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Clinical Investigations: VENOUS THROMBOEMBOLISM |

Delays in Diagnosis of Deep Vein Thrombosis and Pulmonary Embolism* FREE TO VIEW

C. Gregory Elliott, MD, FCCP; Samuel Z. Goldhaber, MD, FCCP; Robert L. Jensen, PhD
Author and Funding Information

Affiliations: *From the Departments of Medicine (Drs. Elliott and Jensen), Pulmonary Division, LDS Hospital, University of Utah, Salt Lake City, UT; and the Cardiovascular Division (Dr. Goldhaber), Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.,  A list of participating investigators and study sites is located in the Appendix.

Correspondence to: C. Gregory Elliott, MD, FCCP, Pulmonary Division, LDS Hospital, Eighth Ave & C St, Salt Lake City, UT 84143; e-mail: Greg.Elliott@ihc.com



Chest. 2005;128(5):3372-3376. doi:10.1378/chest.128.5.3372
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Published online

Purpose: To investigate delays in the diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE).

Subjects and methods: We prospectively identified 1,152 patients in whom DVT or PE had been diagnosed at 70 North American medical centers. We recorded demographic characteristics and dates of symptom onset, initial medical evaluation, and confirmatory diagnostic tests.

Results: We identified substantial numbers of patients for whom there were delays in the diagnosis of DVT, PE, or both. For acute DVT, 170 of 808 patients (21%) received diagnoses > 1 week after symptom onset, and 40 of 808 patients (5%) received diagnoses > 3 weeks after symptom onset. On average, 80% of the delay in diagnosis of DVT occurred between symptom onset and medical evaluation. Acute PE was diagnosed in 59 of 344 patients (17%) > 1 week after symptom onset, and in 17 of 344 patients (5%) > 3 weeks after the onset of symptoms. Delays in the diagnosis of PE represented both delays in seeking medical attention (mean, 3 days; upper limit of 95% confidence interval [CI], 12 days); and delays from the first medical evaluation to diagnosis (mean, 2 days; upper limit of 95% CI, 9 days).

Conclusions: Although the majority of patients with DVT and PE seek medical attention and receive diagnoses promptly after symptom onset, substantial delays exist in the diagnosis of DVT and PE for many patients. There is a need to develop and test strategies that reduce delays in diagnosis.

Figures in this Article

Pulmonary embolism (PE) is a common cardiovascular and cardiopulmonary illness with an annual incidence in the United States that exceeds 1 case per 1,000 population and a mortality rate of > 15% in the first 3 months after diagnosis.1This makes PE as deadly an illness as acute myocardial infarction. The majority of deaths occur within hours of acute PE, often as the consequence of previously unrecognized and untreated deep vein thrombosis (DVT) or acute PE.2In addition, PE survivors may experience pulmonary hypertension and eventually die from right heart failure years after the occurrence of PE.3

Earlier diagnoses of DVT and PE will reduce the morbidity and mortality associated with venous thromboembolism.2 However, data regarding delays in the diagnosis of venous thromboembolism are sparse. Therefore, to better understand delays in the diagnosis of venous thromboembolism, we undertook a prospective study of the diagnosis of venous thromboembolism at 70 North American medical centers.

Investigators at 70 medical centers (see “Appendix”) identified consecutive medical records with the hospital discharge diagnosis of DVT without symptoms of PE (“DVT”) or PE from August 1, 1999, through November 30, 1999. We included only patients who underwent a confirmatory objective imaging test (eg, compression ultrasonography) for DVT. Physicians and patients were not interviewed by the investigators. Data collection was approved by the local institutional review board.

Demographics (ie, date of birth, sex, weight, and race), risk factors for venous thromboembolism (ie, previous DVT or PE), malignancy, thrombophilia, recent (ie, within 8 weeks) major surgery or immobilization, pregnancy (ie, within 6 months), and post-phlebitic syndrome were recorded. The date of symptom onset, the date that the subject was first seen by medical personnel for these symptoms, and the date on which the diagnosis was confirmed were recorded. The calendar date was the unit of measure for the delay in diagnosis. No attempt was made to subdivide data by the hour of the day. Thus, if the patient first developed symptoms on August 1, 1999, presented for medical attention on August 3, and received a diagnosis on August 4, the delay to presentation was 2 days and the delay to diagnosis was 1 day.

Statistical Analysis

Delay times were initially examined with half-normal plots and histograms that showed considerable skewness. These data were then tested using Kolmogorov-Smirnov and Lillefors tests for normality (Statistica; Tulsa, OK). All delay time distributions were significantly different from normal distributions, as expected.

Patient Population and Diagnostic Tests

Study sites enrolled 1,160 patients with venous thromboembolism from August 1, 1999, through November 30, 1999. Eight patients were excluded from the study because the data were incomplete, leaving a study population of 1,152 patients. This population included 808 patients in whom isolated DVT had been diagnosed, and 344 patients in whom PE had been diagnosed. Two hundred fifty-one patients (31.1%) had deep vein thrombi limited to calf veins, and 557 patients (68.9%) had proximal deep vein thrombi. The clinical characteristics are described in Table 1 . The risk factors for venous thromboembolism included recent surgery (28.6%), underlying malignancy (29.0%), previous venous thromboembolism (30.4%), and immobility (37.6%).

Diagnostic Tests

The majority of 808 patients (92.6%) with isolated DVT had the diagnosis confirmed by compression ultrasonography. The remaining patients had DVT confirmed by venography (6.1%) or other tests (eg, magnetic resonance angiography) [1.3%].

Many different tests, alone or in combination, were used to diagnose acute PE. A single diagnostic test confirmed acute PE in 137 of 344 patients (39.2%). Lung scans were the most common single test used to confirm acute PE (n = 84; 24.1%). Spiral chest CT scanning alone confirmed the diagnosis in 42 patients (11.9%), and pulmonary angiography alone confirmed the diagnosis in 11 patients (3.2%).

Two hundred seven patients (60.8%) required more than one diagnostic test to confirm the diagnosis of acute PE. One hundred twenty-eight patients underwent one additional test (ie, compression ultrasonography, 109 patients; pulmonary angiography, 9 patients; spiral CT scan, 5 patients; venography, 3 patients; magnetic resonance angiography, 1 patient; and lung biopsy, 1 patient) after a undergoing a nondiagnostic ventilation-perfusion lung scan. Twenty-two additional patients received the diagnosis of PE after undergoing compression ultrasonography and spiral CT scanning, and 1 additional patient had the diagnosis established after undergoing venography and spiral CT scanning. Fifty-seven patients underwent three or more diagnostic tests in order to confirm the diagnosis of PE.

Delays in Diagnosis

Figures 1and 2 identify the delays in the diagnosis of DVT and PE. One hundred seventy of 808 patients (21%) with acute DVT had > 7 days elapse between symptom onset and the confirmation of the diagnosis (Fig 1). Forty of 808 patients (5%) had > 21 days elapse between symptom onset and the diagnosis. The time to presentation (ie, the time from symptom onset to medical evaluation) contributed most to delays in the diagnosis of DVT. On average, 4.4 days elapsed between the earliest symptoms and medical evaluation. Ninety-five percent of patients with isolated DVT were seen within 2 weeks of symptom onset. In contrast, the delay between presentation with symptoms and/or signs of DVT and diagnosis was short. On average, only 1 day elapsed, and 95% of patients received diagnoses within 5 days.

Fifty-nine of 344 patients (17%) with acute PE had > 7 days elapse between symptom onset and diagnosis, and 17 of 344 patients (5%) had > 25 days elapse between symptom onset and the diagnosis (Fig 2). Delays in the diagnosis of PE represented both delays between the onset of symptoms and the receipt of medical attention, and between the initial medical evaluation and confirmatory diagnostic testing.

This report documents and quantifies delays in the diagnosis of DVT and PE. Delays in the diagnosis of DVT and PE were common and substantial. Most of the delay in the diagnosis of DVT represented the delay from symptom onset to the date of medical evaluation. The delays from the date of medical evaluation to the occurrence of the confirmatory test were generally brief, perhaps reflecting the widespread availability of compression ultrasonography and a sense of urgency on the part of health-care providers. Furthermore, if treatment was begun prior to obtaining the confirmatory test, then the effective delay in diagnosis was less than we reported. However, it is unlikely that patients were treated for several days prior to obtaining a confirmatory objective test; therefore, our findings that there were substantial numbers of patients who experienced delays in diagnosis appears to be valid. Conversely, the delays were longer from the time of medical evaluation to time of the confirmatory diagnostic test for acute PE. This may occur because other common disorders mimic PE and because diagnostic algorithms for PE are more complex than those for DVT. It is also possible that there was limited access to pulmonary angiography or spiral CT scanning at the time of this study.4

Our findings appear to be valid and generalizable. We enrolled a large number of consecutive patients at 70 medical centers throughout North America. Diagnoses were confirmed by widely accepted objective imaging tests. The characteristics of the patient population were similar to those in other large studies of patients with DVT or PE.1,56

The present study has limitations. We do not provide outcome data to link delays in diagnosis to clinically important outcomes such as death, recurrent PE, or post-phlebitic syndrome. However, previous studies78 have shown that delays in achieving an adequate anticoagulant effect are linked to increased rates of recurrent thromboembolism among patients who present with proximal DVT.

Public and professional education represents a critical step for the early diagnosis and treatment of other common and serious disorders such as myocardial infarction and stroke. In the case of DVT, delays in diagnosis may abate by increasing public awareness of common symptoms and signs such as leg pain and swelling. Unexplained shortness of breath should trigger the suspicion of PE by lay persons and health-care professionals. The widespread implementation of protocols for CT pulmonary angiography may reduce the time to diagnosis of acute PE.

Participating Investigators and Study Sites

Kenneth Anderson, MD, Bluegrass Clinical Research, Louisville, KY; Jack E. Ansell, MD, Boston University Medical Center, Boston, MA; Amy Arouni, MD, Creighton Cardiac Center, Omaha, NE; Jeremy Brown, MD, Beth-Israel Deaconess Medical Center, Boston, MA; Frederick Brown, MD, Muskegon Surgical Group, Muskegon, MI; Paul Brownstone, MD, Alpine Clinical Research Center, Boulder, CO; Frank Burke, MD, Bluegrass Orthopaedics, Lexington, KY; Thomas Chippendale, MD, North County Neurology Associates, Oceanside, CA; Anthony Comerota, MD, Temple University School of Medicine, Philadelphia, PA; John D. Corson, MD, ChB, University of Iowa Hospitals & Clinics, Iowa City, IA; Steven Coutre, MD, Stanford University Medical Center, Stanford, CA; Bruce Davidson, MD, MPH, VA Mason Medical Center, Seattle, WA; Steven R. Deitcher, MD, Cleveland Clinic Foundation, Cleveland, OH; James Douketis, MD, St. Joseph’s Health Care, Hamilton, ON; Darlene J. Elias, MD, Scripps Clinic, LaJolla, CA; Greg Elliott, MD, LDS Hospital, Salt Lake City, UT; Charlie W. Francis, MD, University of Rochester Medical Center, Rochester, NY; Marc H. Glickman, MD, FACS, VA Vascular Associates, Norfolk, VA; Samuel Z. Goldhaber, MD, Brigham Women’s Hospital, Boston, MA; David Green, MD, PhD, Northwestern University, Chicago, IL; Leonard Gutnick, MD, Avera Research Institute, Sioux Falls, SD; Gregory Guy, MD, Riverside Methodist Hospital, Columbus, OH; Linda Harris, MD, University Surgical Associates, Buffalo, NY; John Heit, MD –Mayo Foundation, Rochester, MN; Mark A. Holguin, MD, Scott & White Memorial Hospital and Clinic, Temple, TX; Allen G. Holloway, Jr., MD, Maricopa Medical Center, Phoenix, AZ; James Jaffe, MD, Lehigh Valley Hospital, Allentown, PA; Gerald John, MD, Sarasota Memorial Hospital, Sarasota, FL; Thomas Jones, MD, MPH, Hershey Medical Center, Hershey, PA; Michael Kalafer, MD, Sharp Memorial Hospital, San Diego, CA; Clive Kearon, MD, McMaster Clinic, Henderson Hospital, Hamilton, ON; Michael Kirkpatrick, MD, USA College of Medicine, Mobile, AL; Robert Lavendar, MD, University of Arkansas for Medical Services–College of Medicine, Little Rock, AR; L. Veronica Lee, MD, WA University School of Medicine, St. Louis, MO; Robert G. Lerner, MD, NY Medical College at Westchester Medical Center, Valhalla, NY; Michel Makaroun, MD, Department of Surgery, UPMC, Pittsburgh, PA; Carlos Marchini, MD, Americas Doctor, Grants Pass, OR; Ben Margolis, MD, FCCP, West Surburban Hospital, Oak Park, IL; Louis G. Martin, MD, Emory University Hospital, Atlanta, GA; Joseph McShannic, MD, Summa Health System, Canfield, OH; Geno J. Merli, MD, Thomas Jefferson University –Jefferson Medical College, Philadelphia, PA: Warren C. Miller, MD, Bay Area Pulmonary Associates, Webster, CA; Melvin Morganroth, MD, The Oregon Clinic, Portland, OR;James Murray, MD, LAC-USC Medical Center, Los Angeles, CA: William Navigato, MD, Duurga Clinical Service, Fountain Valley, CA: Michael E. Nelson, MD, Shawnee Mission Pulmonary Consultants, Shawnee Mission, KA; Paul Norwood, MD, Saint Agnes Medical Center, Fresno, CA; William D. O’Riordan, MD, eStudySite.com, La Jolla, CA; Gary Papuchis, MD, WA County Hospital, Hagerstown, MD; Vandana Patel, MD, FCCP, FAAC, Medsource, Inc., Richmond, VA; Jeffrey Pesin, MD, Middlesex Pulmonary, Edison, NJ; William P. Saliski, DO, Montgomery Pulmonary Consultants, Montgomery, AL; Howard Schuele, MD, Morton Plant Mease Health Care, Clearwater, FL; Harshad Shah, MD, Shreenath Clinical Service, Fountain Valley, CA; Jamie Siegel, MD, UMDNJ –Robert Wood Johnson Medical School, New Brunswick, NJ; Ross Siemers, MD, FACP, North Memorial Health Care, Robbinsdale, MN; Thomas M. Siler, MD, Midwest Chest Consultants, St. Charles, MO; Alex Spyropolous, MD, Lovelace Health Systems, Albuquerque, NM; James Stannard, MD, University of Alabama at Birmingham, Birmingham, AL; Brian Steingo, MD, Horizon I.C.R. Fort Lauderdale, FL; Barry Stults, MD, University of Utah Medical Center, Salt Lake City, UT; Michael Sullivan, MD, Center for Clinical and Biological Research, Inc., San Diego, CA; James R. Taylor, MD, Pulmonary Consultants, Tacoma, WA; Robert Toltzis, MD, The Lindner Center, Cincinnati, OH; Peter Vrooman, MD, PW Clinical Research LLC, Winston-Salem, NC; Daniel Walsh, MD, Dartmouth Hitchcock Medical Center, Hanover, NH; Thomas Whitsett, MD, University of Oklahoma Science Center, Tulsa, OK; Jeff D. Williamson, MD, Wake Forest University, Winston-Salem, NC; Gregory R. Wise, MD, Kettering Hospital, Dayton, OH; and Lisa Youkeles, MD, North Shore University Hospital at Forest Hills, Chicago, IL

Abbreviations: DVT = deep vein thrombosis; PE = pulmonary embolism

Table Graphic Jump Location
Table 1. Clinical Characteristics*
* 

Values are given as the mean ± SD, No. (%), or mean (range).

Figure Jump LinkFigure 1. Comparison of the mean delay from symptom onset to the diagnosis of DVT (n = 808) presented as a frequency distribution plot. Twenty-one percent of patients received diagnoses > 1 week after symptom onset, and 5% of patients received diagnoses > 3 weeks after symptom onset. The mean delay to diagnosis was 5.6 days (upper limit of 95% confidence interval, 21 days), and the mean delay from symptom onset to medical attention was 4.4 days (upper limit of 95% confidence interval, 14 days).Grahic Jump Location
Figure Jump LinkFigure 2. Delays in the diagnosis of acute pulmonary embolism (n = 344) presented as a frequency distribution plot. Seventeen percent of patients received diagnoses > 1 week after symptom onset, and 5% of patients received diagnoses > 3 weeks after symptom onset. The mean delay to diagnosis was 4.8 days (upper limit of 95% confidence interval, 25 days), and the mean delay from symptom onset to medical attention was 2.9 days (upper limit of 95% confidence interval, 12 days).Grahic Jump Location
Goldhaber, SZ, Visani, L, DeRosa, M (1999) Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry.Lancet353,1386-1389. [CrossRef] [PubMed]
 
Dalen, JE Pulmonary embolism: what have we learned since Virchow?Chest2002;122,1440-1446. [CrossRef] [PubMed]
 
Pengo, V, Lensing, AWA, Prins, MH, et al Incidence of chronic thromboembolic pulmonary hypertension after pulmonary emboli.N Engl J Med2004;250,2257-2264
 
Stein, PD, Kayali, F, Olson, RE Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism.Am J Card2004;93,1316-1317. [CrossRef] [PubMed]
 
Birdwell, BG, Raskob, GE, Whitsett, TL, et al The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis.Ann Intern Med1998;128,1-7. [PubMed]
 
Goldhaber, SZ, Dunn, K, MacDougall, RC New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment.Chest2004;125,1595-1596. [CrossRef] [PubMed]
 
Hull, RD, Raskob, GE, Hirsh, J, et al Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.N Engl J Med1986;315,1109-1114. [CrossRef] [PubMed]
 
Brandjes, DP, Heijboer, H, Buller, HR Acenocoumarol and heparin compared with acenocoumarol alone in the treatment of proximal-vein thrombosis.N Engl J Med1992;327,1485-1489. [CrossRef] [PubMed]
 

Figures

Figure Jump LinkFigure 1. Comparison of the mean delay from symptom onset to the diagnosis of DVT (n = 808) presented as a frequency distribution plot. Twenty-one percent of patients received diagnoses > 1 week after symptom onset, and 5% of patients received diagnoses > 3 weeks after symptom onset. The mean delay to diagnosis was 5.6 days (upper limit of 95% confidence interval, 21 days), and the mean delay from symptom onset to medical attention was 4.4 days (upper limit of 95% confidence interval, 14 days).Grahic Jump Location
Figure Jump LinkFigure 2. Delays in the diagnosis of acute pulmonary embolism (n = 344) presented as a frequency distribution plot. Seventeen percent of patients received diagnoses > 1 week after symptom onset, and 5% of patients received diagnoses > 3 weeks after symptom onset. The mean delay to diagnosis was 4.8 days (upper limit of 95% confidence interval, 25 days), and the mean delay from symptom onset to medical attention was 2.9 days (upper limit of 95% confidence interval, 12 days).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Clinical Characteristics*
* 

Values are given as the mean ± SD, No. (%), or mean (range).

References

Goldhaber, SZ, Visani, L, DeRosa, M (1999) Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry.Lancet353,1386-1389. [CrossRef] [PubMed]
 
Dalen, JE Pulmonary embolism: what have we learned since Virchow?Chest2002;122,1440-1446. [CrossRef] [PubMed]
 
Pengo, V, Lensing, AWA, Prins, MH, et al Incidence of chronic thromboembolic pulmonary hypertension after pulmonary emboli.N Engl J Med2004;250,2257-2264
 
Stein, PD, Kayali, F, Olson, RE Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism.Am J Card2004;93,1316-1317. [CrossRef] [PubMed]
 
Birdwell, BG, Raskob, GE, Whitsett, TL, et al The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis.Ann Intern Med1998;128,1-7. [PubMed]
 
Goldhaber, SZ, Dunn, K, MacDougall, RC New onset of venous thromboembolism among hospitalized patients at Brigham and Women’s Hospital is caused more often by prophylaxis failure than by withholding treatment.Chest2004;125,1595-1596. [CrossRef] [PubMed]
 
Hull, RD, Raskob, GE, Hirsh, J, et al Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal-vein thrombosis.N Engl J Med1986;315,1109-1114. [CrossRef] [PubMed]
 
Brandjes, DP, Heijboer, H, Buller, HR Acenocoumarol and heparin compared with acenocoumarol alone in the treatment of proximal-vein thrombosis.N Engl J Med1992;327,1485-1489. [CrossRef] [PubMed]
 
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