Prognostic Significance of Concomitant Superficial Vein Thrombosis in Patients with Deep Vein Thrombosis of the Lower Limbs

Álvaro Dubois-Silva; Cristina Barbagelata-López; Patricia Piñeiro-Parga; Iria Francisco; Conxita Falgá; Raimundo Tirado; José María Suriñach; Jerónimo Ramón Vela; Carmen Mella; Isabelle Quere; Carmine Siniscalchi; Manuel Monreal; the RIETE Investigators

doi:10.1055/a-1414-5055

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2021; 121(12): 1650-1659
DOI: 10.1055/a-1414-5055

Stroke, Systemic or Venous Thromboembolism

Prognostic Significance of Concomitant Superficial Vein Thrombosis in Patients with Deep Vein Thrombosis of the Lower Limbs

Authors

Álvaro Dubois-Silva

¹Department of Internal Medicine, Complexo Hospitalario Universitario de A Coruña, Servizo Galego de Saúde, A Coruña, Spain

²Universidade da Coruña, A Coruña, Spain
Cristina Barbagelata-López

¹Department of Internal Medicine, Complexo Hospitalario Universitario de A Coruña, Servizo Galego de Saúde, A Coruña, Spain
Patricia Piñeiro-Parga

¹Department of Internal Medicine, Complexo Hospitalario Universitario de A Coruña, Servizo Galego de Saúde, A Coruña, Spain
Iria Francisco

³Department of Internal Medicine, Hospital Universitari de Girona Dr. Josep Trueta, Gerona, Spain
Conxita Falgá

⁴Department of Internal Medicine, Hospital de Mataró, Barcelona, Spain
Raimundo Tirado

⁵Department of Internal Medicine, Hospital Infanta Margarita, Córdoba, Spain
José María Suriñach

⁶Department of Internal Medicine, Hospital Universitario Vall d'Hebron, Barcelona, Spain
Jerónimo Ramón Vela

⁷Department of Internal Medicine, Hospital Universitario Miguel Servet, Zaragoza, Spain
Carmen Mella

⁸Department of Internal Medicine, Complejo Hospitalario Universitario de Ferrol, A Coruña, Spain
Isabelle Quere

⁹Department of Vascular Medicine, Hôpital Saint Eloi, Montpellier, France
Carmine Siniscalchi

¹⁰Department of Angiology, Azienda Ospedaliera Universitaria, Parma, Italy
Manuel Monreal

¹¹Department of Internal Medicine, Hospital Germans Trias i Pujol, Badalona, Barcelona, Universidad Autónoma de Barcelona, Spain

the RIETE Investigators

Abstract

Background The prognostic significance of concomitant superficial vein thrombosis (SVT) in patients with lower-limb deep vein thrombosis (DVT) has not been consistently evaluated.

Methods We used the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the rates of subsequent pulmonary embolism (PE), recurrent DVT, major bleeding or death in patients with lower-limb DVT, according to the presence or absence of concomitant SVT.

Results From March 2015 to May 2020, there were 8,743 patients with lower-limb DVT. Of these, 745 (8.5%) had concomitant SVT. Most patients (97.4% in both subgroups) received anticoagulant therapy (median duration: 138 vs. 147 days). During follow-up (median: 193 vs. 210 days), 156 (1.8%) patients developed subsequent PE, 336 (3.8%) had recurrent DVT, 201 (2.3%) had major bleeding and 844 (9.7%) died. Patients with concomitant SVT had a higher rate of subsequent PE (rate ratio [RR]: 2.11; 95% confidence interval [95%CI]: 1.33–3.24) than those with isolated DVT, with no significant differences in the rates of recurrent DVT (RR: 0.80; 95%CI: 0.50–1.21), major bleeding (RR: 0.77; 95%CI: 0.41–1.33) or death (RR: 0.81; 95%CI: 0.61–1.06). On multivariable analysis, patients with DVT and SVT concomitantly were at increased risk of subsequent PE during anticoagulation (adjusted hazard ratio [HR]: 2.23; 95%CI: 1.22–4.05) and also during the entire follow-up period (adjusted HR: 2.33; 95%CI: 1.49–3.66).

Conclusion Patients with lower-limb DVT and SVT concomitantly are at increased risk of developing PE. Further studies are needed to externally validate our findings and to determine if these patients could benefit from a different management strategy.

Keywords

anticoagulants - deep vein thrombosis - pulmonary embolism - recurrences - superficial vein thrombosis

Full Text

References

References
1 Evans NS, Ratchford EV. Superficial vein thrombosis. Vasc Med 2018; 23 (02) 187-189
2 Décousus H, Bertoletti L, Frappé P. Spontaneous acute superficial vein thrombosis of the legs: do we really need to treat?. J Thromb Haemost 2015; 13 (Suppl. 01) S230-S237
3 Cosmi B. Management of superficial vein thrombosis. J Thromb Haemost 2015; 13 (07) 1175-1183
4 Decousus H, Prandoni P, Mismetti P. et al; CALISTO Study Group. Fondaparinux for the treatment of superficial-vein thrombosis in the legs. N Engl J Med 2010; 363 (13) 1222-1232
5 Beyer-Westendorf J, Schellong SM, Gerlach H. et al; SURPRISE investigators. Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. Lancet Haematol 2017; 4 (03) e105-e113
6 Duffett L, Kearon C, Rodger M, Carrier M. Treatment of superficial vein thrombosis: a systematic review and meta-analysis. Thromb Haemost 2019; 119 (03) 479-489
7 Galanaud JP, Bosson JL, Genty C. et al. Superficial vein thrombosis and recurrent venous thromboembolism: a pooled analysis of two observational studies. J Thromb Haemost 2012; 10 (06) 1004-1011
8 Galanaud JP, Sevestre MA, Pernod G. et al. Long-term risk of venous thromboembolism recurrence after isolated superficial vein thrombosis. J Thromb Haemost 2017; 15 (06) 1123-1131
9 Kudlaty E, Oriowo B, Yang MJ, Go MR, Satiani B. Isolated great saphenous vein thrombus is associated with high rates of complications regardless of management. Ann Vasc Surg 2017; 45: 154-159
10 Bell LN, Berg RL, Schmelzer JR. et al. Thromboembolic complications following a first isolated episode of superficial vein thrombosis: a cross-sectional retrospective study. J Thromb Thrombolysis 2017; 43 (01) 31-37
11 Di Minno MND, Ambrosino P, Ambrosini F, Tremoli E, Di Minno G, Dentali F. Prevalence of deep vein thrombosis and pulmonary embolism in patients with superficial vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost 2016; 14 (05) 964-972
12 Pomero F, Di Minno MND, Tamburini Premunian E. et al. A clinical score to rule out the concomitant presence of deep vein thrombosis in patients presenting with superficial vein thrombosis: the ICARO study. Thromb Res 2015; 136 (05) 938-942
13 Frappé P, Brosse Q, Seffert B, Décousus H, Bertoletti L. STEPH Study Group. Ruling out deep vein thrombosis in patients with superficial vein thrombosis: external validation of the ICARO score. J Thromb Thrombolysis 2019; 47 (01) 96-101
14 Hirmerova J, Seidlerova J, Subrt I. Deep vein thrombosis and/or pulmonary embolism concurrent with superficial vein thrombosis of the legs: cross-sectional single center study of prevalence and risk factors. Int Angiol 2013; 32 (04) 410-416
15 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
16 Mazzolai L, Aboyans V, Ageno W. 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 vascular diseases and pulmonary circulation and right ventricular function. Eur Heart J 2018; 39 (47) 4208-4218
17 Baglin T, Bauer K, Douketis J, Buller H, Srivastava A, Johnson G. SSC of the ISTH. Duration of anticoagulant therapy after a first episode of an unprovoked pulmonary embolus or deep vein thrombosis: guidance from the SSC of the ISTH. J Thromb Haemost 2012; 10 (04) 698-702
18 Chengelis DL, Bendick PJ, Glover JL, Brown OW, Ranval TJ. Progression of superficial venous thrombosis to deep vein thrombosis. J Vasc Surg 1996; 24 (05) 745-749
19 Laporte S, Mismetti P, Décousus H. et al; RIETE Investigators. Clinical predictors for fatal pulmonary embolism in 15,520 patients with venous thromboembolism: findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry. Circulation 2008; 117 (13) 1711-1716
20 Muñoz FJ, Mismetti P, Poggio R. et al; RIETE Investigators. Clinical outcome of patients with upper-extremity deep vein thrombosis: results from the RIETE Registry. Chest 2008; 133 (01) 143-148
21 Bikdeli B, Jimenez D, Hawkins M. et al; RIETE Investigators. Rationale, design and methodology of the computerized registry of patients with venous thromboembolism (RIETE). Thromb Haemost 2018; 118 (01) 214-224
22 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
23 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
24 Prandoni P, Noventa F, Ghirarduzzi A. et al. The risk of recurrent venous thromboembolism after discontinuing anticoagulation in patients with acute proximal deep vein thrombosis or pulmonary embolism. A prospective cohort study in 1,626 patients. Haematologica 2007; 92 (02) 199-205
25 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
26 Frappé P, Buchmuller-Cordier A, Bertoletti L. et al; STEPH Study Group. Annual diagnosis rate of superficial vein thrombosis of the lower limbs: the STEPH community-based study. J Thromb Haemost 2014; 12 (06) 831-838
27 Decousus H, Quéré I, Presles E. et al; POST (Prospective Observational Superficial Thrombophlebitis) Study Group. Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med 2010; 152 (04) 218-224
28 Quéré I, Leizorovicz A, Galanaud JP. et al; Prospective Observational Superficial Thrombophlebitis (POST) Study Investigators. Superficial venous thrombosis and compression ultrasound imaging. J Vasc Surg 2012; 56 (04) 1032-8.e1
29 Bikdeli B, Sharif-Kashani B, Bikdeli B. et al; RIETE Investigators. Impact of thrombus sidedness on presentation and outcomes of patients with proximal lower extremity deep vein thrombosis. Semin Thromb Hemost 2018; 44 (04) 341-347
30 Galanaud JP, Genty C, Sevestre MA. et al; OPTIMEV SFMV investigators. Predictive factors for concurrent deep-vein thrombosis and symptomatic venous thromboembolic recurrence in case of superficial venous thrombosis. The OPTIMEV study. Thromb Haemost 2011; 105 (01) 31-39
31 Francis CW, Kessler CM, Goldhaber SZ. et al. Treatment of venous thromboembolism in cancer patients with dalteparin for up to 12 months: the DALTECAN Study. J Thromb Haemost 2015; 13 (06) 1028-1035
32 Kyrle PA, Minar E, Bialonczyk C, Hirschl M, Weltermann A, Eichinger S. The risk of recurrent venous thromboembolism in men and women. N Engl J Med 2004; 350 (25) 2558-2563
33 Christiansen SC, Lijfering WM, Helmerhorst FM, Rosendaal FR, Cannegieter SC. Sex difference in risk of recurrent venous thrombosis and the risk profile for a second event. J Thromb Haemost 2010; 8 (10) 2159-2168
34 Blanco-Molina A, Enea I, Gadelha T. et al; RIETE Investigators. Sex differences in patients receiving anticoagulant therapy for venous thromboembolism. Medicine (Baltimore) 2014; 93 (17) 309-317
35 Yoshikawa Y, Yamashita Y, Morimoto T. et al; COMMAND VTE Registry Investigators. Sex differences in clinical characteristics and outcomes of patients with venous thromboembolism: from the COMMAND VTE registry. Circ J 2019; 83 (07) 1581-1589
36 Tosetto A, Iorio A, Marcucci M. et al. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH). J Thromb Haemost 2012; 10 (06) 1019-1025
37 Waljee AK, Rogers MAM, Lin P. et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ 2017; 357: j1415
38 Kearon C, Akl EA, Comerota AJ. et al. 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 (2, Suppl): e419S-e496S
39 Tait C, Baglin T, Watson H. et al; British Committee for Standards in Haematology. Guidelines on the investigation and management of venous thrombosis at unusual sites. Br J Haematol 2012; 159 (01) 28-38
40 Kalodiki E, Stvrtinova V, Allegra C. et al. Superficial vein thrombosis: a consensus statement. Int Angiol 2012; 31 (03) 203-216

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