Deep vein thromboses (DVT) are both common, with a 5% lifetime risk in the United States, and clinically important, as these events can result in significant morbidity.¹ Post-thrombotic syndrome (PTS) is an unfortunate and frequent sequela, occurring in up to 50% of all patients with DVT.  Furthermore, it is estimated that up to 10% of DVT patients experience severe PTS.² The risk of PTS decreases with timely recognition and treatment of initial DVTs, as well as the prevention of subsequent DVTs. The clinical severity of PTS (mild, moderate, or severe) is captured by the widely accepted Villalta score. This score includes patient-rated symptoms, clinical signs, and ulcer presence,³ but is not well validated for use in guiding DVT management strategy.

Historically, the mainstays of DVT therapy have been anticoagulation (AC) and venous compressive therapies. However, since the 1990s new interventional tools and techniques have expanded management options, which now include catheter-directed thrombolysis (CDT), pharmacomechanical catheter-directed thrombolysis (PCDT), ultrasound-accelerated thrombolysis, percutaneous aspiration thrombectomy, inferior vena cava (IVC) filters, venous balloon dilatation, and venous stent implantation.^4,5 An important risk with interventional approaches, and particularly aspiration thrombectomy, is thrombus embolization, which is more common in the setting of acute thrombus. Knowledge of sufficient right ventricular reserve to tolerate potential embolization is important when considering thrombectomy. Embolic protection can be considered (e.g., IVC filter placement) in these cases, although this approach is not supported by previous studies.

Two key factors influence the decision to treat with medical therapy alone versus medical therapy combined with an invasive approach: clinical features and thrombus characteristics (location, age, burden, etc.). A more aggressive approach using thrombolysis and thrombectomy may be utilized in the setting of phlegmasia cerulea dolens, given its high rates of gangrene and subsequent need for major lower extremity amputation.⁶ DVT chronicity also impacts management. Acute DVT (age <2 weeks) is generally more amenable to lysis and easier to recanalize due to the pliability of the thrombus, whereas chronic DVT (age >4 weeks) is usually more complex with clot fibrosis and calcification.⁷ IVC filter use is considered in patients with iliofemoral DVT who are unable to tolerate AC to minimize the risk of pulmonary embolism.⁸

Two randomized controlled trials (RCTs) have evaluated CDT/PCDT on a background of AC versus AC alone. CaVenT was a multicenter Norwegian study that recruited from 2006 through 2009 and included patients aged 18-75 years with first-time iliofemoral DVTs and symptom duration less than 21 days (n=189). The trial showed a modestly lower rate of PTS (absolute risk reduction [ARR] 14.4%, 95% confidence interval [CI] 0.2-27.9, number needed to treat [NNT] 7, 95% CI 4-502) and higher rate of iliofemoral patency (65.9% vs. 47.4%) at 6 months with CDT (mean duration 2.4 days) compared to AC alone. However, higher bleeding risk was observed (9% vs. 0%).⁹ The second RCT published was ATTRACT — a United States study that enrolled between 2009 and 2014 and included patients aged 16-75 years with symptomatic proximal DVT for 14 days or less (n=692). ATTRACT showed no difference in PTS between 6 and 24 months after PCDT with AC versus AC alone (47% vs. 48%, P=0.56), and with a higher major bleeding risk within 10 days following PCDT (1.7% vs. 0.3%, P=0.049).¹⁰ PTS severity scores (Villalta scores) were lower in the PCDT group at each time point in the ATTRACT trial (P <0.01 at all timepoints). A subgroup analysis of iliofemoral DVTs in the ATTRACT trial showed no benefit in the occurrence of PTS or recurrent venous thromboembolism (VTE). However, the analysis showed a reduction in PTS severity and improvement in disease-specific quality of life in the PCDT group.¹¹ While not an RCT, the ACCESS PTS study — a multicenter, single arm, prospective study of 82 patients — showed that among patients who had failed a 3-month trial of conservative therapy (AC and compression), combined percutaneous transluminal venoplasty and ultrasound-accelerated thrombolysis reduced symptoms of chronic DVT and improved quality of life at 30 days and 1 year.¹²

Venous stenting is another invasive strategy that may be considered as part of DVT management. It is estimated that iliac vein compression syndrome (or May-Thurner syndrome [MTS]) causes 2-3% of all lower extremity DVTs; consequently, this diagnosis should be considered in all patients presenting with DVT.¹³ Intravascular ultrasound (IVUS) is the gold standard for the diagnosis of MTS and shows venous wall fibrosis or spurs. Sometimes dynamic compression by the iliac artery is also observed.¹⁴ Underappreciation of venous fibrosis in the setting of chronic DVT's is an important imaging limitation, so operators should maintain a high degree of suspicion in this setting. Once diagnosed, the treatment of iliac vein compression includes venous stenting, which may be performed for acute and/or chronic iliofemoral DVTs. Venous stenting is typically used when there is stenosis, residual thrombus, or obstruction after medical management, or in patients with chronic DVTs and moderate/severe PTS.⁴ Venous stenting for MTS involves the iliac vein; stenting into the common femoral vein is avoided when possible due to increased stent fracture risk. Additionally, dedicated venous stents are utilized to decrease the risk of stent embolization. Complications of stenting include an estimated 2% bleeding risk and 6% stent migration risk.¹⁵ Stenting may allow for cessation of AC within 3-12 months after intervention, particularly in younger patients with MTS.¹⁶ In the trials mentioned above, venous stenting rates were low (17% of patients who received CDT in CaVenT, 28% of patients who received PCDT in ATTRACT, and 49% in ACCESS PTS).^8-10,12

Treatment approaches for DVT differ widely based on clinical factors and thrombus characteristics. Invasive interventions (including lysis, thrombectomy, and venous stenting) are beneficial in specific scenarios, and are more successful when patients present earlier with acute thrombus. While invasive interventions can improve immediate DVT-associated symptoms and may decrease PTS, these potential benefits must be weighed against bleeding and other invasive procedural risks. Given the prevalence of DVTs in clinical practice, guidelines based on current research and expert opinion are much needed to help clinicians and patients navigate this increasingly complex management space. Additionally, further randomized trials are required to better understand what populations benefit most from more aggressive, higher-risk strategies.

References

1. Henke PK, Kahn SR, Pannucci CJ, et al. Call to action to prevent venous thromboembolism in hospitalized patients: a policy statement from the American Heart Association. Circulation 2020;141:e914-e931.
2. Pikovsky O, Rabinovich A. Prevention and treatment of the post-thrombotic syndrome. Thromb Res 2018;164:116-24.
3. Lee A, Gu CS, Vedantham S, Kearon C, Blostein M, Kahn SR. Performance of two clinical scales to assess quality of life in patients with post-thrombotic syndrome. J Vasc Surg Venous Lymphat Disord 2021;9:1257-65.e2.
4. Breen K. Role of venous stenting for venous thromboembolism. Hematology Am Soc Hematol Educ Program 2020;2020:606-11.
5. Goktay AY, Senturk C. Endovascular treatment of thrombosis and embolism. Adv Exp Med Biol 2017;906:195-213.
6. Rahmatzadeh M, Clarke J, Jaya J, et al. The urgency of phlegmasia cerulea dolens: management for physicians and surgeons. Med J Aust 2022;216:285-86.
7. Wadhwa V, Srinivasa RN, Cooper KJ, et al. Endovascular therapy for lower extremity chronic deep venous occlusive disease: state of practice. Semin Intervent Radiol 2018;35:333-41.
8. Salahuddin T, Armstrong EJ. Intervention for iliofemoral deep vein thrombosis and May-Thurner syndrome. Interv Cardiol Clin 2020;9:243-54.
9. Enden T, Haig Y, Kløw NE, et al. 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;379:31-8.
10. Vedantham S, Goldhaber SZ, Julian JA, et al. Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis. N Engl J Med 2017;377:2240-52.
11. Kahn SR, Julian JA, Kearon C, et al. Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis. J Vasc Surg Venous Lymphat Disord 2020;8:8-23.e18.
12. Garcia MJ, Sterling KM, Kahn SR, et al. Ultrasound-accelerated thrombolysis and venoplasty for the treatment of the post thrombotic syndrome: results of the ACCESS PTS Study. J Am Heart Assoc 2020;9:e013398.
13. Ahsan I, Qureshi BG, Ghani AR, Malik F, Arif Z. An extensive unprovoked left lower extremity deep vein thrombosis secondary to an anatomical anomaly: a case of May-Thurner syndrome. Clin Pract 2017;7:938.
14. Radaideh Q, Patel NM, Shammas NW. Iliac vein compression: epidemiology, diagnosis and treatment. Vasc Health Risk Manag 2019;15:115-22.
15. Badesha AS, Siddiqui MM, Bains BRS, Bains PRS, Khan T. A systematic review on the incidence of stent migration in the treatment of acute and chronic iliofemoral disease using dedicated venous stents. Ann Vasc Surg 2022;83:328-48.
16. Sebastian T, Engelberger RP, Spirk D, et al. Cessation of anticoagulation therapy following endovascular thrombus removal and stent placement for acute iliofemoral deep vein thrombosis. Vasa 2019;48:331-39.

Clinical Topics: Anticoagulation Management, Cardiac Surgery, Cardiovascular Care Team, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Anticoagulation Management and Venothromboembolism, Interventions and Imaging, Interventions and Vascular Medicine, Echocardiography/Ultrasound

Keywords: Vena Cava, Inferior, Dilatation, Gangrene, Pliability, Ulcer, Venous Thrombosis, Thrombolytic Therapy, Thrombectomy, Pulmonary Embolism, Lower Extremity, Stents, Anticoagulants, Amputation, Catheters, Morbidity, Fibrosis, Quality of Life, Prospective Studies, Venous Thromboembolism, Confidence Intervals, Conservative Treatment, Numbers Needed To Treat, Hemorrhage, May-Thurner Syndrome, Iliac Vein, Femoral Vein, Constriction, Pathologic, Expert Testimony, Iliac Artery, Prevalence, Ultrasonography, Interventional

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