faisse P. et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol 2016; Dec; 03 (12) e556-e62 PubMed PMID: 27836513. Epub 2016/11/12. eng.
  • 26 Franco L, Giustozzi M, Agnelli G, Becattini C. Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis. Journal of thrombosis and haemostasis : JTH 2017; Jun; 15 (06) 1142-54 PubMed PMID: 28316124. Epub 2017/03/21. eng.
  • 27 Pinede L, Ninet J, Duhaut P, Chabaud S, Demolombe-Rague S, Durieu I. et al. Comparison of 3 and 6 months of oral anticoagulant therapy after a first episode of proximal deep vein thrombosis or pulmonary embolism and comparison of 6 and 12 weeks of therapy after isolated calf deep vein thrombosis. Circulation 2001; May 22; 103 (20) 2453-2460 PubMed PMID: 11369685.
  • 28 Ferrara F, Meli F, Amato C, Cospite V, Raimondi F, Novo G. et al. Optimal duration of treatment in surgical patients with calf venous thrombosis involving one or more veins. Angiology 2006; Aug-Sep; 57 (04) 418-423 PubMed PMID: 17022376.
  • 29 Schulman S, Rhedin AS, Lindmarker P, Carlsson A, Larfars G, Nicol P. et al. A comparison of six weeks with six months of oral anticoagulant therapy after a first episode of venous thromboembolism. Duration of Anticoagulation Trial Study Group. The New England journal of medicine 1995; Jun 22; 332 (25) 1661-1665 PubMed PMID: 7760866.
  • 30 Li AY, Woulfe T, Rolfe-Vyson V, Rowland V, Simpson D, Merriman E. Management and outcomes of axial isolated distal deep vein thrombosis at North Shore Hospital, New Zealand: a retrospective audit. Intern Med J 2015; Feb; 45 (02) 177-182 PubMed PMID: 25521797. Epub 2014/12/19. eng.
  • 31 VASA Zeitschrift fur Gefasskrankheiten. 2016; Nov; 45 (Suppl. 95) 1-100 PubMed PMID: 27855568. S3-Leitlinie PAVK – Diagnostik, Therapie und Nachsorge der peripheren arteriellen Verschlusskrankheit.
  • 32 Kamphuisen PW, Lee AYY, Meyer G, Bauersachs R, Janas MS, Jarner MF. et al. Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study. Journal of thrombosis and haemostasis JTH 2018; Mar 24 PubMed PMID: 29573330.
  • 33 Lee AYY, Kamphuisen PW, Meyer G, Bauersachs R, Janas MS, Jarner MF. et al. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer: A Randomized Clinical Trial. Jama 2015; Aug 18; 314 (07) 677-686 PubMed PMID: 26284719.
  • 34 Decousus H, Prandoni P, Mismetti P, Bauersachs RM, Boda Z, Brenner B. et al. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. The New England journal of medicine 2010; Sep 23; 363 (13) 1222-1232 PubMed PMID: 20860504.
  • 35 Beyer-Westendorf J, Schellong SM, Gerlach H, Rabe E, Weitz JI, Jersemann K. et al. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, noninferiority SURPRISE phase 3b trial. The Lancet Haematology 2017; Mar; 04 (03) e105-e13 PubMed PMID: 28219692.
  • 36 Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H. et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest 2016; Feb; 149 (02) 315-352 PubMed PMID: 26867832.