Post-thrombotic syndrome prevention – do we really know the predictive factors?

Abstract

Despite an increasing knowledge and experience regarding deep vein thrombosis (DVT) treatment, the rate of post-thrombotic syndrome (PTS) remains still relatively high. According to the current knowledge it is still difficult to predict on the individual basis, who of the DVT patients will develop PTS as late complication of the vein thrombosis. Among the factors influencing the higher prevalence of PTS, the ipsilateral DVT recurrence is of the highest importance. The other factors which should be mentioned are age, obesity, previous chronic venous disease as well as a proximal DVT location or lack of symptoms’ resolution in the early treatment. Looking for the most effective PTS prevention method several clinical trials were performed regarding pharmacological DVT treatment, use of early mobilization and medical compression stocking as well as an implementation of the thrombectomy and thrombolysis. This paper presents a review of the current knowledge regarding the PTS predictive factors and prevention.

Zusammenfassung

Obwohl wir zunehmend mehr über die tiefe Beinvenenthrombose (TBVT) wissen und mehr Erfahrung im Umgang damit haben, bleibt die Rate des post-thrombotischen Syndroms (PTS) relativ hoch. Es ist heute noch sehr schwer, nach der Diagnose der tiefen Beinvenen-Thrombose vorherzusagen, welcher Patient ein PTS entwickeln wird. Unter den Faktoren, die eine höhere Prävalenz des PTS bedingen, finden wir als wichtigstes Kriterium das ipsilaterale Thrombose-Rezidiv. Außerdem scheinen Alter, Übergewicht, vorausgegangene chronische venöse Insuffizienz sowie eine proximale TBVT oder die ausbleibende Symptomrückbildung nach Start der Behandlung Risikofaktoren für ein PTS zu sein.

Mit Blick auf eine möglichst effektive PTS-Vorbeugung wurden viele klinische Studien zur Pharmakologie, zur frühen Bewegung und zum Einsatz von medizinischen Kompressionsstrümpfen bis hin zur chirurgischen Thrombektomie und Thrombolyse aufgelegt.

In dem vorliegen Artikel wird die Datenlage in Bezug auf Vorhersagefaktoren und Prävention des post-thrombotischen Syndroms zusammengetragen.

Key words

post-thrombotic syndrome - deep vein thrombosis - predictive factors - anticoagulation - compression - thrombolysis

Schlüsselwörter

Post-thrombotisches Syndrom - tiefe Beinvenenthrombose - prädiktive Faktoren - Antikoagulation - medizinische Kompression - Thrombolyse

• References

• 1 Kahn SR, Comerota AJ, Cushman M. et al. American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing: The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation 2014; 130: 1636-1661
• 2 Kahn SR, Galanaud JP, Vedantham S. et al. Guidance for the prevention and treatment of the post-thrombotic syndrome. J Thromb Thrombolysis 2016; 41: 144-153
• 3 Shrier I, Julian JA, Ducruet T. et al. Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis. Ann Intern Med 2008; 149: 698-707
• 4 Rabinovich A, Kahn SR. The postthrombotic syndrome: current evidence and future challenges. J Thromb Haemost 2017; 15: 230-241
• 5 Kahn SR, Partsch H, Vedantham S. et al. on behalf of the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009; 7: 879-83
• 6 Villalta S, Bagatella P, Piccioli A. Assessment of validity and reproducibility of a clinical scale for the postthrombotic syndrome. Haemostasis 1994; 24: 158a [Abstract]
• 7 Bouman AC, Smith JJM, Ten Cate H. et al. Markers of coagulation, fibrinolysis and inflammation in relation to post-thrombotic syndrome. J Thromb Haemost 2012; 10: 1532-1538
• 8 Kearon C, Akl EA, Ornelas J. et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest 2016; 149: 315-352
• 9 Tick LW, Kramer MH, Rosendaal FR. et al. Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis. J Thromb Haemost 2008; 6: 2075-2081
• 10 Rabinovich A, Kahn SR. How to predict and diagnose postthrombotic syndrome. Pol Arch Med Wewn 2014; 124: 410-416
• 11 Erkens PM, ten Cate H, Büller HR. et al. Benchmark for time in therapeutic range in venous thromboembolism: a systematic review and meta-analysis. PLoS One 2012; 7: e42269
• 12 Chitsike RS, Rodger MA, Kovacs MJ. Risk of post-thrombotic syndrome after subtherapeutic warfarin anticoagulation for a first unprovoked deep vein thrombosis: results from the REVERSE study. J Thromb Haemost 2012; 10: 2039-2044
• 13 van Dongen CJ, Prandoni P, Frulla M. i wsp.: Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005; 3: 939-942
• 14 Galanaud JP, Holcroft CA, Rodger MA. et al. Comparison of the Villalta post-thrombotic syndrome score in the ipsilateral vs. contralateral leg after a first unprovoked deep vein thrombosis. J Thromb Haemost 2012; 10: 1036-1042
• 15 Rabinovich A, Cohen JM, Prandoni P. et al. Association between thrombophilia and the post-thrombotic syndrome: a systemic review and meta-analysis. J Thromb Heamost 2014; 82: 14-23
• 16 Comerota AJ, Grewal N, Martinez JT. et al. Postthrombotic morbidity correlates with residual thrombus following catheter-directed thrombolysis for iliofemoral deep vein thrombosis. J Vasc Surg 2012; 55: 768-773
• 17 Kahn S. Predictors of the Development of Post-Thrombotic Syndrome after Acute Symptomatic Deep Vein Thrombosis: Two-Year Results from a Canadian Multicenter Prospective Cohort Study (The VETO Study). Blood 2005; 106: 1635
• 18 van Rij AM, Hill G, KRysa J. et al. Prospective study on natural history of deep vein thrombosis: early predictors of poor late outcomes. Anbnals of vascular Surgery 2013; 27: 924-931
• 19 Rabinovich A, Ducruet T, Kahn R. SOX trial investigators. Development of a clinical prediction model for the postthrombotic syndrome in a prospective cohort of patients with proximal deep vein thrombosis. J Thromb Haemost 2018; 16: 262-227
• 20 Amin EE, van Kuijk S, Joore M. et al. Development and Validation of a Practical Two-Step Prediction Model and Clinical Risk Score for Post-Thrombotic Syndrome. Thromb Haemost 2018; 118: 1242-1249
• 21 Wojtukiewicz M, Sierko E, Tomkowski W. Guidelines for the prevention and treatment of venous thromboembolism in patients with cancers treated conservatively. Onkol Clin Pract 2016; 12: 67-91
• 22 Falck-Ytter Y, Francis CW, Johanson NA. et al. American College of Chest Physicians. Prevention of VTE in orthopaedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e278S-e325S
• 23 Kahn SR, Lim W, Dunn AS. et al. American College of Chest Physicians: Prevention of VTE in Nonsurgical Patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e195S-e226S
• 24 Gould MK, Garcia DA, Wren SM. et al. American College of Chest Physicians: Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141: e227S-e277S
• 25 Brandjes DP, Büller HR, Heijboer H. et al. Randomized trial of effect of compression stockings in patients with symptomatic proximal – vein thrombosis. Lancet 1997; 349: 759-62
• 26 Prandoni P, Lensing AW, Prins MH. et al. Below–knee elastic compression stocking to prevent the post-thrombotic syndrome. Ann Int Med 2004; 141 (04) 249-256
• 27 Prandoni P, Noventa F, Quintavalla R. et al. Thigh-length versus below-knee compression elastic stockings for prevention of the postthrombotic syndrome in patients with proximal-venous thrombosis: a randomized trial. Blood 2012; 119: 1561-1565
• 28 Aschwanden M, Jeanneret C, Koller MT. et al. Effect of prolonged treatment with compression stockings to prevent post-thrombotic sequelae: a randomized controlled trial. J Vasc Surg 2008; 47: 1015-21
• 29 Musani MH, Matta F, Yaekoub AY. et al. Venous compression for prevention of postthrombotic syndrome: a meta-analysis. Am J Med 2010; 123: 735-40
• 30 Jayaraj A, Meissner M. mpact of graduated compression stockings on the prevention of post-thrombotic syndrome – results of a randomized controlled trial. Phlebology 2015; 30: 541-8
• 31 Blattler W, Partsch H. Leg compression and ambulation is better than bed rest for the treatment of acute deep venous thrombosis. Int Angiol 2003; 22: 393-400
• 32 Kahn SR, Shapiro S, Wells PS. et al. SOX trial investigators. Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial. Lancet 2014; 383: 880-888
• 33 Appelen D, van Loo E, Prins MH. et al. Compression therapy for prevention of post-thrombotic syndrome (Review). Cochrane Database of Systematic Reviews. 2017 9: Art. No.: CD004174
• 34 Rabe E, Partsch H, Hafner J. et al. Indications for medical compression stockings in venous and lymphatic disorders: An evidence-based consensus statement. Phlebology 2018; 33: 163-184
• 35 Ten Cate-Hoek AJ, Amin EE, Bouman AC. et al. IDEAL DVTinvestigators. Individualised versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial. Lancet Haematol 2018; 5: e25-e33
• 36 Breddin HK, Hach-Wunderle V, Nakov R. et al. CORTES Investigators. Clivarin: Assessment of Regression of Thrombosis, Efficacy, and Safety. Effects of low molecular weight heparin on thrombus regression and recurrent thromboembolism in patients with DVT. N Engl J Med 2001; 34: 626-631
• 37 Kirchmaier CM, Wolf H, Schäfer H. et al. Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group. Int Angiol 1998; 17: 135-145
• 38 Gómez-Outes A, Lecumberri R, Lafuente-Guijosa A. et al. Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low-molecular-weight heparins: a meta-analysis. J Thromb Haemost 2004; 2: 1581-1587
• 39 Leizorowicz A. Comparison of efficiacy and safety of LMWH and UFH in the initial treatment of DVT: a meta-analysis. Br Med J 1994; 309: 299-309
• 40 González-Fajardo JA, Martin-Pedrosa M, Castrodeza J. et al. Effect of the anticoagulant therapy in the incidence of post-thrombotic syndrome and recurrent thromboembolism: compartive study of enoxaparin versus coumarin. J Vasc Surg 2008; 48: 953-959
• 41 Hull RD, Liang J, Merali T. Effect of long term LMWH on Post-thrombotic syndrome in patients with iliac/non iliac venous thrombosis. A subanalysis from HOME LITe studies. Clinical and Applied Thrombosis/Hemosis 2013; 19: 476-481
• 42 Hull RD, Liang J, Townshend G. Long-term low-molecularweight heparin and the post-thrombotic syndrome: a systematic review. Am J Med 2011; 124: 756-765
• 43 Cheung YW, Middeldorp S, Prins MH. et al. Einstein PTS Investigators Group.; Einstein ZPZ Investigators Group: Post-thrombotic syndrome in patients treated with rivaroxaban or enoxaparin/vitamin K antagonists for acute deep-vein thrombosis. A post-hoc analysis. Thromb. Haemost 2016; 116: 733-738
• 44 Jeraj L, Jezovnik MK, Poredos Pl. Rivaroxaban versus warfarin in the prevention of post-thrombotic syndrome. Thromb Res 2017; 157: 46-48
• 45 Vedantham S, Piazza G, Sista AK. et al. Guidance for the use of thrombolytic therapy for the treatment of venous thromboembolism. J Thromb Thrombolysis 2016; 41: 68-80
• 46 Akesson H, Brudin L, Dahlström JA. et al. Venous function assessed during a 5-year period after acute iliofemoral venous thrombosis treated with anticoagulation. Eur J Vasc Surg 1990; 4: 43-48
• 47 Enden T, Haig Y, Kløw NE. et al. CaVenT Study Group. CaVenT Study Group: “Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial”. Lancet 2012; 379: 31-38
• 48 Enden T, Wik HS, Kvam AK. et al. Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study. BMJ Open 2013; 3: e002984
• 49 Oklu R, Wicky S. Catheter-directed thrombolysis of deep venous thrombosis. Semin Thromb Hemost 2013; 39: 446-451
• 50 Chen JX, Sudheendra D, Stavropoulos SW. et al. “Role of catheter-directed thrombolysis in management of iliofemoral deep venous thrombosis”. Radioraphics 2016; 36: 1565-1575
• 51 Vedantham S, Goldhaber SZ, Julian JA. i wsp.; ATTRACT Trial Investigators: Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis. N Engl J Med 2017; 377: 2240-2252
• 52 Comerota AJ, Kearon C, Gu CS. et al. ATTRACT Trial Investigators. / Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis. Circulation 2019; 139: 1162-1173