Download PDF
Thromb Haemost
DOI: 10.1055/a-2595-5458
Stroke, Systemic or Venous Thromboembolism

Predictors, Incidence, and Proximal Extension Rate of Distal Deep Vein Thrombosis in Internal Medicine Wards: Insights from the AURELIO Study

Lorenzo Loffredo 
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Enrico Maggio
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Arianna Magna
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Gianpaolo Vidili
2   Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy
,
Angela Sciacqua
3   Department of Medical and Surgical Sciences, University Magna-Græcia of Catanzaro, Catanzaro, Italy
,
Chiara Cogliati
4   Department of Internal medicine, L. Sacco Hospital, ASST-fbf-Sacco, Milan, Italy
,
Sciaila Bernardini
5   Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Italy
,
Alessia Fallarino
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Ilaria Maria Palumbo
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Arianna Pannunzio
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Chiara Bagnato
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Nausica Polisena
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Carla Serra
6   Interventional, Diagnostic and Therapeutic Ultrasound Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
,
Lorenzo Falsetti
7   Clinica Medica, Dipartimento di Scienze Cliniche e Molecolari, Università Politecnica delle Marche, Ancona, Italy
,
Vincenzo Zaccone
8   Internal and Subintensive Medicine, Azienda Ospedaliero-Universitaria delle Marche, Ancona, Italy
,
Evaristo Ettorre
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Giovambattista Desideri
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Luca Santoro
9   Catholic University of the Sacred Heart, Rome, Italy
,
Vito Cantisani
10   Department of Radiology, Oncology and Pathology, Sapienza University of Rome, Roma, Italy
,
Pasquale Pignatelli
1   Department of Clinical, Internal Medicine, Anesthesiologic and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy
,
Angelo Santoliquido
9   Catholic University of the Sacred Heart, Rome, Italy
,
Francesco Violi 
11   Department of Radiology, Sapienza University of Rome, Roma, Italy
,
AURELIO Study Group › Author Affiliations Funding This study was supported by a grant from the University of Rome “La Sapienza” (Università degli Studi di ROMA “la Sapienza” Progetti di COOPERAZIONE E SVILUPPO 2021 to LL).
› Further Information
Also available at
    Permissions and Reprints


Abstract

Background

Distal deep venous thrombosis (DDVT) is a clinical condition that can affect patients hospitalized in internal medicine wards and may result in pulmonary embolism. However, many aspects of distal thrombosis in hospitalized medical patients remain poorly understood.

Objective

This study aimed to evaluate the rate of asymptomatic DDVT at admission, the occurrence of DDVT during hospitalization, and to analyze the factors associated with thrombotic events.

Methods

A multicenter, prospective observational study (AURELIO) was conducted across eight centers affiliated with the Ultrasound Study Group of the Italian Society of Internal Medicine. Venous ultrasound of the lower limb veins was performed within 48 hours of admission and at discharge to diagnose distal deep vein thrombosis.

Results

Among 1,458 patients (721 males and 737 females; mean age 71 ± 16 years), asymptomatic distal thrombosis was detected in 59 patients (4%) upon admission. Of these, 47% (n = 28) were classified as isolated DDVT, while 31 cases involved DDVT that extended to the proximal tract. At discharge, 9 additional cases of distal thrombosis were identified, bringing the total to 68 cases. Of these, 46% were DDVT, while 54% DDVT extended to the proximal venous system. Multivariate analysis identified reduced mobility (p = 0.036) and active malignancy (p = 0.02) as independent risk factors for DDVT extending to the proximal tract. Additionally, pneumonia (p = 0.043) and active malignancy (p = 0.008) were associated with DDVT.

Conclusion

The study emphasizes the high prevalence of DDVT in hospitalized patients and the risk of proximal extension. Ultrasound screening should be considered for oncology patients and those with pneumonia to ensure early diagnosis and timely anticoagulant therapy.

Keywords

distal vein thrombosis - ultrasound analysis - medical patients

Authors' Contribution

L.L. is the guarantor of the content of the manuscript, including the data and analysis. Study concept and design: L.L. and F.V. Acquisition, analysis, and interpretation of data: L.L., G.V., C.C., E.M., A.M., A.S., S.B., A.F., I.M.P., A.P., C.B., N.P., C.S., L.F., V.Z., E.E., G.D., L.S., V.C., and P.P. Drafting of the manuscript: F.V. and L.L. Critical revision of the manuscript for important intellectual content: A.S., P.P., F.V., and L.S. Statistical analysis: L.L. and E.M. Study supervision: L.L. All the authors have read and approved the final manuscript.


* The details of the AURELIO study group are mentioned in the Supplementary Material (available in the online version).


Supplementary Material



Publication History

Received: 07 March 2025

Accepted: 27 April 2025

Accepted Manuscript online:
28 April 2025

Article published online:
16 May 2025

© 2025. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • References

  • 1 Lyman GH, Culakova E, Poniewierski MS, Kuderer NM. Morbidity, mortality and costs associated with venous thromboembolism in hospitalized patients with cancer. Thromb Res 2018; 164 (Suppl. 01) S112-S118
    CrossrefPubMedSearch in Google Scholar
  • 2 Loffredo L, Arienti V, Vidili G. et al; AURELIO Study Group. Low rate of intrahospital deep venous thrombosis in acutely ill medical patients: results from the AURELIO study. Mayo Clin Proc 2019; 94 (01) 37-43
    CrossrefPubMedSearch in Google Scholar
  • 3 Palareti G, Schellong S. Isolated distal deep vein thrombosis: what we know and what we are doing. J Thromb Haemost 2012; 10 (01) 11-19
    CrossrefPubMedSearch in Google Scholar
  • 4 Bikdeli B, Caraballo C, Trujillo-Santos J. et al; RIETE Investigators. Clinical presentation and short- and long-term outcomes in patients with isolated distal deep vein thrombosis vs proximal deep vein thrombosis in the RIETE registry. JAMA Cardiol 2022; 7 (08) 857-865
    CrossrefPubMedSearch in Google Scholar
  • 5 Schellong SM, Goldhaber SZ, Weitz JI. et al. Isolated distal deep vein thrombosis: perspectives from the GARFIELD-VTE registry. Thromb Haemost 2019; 119 (10) 1675-1685
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Makedonov I, Galanaud JP, Kahn SR. Significance and management of isolated distal deep vein thrombosis. Curr Opin Hematol 2021; 28 (05) 331-338
    PubMedSearch in Google Scholar
  • 7 Garry J, Duke A, Labropoulos N. Systematic review of the complications following isolated calf deep vein thrombosis. Br J Surg 2016; 103 (07) 789-796
    PubMedSearch in Google Scholar
  • 8 Elmi G, Rinaldi ER, Domanico A, Aluigi L. Calf deep vein thrombosis—clinical relevance, diagnostic approaches and therapeutic options. Vasa 2020; 49 (05) 359-366
    PubMedSearch in Google Scholar
  • 9 Shimabukuro N, Mo M, Hashiyama N. et al. Clinical course of asymptomatic isolated distal deep vein thrombosis of the leg: a single-institution study. Ann Vasc Dis 2019; 12 (04) 487-492
    PubMedSearch in Google Scholar
  • 10 Kirkilesis G, Kakkos SK, Bicknell C, Salim S, Kakavia K. Treatment of distal deep vein thrombosis. Cochrane Database Syst Rev 2020; 4 (04) CD013422
    PubMedSearch in Google Scholar
  • 11 Franco L, Giustozzi M, Agnelli G, Becattini C. Anticoagulation in patients with isolated distal deep vein thrombosis: a meta-analysis. J Thromb Haemost 2017; 15 (06) 1142-1154
    CrossrefPubMedSearch in Google Scholar
  • 12 Ciuti G, Grifoni E, Pavellini A. et al. Incidence and characteristics of asymptomatic distal deep vein thrombosis unexpectedly found at admission in an internal medicine setting. Thromb Res 2012; 130 (04) 591-595
    PubMedSearch in Google Scholar
  • 13 Magna A, Maggio E, Vidili G. et al; AURELIO Study Group. Rate and predictors of thromboprophylaxis in internal medicine wards: results from the AURELIO study. Thromb Res 2024; 243: 109148
    PubMedSearch in Google Scholar
  • 14 Akram F, Fan BE, Tan CW, Teoh WC, Prandoni P, Yap ES. The clinical application of venous ultrasound in diagnosis and follow-up of lower extremity deep vein thrombosis (DVT): a case-based discussion. Thromb J 2023; 21 (01) 110
    PubMedSearch in Google Scholar
  • 15 Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107 (23, Suppl 1): I22-I30
    CrossrefPubMedSearch in Google Scholar
  • 16 Loffredo L, Vidili G, Sciacqua A. et al; AURELIO Study Group. Asymptomatic and symptomatic deep venous thrombosis in hospitalized acutely ill medical patients: risk factors and therapeutic implications. Thromb J 2022; 20 (01) 72
    PubMedSearch in Google Scholar
  • 17 Palareti G, Cosmi B, Lessiani G. et al. Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: the blind, prospective CALTHRO study. Thromb Haemost 2010; 104 (05) 1063-1070
    PubMedSearch in Google Scholar
  • 18 Fujioka S, Ohkubo H, Kitamura T. et al. Risk factors for progression of distal deep vein thrombosis. Circ J 2020; 84 (10) 1862-1865
    PubMedSearch in Google Scholar
  • 19 Palareti G, Legnani C, Antonucci E. et al. Management and outcomes of isolated distal deep vein thromboses: a questionable trend toward long-lasting anticoagulation treatment. Results from the START-Register. TH Open 2021; 5 (03) e239-e250
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Valerio L, Ambaglio C, Barone M. et al. Recurrence risk after first symptomatic distal versus proximal deep vein thrombosis according to baseline risk factors. TH Open 2019; 3 (01) e58-e63
    Thieme ConnectPubMedSearch in Google Scholar
  • 21 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
    Thieme ConnectPubMedSearch in Google Scholar
  • 22 Luo X, Zhang L, Hou C. et al. Hospitalized patients with isolated distal deep vein thrombosis: anticoagulation therapy or not?. Thromb J 2022; 20 (01) 52
    PubMedSearch in Google Scholar
  • 23 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
    CrossrefPubMedSearch in Google Scholar
  • 24 Squizzato A, Agnelli G, Campanini M. et al; FADOI-NoTEVole Study Group. Prophylaxis of venous thromboembolism after hospital discharge in internal medicine: findings from the observational FADOI-NoTEVole study. Thromb Haemost 2019; 119 (12) 2043-2052
    Thieme ConnectPubMedSearch in Google Scholar
  • 25 Galanaud JP, Sevestre-Pietri MA, Bosson JL. et al; OPTIMEV-SFMV Investigators. Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost 2009; 102 (03) 493-500
    PubMedSearch in Google Scholar
  • 26 Fernandes CJ, Morinaga LTK, Alves Jr JL. et al. Cancer-associated thrombosis: the when, how and why. Eur Respir Rev 2019; 28 (151) 180119
    CrossrefPubMedSearch in Google Scholar
  • 27 Abdol Razak NB, Jones G, Bhandari M, Berndt MC, Metharom P. Cancer-associated thrombosis: an overview of mechanisms, risk factors, and treatment. Cancers (Basel) 2018; 10 (10) 380
    CrossrefPubMedSearch in Google Scholar
  • 28 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
    CrossrefPubMedSearch in Google Scholar
  • 29 Violi F, Pastori D, Cangemi R, Pignatelli P, Loffredo L. Hypercoagulation and antithrombotic treatment in coronavirus 2019: a new challenge. Thromb Haemost 2020; 120 (06) 949-956
    Thieme ConnectPubMedSearch in Google Scholar
  • 30 Violi F, Pignatelli P, Vestri AR. et al; ADA GROUP. The ADA (Age-D-Dimer-Albumin) score to predict thrombosis in SARS-CoV-2. Thromb Haemost 2022; 122 (09) 1567-1572
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Jimenez-Guiu X, Huici-Sánchez M, Rmera-Villegas A, Izquierdo-Miranda A, Sancho-Cerro A, Vila-Coll R. Deep vein thrombosis in noncritically ill patients with coronavirus disease 2019 pneumonia: deep vein thrombosis in nonintensive care unit patients. J Vasc Surg Venous Lymphat Disord 2021; 9 (03) 592-596
    CrossrefPubMedSearch in Google Scholar
  • 32 Prandoni P, Haas S, Fluharty M. et al; GARFIELD-VTE investigators. Incidence and risk factors of post-thrombotic syndrome in patients with isolated calf vein thrombosis. Findings from the GARFIELD-VTE registry. Thromb Res 2024; 235: 75-78
    PubMedSearch in Google Scholar
  • 33 Sartori M, Favaretto E, Cosmi B. Relevance of immobility as a risk factor for symptomatic proximal and isolated distal deep vein thrombosis in acutely ill medical inpatients. Vasc Med 2021; 26 (05) 542-548
    PubMedSearch in Google Scholar
  • 34 Falanga A, Ay C, Di Nisio M. et al; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Venous thromboembolism in cancer patients: ESMO clinical practice guideline. Ann Oncol 2023; 34 (05) 452-467
    CrossrefPubMedSearch in Google Scholar
  • 35 Wu S, Wang H, Li C. et al. Efficacy and safety of direct oral anticoagulants for preventing venous thromboembolism in hospitalized cancer patients: a national multicenter retrospective cohort study. Front Pharmacol 2024; 15: 1373635
    PubMedSearch in Google Scholar