Harry R. Büller, MD; Arina J. ten Cate-Hoek, MD; Arno W. Hoes, MD; Manuela A. Joore, PhD; Karel G.M. Moons, PhD; Ruud Oudega, MD; Martin H. Prins, MD; Henri E.J.H. Stoffers, MD; Diane B. Toll, PhD; Eit F. van der Velde, MD; Henk C.P.M. van Weert, MD; AMUSE (Amsterdam Maastricht Utrecht Study on thromboEmbolism) Investigators
Acknowledgment: The authors acknowledge the enthusiastic participation of general practitioners and other health care professionals who contributed to the study.
Grant Support: By Netherlands Organization for Scientific Research grant 945-04-009.
Potential Financial Conflicts of Interest: None disclosed.
Reproducible Research Statement:Study protocol: Available from Dr. Prins (e-mail, email@example.com). Statistical code: Not available. Data set: Available from Dr. Prins, subject to steering committee approval (e-mail, firstname.lastname@example.org).
Requests for Single Reprints: Martin H. Prins, MD, Department of Epidemiology, P Debyeplein 1, 6200 MD Maastricht, the Netherlands; e-mail, email@example.com.
Current Author Addresses: Drs. Büller, van der Velde, and van Weert: Academic Medical Center, Departments of Vascular Medicine and General Practice, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands.
Dr. ten Cate-Hoek: Division of Internal Medicine, Maastricht University Medical Center, P Debyelaan 25, 6202 AZ Maastricht, the Netherlands.
Drs. Hoes, Moons, Oudega, and Toll: University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Universiteitsweg 100, Locatie Stratenum, 3584 CG Utrecht, the Netherlands.
Dr. Joore: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, P Debyelaan 25, 6202 MD Maastricht, the Netherlands.
Dr. Prins: Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, P Debyelaan 25, 6202 MD Maastricht, the Netherlands; or Division of Epidemiology, Maastricht University, P Debyeplein 1, 6200 MD Maastricht, the Netherlands.
Dr. Stoffers: Department of General Practice and Family Medicine, Maastricht University, P Debyeplein 1, PO Box 616, 6200 MD Maastricht, the Netherlands.
Author Contributions: Conception and design: H.R. Büller, A.J. ten Cate-Hoek, A.W. Hoes, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, D.B. Toll, E.F. van der Velde, H.C.P.M. van der Weert.
Analysis and interpretation of the data: H.R. Büller, A.J. ten Cate-Hoek, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, D.B. Toll, E.F. van der Velde, H.C.P.M. van der Weert.
Drafting of the article: H.R. Büller, A.J. ten Cate-Hoek, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, D.B. Toll, E.F. van der Velde, H.C.P.M. van der Weert.
Critical revision of the article for important intellectual content: H.R. Büller, A.J. ten Cate-Hoek, A.W. Hoes, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, D.B. Toll, E.F. van der Velde, H.C.P.M. van der Weert.
Final approval of the article: H.R. Büller, A.J. ten Cate-Hoek, A.W. Hoes, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, D.B. Toll, E.F. van der Velde, H.C.P.M. van der Weert.
Statistical expertise: A.W. Hoes.
Obtaining of funding: H.R. Büller, M.A. Joore, K.G.M. Moons, R. Oudega, M.H. Prins, H.E.J.H. Stoffers, H.C.P.M. van der Weert.
Administrative, technical, or logistic support: A.J. ten Cate-Hoek, D.B. Toll, E.F. van der Velde.
Collection and assembly of data: A.J. ten Cate-Hoek, D.B. Toll, E.F. van der Velde.
Büller H., ten Cate-Hoek A., Hoes A., Joore M., Moons K., Oudega R., Prins M., Stoffers H., Toll D., van der Velde E., van Weert H., ; Safely Ruling Out Deep Venous Thrombosis in Primary Care. Ann Intern Med. 2009;150:229-235. doi: 10.7326/0003-4819-150-4-200902170-00003
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Published: Ann Intern Med. 2009;150(4):229-235.
Up to 90% of patients referred for ultrasonography with suspected deep venous thrombosis (DVT) of the leg do not have the disease.
To evaluate the safety and efficiency of using a clinical decision rule that includes a point-of-care d-dimer assay at initial presentation in primary care to exclude DVT.
A prospective management study.
Approximately 300 primary care practices in 3 regions of the Netherlands (Amsterdam, Maastricht, and Utrecht).
1028 consecutive patients with clinically suspected DVT.
Patients were managed on the basis of the result of the clinical decision rule, which included a d-dimer result. Patients with a score of 3 or less were not referred for ultrasonography and received no anticoagulant treatment; patients with a score of 4 or more were referred for ultrasonography.
The primary outcome was symptomatic, objectively confirmed, venous thromboembolism during 3-month follow-up.
The mean age of the 1028 study patients was 58 years, and 37% of patients were men. A valid score was obtained in 1002 patients (98%). In 500 patients (49%), with a score of 3 or less, 7 developed venous thromboembolism within 3 months (incidence, 1.4% [95% CI, 0.6% to 2.9%]). A total of 502 patients (49%) had a score of 4 or more; 3 did not have ultrasonography. Ultrasonography showed DVT in 125 patients (25%), for an overall prevalence in evaluable patients of 13% (125 of 1002). Of the 374 patients who had normal ultrasonography results, 4 developed venous thromboembolism within 3 months (1.1% [CI, 0.3% to 2.7%]).
The study lacked a randomized design and relied on clinical follow-up to detect missed thrombotic disease.
A diagnostic management strategy in primary care by using a simple clinical decision rule and a point-of-care d-dimer assay reduces the need for referral to secondary care of patients with clinically suspected DVT by almost 50% and is associated with a low risk for subsequent venous thromboembolic events.
The Netherlands Organization for Scientific Research.
February 19, 2009
Ignoring the Elephant in the Waitingroom
The article "Much Ado About Nothing" made no sense to me when referring to the reasons patients receive "unnecessary care" (1). No mention was made of the threat of lawsuits. I believe 30% or more of testing,etc. is not absolutely warranted but physicians are not able to use their wisdom or judgement as long as every patient is a lawsuit waiting to happen. Daily, physicians of every specialty order tests,CTs, MRIs, biopsies, hospital admissions,etc. because of fear. Without real tort reform no doc will risk not ordering the test. The article only fits as the study was done I believe in Amsterdam where they are blessed with a great climate of no lawsuits. Here in the US we all continue to pay indirectly the lawyers fees.
1. Harry R. BÃ¼ller, Arina J. ten Cate-Hoek, Arno W. Hoes, Manuela A. Joore, Karel G.M. Moons, Ruud Oudega, Martin H. Prins, Henri E.J.H. Stoffers, Diane B. Toll, Eit F. van der Velde, Henk C.P.M. van Weert for the AMUSE (Amsterdam Maastricht Utrecht Study on thromboEmbolism) Investigators Safely Ruling Out Deep Venous Thrombosis in Primary Care Ann Intern Med 2009; 150: 229-235
Menno V. Huisman
March 3, 2009
Safely ruling out deep vein thrombosis in primary care: possible causes of strategy failures
With great interest we have read the article by BÃ¼ller et al regarding the safety of ruling out deep venous thrombosis (DVT) in primary care by a clinical decision rule (CDR) (1). Several aspects of the study have drawn our attention.
First, in 7 patients with a low CDR score venous thromboembolism (VTE) occurred during the follow-up period; all patients had normal D-dimer tests. The time span between the onset of complaints and the performance of the D-dimer test is of particular interest in these patients since the D-dimer test could be false negative due to a very early presentation.
Second, a qualitative D-dimer test was used in this study. The interobserver variability of another qualitative D-dimer was reported to be considerable with a kappa of only 0.47 (2). We wonder whether the authors could report on the interobserver variability of the used D-dimer assay and its potential impact on the study results. Of note, a very fast quantitative D-dimer test has been shown to have high accuracy for diagnosing DVT and has recently been accommodated for hand held use (3).
Finally, the study protocol did not include a follow-up compression ultrasonography (CUS) in patients with a high CDR score including an abnormal D-dimer test result but normal initial CUS. The rationale for this second CUS is to detect the propagation of a distal DVT into the proximal venous system in high risk patients. A strategy with follow-up CUS after one week in these patients has previously been shown to prevent symptomatic VTE in a follow-up period of 3 months (4). We are therefore curious to know the time between the initial presentation and the development of the VTE event in the 4 patients with a high CDR score and an initially normal CUS and whether they had a positive D-dimer test result, as well as the author's opinion as to whether a repeat CUS could have prevented these VTE events, which included one patient with a fatal PE.
1. BÃ¼ller HR, Ten Cate-Hoek AJ, Hoes AW, Joore MA, Moons KG, Oudega R et al. Safely ruling out deep venous thrombosis in primary care. Ann Intern Med. 2009 17;150:229-35.
2. de MonyÃ© W, Huisman MV, Pattynama PM. Observer dependency of the SimpliRed D-dimer assay in 81 consecutive patients with suspected pulmonary embolism. Thromb Res. 1999;96:293-8.
3. Dempfle CE, Korte W, Schwab M, Zerback R, Huisman MV. Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis. Thromb Haemost. 2006;96:79-83.
4. Righini M, Paris S, Le Gal G, Laroche JP, Perrier A, Bounameaux H. Clinical relevance of distal deep vein thrombosis. Review of literature data. Thromb Haemost. 2006;95:56-64.
William H. Fee, M.D. FACP
March 12, 2009
Safely Ruling Out Deep Venous Thrombosis in Primary Care
I read with interest the article by Buller et al. Often I am faced with the ongoing prospect of "treat me doctor, I have no insurance" situations. I have found, in fact, the Lowenstein test which consists of inflating a blood pressure cuff mid calf bilaterally has been very helpful in the assessment of patients for DVT especially because ultrasound is not an accurate way of determining whether or not there is a clot below the knee in all patients. The Lowenstein test has very reproducible results. Briefly, if patients get pain at 40mm/Hg, they almost always have a phlebitis. If they have pain between 40 and 80mm/Hg, they have a 30-40% chance of having phlebitis and if they have no pain above 100mm/hg there is absolutely no chance of them having phlebitis. Unfortunately, this test does not differentiate cellulitis from phlebitis but it is very helpful in ruling out DVT in many patients-especially obese patients who can be difficult to assess.
William H. Fee Jr., M.D. FACP
UPMC Northwest-Chest Medicine Associates
May 7, 2009
Regarding the article, Safely Ruling Out Deep Venous Thrombosis in Primary Care by H.R. Bueller in the most recent Annals of Internal Medicine Volume 150 Pages 229-235, it brought to my mind alternative methods of treatment of acute phlebitis (not associated with cellulitis) and rarely deep vein thrombosis in patients who lack hospitalization insurance or because of concomitant exsanguinating GI bleeding, intracerebral bleeding when anticoagulation is absolutely contraindicated and therefore cannot be treated in the usual standard fashion of subcutaneous heparin, and/or Lovenox associated with Coumadin. For these patients, I have found that injecting a mixture of Depo Medrol 40mg and Sensorcaine 0.5% 8cc subcutaneously under the patient's vein every 5 cm is curative in the treatment of patients with superficial and rarely deep vein thrombosis. This method not only gives quick pain relief secondary to the Sensorcaine 0.5% portion of the injection, but the injectable steroid also eliminates the phlebitis often in 5 to 14 days. Although I have used this treatment predominantly with outpatients, I have also found this technique to be invaluable for inpatients in the hospital setting who have other significant comorbid problems, which make anticoagulation absolutely contraindicated.
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