0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Imaging Characteristics of a Novel Technetium Tc 99m–Labeled Platelet Glycoprotein IIb/IIIa Receptor Antagonist in Patients With Acute Deep Vein Thrombosis or a History of Deep Vein Thrombosis FREE

Shannon M. Bates, MD, CM; John Lister-James, PhD; Jim A. Julian, MMath; Raymond Taillefer, MD; Brian R. Moyer, BSc, MSc; Jeffrey S. Ginsberg, MD
[+] Author Affiliations

From the Departments of Medicine (Drs Bates and Ginsberg) and Clinical Epidemiology and Biostatistics (Mr Julian), McMaster University, Hamilton, Ontario; Berlex Laboratories, Inc, Montville, NJ (Dr Lister-James and Mr Moyer); and Department of Nuclear Medicine, Centre Hospitalier de l'Université de Montréal, Pavillon Hôtel-Dieu, Montreal, Quebec (Dr Taillefer). Drs Bates and Ginsberg have signed consulting agreements with Berlex Laboratories, Inc (which has acquired Diatide, Inc, Londonderry, NH).


Arch Intern Med. 2003;163(4):452-456. doi:10.1001/archinte.163.4.452.
Text Size: A A A
Published online

Background  The diagnosis of recurrent deep vein thrombosis (DVT) is challenging. Imaging with radiolabeled peptides offers a new approach for detecting acute DVT. Technetium Tc 99m (99mTc)–apcitide binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on activated platelets and, therefore, 99mTc-apcitide scintigraphy should be negative with residual abnormalities caused by old, inactive thrombi and positive with new, active thrombi.

Methods  In a prospective multicenter study, 99mTc-apcitide imaging was performed on 38 patients with a newly diagnosed first DVT (group 1) and 40 patients with previous DVT, symptoms of postthrombotic syndrome, and chronic intraluminal abnormalities on ultrasonography (group 2). Images were interpreted in a blinded fashion by 2 experts and by newly trained nuclear medicine physicians. The sensitivity and specificity of 99mTc-apcitide were determined by calculating the proportion of scans in group 1 patients that were read as "positive for acute DVT" and the proportion of scans in group 2 patients that were read as "negative for acute DVT," respectively.

Results  When read by 2 experts, 99mTc-apcitide had a sensitivity of 92% for both readers and specificities of 82% and 90%. Agreement between the experts was excellent. However, the accuracy and interreader agreement for newly trained nuclear medicine physicians were lower.

Conclusions  Technetium Tc 99m–apcitide scintigraphy has potential utility in suspected recurrent DVT because it detects most acute thrombi and has few false-positive results in patients with previous DVT. However, the accuracy appears to depend on the training and experience of the interpreters.

CLINICAL DIAGNOSIS of deep vein thrombosis (DVT) alone is inaccurate.14 Therefore, accurate objective testing is required to avoid incorrectly concluding that DVT is absent and placing the patient at high risk of potentially fatal pulmonary embolism5 or misdiagnosing DVT and exposing the patient unnecessarily to the risks of anticoagulant therapy.57 Although several diagnostic algorithms for suspected first DVT have been validated,8 the diagnosis of recurrent DVT continues to pose a problem. Venous compression ultrasonography (CUS) is the most widely used noninvasive test for the investigation of a suspected first DVT, with noncompressibility of the common femoral vein or popliteal vein considered diagnostic of acute DVT in symptomatic patients.8 However, the diagnosis of recurrent DVT by means of CUS is problematic because persistent abnormalities are present in approximately 80% of patients 3 months and 50% of patients 1 year after proximal DVT.912 Therefore, when a patient with suspected recurrence has a noncompressible venous segment, it can be difficult to determine whether this represents new disease or a residual abnormality from previous DVT. Similarly, persistent abnormalities as well as nonfilling segments in patients with previous DVT often make contrast venography, the reference standard test for a suspected first episode of DVT, nondiagnostic.13 Although the combination of impedance plethysmography14 and radioactive fibrinogen uptake scanning13 has been validated for the diagnosis of recurrence, impedance plethysmography is obsolete and radioactive fibrinogen uptake scanning is no longer available. As a result, there is a clear need for a test (or combination of tests) that is able to accurately diagnose recurrent DVT.

Scintigraphic imaging with radiolabeled peptides offers a promising approach for the detection of recurrent DVT. A technetium Tc 99m (99mTc)–labeled synthetic arginine–glycine–aspartic acid analogue that competes with fibrinogen for binding to the platelet glycoprotein IIb/IIIa receptor, 99mTc-apcitide (AcuTect; Berlex Laboratories, Inc, Wayne, NJ), has recently been developed. As only that receptor present on activated platelets is able to bind the arginine–glycine–aspartic acid tripeptide, 99mTc-apcitide is incorporated into an actively forming thrombus and emits radioactivity, which can be quantitated and localized by a gamma camera, making it suitable for photographic imaging. Consequently, this test should be negative in the presence of residual abnormalities caused by old, inactive thrombi and positive with new, actively forming thrombi. Therefore, the test has the potential to differentiate old from new thrombosis in patients with suspected acute recurrence and to overcome the limitations of CUS and venography. However, neither the specificity nor the sensitivity of this test in patients with symptoms consistent with acute DVT (initial or recurrent) has been well characterized. Moreover, inflammation, edema, and persistent intravascular changes present in patients who have developed postthrombotic syndrome after a previous DVT could alter the image characteristics of 99mTc-apcitide scans and cause false-positive results.

Before embarking on a large, definitive study using this technique, we performed a pilot study to determine whether the test has the potential to be useful in patients with suspected recurrence. The study had 2 objectives: (1) to determine the sensitivity of 99mTc-apcitide scintigraphy by testing patients with a first episode of acute DVT and (2) to estimate the specificity of the test by examining patients with a history of DVT, symptoms of postthrombotic syndrome, no acute DVT, and residual intraluminal abnormalities (by CUS). We reasoned that if the test were sensitive for initial DVT, it should be sensitive for recurrent DVT, since localized platelet activation in a thrombus is common to both and a normal test should rule out recurrent DVT. On the other hand, if there were few false-positive results in patients with previous DVT and intraluminal abnormalities by CUS, the test's specificity would be high and an abnormal result would be diagnostic of recurrence.

Study subjects were enrolled between February 19, 1999, and March 16, 2000, at 8 centers, 2 in Canada and 6 in the United States (a list of participating centers appears at the end of the article). Each center's research ethics board approved the study, and all patients provided informed written consent.

PATIENTS

Two groups of patients were studied: (1) those with a first episode of acute DVT (group 1) and (2) those with previous DVT, symptoms of postthrombotic syndrome but not acute DVT, and persistent intravascular abnormalities on CUS (group 2). In both groups, patients were potentially eligible if they were at least 18 years of age and able and willing to provide informed consent. Eligible consenting patients were enrolled into group 1 if they had a newly diagnosed first acute DVT with symptom onset within 10 days of 99mTc-apcitide imaging, noncompressibility of the common femoral vein and/or the popliteal vein on CUS, and a positive D-dimer test (SimpliRED D-Dimer; AGEN Biomedical Limited, Brisbane, Australia). Patients were enrolled into group 2 if they had previous objectively diagnosed DVT, chronic symptoms typical of postthrombotic syndrome15 but no symptoms of acute DVT, complete or partial noncompressibility of 1 or more proximal deep veins on CUS, and a negative D-dimer test.

Patients were excluded from the study if they had received an investigational drug within 30 days of enrollment, had undergone a nuclear medicine study with 99mTc (except a 99mTc lung ventilation-perfusion study) in the previous 48 hours or with indium In 111 or gallium Ga 67 in the previous 7 days, had previously been injected with 99mTc-apcitide, or had a known or suspected hypersensitivity to any component of the product. Pregnant or lactating women, patients with lower-limb amputation, and those with a medical condition, associated illness, or extenuating circumstances that made it unlikely that the study procedure would be completed were also excluded.

INTERVENTION
Clinical Examination

Patients were considered to have symptoms consistent with acute DVT if they had ongoing pain, swelling, tenderness, warmth, and/or erythema of the leg of recent onset (within the past 10 days). Postthrombotic syndrome was diagnosed in patients with previous objectively diagnosed DVT if they had at least 3 of the following chronic symptoms or signs: (1) spontaneous calf pain, (2) spontaneous thigh pain, (3) calf pain on standing or walking, (4) thigh pain on standing or walking, (4) "heaviness" of the leg, (5) edema of the foot or calf, (6) swelling of the calf, (7) swelling of the ankle, (8) stasis pigmentation, (9) venous dilatation, and (10) venous ulcer.15

Compression Ultrasonography

Lower-limb venous CUS was performed and interpreted as described elsewhere.16 The CUS was considered diagnostic of acute DVT in group 1 patients if there was noncompressibility of the common femoral and/or popliteal vein in the transverse plane. Partial or complete noncompressibility of 1 or more of the proximal deep veins was required to demonstrate chronic intravascular change in group 2 patients.

D-Dimer Testing

The method for the performance of this assay has previously been described in detail.17 Results were categorized as negative or positive on the basis of the absence (negative) or presence (positive) of erythrocyte agglutination. This test is sensitive for acute DVT and is expected to have normal results in individuals without acute DVT.1820 Thus, it was performed to rule out acute DVT in group 2 patients. Although nonspecific and associated with frequent false-positive results, it was performed in group 1 patients to ensure that acute DVT was present, as a normal D-dimer result would suggest that acute DVT was absent.

99mTc-Apcitide Scintigraphy

The 99mTc-apcitide was prepared from single-dose, sterile, nonpyrogenic lyophilized kits (AcuTect) in accordance with the package insert. Each kit was formulated to contain 100 µg of the peptide bibapcitide. To radiolabel the peptide with 99mTc, each kit was reconstituted with 1 to 3 mL of sterile, nonpyrogenic, oxidant-free sodium 99mTc-pertechnetate in isotonic sodium chloride solution. The reconstituted kit was heated in a boiling water bath for 15 minutes and then allowed to cool to provide a solution containing 99mTc-apcitide that was used within 6 hours of preparation. The radiochemical purity of the 99mTc-apcitide solution as determined by means of instant thin-layer chromatography was required to be at least 90%.

Patients received approximately 100 µg of peptide radiolabeled with approximately 20 mCi (740 MRq) of 99mTc via an intravenous injection in the arm. Focal planar imaging was conducted by means of gamma cameras with a large field of view and fitted with low-energy, high-resolution parallel-hold collimators 10 minutes and again 60 to 90 minutes after the injection. Images were acquired for a minimum of 750 000 counts over the pelvis and 500 000 counts over the thighs, knees, and calves. Vital signs and local and systemic tolerance to the injection were assessed at 10, 30, and 90 minutes after injection. A follow-up evaluation of adverse events was also conducted by telephone 24 hours after injection.

The scintigraphic images were interpreted in a blinded fashion (ie, without knowledge of group 1 or 2 status) by readers who were not involved with the patients. Image interpretation was conducted by means of digital images, allowing the readers the opportunity to adjust image brightness, contrast, and threshold, and to use color. Uptake of 99mTc-apcitide in the location of a deep vein segment that is greater than that observed in the corresponding contralateral deep vein segment or in contiguous segments of the ipsilateral vein and that persists or intensifies with time is considered diagnostic of acute DVT. Abnormal localization in collateral vessels, superficial veins, postsurgical sites, and nonvascular locations is not considered indicative of acute DVT.

Four separate groups of readers interpreted the images: (1) 2 independent experts with considerable experience in interpreting the tests, (2) 2 independent groups in which 3 nuclear medicine physicians evaluated the images independently and then used a majority interpretation (majority 1 and majority 2), and (3) a fourth group of 3 nuclear medicine physicians who interpreted and discussed the scans together to reach a consensus (consensus 1). All nuclear medicine physicians received standardized training in the interpretation of 99mTc-apcitide images. The second majority-read group was assembled because of the relatively poor results of the first group.

ANALYSIS AND STATISTICS

The primary requirement for this pilot study was a sample size sufficiently large to provide reasonable estimates of the sensitivity and specificity of 99mTc-apcitide imaging. A sample size of 40 patients in each of groups 1 and 2 was chosen because, with this sample size and an expected sensitivity of greater than 85%, the 95% confidence intervals on the point estimates would have a bandwidth of approximately ±10%, ensuring that the point estimate was sufficiently accurate to make decisions about the appropriateness and safety of a definitive management study.

A diagnosis (positive for acute DVT, negative for acute DVT, or nondiagnostic) for each leg of interest based on an aggregate reading of the 10- and 60- to 90-minute 99mTc-apcitide images was made by each of the 4 panels described above. For each read, the sensitivity of 99mTc-apcitide was determined by calculating the proportion of scans that were read as "positive for acute DVT" in group 1 patients, and the specificity was determined by calculating the proportion of scans that were read as "negative for acute DVT" in group 2 patients. The corresponding exact 95% confidence interval for each of the point estimates was calculated. In addition to these estimates, sensitivity and specificity estimates with corresponding 95% confidence intervals were calculated for the initial independent assessment of each reader participating in a majority read. The κ values with 95% confidence intervals were also calculated for each of the 3 reader pairings in each majority read.21

Eighty-one patients (41 in group 1 and 40 in group 2) met the eligibility criteria and received at least 1 dose of 99mTc-apcitide. Two patients were unable to complete imaging and 1 patient's scans were uninterpretable, leaving 78 patients for final analysis (38 in group 1 and 40 in group 2). Three of the 40 group 2 patients had bilateral symptoms of postthrombotic syndrome and chronic intravascular changes on ultrasonography. Therefore, a total of 43 legs were available for evaluation in this group.

BASELINE CHARACTERISTICS

The mean age of the study patients was 63.1 years, with a range of 21 to 94 years; 45 (56%) were male.

SENSITIVITY AND SPECIFICITY OF 99mTc-APCITIDE SCINTIGRAPHY

The results of the 4 reads are summarized in Table 1. The sensitivities and specificities achieved by the experienced expert readers were high. The κ score for these 2 readers was 0.87, indicating excellent agreement (Table 2). There was agreement in the interpretation of 38 (100%) of 38 scans in group 1 patients and 35 (88%) of 40 scans in group 2 patients. The sensitivities and specificities obtained by the majority and consensus readers, both individually and as groups, were lower than those of the expert readers. The interreader agreement, as determined by κ values, ranged from poor to good (Table 2).

Table Graphic Jump LocationTable 1. Sensitivity and Specificity of Technetium Tc 99m Apcitide Scintigraphy

The scans of 3 patients in group 1 were read as negative for acute DVT by either all or all but 1 of the readers. We explored possible reasons for these false-negative scans (Table 3) but could find no consistent explanation. One group 2 scan was read as positive by all but 1 reader. Again, no obvious explanation was evident (eg, inflammation of the knee or hip, infection, or recent surgery or trauma to the leg).

Table Graphic Jump LocationTable 3. Clinical Variables in Patients With False-Negative Results

No serious adverse events were reported during the study.

Despite advances in the diagnosis of DVT, the diagnosis of patients who present with suspected recurrent DVT remains a substantial problem. These difficulties primarily result from the high frequency of residual abnormalities in 2 of the most commonly used tests, CUS912 and contrast venography.13 These persistent abnormalities make differentiation of old and new DVT difficult. There is a clear need for a test that is able to accurately diagnose acute recurrence. Scintigraphic imaging with radiolabeled peptides that are incorporated into an actively forming thrombus offers a new approach for the detection of acute DVT. One of these peptides, 99mTc-apcitide, binds with high affinity and specificity to the glycoprotein IIb/IIIa receptors expressed on activated platelets and, therefore, should give normal results in the presence of residual abnormalities caused by old, inactive thrombi and abnormal results with new, actively forming thrombi.22

The results of this study show that, when the test is interpreted by experienced experts, the accuracy of 99mTc-apcitide scintigraphy is sufficiently high to be potentially useful in the exclusion of initial and recurrent DVT. For example, in a referral population with a prevalence of DVT of 20%, if the true sensitivity of 99mTc-apcitide scintigraphy is approximately 90% and the specificity is 85% to 90%, a scan with normal results would have a negative predictive value of approximately 98%. This negative predictive value is similar to that of ascending venography23 and serial CUS,24,25 2 widely accepted diagnostic strategies for DVT. This suggests that this technique has the potential to be used alone to exclude DVT in patient populations with a prevalence of DVT of 20% or less, for example, in patients with a low pretest probability of DVT. In addition, if the true specificity of this test is as high as 90%, the positive predictive value of this assay would be 90% in a subgroup of patients with a prevalence of DVT of 50% or greater (for example, those with a high pretest probability of DVT). This positive predictive value is similar to that of a high-probability ventilation-perfusion lung scan26 and is sufficiently high to justify anticoagulant therapy.

When newly trained nuclear medicine physicians interpret 99mTc-apcitide scintigraphy, the sensitivity and specificity of this test appear to be lower than those seen with experienced experts. This finding suggests that this technique, as currently performed, requires considerable experience to interpret accurately. Improved reading criteria or modifications in technique may alleviate this problem. The latter might include imaging at a later time point27 so as to permit further clearance of radiotracer from the veins, thereby enhancing image resolution.

This assay was not assessed in a consecutive series of patients with suspected DVT, but rather, to optimize efficiency, the patients entered into this study included a group with known acute DVT and a group with postthrombotic syndrome and no acute DVT. The patients included in our study were meant to simulate those with suspected recurrent DVT. The extent of thrombosis in group 1 patients varied from isolated popliteal DVT to that extending from the common femoral vein through the trifurcation vessels and did not appear to be skewed toward more extensive thrombosis. As well, the patients in group 2 all had intravascular abnormalities and represent patients with suspected recurrence in whom there is the greatest difficulty in diagnosing or excluding acute recurrent DVT.

Patients who present with suspected recurrent DVT continue to be challenging. The clinician is often left guessing as to whether such patients have new DVT because of the lack of a true reference standard test. This pilot study demonstrates that 99mTc-apcitide scintigraphy has potential utility in this patient population. However, before management studies using 99mTc-apcitide scintigraphy are undertaken, larger patient numbers to obtain more reliable estimates of sensitivity and specificity are required, as well as more experience with the performance and interpretation of this technique.

Corresponding author and reprints: Shannon M. Bates, MD, CM, Thromboembolism Unit Office, HSC 3W11, McMaster University Medical Centre, 1200 Main St W, Hamilton, Ontario, Canada L8N 3Z5 (e-mail: batesm@mcmaster.ca).

Accepted for publication June 14, 2002.

This study was funded by an unrestricted grant from Diatide, Inc, Londonderry, NH (now Diatide Research Laboratories, a division of Berlex Laboratories, Inc). Dr Bates is a recipient of a New Investigator Award from the Canadian Institutes of Health Research University/Industry (bioMérieux, Inc, Durham, NC) Program, Toronto, Ontario. Dr Ginsberg is a recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario, Toronto, and a recipient of a Research Chair from the Canadian Institutes of Health Research, Ottawa, Ontario.

The funding source had no role in the analysis or interpretation of the data or in the decision to publish the manuscript. Drs Bates and Ginsberg had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.

Hamilton Health Sciences Corporation, Hamilton, Ontario (Shannon M. Bates, MD, CM, Jeffrey S. Ginsberg, MD, and Geoffrey Coates, MD); Centre Hospitalier Université de Montréal, Hôpital Hôtel-Dieu, Montréal, Québec (Raymond Taillefer, MD); Bay Pines Veterans Affairs Medical Center, Bay Pines, Fla (Steven J. Harwood, MD); Sutter Roseville Medical Center, Roseville, Calif (Frederick Weiland, MD); University of Arizona Medical Center, Tucson (Joseph Alpert, MD); Metro West Medical Center, Natick, Mass (Arnold Miller, MD); Brooke Army Medical Center, San Antonio, Tex (Robert S. Bridwell, MD); and Henry Ford Health System Cardiac Wellness Center, Detroit, Mich (Paul Stein, MD).

Haeger  K Problems of acute deep venous thrombosis, I: the interpretation of signs and symptoms. Angiology. 1969;20219- 223
Link to Article
Cranley  JJCanos  AJSull  WJ The diagnosis of deep venous thrombosis: the fallibility of clinical symptoms and signs. Arch Surg. 1976;11134- 35
Link to Article
Anand  SSWells  PSHunt  DBrill-Edwards  PCook  DGinsberg  JS Does this patient have deep vein thrombosis? JAMA. 1998;2791094- 1099[published corrections appear in JAMA. 1998;279:1614 and JAMA. 1998;280:328].
Link to Article
Barnes  RWWu  KKHoak  JC The fallibility of the clinical diagnosis of venous thrombosis. JAMA. 1975;234605- 607
Link to Article
Ginsberg  JS Management of venous thromboembolism. N Engl J Med. 1996;3351816- 1828
Link to Article
Mant  MJO'Brien  BDThrong  KLHammond  GWBirtwhistle  RVGrace  MG Haemorrhagic complications of heparin therapy. Lancet. 1977;11133- 1135
Link to Article
Palareti  GLeali  NCoccheri  S  et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT): Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348423- 428
Link to Article
Kearon  CJulian  JANewman  TEGinsberg  JSfor the McMaster Diagnostic Imaging Practice Guidelines Initiative, Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med. 1998;128663- 677
Link to Article
Heijboer  HJongbloets  MMBuller  HRLensing  AWAten Cate  JW Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis. Acta Radiol. 1992;33297- 300
Link to Article
Cronan  JJLeen  V Recurrent deep venous thrombosis: limitations of US. Radiology. 1989;170 ((3, pt 1)) 739- 742
Mantoni  M Deep venous thrombosis: longitudinal study with duplex US. Radiology. 1991;179271- 273
Prandoni  PCogo  ABernardi  E  et al.  A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation. 1993;88 ((4, pt 1)) 1730- 1735
Link to Article
Hull  RDCarter  CJJay  RM  et al.  The diagnosis of acute, recurrent deep-vein thrombosis: a diagnostic challenge. Circulation. 1983;67901- 906
Link to Article
Huisman  MVBuller  HRten Cate  JW Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis. Arch Intern Med. 1988;148681- 683
Link to Article
Brandjes  DPMBuller  HRHeijboer  H  et al.  Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349759- 762
Link to Article
Lensing  AWPrandoni  PBrandjes  DP  et al.  Detection of deep vein thrombosis by real-time B-mode ultrasonography. N Engl J Med. 1989;328342- 345
Link to Article
John  MAElms  MJO'Reilly  EKRylatt  DBBundesen  PGHillyard  CJ The SimpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood. Thromb Res. 1990;58273- 281
Link to Article
Wells  PSBrill-Edwards  PStevens  P  et al.  A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Circulation. 1995;912184- 2187
Link to Article
Ginsberg  JSKearon  CDouketis  J  et al.  The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Arch Intern Med. 1997;1571077- 1081
Link to Article
Kearon  CGinsberg  JSDouketis  J  et al.  Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing. Ann Intern Med. 2001;135108- 111
Link to Article
Fleiss  JL Statistical Methods for Rates and Proportions. 2nd ed. New York, NY John Wiley & Sons Inc1981;211- 234
Taillefer  RTheresse  ETurpin  SLambert  RRobillard  PSoulez  G Comparison of early and delayed scintigraphy with 99mTc-apcitide and correlation with contrast-enhanced venography in detection of acute deep vein thrombosis. J Nucl Med. 1999;402029- 2035
Hull  RHirsh  JSackett  DL  et al.  Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. Circulation. 1981;64622- 625
Link to Article
Heijboer  HBuller  HRLensing  AWTurpie  AGColly  LPten Cate  JW A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med. 1992;3291365- 1369
Link to Article
Cogo  ALensing  AWKoopman  MMW  et al.  Compression ultrasound for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;31617- 20
Link to Article
PIOPED Investigators, Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;2632753- 2759
Link to Article
Taillefer  REdell  SInnes  GLister-James  Jand the Multicenter Trial Investigators, Acute thromboscintigraphy with 99mTc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. J Nucl Med. 2000;411214- 1223

Figures

Tables

Table Graphic Jump LocationTable 1. Sensitivity and Specificity of Technetium Tc 99m Apcitide Scintigraphy
Table Graphic Jump LocationTable 3. Clinical Variables in Patients With False-Negative Results

References

Haeger  K Problems of acute deep venous thrombosis, I: the interpretation of signs and symptoms. Angiology. 1969;20219- 223
Link to Article
Cranley  JJCanos  AJSull  WJ The diagnosis of deep venous thrombosis: the fallibility of clinical symptoms and signs. Arch Surg. 1976;11134- 35
Link to Article
Anand  SSWells  PSHunt  DBrill-Edwards  PCook  DGinsberg  JS Does this patient have deep vein thrombosis? JAMA. 1998;2791094- 1099[published corrections appear in JAMA. 1998;279:1614 and JAMA. 1998;280:328].
Link to Article
Barnes  RWWu  KKHoak  JC The fallibility of the clinical diagnosis of venous thrombosis. JAMA. 1975;234605- 607
Link to Article
Ginsberg  JS Management of venous thromboembolism. N Engl J Med. 1996;3351816- 1828
Link to Article
Mant  MJO'Brien  BDThrong  KLHammond  GWBirtwhistle  RVGrace  MG Haemorrhagic complications of heparin therapy. Lancet. 1977;11133- 1135
Link to Article
Palareti  GLeali  NCoccheri  S  et al.  Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT): Italian Study on Complications of Oral Anticoagulant Therapy. Lancet. 1996;348423- 428
Link to Article
Kearon  CJulian  JANewman  TEGinsberg  JSfor the McMaster Diagnostic Imaging Practice Guidelines Initiative, Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med. 1998;128663- 677
Link to Article
Heijboer  HJongbloets  MMBuller  HRLensing  AWAten Cate  JW Clinical utility of real-time compression ultrasonography for diagnostic management of patients with recurrent venous thrombosis. Acta Radiol. 1992;33297- 300
Link to Article
Cronan  JJLeen  V Recurrent deep venous thrombosis: limitations of US. Radiology. 1989;170 ((3, pt 1)) 739- 742
Mantoni  M Deep venous thrombosis: longitudinal study with duplex US. Radiology. 1991;179271- 273
Prandoni  PCogo  ABernardi  E  et al.  A simple ultrasound approach for detection of recurrent proximal-vein thrombosis. Circulation. 1993;88 ((4, pt 1)) 1730- 1735
Link to Article
Hull  RDCarter  CJJay  RM  et al.  The diagnosis of acute, recurrent deep-vein thrombosis: a diagnostic challenge. Circulation. 1983;67901- 906
Link to Article
Huisman  MVBuller  HRten Cate  JW Utility of impedance plethysmography in the diagnosis of recurrent deep-vein thrombosis. Arch Intern Med. 1988;148681- 683
Link to Article
Brandjes  DPMBuller  HRHeijboer  H  et al.  Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis. Lancet. 1997;349759- 762
Link to Article
Lensing  AWPrandoni  PBrandjes  DP  et al.  Detection of deep vein thrombosis by real-time B-mode ultrasonography. N Engl J Med. 1989;328342- 345
Link to Article
John  MAElms  MJO'Reilly  EKRylatt  DBBundesen  PGHillyard  CJ The SimpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood. Thromb Res. 1990;58273- 281
Link to Article
Wells  PSBrill-Edwards  PStevens  P  et al.  A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Circulation. 1995;912184- 2187
Link to Article
Ginsberg  JSKearon  CDouketis  J  et al.  The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis. Arch Intern Med. 1997;1571077- 1081
Link to Article
Kearon  CGinsberg  JSDouketis  J  et al.  Management of suspected deep venous thrombosis in outpatients by using clinical assessment and D-dimer testing. Ann Intern Med. 2001;135108- 111
Link to Article
Fleiss  JL Statistical Methods for Rates and Proportions. 2nd ed. New York, NY John Wiley & Sons Inc1981;211- 234
Taillefer  RTheresse  ETurpin  SLambert  RRobillard  PSoulez  G Comparison of early and delayed scintigraphy with 99mTc-apcitide and correlation with contrast-enhanced venography in detection of acute deep vein thrombosis. J Nucl Med. 1999;402029- 2035
Hull  RHirsh  JSackett  DL  et al.  Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. Circulation. 1981;64622- 625
Link to Article
Heijboer  HBuller  HRLensing  AWTurpie  AGColly  LPten Cate  JW A comparison of real-time compression ultrasonography with impedance plethysmography for the diagnosis of deep-vein thrombosis in symptomatic outpatients. N Engl J Med. 1992;3291365- 1369
Link to Article
Cogo  ALensing  AWKoopman  MMW  et al.  Compression ultrasound for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;31617- 20
Link to Article
PIOPED Investigators, Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the prospective investigation of pulmonary embolism diagnosis (PIOPED). JAMA. 1990;2632753- 2759
Link to Article
Taillefer  REdell  SInnes  GLister-James  Jand the Multicenter Trial Investigators, Acute thromboscintigraphy with 99mTc-apcitide: results of the phase 3 multicenter clinical trial comparing 99mTc-apcitide scintigraphy with contrast venography for imaging acute DVT. J Nucl Med. 2000;411214- 1223

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 36

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

Users' Guides to the Medical Literature
Deep Venous Thrombosis

Users' Guides to the Medical Literature
Scenario 2