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Original Investigation |

Nonleg Venous Thrombosis in Critically Ill Adults:  A Nested Prospective Cohort Study

Francois Lamontagne, MD, MSc1; Lauralyn McIntyre, MD, MSc2; Peter Dodek, MD, MHSc3; Diane Heels-Ansdell, MS4; Maureen Meade, MD, MSc4,5; Julia Pemberton, MSc6; Yoanna Skrobik, MD7; Ian Seppelt, MBBS8; Nicholas E. Vlahakis, MBBS9; John Muscedere, MD10; Graham Reece, MD11; Marlies Ostermann, MBBS12; Soundrie Padayachee, PhD, CSci13; Jamal Alhashemi, MBBS, MSc14; Michael Walsh, MD, PhD4,5; Bradley Lewis, MD15; David Schiff, MD16; Alan Moody, MBBS17; Nicole Zytaruk, RN4; Martine LeBlanc, MD7; Deborah J. Cook, MD, MSc4,5 ; for the PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial) Investigators, on behalf of the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group
[+] Author Affiliations
1Centre de recherche Clinique Étienne-Le Bel, Université de Sherbrooke, Sherbrooke, Quebec, Canada
2Department of Medicine (Division of Critical Care), The Ottawa Hospital, Ottawa, Ontario, Canada
3Center for Health Evaluation and Outcome Sciences and Department of Medicine, St Paul’s Hospital and University of British Columbia, Vancouver, British Columbia, Canada
4Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada
5Department of Medicine, McMaster University, Hamilton, Ontario, Canada
6Department of Surgery, McMaster University, Hamilton, Ontario, Canada
7Department of Medicine, Hôpital Maisonneuve Rosemont, Montreal, Quebec, Canada
8Department of Intensive Care Medicine, Nepean Hospital, University of Sydney, Sydney, Australia
9Department of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota
10Department of Critical Care, Queen’s University, Kingston, Ontario, Canada
11Department of Intensive Care Medicine, Blacktown Hospital, Sydney, Australia
12Department of Critical Care, Guys and St Thomas Hospital, London, England
13Department of Ultrasonic Angiology, Guys and St Thomas Hospital, London, England
14Department of Anesthesia and Critical Care, King Abdulaziz University, Jeddah, Saudi Arabia
15Department of Radiology, Mayo Clinic, Rochester, Minnesota
16Department of Radiology, McMaster University, Hamilton, Ontario, Canada
17Department of Medical Imaging, University of Toronto, Toronto, Ontario, Canada
JAMA Intern Med. 2014;174(5):689-696. doi:10.1001/jamainternmed.2014.169.
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Importance  Critically ill patients are at risk of venous thrombosis, and therefore guidelines recommend daily thromboprophylaxis. Deep vein thrombosis (DVT) commonly occurs in the lower extremities but can occur in other sites including the head and neck, trunk, and upper extremities. The risk of nonleg deep venous thromboses (NLDVTs), predisposing factors, and the association between NLDVTs and pulmonary embolism (PE) or death are unclear.

Objective  To describe the frequency, anatomical location, risk factors, management, and consequences of NLDVTs in a large cohort of medical-surgical critically ill adults.

Design, Setting, and Participants  A nested prospective cohort study in the setting of secondary and tertiary care intensive care units (ICUs). The study population comprised 3746 patients, who were expected to remain in the ICU for at least 3 days and were enrolled in a randomized clinical trial of dalteparin vs standard heparin for thromboprophylaxis.

Main Outcomes and Measures  The proportion of patients who had NLDVTs, the mean number per patient, and the anatomical location. We characterized NLDVTs as prevalent or incident (identified within 72 hours of ICU admission or thereafter) and whether they were catheter related or not. We used multivariable regression models to evaluate risk factors for NLDVT and to examine subsequent anticoagulant therapy, associated PE, and death.

Results  Of 3746 trial patients, 84 (2.2%) developed 1 or more non–leg vein thromboses (superficial or deep, proximal or distal). Thromboses were more commonly incident (n = 75 [2.0%]) than prevalent (n = 9 [0.2%]) (P < .001) and more often deep (n = 67 [1.8%]) than superficial (n = 31 [0.8%]) (P < .001). Cancer was the only independent predictor of incident NLDVT (hazard ratio [HR], 2.22; 95% CI, 1.06-4.65). After adjusting for Acute Physiology and Chronic Health Evaluation (APACHE) II scores, personal or family history of venous thromboembolism, body mass index, vasopressor use, type of thromboprophylaxis, and presence of leg DVT, NLDVTs were associated with an increased risk of PE (HR, 11.83; 95% CI, 4.80-29.18). Nonleg DVTs were not associated with ICU mortality (HR, 1.09; 95% CI, 0.62-1.92) in a model adjusting for age, APACHE II, vasopressor use, mechanical ventilation, renal replacement therapy, and platelet count below 50 × 109/L.

Conclusions and Relevance  Despite universal heparin thromboprophylaxis, nonleg thromboses are found in 2.2% of medical-surgical critically ill patients, primarily in deep veins and proximal veins. Patients who have a malignant condition may have a significantly higher risk of developing NLDVT, and patients with NLDVT, compared with those without, appeared to be at higher risk of PE but not higher risk of death.

Trial Registration  clinicaltrials.gov Identifier: NCT00182143

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Reference Nomenclature for Upper-Extremity Venous Segments

This nomenclature is based on anatomy and reported ultrasonography results from the calibration exercise of the upper-extremity thromboses adjudication process.

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