Highlights
- •Post-thrombotic syndrome is the most frequent complication of DVT.
- •After a proximal DVT, 20–50% of patients will develop PTS.
- •Most important PTS predictors are extensive proximal DVT and ipsilateral recurrence.
Abstract
The post thrombotic syndrome (PTS) refers to clinical manifestations of chronic venous
insufficiency (CVI) following a deep-vein thrombosis (DVT). PTS is the most frequent
complication of DVT, which develops in 20 to 50% of cases after proximal DVT and is
severe in 5–10% of cases. The reported prevalence of PTS differs widely among studies
because of differences in study populations, tools used to assess PTS, and time interval
between acute DVT and PTS assessment. The two most important predictors of PTS are
extensive proximal character of DVT and previous ipsilateral DVT. Other reported risk
factors include pre-existing CVI, obesity, quality of anticoagulant treatment, older
age and residual venous obstruction. Standardization of PTS assessment tools combined
with the development of patient self-reported PTS scales are likely to constitute
a breakthrough in research of the epidemiology of PTS, by allowing comparison between
studies, meta-analyses and increasing the feasibility of longer follow-up of DVT patients.
This should enable identification of patient populations at high risk of severe PTS,
new predictors of PTS and targets for potential new treatments. In this perspective,
identification of biomarkers that are predictive of PTS such as markers of inflammation
is crucial in ongoing research.
Abbreviations:
AHA (American Heart Association), CDT (catheter directed thrombolysis), CVI (chronic venous insufficiency), DOAC (direct oral anticoagulant), DVT (deep-vein thrombosis), FU (follow-up), ISTH (International Society on Thrombosis and Haemostasis), LMWH (low molecular weight heparin), LT (long term), NA (not assessed or not assessable), NNT (number of patients needed to treat), OR (odds ratio), PE (pulmonary embolism), PTS (post-thrombotic syndrome), QOL (quality of life), RCT (randomized controlled trial), RR (relative risk), RVO (residual venous obstruction), VKA (vitamin K antagonist), VR (venous reflux), VTE (venous thromboembolism)Keywords
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References
- Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization.J. Thromb. Haemost. 2009; 7: 879-883
- How I treat postthrombotic syndrome.Blood. 2009; 114: 4624-4631
- What is the effect of venous thromboembolism and related complications on patient reported health-related quality of life? A meta-analysis.Thromb. Haemost. 2016; 116: 417-431
- Determinants of health-related quality of life during the 2 years following deep vein thrombosis.J. Thromb. Haemost. 2008; 6: 1105-1112
- Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants.Eur. J. Haematol. 2012; 88: 185-194
- Economic burden and cost determinants of deep vein thrombosis during 2 years following diagnosis: a prospective evaluation.J. Thromb. Haemost. 2011; 9: 2397-2405
- Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report.Chest. 2016; 149: 315-352
- The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association.Circulation. 2014; 130: 1636-1661
- Guidance for the prevention and treatment of the post-thrombotic syndrome.J. Thromb. Thrombolysis. 2016; 41: 144-153
- Compression stockings to prevent post-thrombotic syndrome: a randomised placebo-controlled trial.Lancet. 2014; 383: 880-888
- 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
- The post-thrombotic syndrome: a 2012 therapeutic update.Curr. Treat. Options Cardiovasc. Med. 2013; 15: 153-163
- Definition of the post-thrombotic syndrome, differences between existing classifications.Eur. J. Vasc. Endovasc. Surg. 2005; 30: 404-414
- Measurement properties of the Villalta scale to define and classify the severity of the post-thrombotic syndrome.J. Thromb. Haemost. 2009; 7: 884-888
- Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.CMAJ. 2008; 179: 417-426
- Individually tailored duration of elastic compression therapy in relation to incidence of the postthrombotic syndrome.J. Vasc. Surg. 2010; 52: 132-138
- 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
- Impact of Primary Venous Insufficiency on the Prevalence and Risk of Post-thrombotic Syndrome.2015 (ISTH 2015 ABS-3195)
- Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial.Lancet Haematol. 2016; 3: e64-71
- 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
- Isolated distal deep vein thrombosis: what we know and what we are doing.J. Thromb. Haemost. 2012; 10: 11-19
- Epidemiology and management of isolated distal deep venous thrombosis.Rev. Med. Interne. 2012; 33: 678-685
- Five-year outcome study of deep vein thrombosis in the lower limbs.J. Vasc. Surg. 2004; 40: 1184-1189
- How I treat isolated distal deep vein thrombosis (IDDVT).Blood. 2014; 123: 1802-1809
- The controversy of managing calf vein thrombosis.J. Vasc. Surg. 2012; 55: 550-561
- Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis.J. Thromb. Haemost. 2005; 3: 718-723
- The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients.Haematologica. 1997; 82: 423-428
- Determinants and time course of the postthrombotic syndrome after acute deep venous thrombosis.Ann. Intern. Med. 2008; 149: 698-707
- One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial.BMJ. 2016; 353: i2691
- Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome.J. Thromb. Haemost. 2005; 3: 939-942
- Development and validation of a tool for patient reporting of symptoms and signs of the post-thrombotic syndrome.Thromb. Haemost. 2016; 115: 361-367
- The post-thrombotic syndrome: incidence and prognostic value of non-invasive venous examinations in a six-year follow-up study.Thromb. Haemost. 2005; 94: 825-830
- Thrombosis; early diagnosis and abortive treatment with heparin.Lancet. 1946; 1: 447-454
- Compression stockings to prevent post-thrombotic syndrome.Lancet. 2014; 384: 129
- The effect of venous thrombus location and extent on the development of post-thrombotic signs and symptoms.J. Vasc. Surg. 2008; 48: 407-412
- Venous claudication in iliofemoral thrombosis: long-term effects on venous hemodynamics, clinical status, and quality of life.Ann. Surg. 2004; 239: 118-126
- Intravenous pressure changes in patients with postthrombotic deep venous obstruction: results using a treadmill stress test.J. Thromb. Haemost. 2016; 14: 1163-1170
- Excellent long-term results with iliac stenting in local anesthesia for post-thrombotic syndrome.Acta Radiol. Open. 2015; 42058460115592164
- Stenting for chronic post-thrombotic vena cava and iliofemoral venous occlusions: mid-term patency and clinical outcome.Eur. J. Vasc. Endovasc. Surg. 2010; 40: 234-240
- Clinical predictors of leg ulcer healing.Br. J. Dermatol. 2010; 162: 51-58
- Chronic venous insufficiency.Circulation. 2014; 130: 333-346
- The post-thrombotic syndrome: risk factors and impact on the course of thrombotic disease.J. Thromb. Haemost. 2005; 3: 2671-2676
- Post-thrombotic syndrome, recurrence, and death 10 years after the first episode of venous thromboembolism treated with warfarin for 6 weeks or 6 months.J. Thromb. Haemost. 2006; 4: 734-742
- Late sequelae of deep venous thrombosis: a 13-year follow-up of 223 patients.Vasa. 1994; 23: 234-243
- Prospective 12-year follow-up study of clinical and hemodynamic sequelae after deep vein thrombosis in low-risk patients (Zurich study).Circulation. 1996; 93: 74-79
- Trends in the incidence of venous stasis syndrome and venous ulcer: a 25-year population-based study.J. Vasc. Surg. 2001; 33: 1022-1027
- Relationship between changes in the deep venous system and the development of the postthrombotic syndrome after an acute episode of lower limb deep vein thrombosis: a one- to six-year follow-up.J. Vasc. Surg. 1995; 21 (discussion 13): 307-312
- Post-thrombotic syndrome after primary event of deep venous thrombosis 10 to 20 years ago.Thromb. Res. 2001; 101: 23-33
- The venous stasis syndrome after deep venous thrombosis or pulmonary embolism: a population-based study.Mayo Clin. Proc. 2000; 75: 1249-1256
- Risk factors for venous ulcer following acute venous thromboembolism: results from the riete registry.in: Abstract ASH 2015. 2016
- Incidence and cost burden of post-thrombotic syndrome.J. Thromb. Thrombolysis. 2009; 28: 465-476
- Predictors of the post-thrombotic syndrome and their effect on the therapeutic management of deep vein thrombosis.J. Vasc. Surg. Venous Lymphat. Disord. 2016; 4: 531-534
- Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial.Ann. Intern. Med. 2004; 14: 249-256
- The long-term clinical course of acute deep venous thrombosis.Ann. Intern. Med. 1996; 125: 1-7
- Risk factors for post-thrombotic syndrome in patients with a first deep venous thrombosis.J. Thromb. Haemost. 2008; 6: 2075-2081
- Long-term adverse effects associated with isolated below-knee deep-vein thrombosis: a 10-year follow-up study.Clin. Radiol. 2016; 71: 369-374
- Venographic assessment of deep vein thrombosis and risk of developing post-thrombotic syndrome: a prospective study.J. Intern. Med. 1993; 233: 233-238
- Incidence of post-thrombotic syndrome and its association with various risk factors in a cohort of Spanish patients after one year of follow-up following acute deep venous thrombosis.Thromb. Haemost. 2004; 92: 328-336
- Biomarkers for post thrombotic syndrome: a case-control study.Thromb. Res. 2014; 134: 369-375
- Impact and clinical significance of recurrent venous thromboembolism.Br J Surg. 2010; 97: 989-999
- Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2012; 141: e419S-e496S
- Predictors of post-thrombotic syndrome in a population with a first deep vein thrombosis and no primary venous insufficiency.J. Thromb. Haemost. 2013; 11: 474-480
- Role of coexisting contralateral primary venous disease in development of post-thrombotic syndrome following catheter-based treatment of iliofemoral deep venous thrombosis.J. Vasc. Surg. Venous Lymphat. Disord. 2015; 3: 354-357
- Long-term impact of pregnancy-related venous thrombosis on quality-of-life, general health and functioning: results of a cross-sectional, case-control study.BMJ Open. 2012; 2: e002048
- Postthrombotic syndrome: a 2014 update.Curr. Opin. Cardiol. 2014; 29: 514-519
- Residual vein thrombosis and trans-popliteal reflux in patients with and without the post-thrombotic syndrome.Thromb. Haemost. 2013; 110: 854-855
- The impact of residual thrombosis on the long-term outcome of patients with deep venous thrombosis treated with conventional anticoagulation.Semin. Thromb. Hemost. 2015; 41: 133-140
- Residual vein thrombosis and onset of post-thrombotic syndrome: influence of the 4G/5G polymorphism of plasminogen activator inhibitor-1 gene.Thromb. Res. 2014; 133: 371-374
- Predictors of the post-thrombotic syndrome with non-invasive venous examinations in patients 6 weeks after a first episode of deep vein thrombosis.J. Thromb. Haemost. 2010; 8: 2685-2692
- Postthrombotic syndrome after asymptomatic deep vein thrombosis following total knee and hip arthroplasty.Am. J. Orthop. 2006; 35: 469-472
- Asymptomatic deep venous thrombosis is associated with a low risk of post-thrombotic syndrome.Eur. J. Vasc. Endovasc. Surg. 2009; 38: 229-233
- Asymptomatic postoperative deep vein thrombosis and the development of postthrombotic syndrome. A systematic review and meta-analysis.Thromb. Haemost. 2005; 93: 236-241
- Association between thrombophilia and the post-thrombotic syndrome: a systematic review and meta-analysis.J. Thromb. Haemost. 2014; 12: 14-23
- Relationship between development of post-thrombotic syndrome and serial ultrasound, D-dimer, and factor VIII activity after a first deep venous thrombosis.J. Vasc. Surg. Venous Lymphat. Disord. 2016; 4: 28-35
- Long-term increased factor VIII levels are associated to interleukin-6 levels but not to post-thrombotic syndrome in patients with deep venous thrombosis.Thromb. Res. 2015; 135: 497-501
- Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial.Lancet Haematol. 2016; 3: e556-e562
- Long-term low-molecular-weight heparin and the post-thrombotic syndrome: a systematic review.Am. J. Med. 2011; 124: 756-765
- 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
- Inflammation markers and their trajectories after deep vein thrombosis in relation to risk of post-thrombotic syndrome.J. Thromb. Haemost. 2015; 13: 398-408
- Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study.J. Thromb. Haemost. 2009; 7: 582-587
- Predictive value of markers of inflammation in the postthrombotic syndrome: a systematic review: inflammatory biomarkers and PTS.Thromb. Res. 2015; 136: 289-297
- Effects of rosuvastatin as an adjuvant treatment for deep vein thrombosis.Vasa. 2016; 45: 133-140
- Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.PLoS One. 2015; 10e0116621
- Tinzaparin vs warfarin for treatment of acute venous thromboembolism in patients with active cancer: a randomized clinical trial.JAMA. 2015; 314: 677-686
- Prevention and treatment of postphlebitic syndrome: results of a 3-part study.Arch. Intern. Med. 2001; 161: 2105-2109
- Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.Lancet. 1997; 349: 759-762
- A. Sd. Venen-, Arterien-,Krankheiten, koronaire Herzkrankhei bei berufstatigen.Verlag Hans Huber, Bern1981: 66-82
- Scoring systems for the post-thrombotic syndrome.J. Vasc. Surg. 2013; 57: 254-261
- Revision of the venous clinical severity score: venous outcomes consensus statement: special communication of the American Venous Forum Ad Hoc Outcomes Working Group.J. Vasc. Surg. 2010; 52: 1387-1396
- 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
- Incidence, risk factors and skin manifestations of post-thrombotic syndrome: a four-year follow-up of patients included in the EDITH study.Rev. Med. Interne. 2010; 31: 729-734
Article info
Publication history
Published online: July 24, 2017
Accepted:
July 21,
2017
Received in revised form:
July 20,
2017
Received:
April 21,
2017
Footnotes
☆Authors have no relevant conflicts of interests to disclose.
Identification
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© 2017 Elsevier Ltd. All rights reserved.
