Recurrence Risk after First Symptomatic Distal versus Proximal Deep Vein Thrombosis According to Baseline Risk Factors

Luca Valerio; Chiara Ambaglio; Marisa Barone; Mariella Ciola; Stavros V. Konstantinides; Seyed H. Mahmoudpour; Chiara Picchi; Carla Pieresca; Alice Trinchero; Stefano Barco

doi:10.1055/s-0039-1683374

TH Open, Table of Contents

CC BY 4.0 · TH Open 2019; 03(01): e58-e63
DOI: 10.1055/s-0039-1683374

Original Article

Georg Thieme Verlag KG Stuttgart · New York

Recurrence Risk after First Symptomatic Distal versus Proximal Deep Vein Thrombosis According to Baseline Risk Factors

Luca Valerio

¹Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University-Mainz, Mainz, Germany

,

Chiara Ambaglio

²Department of Internal Medicine, Fondazione IRCCS Policlinico “San Matteo,” Pavia, Italy

,

Marisa Barone

³Thromboembolic Disease Unit, Istituti Clinici Scientifici Spa SB IRCCS Maugeri, Pavia, Italy

,

Mariella Ciola

²Department of Internal Medicine, Fondazione IRCCS Policlinico “San Matteo,” Pavia, Italy

,

Stavros V. Konstantinides

¹Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University-Mainz, Mainz, Germany

⁴Department of Cardiology, Democritus University of Thrace, Alexandroupolis, Greece

,

Seyed H. Mahmoudpour

¹Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University-Mainz, Mainz, Germany

⁵Department of Biometry and Bioinformatics, Institute for Medical Biostatistics, Epidemiology, and Informatics (IMBEI), University Medical Center of the Johannes Gutenberg University, Mainz, Germany

,

Chiara Picchi

⁶Department of Internal Medicine, Presidio Ospedaliero “Macedonio Melloni” ASST FBF “Sacco,” Milano, Italy

,

Carla Pieresca

²Department of Internal Medicine, Fondazione IRCCS Policlinico “San Matteo,” Pavia, Italy

,

Alice Trinchero

¹Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University-Mainz, Mainz, Germany

,

Stefano Barco

¹Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University-Mainz, Mainz, Germany

› Author Affiliations

Abstract

Background It remains unclear whether the distal location of deep vein thrombosis (DVT) is independently associated with a lower risk of recurrence in all patients, or represents a marker of the presence and severity of provoking factors for venous thromboembolism (VTE).

Methods We investigated the impact of distal (vs. proximal) DVT location on the risk of developing symptomatic, objectively confirmed recurrent VTE in 831 patients with a first acute symptomatic DVT not associated with pulmonary embolism (PE), who were stratified by the presence of transient or persistent risk factors at baseline. The primary outcome was symptomatic, objectively diagnosed recurrent VTE, including proximal DVT and PE.

Results A total of 205 (24.7%) patients presented with a transient risk factor, 189 (22.7%) with a minor persistent risk factor, 202 (24.3%) with unprovoked DVT, and 235 (28.3%) with cancer-associated DVT. One-hundred twenty-five patients (15.0%) experienced recurrent DVT or PE. The largest relative difference between patients with distal (vs. proximal) DVT was observed in the absence of identifiable risk factors (adjusted hazard ratio [aHR]: 0.11; 95% CI [confidence interval]: 0.03–0.45). In patients with cancer, distal and proximal DVT had a comparable risk of recurrence (aHR: 0.70; 95% CI: 0.28–1.78]).

Conclusions The distal (vs. proximal) location of first acute symptomatic DVT represented, in the absence of any identifiable transient or persistent risk factors, a favorable prognostic factor for recurrence. In contrast, the prognostic impact of DVT location was weaker if persistent provoking risk factors for VTE were present, notably cancer.

Keywords

venous thromboembolism - pulmonary embolism - prognosis - epidemiology

Full Text

References

References
1 Posch F, Riedl J, Reitter EM. , et al. Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A multi-state model. Thromb Haemost 2016; 115 (04) 817-826
2 Børvik T, Brækkan SK, Enga K. , et al. COPD and risk of venous thromboembolism and mortality in a general population. Eur Respir J 2016; 47 (02) 473-481
3 Konstantinides SV, Barco S, Lankeit M, Meyer G. Management of pulmonary embolism: an update. J Am Coll Cardiol 2016; 67 (08) 976-990
4 Vaitkus PT, Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Goldhaber SZ. ; PREVENT Medical Thromboprophylaxis Study Group. Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients. Thromb Haemost 2005; 93 (01) 76-79
5 Kearon C, Akl EA, Ornelas J. , et al. Antithrombotic therapy for VTE disease: CHEST Guideline and Expert Panel Report. Chest 2016; 149 (02) 315-352
6 Konstantinides SV, Torbicki A, Agnelli G. , et al; Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism. Eur Heart J 2014; 35 (43) 3033-3069 , 3069a–3069k
7 Galanaud JP, Quenet S, Rivron-Guillot K. , et al; RIETE Investigators. Comparison of the clinical history of symptomatic isolated distal deep-vein thrombosis vs. proximal deep vein thrombosis in 11 086 patients. J Thromb Haemost 2009; 7 (12) 2028-2034
8 Kyrle PA, Kammer M, Eischer L. , et al. The long-term recurrence risk of patients with unprovoked venous thromboembolism: an observational cohort study. J Thromb Haemost 2016; 14 (12) 2402-2409
9 Pinede L, Ninet J, Duhaut P. , et al; Investigators of the “Durée Optimale du Traitement AntiVitamines K” (DOTAVK) Study. 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; 103 (20) 2453-2460
10 Galanaud JP, Sevestre MA, Genty C. , et al; OPTIMEV-SFMV Investigators. Incidence and predictors of venous thromboembolism recurrence after a first isolated distal deep vein thrombosis. J Thromb Haemost 2014; 12 (04) 436-443
11 Baglin T, Douketis J, Tosetto A. , et al. Does the clinical presentation and extent of venous thrombosis predict likelihood and type of recurrence? A patient-level meta-analysis. J Thromb Haemost 2010; 8 (11) 2436-2442
12 Boutitie F, Pinede L, Schulman S. , et al. Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials. BMJ 2011; 342: d3036
13 Robert-Ebadi H, Righini M. Management of distal deep vein thrombosis. Thromb Res 2017; 149: 48-55
14 Barco S, Klok FA, Mahe I. , et al. RIETE Investigators. Impact of sex, age, and risk factors for venous thromboembolism on the initial presentation of first isolated symptomatic acute deep vein thrombosis. Thromb Res 2019; 173: 166-171
15 Trinchero A, Scheres LJJ, Prochaska JH. , et al. Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis. Thromb Res 2018; 172: 74-79
16 Dentali F, Barco S, Pegoraro S. , et al. Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer. J Thromb Thrombolysis 2018; 46 (03) 404-408
17 Dentali F, Pegoraro S, Barco S. , et al. Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study. J Thromb Haemost 2017; 15 (09) 1757-1763
18 Brateanu A, Patel K, Chagin K. , et al. Probability of developing proximal deep-vein thrombosis and/or pulmonary embolism after distal deep-vein thrombosis. Thromb Haemost 2016; 115 (03) 608-614
19 Barco S, Corti M, Trinchero A. , et al. Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism. J Thromb Haemost 2017; 15 (07) 1436-1442
20 Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood 2014; 123 (12) 1802-1809
21 Kearon C, Ageno W, Cannegieter SC, Cosmi B, Geersing GJ, Kyrle PA. ; Subcommittees on Control of Anticoagulation, and Predictive and Diagnostic Variables in Thrombotic Disease. Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH. J Thromb Haemost 2016; 14 (07) 1480-1483
22 Kearon C, Iorio A, Palareti G. ; Subcommittee on Control of Anticoagulation of the SSC of the ISTH. Risk of recurrent venous thromboembolism after stopping treatment in cohort studies: recommendation for acceptable rates and standardized reporting. J Thromb Haemost 2010; 8 (10) 2313-2315
23 Prins MH, Lensing AWA, Prandoni P. , et al. Risk of recurrent venous thromboembolism according to baseline risk factor profiles. Blood Adv 2018; 2 (07) 788-796
24 Iorio A, Kearon C, Filippucci E. , et al. Risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic review. Arch Intern Med 2010; 170 (19) 1710-1716
25 Albertsen IE, Nielsen PB, Søgaard M. , et al. Risk of recurrent venous thromboembolism: a Danish Nationwide Cohort Study. Am J Med 2018; 131 (09) 1067-1074.e4
26 Albertsen IE, Piazza G, Goldhaber SZ. Let's stop dichotomizing venous thromboembolism as provoked or unprovoked. Circulation 2018; 138 (23) 2591-2593
27 Righini M, Galanaud JP, Guenneguez H. , et al. Anticoagulant therapy for symptomatic calf deep vein thrombosis (CACTUS): a randomised, double-blind, placebo-controlled trial. Lancet Haematol 2016; 3 (12) e556-e562
28 Galanaud JP, Sevestre MA, Pernod G. , et al. Long-term outcomes of cancer-related isolated distal deep vein thrombosis: the OPTIMEV study. J Thromb Haemost 2017; 15 (05) 907-916