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 ......
Review Article |

Plasma D-Dimers in the Diagnosis of Venous Thromboembolism FREE

James Kelly, BSC, MRCP; Anthony Rudd, FRCP; Roger R. Lewis, MD, FRCP; Beverley J. Hunt, MD, FRCP, FRCPath
[+] Author Affiliations

From the Specialist Registrar in Elderly Care and GIM (Dr Kelly); Consultant in Elderly Care and Stroke Medicine (Dr Rudd); Consultant in Elderly Care, General Internal Medicine, and Stroke Medicine (Dr Lewis); and Consultant Haematologist (Dr Hunt), St Thomas' Hospital, London, England.


Arch Intern Med. 2002;162(7):747-756. doi:10.1001/archinte.162.7.747.
Text Size: A A A
Published online

Clinical suspicion for venous thromboembolism (VTE) mandates objective testing to confirm or exclude the diagnosis. However, current imaging modalities are imperfect because of a small but important risk of complications with invasive techniques or limited sensitivity with noninvasive ones. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. Plasma D-dimers (D-ds), specific cross-linked fibrin derivatives, partially fulfill these criteria in that they are sensitive markers for thrombosis but lack specificity. They therefore cannot be used to make a positive diagnosis of VTE; however, they generally have high negative predictive value and are useful as an exclusionary test, a potentially important role given that VTE is eventually ruled out in most patients investigated. Clinical management studies are clarifying the role of D-ds in the diagnostic paradigm of VTE: negative ultrasound and D-d findings obviate the need for serial imaging in suspected deep vein thrombosis, and anticoagulant therapy can be safely withheld in patients with non–high clinical suspicion for pulmonary embolism and non–high probability ventilation perfusion scan if D-d test results are negative. More recently, the combination of a negative SimpliRED (AGEN Biomedical Ltd, Brisbane, Australia) D-d result and low clinical suspicion derived using a formal scoring system has been shown to exclude deep vein thrombosis and pulmonary embolism and to obviate the need for imaging. Several different D-d assays are now available, and clinicians should be aware of the performance characteristics of the test used before incorporation into diagnostic algorithms as these will differ between assays, and the results of clinical management studies cannot necessarily be safely extrapolated to assays other than those specifically evaluated. If alternative assays are to be substituted, these should consistently have been shown to possess equivalent or greater sensitivity.

The incidence of venous thromboembolism (VTE) rises progressively with age,1,2 with a cumulative event rate greater than 10% by age 80 years,2 and is associated with substantial morbidity and mortality in the absence of treatment.3,4 The clinical signs and symptoms are not sufficiently specific to establish or exclude the diagnosis,5 and objective testing is required in the presence of clinical suspicion to aid management decisions,6 although all imaging techniques currently used have clinical or practical limitations.

Contrast venography (CV) and pulmonary angiography remain the gold standard diagnostic tests for deep vein thrombosis (DVT) and pulmonary embolism (PE), respectively, but they are invasive and are associated with a small but significant risk of complications.7 These tests are therefore no longer widely used as first-line investigations. Noninvasive diagnostic strategies have been developed, usually using ultrasound, the most accurate noninvasive test for suspected DVT,8 and ventilation-perfusion (VQ) scanning for suspected PE. However, VTE can only be diagnosed or excluded with reasonable confidence using a 1-step process in a few patients. Three fourths or more of the patients with suspected DVT have negative ultrasound findings8,9 and require repeated imaging to identify the further 2% to 6% in whom occlusive proximal DVT becomes apparent in a week.8,10 In addition, 70% of patients with suspected PE have a nondiagnostic VQ scan11 (low or intermediate probability) and require further imaging using either pulmonary angiography or serial noninvasive imaging with ultrasonography to identify residual proximal DVT, a valid approach in patients with adequate cardiopulmonary reserve.1214

Given these shortcomings, a simple but reliable noninvasive test for VTE is highly desirable and should ideally have a sensitivity and negative predictive value of 100% as the consequences of nondiagnosis are potentially life threatening.3,4 Plasma D-dimers (D-ds) have proved to be the most useful blood markers of intravascular fibrinolysis15 and are of interest as an adjunctive exclusionary test in suspected VTE, potentially increasing the number of patients who can be satisfactorily treated without recourse to a second level of investigation.16 We review D-ds in relation to VTE and their incorporation into diagnostic strategies.

Plasma D-ds are generated when the endogenous fibrinolytic system degrades fibrin, as in VTE, and they consist of 2 identical subunits derived from 2 fibrin molecules. Unlike fibrinogen degradation products, which are derived from fibrinogen and fibrin, D-ds are a specific cross-linked fibrin derivative.17,18 Because 2% to 3% of plasma fibrinogen is degraded to fibrin, small amounts are detectable in the plasma of healthy individuals. The half-life is approximately 8 hours, with plasma clearance via urinary excretion and the action of the reticuloendothelial system.19

D-dimer levels are increased by any condition in which fibrin is formed and degraded by plasmin19 and are the best currently available laboratory marker of activation of coagulation.20 D-dimer levels are elevated approximately 8-fold after VTE compared with controls, with levels falling to approximately one quarter of the initial value between weeks 1 and 221; they are significantly higher in patients with extensive proximal DVT than in those with below-the-knee DVT,22 with peak levels corresponding to the extent of thrombosis.23 D-dimer levels may be particularly useful in the diagnosis of recurrent DVT, a subgroup in which conventional imaging has important shortfalls.18 Using direct thrombus magnetic resonance imaging (MRI), Fraser et al24 recently showed that D-d levels correlate with clot volume and surface area. Clot surface area seemed to be the more important determinant, supporting the concept that D-d generation, release, or both occur primarily at the surface of the thrombus.

After a thrombotic event, D-d levels may normalize within 15 to 20 days20,23 and are probably most useful for diagnosis within 11 days of symptom onset.21 Although initiation of heparin calcium therapy causes a sharp decline in levels, absolute values remain increased compared with those of controls, and the test remains useful in patients awaiting investigation in whom treatment has already been started.20,25,26

Levels of D-ds are rarely elevated in healthy individuals22 but may be increased in any condition involving the formation and degradation of fibrin, such as infections, cancer, surgery, cardiac or renal failure, acute coronary syndromes, acute nonlacunar stroke, pregnancy, and sickle cell crises.19,2730 Furthermore, many of these conditions are also risk factors for VTE and may have initial symptoms or signs similar to PE.29 D-dimer levels are therefore less likely to be useful in patients with suspected VTE and 1 or more of these diagnoses because, for example, increased values occur in 80% to 90% of those with infections or malignancy.31

Measurement of D-d levels has been enabled by the development of monoclonal antibodies that bind to epitopes on D-d fragments that are absent on fibrin, fibrinogen, and non–cross-linked fragments of fibrin, with detection of resulting complexes by enzyme-linked immunosorbent assay (ELISA) or agglutination techniques.29,32,33 The classic microplate ELISA technique is considered the gold standard,34 but it is not useful as a routine emergency test as it is suitable for batch analysis and is labor intensive. However, the recently developed VIDAS test (bioMérieux SA, Marcy-Étoile, France), which combines the ELISA method with a final detection in fluorescence,35 is fully automated and provides a result within 35 minutes and can therefore be used for single-sample testing.36 Two immunofiltration (membrane ELISA) techniques have also been introduced that have sensitivities similar to those of conventional ELISAs but higher specificities: the Instant IA D-d assay (Diagnostica Stago, Inc, Parsippany, NJ) gives a result in less than 8 minutes but is performed manually and is qualitative (positive or negative),37 and the NycoCard D-d assay (Nycomed Pharma AS, Asker, Norway) is semiquantitative and provides a result in less than 2 minutes.37,38

Other techniques involve agglutination of latex beads or red blood cells and give a qualitative or semiquantitative result within a few minutes. For example, the SimpliRED test (AGEN Biomedical Ltd, Brisbane, Australia) is a red blood cell agglutination assay designed for use with fresh capillary or venous whole blood. It provides a result in less than 5 minutes and is therefore suitable for near-patient testing.39 More recently, immunoturbidimetric techniques have been developed that allow a quantitative estimation and represent a second generation in latex agglutination technology (eg, TinaQuant assay [Roche Diagnostics, F. Hoffmann-La Roche Ltd, Basel, Switzerland], Liatest assay [Diagnostica Stago, Inc], and MDA D-d [Organon Teknika B.V., Boxtel, the Netherlands]). Immunofiltration and immunoturbidimetric techniques may therefore combine the advantageous properties of the ELISA with the speed and simplicity of the latex tests. The properties of the main D-d detection techniques are given in Table 1.

Table Graphic Jump LocationTable 1. Characteristics of the Different Classes of D-Dimer Detection Techniques*

Pooled data from 20 studies of more than 2000 outpatients with clinically suspected VTE using 3 different classic microplate ELISA assays (Dimertest [American Diagnostica Inc, Greenwich, Conn], Asserachrom Ddi [Diagnostica Stago, Inc], and Fibrinostika FbDP [Organon Teknika B.V.]) have shown a diagnostic sensitivity of 97% at a cutoff value of 500 ng/mL,40 with false-negatives presumably explained on the basis of a small thrombus mass (sensitivity may be lower in patients with isolated below-the-knee DVT22,41), a long time lag between thrombus formation and D-d testing,20 and, possibly, an impaired pathophysiological fibrinolytic response in the occasional patient.42 Specificity in these studies was approximately 35% to 45%, and D-d levels are currently regarded as useful only as exclusionary tests for VTE and are less useful in inpatient populations because of lower specificity consequent on comorbidity.31 More recent data21,3638,40,41,4353 also show high sensitivities for the 3 novel rapid ELISA-based assays; indeed, several studies36,41,4346 evaluating the VIDAS assay have reported a sensitivity of 100%.

Whereas conventional latex agglutination assays are not regarded as sufficiently sensitive to be of clinical value,40,54,55 second-generation kits using either whole blood agglutination (SimpliRED) or immunoturbidimetric techniques (eg, TinaQuant, Liatest, and MDA D-d) have emerged with higher sensitivities and are clinically useful.41,5561

Van der Graaf et al41 recently assessed the diagnostic performance of 10 novel rapid tests based on ELISA or latex agglutination technology and 3 conventional ELISAs in 99 outpatients with suspected DVT who underwent CV (Table 2). Correlation between different assays is poor,20,54 and it is not currently possible to standardize D-d results from different assays, making it difficult to extrapolate results from one setting to another. Also, important interobserver variation may occur with semiquantitative tests.36 Studies58,62,63 have also shown that combining an additional variable, such as a clinical probability assessment, respiratory rate, arterial blood gas estimation, or measurement of alveolar dead space, augments the negative predictive value of a normal D-d value. For example, in a study62 of patients undergoing evaluation for suspected PE, the combination of a negative SimpliRED assay result and a PaO2 greater than 10.7 kPa had a negative predictive value of 100%.

Table Graphic Jump LocationTable 2. Performance Characteristics of 13 D-Dimer (D-d) Assays in Suspected Deep Vein Thrombosis*

The VIDAS and SimpliRED assays are the most extensively studied and widely used in the diagnosis of VTE. Pooled data indicate that although the VIDAS assay is the more sensitive of the two (90%-100% [generally 98%-100%]), specificity (5%-55% [generally, 40%]) is relatively poor so that a normal result has high negative predictive value but occurs in a small proportion of patients, limiting its diagnostic utility (only data from studies using a threshold of 500 ng/mL were included).36,41,4353 By contrast, the SimpliRED assay is somewhat less sensitive (61%-100% [generally, 85%]) but more specific (20%-94% [generally, 70%]) so that the negative predictive value is lower but the test is likely to be diagnostically useful in a greater proportion of patients.41,43,56,59,60,6471 The utility of these two tests in clinical management studies are reviewed herein. Note that specificity of assays vary depending on the population studied and will be highest in outpatient populations with a low prevalence of comorbidity.

D-dimer levels increase linearly with age, particularly in the presence of coexisting functional impairment,72 because of a combination of factors, including reduced renal clearance, increased levels of plasma fibrinogen, and the presence of occult disease.19,73 In one study19 of healthy individuals, average levels in the highest age quartile (71-90 years) were approximately 4 times greater than those in the lowest quartile (11-30 years), hence specificity and therefore diagnostic utility for VTE is lower in older patients (Table 347,74,75), although a negative result retains the same clinical value as in younger patients.47,72,74,75 In one study53 evaluating the optimal discriminatory threshold of the VIDAS assay in elderly inpatients (average age, 86 years) with suspected DVT, specificity improved at a cutoff value of 750 ng/mL compared with 500 ng/mL without a decrease in sensitivity, but it was still poor at only 20%.

Table Graphic Jump LocationTable 3. Performance Characteristics of the Asserachrom Ddi ELISA (Diagnostica Stago, Inc, Parsippany, NJ) in Different Age Strata at a Cutoff Value of 500 ng/mL in 671 Outpatients Investigated for Suspected Pulmonary Embolism*

The positive predictive value for VTE rises as D-d levels increase progressively above the diagnostic threshold,76 and in a study74 evaluating 671 outpatients with suspected PE, the specificity of D-d (Asserachrom Ddi ELISA) was 93% when levels exceeded 4000 ng/mL. This raises the possibility that, depending on the pretest probability, in certain situations a high D-d level might be sufficient grounds to initiate treatment.74,77 However, this issue requires further study and, in the absence of further data, D-d levels should be used in an exclusionary capacity only at this stage.

Data demonstrating the high sensitivity of certain D-d assays for the diagnosis of symptomatic VTE under the optimal conditions of performance studies suggest a putative role as an exclusionary test. However, outcome studies demonstrating that treatment can be safely withheld in suspected VTE using diagnostic approaches incorporating D-d assays under routine conditions are required, as similar performance cannot be assumed in the less predictable domain of clinical practice, and even a small margin of error may not be acceptable with a potentially lethal disease.78 For example, previous studies have demonstrated that outcome is excellent when treatment is withheld in suspected DVT on the basis of negative CV79 or serial ultrasound8 findings and in suspected PE with negative pulmonary angiographic findings80 or normal VQ scintigraphy results.81 Without similar data, routine clinical use of D-d assays would be premature and could not be recommended.77

Several management studies have now evaluated D-ds in diagnostic algorithms for VTE incorporating noninvasive imaging55 and/or information from an a priori clinical probability assessment, the complimentary role of which in diagnosis has been previously demonstrated.8285 Bernardi et al86 investigated 946 outpatients with suspected DVT. Treatment was withheld in patients with negative initial ultrasound findings and normal D-d levels (Instant IA ELISA: <500 ng/mL regarded as normal) and the risk of VTE was less than 0.2% at 3 months in this subgroup. D-dimer results were negative in almost 90% of patients with negative initial ultrasound findings so that management decisions could be made in most patients the day of presentation. In a similar study, Kraaijenhagen et al87 also found that the combination of negative initial ultrasound findings and normal D-d levels (SimpliRED assay) in 552 outpatients with suspected DVT was associated with a risk of clinically apparent VTE of only 0.4% at 3 months in the absence of treatment. The results of these 2 studies show that serial testing is obviated in the presence of normal D-d levels, and a recent decision analysis model has shown that this strategy is likely to be cost-effective.88

In a study by de Groot et al59 evaluating 245 patients for suspected PE, anticoagulant therapy was withheld in the presence of a nondiagnostic VQ scan, non–high clinical probability, and negative SimpliRED test results. Only 1 patient (1.5%) in this subgroup experienced a possible VTE event at 3-month follow-up, an incidence similar to that in those with normal VQ scan findings, suggesting that this approach was safe. Similarly, Perrier et al89 evaluated a diagnostic protocol for PE in 308 patients combining clinical probability, D-d assay (Asserachrom Ddi ELISA), and ultrasonography in patients with nondiagnostic VQ scans, with pulmonary angiography reserved for cases in which the noninvasive workup was inconclusive. Treatment was withheld in 53 patients with nondiagnostic VQ scans and intermediate clinical probability of PE in whom D-d levels were less than 500 ng/mL, none of whom developed VTE during the following 6 months. An additional 363 patients were subsequently recruited, including another 74 with an intermediate clinical probability of PE, nondiagnostic VQ scans, and negative D-d test results. Again, no cases of VTE occurred in this subgroup during another 3 months of follow-up.74

Three trials have assessed the safety of obviating imaging in patients with suspected VTE on the basis of D-d level alone or in combination with a clinical probability assessment. Perrier et al90 evaluated a noninvasive diagnostic algorithm in 918 patients with suspected DVT or PE using D-d estimation (VIDAS assay) as the first step. Levels were less than 500 ng/mL in 159 patients (36%) with suspected PE. These patients were not investigated further, irrespective of clinical suspicion, and none developed VTE during the next 3 months. Patients with elevated D-d levels underwent VQ scanning or ultrasonography, whereas those with suspected DVT underwent US irrespective of D-d levels. By incorporating a clinical probability assessment, noninvasive diagnosis was possible in 94% of the entire cohort, and the risk of VTE at 3 months in those not given anticoagulants using this algorithm was 1.8%; only 2 of the 12 patients in this subgroup had normal D-d levels at presentation.

Kearon et al91 evaluated 445 outpatients with a suspected first episode of DVT who underwent a standardized assessment of clinical probability (Table 483) and D-d assay (SimpliRED); 40% had a low clinical probability for DVT and negative D-d findings, and this subgroup was not investigated further. This strategy was safe, with only 1 of 177 patients developing VTE during the subsequent 3 months, giving a negative predictive value for this combination of 99.4%. Finally, Wells et al92 evaluated a predominantly noninvasive diagnostic strategy in 930 outpatients with suspected PE in which the initial step comprised a standard assessment of pretest clinical probability93 (Table 5) and D-d assay (SimpliRED), as in the previous study. Those with low suspicion and negative D-d findings did not undergo further investigation, with all other patients undergoing VQ scanning. If the VQ scan was nondiagnostic, bilateral, lower-limb ultrasonography was performed, with further testing guided by the results of the clinical assessment, D-d assay, and VQ. Forty-seven percent of the entire group were considered not to have PE on the basis of low suspicion and negative D-d findings, and only 1 of these 437 patients developed VTE during the next 3 months, giving a negative predictive value of 99.5% for this combination. The overall frequency of VTE during follow-up in the cohort in whom PE was thought to have been initially excluded and in whom the protocol was followed correctly was 0.1%, and pulmonary angiography was required in only 1% of the total.

Table Graphic Jump LocationTable 4. Clinical Probability Score Used in Patients With Suspected Deep Vein Thrombosis*
Table Graphic Jump LocationTable 5. Clinical Probability Score Used in Patients With Suspected PE*

These studies provide an evidence base for the use of D-d tests in noninvasive diagnostic algorithms for suspected VTE. In particular, the studies of Kearon et al91 and Wells et al92 demonstrate that imaging can safely be obviated in up to half of patients with suspected VTE using a formal clinical probability assessment in combination with a SimpliRED D-d test, and invasive testing is rarely required in the remainder. However, 3 caveats should be borne in mind. First, these results apply to a specific D-d test and method of clinical probability assessment. Substitution of an alternative assay would be safe only if its sensitivity equaled or exceeded that of SimpliRED, though diagnostic utility might be inferior if specificity were lower. Less sensitive assays should not be used. Second, the overall prevalences of VTE in these cohorts were less than 15% so that the frequency of thromboses in the low-probability groups was only 1% to 2%. The negative predictive value of a combined low probability and negative D-d finding will diminish as disease prevalence rises so that the safety of this approach cannot be assumed if a significantly higher prevalence of VTE is anticipated. Third, VTE was diagnosed in up to 20% of patients with a negative D-d result and high clinical suspicion, demonstrating that the SimpliRED assay cannot be used in isolation and reinforcing the need for a careful clinical assessment. In contradistinction, exclusion of PE on the basis of a negative VIDAS assay finding seemed safe in one study.90 Such an approach would not be acceptable unless sensitivity of the assay used approximated to 100%, although in the absence of further confirmatory data, it would seem prudent to exercise caution when the results of D-d testing using a highly sensitive assay and clinical suspicion are at odds.

Screening studies94,95 in patients at high risk of DVT clearly demonstrate that only a few patients have local signs or symptoms. However, subclinical DVT is important as fatal PE may be its initial manifestation,11 and postthrombotic syndrome is an important sequela, particularly after proximal thrombosis.96 Although D-d testing alone would not allow positive diagnosis of DVT, the concept of its use as a screening tool in populations at high risk of VTE, potentially optimizing use of noninvasive imaging in a diminished subgroup, is theoretically attractive. The need for screening is debatable in general surgical and orthopedic patients as increasingly effective thromboprophylactic strategies are used.9799 However, a strong case might exist in, for example, patients after stroke97 in whom prophylactic heparin use is no longer routinely recommended.100

A few studies evaluating the role of D-d testing as a screening tool have been reported. Harvey et al101 studied 105 nonambulatory stroke rehabilitation patients an average of 25 days after ictus. Patients were screened with bilateral lower-limb ultrasonography and D-d (Asserachrom Ddi ELISA) within the same 24 hours. Fourteen DVTs were identified, and a D-d threshold of 1092 ng/mL had a sensitivity of 100% and a specificity of 66%. Positive and negative predictive values were 31% and 100%, respectively. At this threshold, therefore, the D-d test excluded DVT with the same confidence as a negative ultrasound finding. Overall, this study demonstrated that DVT could be excluded in 57% of patients by D-d testing alone. These data cannot be extrapolated to patients in the acute phase of stroke because of potential confounding by the effect of stroke itself on D-d levels,30 and the evaluation of D-d as a screening tool in this context requires a separate study.

Bounameaux et al102 performed D-d measurements (Asserachrom Ddi ELISA) and bilateral CV on postoperative day 8 in 185 patients who had undergone gastrointestinal tract surgery. Although D-d levels were increased substantially by surgery, a threshold of 3000 ng/mL had an 89% sensitivity and a 48% specificity (positive and negative predictive values, 35% and 93%, respectively) for the diagnosis of DVT.

Roussi et al103 studied D-d (Asserachrom Ddi ELISA and Liatest) as a screening test for DVT with ultrasonography, CV, or both in 67 patients with spinal cord injuries and found that DVT could be excluded using a standard D-d threshold of 500 ng/mL (either technique) in 31%, obviating ultrasonography in these patients.

Studies evaluating the screening potential of D-d assays in the context of orthopedic surgery have yielded conflicting results. Crippa et al104 screened 68 patients undergoing elective hip surgery with serial D-d measurements (LPIA D-d; Mitsubishi Kasei Corp, Tokyo, Japan; a quantitative automated immunoturbidimetric assay) and CV at day 10. At a cutoff value of 3500 ng/mL, the assay had a sensitivity of 100% and a specificity of 32% for DVT (positive and negative predictive values, 40% and 100%, respectively). Bongard et al105 evaluated 173 patients undergoing hip surgery (elective and emergency) using a D-d assay (Asserachrom Ddi ELISA) and ultrasonography on postoperative day 12. At a cutoff value of 2000 ng/mL, the sensitivity and specificity for proximal DVT were 79% and 36%, respectively. Whereas the negative predictive value at this threshold was 95%, the positive predictive value was only 9%, limiting its usefulness. A preoperative D-d threshold greater than 500 ng/mL had a sensitivity of 93% and a specificity of 23% for the subsequent development of proximal DVT (negative and positive predictive values, 96% and 36%, respectively), and preoperative D-d levels were also predictive of postoperative DVT in a study106 evaluating patients undergoing major abdominal surgery. Although this might support the concept that increased fibrin turnover identified patients with a preoperative hypercoagulable state at increased risk of subsequent DVT,107 preoperative D-d measurement did not predict postoperative DVT in the European Concerted Action on Thrombosis DVT study, the largest of its kind evaluating the relationship between preoperative hemostatic variables and subsequent thrombosis in patients undergoing hip arthroplasty.108 Last, Dunn et al109 measured D-d (Dimertest ELISA) in 90 patients after orthopedic surgery undergoing CV between days 5 and 7. Although D-d levels were significantly higher in patients with DVT, the degree of overlap was too great for the test to be discriminatory in individuals, and the SimpliRED D-d assay was not a useful screening test in another study110 of patients after orthopedic surgery.

Although D-d assays have not generally proved useful as a screening modality after orthopedic surgery because of the overwhelming effect of surgery per se on levels, these studies indicate that in certain subgroups of high-risk patients, a 2-step screening process involving an initial D-d estimation might significantly decrease the number of patients requiring imaging, although in postoperative patients, optimal cutoff values may change with new surgical techniques and new thromboprophylactic drugs.18 In general, D-d testing may facilitate identification of a subgroup with an approximately 1 in 3 probability of having DVT on ultrasound screening, which compares favorably with the 1 in 4 patients with clinically suspected DVT in whom the diagnosis is confirmed.111 Studies are required to evaluate the utility of such an approach in improving clinical end points and its cost-effectiveness.

Experience is increasing with spiral computed tomography and contrast-enhanced electron-beam computed tomography for the diagnosis of PE.34,112118 Furthermore, MRI seems promising for the evaluation of DVT and PE,34,113,114,119 particularly direct thrombus MRI, which detects methemoglobin in maturing clots and provides a positive image of thrombi.120,121 A major advantage of MRI is that it allows evaluation of the lower limbs and thorax for clots at the same time, potentially facilitating a more titrated approach to treatment. For example, the presence or absence of residual proximal DVT in a patient with PE, the major factor determining the risk of PE recurrence in the absence of treatment,122125 could affect decisions about the intensity and duration of treatment. Use of these techniques is likely to increase as technology advances, and invasive diagnosis of VTE may be completely obviated in the future. However, further data from prospective management studies in which anticoagulant treatment is withheld without further testing for VTE on the basis of negative imaging findings and large, multicenter studies are required to clarify the role of computed tomography and MRI in the diagnostic paradigm of VTE.7,112,125

During the past decade, D-d assays have evolved from a theoretically attractive exclusionary test in suspected VTE to one of practical value that seems to be safe and cost-effective when used within defined diagnostic strategies, obviating the need for imaging in a significant proportion of patients, minimizing the need for repeated or invasive investigations in the remainder, and allowing immediate treatment decisions to be made more frequently. However, many different assays are now commercially available, and clinicians should appreciate that these cannot necessarily be used interchangeably and should ensure that they are familiar with the diagnostic performance of the assay used in their own institution.

Ongoing studies will continue to define the role of D-ds in diagnosis. Further research is needed, for example, to evaluate the safety of using highly sensitive rapid assays, such as VIDAS, as stand-alone tests. In the absence of an assay that is highly sensitive and specific, studies evaluating a 2-step approach consisting of an initial clinical probability assessment and D-d assay using one of the more specific tests (eg, SimpliRED), followed by a highly sensitive assay in those with a negative result and non–low clinical suspicion, would be of interest as this approach would combine the merits of both classes of assay and potentially further reduce the need for imaging.

Accepted for publication August 27, 2001.

Corresponding author and reprints: James Kelly, BSC, MRCP, SpR in Elderly Care/GIM, Elderly Care Dept, c/o Alexandra Ward, North Wing, Ninth Floor, St Thomas' Hospital, Lambeth Palace Road, Lambeth, London SE1 7EH, England (e-mail: jameskelly@northbrookfm.fsnet.co.uk).

Kniffin  WDBaron  JABarrett  JBirkmeyer  JDAnderson  FA The epidemiology of diagnosed pulmonary embolism and deep vein thrombosis in the elderly. Arch Intern Med. 1994;154861- 866
Hansson  PWelin  LTibblin  GEriksson  H Deep vein thrombosis and pulmonary embolism in the general population. Arch Intern Med. 1997;1571665- 1670
Byrne  JJ Phlebitis: a study of 748 cases at the Boston City Hospital. N Engl J Med. 1955;253579- 586
Dalen  JEAlpert  JS Natural history of pulmonary embolism. Prog Cardiovasc Dis. 1975;17259- 270
Not Available, NIH Consensus Development: prevention of venous thrombosis and pulmonary embolism. JAMA. 1986;256744- 749
Sasahara  AASharma  GVBarsamian  EMSchoolman  MCella  G Pulmonary thromboembolism: diagnosis and treatment. JAMA. 1983;2492945- 2950
American Thoracic Society, The diagnostic approach to acute venous thromboembolism: clinical practice guideline. Am J Respir Crit Care Med. 1999;1601043- 1066
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. 1993;3291365- 1369
Cogo  ALensing  AWKoopman  MM  et al.  Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;31617- 20
Birdwell  BGRaskob  GEWhitsett  TL  et al.  The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis. Ann Intern Med. 1998;1281- 7
The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) investigators, Value of the ventilation-perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) investigators. JAMA. 1990;2632753- 2759
Hull  RDRaskob  GEGinsberg  JS  et al.  A noninvasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154289- 297
Dalen  JE When can treatment be withheld in patients with suspected pulmonary embolism? Arch Intern Med. 1993;1531415- 1418
Stein  PDHull  RDPineo  G Strategy that includes serial noninvasive leg tests for diagnosis of thromboembolic disease in patients with suspected acute pulmonary embolism based on data from PIOPED. Arch Intern Med. 1995;1552101- 2104
Hansson  POEriksson  HEriksson  EJagenburg  RLukes  PRisberg  B Can laboratory testing improve screening strategies for deep vein thrombosis at an emergency unit? J Intern Med. 1994;235143- 151
Kraaijenhagen  RALensing  AWLijmer  JG  et al.  Diagnostic strategies for the management of patients with clinically suspected deep vein thrombosis. Curr Opin Pulm Med. 1997;3268- 274
Kario  KMatsuo  TKobayashi  H Which factors affect D-dimer levels in the elderly? Thromb Res. 1991;62501- 508
Crippa  LD'Angelo  SVTomassini  LRizzi  BD'Alessandro  GD'Angelo  A The utility and cost-effectiveness of D-dimer measurements in the diagnosis of deep vein thrombosis. Haematologica. 1997;82446- 451
Hager  KPlatt  D Fibrin degeneration product concentrations (D-dimers) in the course of ageing. Gerontology. 1995;41159- 165
Sie  P The value of laboratory tests in the diagnosis of venous thromboembolism. Haematologica. 1995;80 (suppl) 57- 60
D'Angelo  AD'Alessandro  GTomassini  L Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis. Thromb Haemost. 1996;75412- 416
Chapman  CSAkhtar  NCampbell  SMiles  KO'Connor  JMitchell  VE The use of D-dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis. Clin Lab Haematol. 1990;1237- 42
The DVTENOX Study Group, Markers of haemostatic system activation in acute deep venous thrombosis evolution during the first days of heparin treatment. Thromb Haemost. 1993;70909- 914
Fraser  DGMoody  ARMartel  AMorgan  P Determinants of D-dimer level in patients presenting with deep venous thrombosis: assessment using magnetic resonance thrombus imaging. Abstracts from the European Haematology Association 5th Congress; June 27, 2000; Birmingham, Ala. Abstract 513.
Speiser  WMallek  RKoppensteiner  R  et al.  D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness. Thromb Haemost. 1990;64196- 201
Estivals  MPelzer  HSie  PPichon  JBoccalon  HBoneu  B Prothrombin fragment 1 + 2, thrombin-antithrombin 3 complexes and D-dimers in acute deep vein thrombosis: effects of heparin treatment. Br J Haematol. 1991;78421- 424
Kruskal  JBCommerford  PJFranks  JJKirsch  RE Fibrin and fibrinogen related antigens in patients with stable and unstable coronary disease. N Engl J Med. 1987;3171361- 1365
Gustafsson  CBlomback  MBritton  M Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke. 1990;2147- 51
Becker  DMPhilbrick  JTBachhuber  TLHumphries  JE D-dimer testing and acute venous thromboembolism. Arch Intern Med. 1996;156939- 946
Giroud  MDutrillaux  FLemesle  M  et al.  Coagulation abnormalities in lacunar and cortical ischaemic stroke are quite different. Neurol Res. 1998;2015- 18
Raimondi  PBongard  Ode Moerloose  PReber  GWaldvogel  FBounameaux  H D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res. 1993;69125- 130
Whitaker  ANElms  MJMasci  PP  et al.  Measurement of cross linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies. J Clin Pathol. 1984;37882- 887
Elms  MJBunce  IHBundesen  PG  et al.  Measurement of cross-linked fibrin degradation products: an immunoassay using monoclonal antibodies. Thromb Haemost. 1983;50591- 594
Indik  JHAlpert  JS Detection of pulmonary embolism by D-dimer assay, spiral computed tomography and magnetic resonance imaging. Prog Cardiovasc Dis. 2000;42261- 272
Pittet  JLde Moerloose  PReber  G  et al.  VIDAS D-dimer: fast quantitative ELISA for measuring D-dimer in plasma. Clin Chem. 1996;42410- 415
de Moerloose  PDesmarais  SBounameaux  H  et al.  Contribution of a new, rapid, individual and quantitative automated D-dimer ELISA to exclude pulmonary embolism. Thromb Haemost. 1996;7511- 13
Scarano  LBernardi  EPrandoni  P  et al.  Accuracy of two newly described D-dimer tests in patients with suspected deep venous thrombosis. Thromb Res. 1997;8693- 99
Dale  SGogstad  GOBrosstad  F  et al.  Comparison of three D-dimer assays for the diagnosis of DVT: ELISA, latex and an immunofiltration assay (NycoCard D-dimer). Thromb Haemost. 1994;71270- 274
John  MAElms  MJO'Reilly  EJRylatt  DBBundesen  PGHillyard  CJ The SimpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood. Thromb Res Suppl. 1990;58273- 281
Bounameaux  Hde Moerloose  P Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost. 1994;711- 6
Van der Graaf  Fvan den Borne  Hvan der Kolk  Mde Wild  PJJanssen  GWvan Uum  SH Exclusion of deep venous thrombosis with D-dimer testing. Thromb Haemost. 2000;83191- 198
Eisenberg  PR Does a negative D-dimer exclude thrombosis? Fibrinolysis. 1993;732- 35
Janssen  MCHeebels  AEde Metz  M  et al.  Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis. Thromb Haemost. 1997;77262- 266
Freyburger  GTrillaud  HLabrouche  S  et al.  D-dimer strategy in thrombosis exclusion. Thromb Haemost. 1998;7932- 37
Keeling  DMWright  MBaker  PSackett  D D-dimer for the exclusion of venous thromboembolism: comparison of a new automated latex particle immunoassay (MDA D-dimer) with an established enzyme-linked fluorescent assay (VIDAS D-dimer). Clin Lab Haematol. 1999;21359- 362
Shitrit  DHeyd  JRaveh  DRudensky  B Diagnostic value of the D-dimer test in deep vein thrombosis: improved results by a new assay method and by using discriminating methods. Thromb Res. 2001;102125- 131
Righini  MGoehring  CBounameaux  HPerrier  A Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med. 2000;109357- 361
Legnani  CPancani  CPalareti  GGuazzaloca  GCoccheri  S Contribution of a new rapid, quantitative and automated method for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis. 1999;1069- 74
Bonnin  FHadjikostova  HJebrak  G  et al.  Complementarity of lung scintigraphy and D-dimer test in pulmonary embolism. Eur J Nucl Med. 1997;24444- 447
Legnani  CPancani  CPalareti  G  et al.  Comparison of new rapid methods for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis. 1997;8296- 302
Sijens  PEvan Ingen  HEvan Beek  EJBerghout  AOudkerk  M Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. Thromb Haemost. 2000;84156- 159
Elias  AAptel  IHuc  B  et al.  D-dimer test and diagnosis of deep vein thrombosis: a comparative study of 7 assays. Thromb Haemost. 1996;76518- 522
Le Blanche  AFSiguret  VSettegrana  C  et al.  Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old. Angiology. 1999;50873- 882
van Beek  EJvan den Ende  BBerckmans  RJ  et al.  A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism. Thromb Haemost. 1993;70408- 413
De Moerloose  P D-dimer assays for the exclusion of venous thromboembolism: which test for which diagnostic strategy? Thromb Haemost. 2000;83180- 181
Ginsberg  JSWells  PSBrill-Edwards  P  et al.  Application of a novel and rapid whole blood assay for D-dimer inpatients with clinically suspected pulmonary embolism. Thromb Haemost. 1995;7335- 38
Oger  ELeroyer  CBressollette  L  et al.  Evaluation of a new, rapid, and quantitative D-dimer test in patients with suspected pulmonary embolism. Am J Respir Crit Care Med. 1998;15865- 70
Bates  SMGrand'Maison  AJohnston  MNaguit  IKovacs  MJGinsberg  JS A latex D-dimer reliably excludes venous thromboembolism. Arch Intern Med. 2001;161447- 453
de Groot  MRvan Marwijk Kooy  MPouwels  JGEngelage  AHKuipers  BFBuller  HR The use of a rapid D-dimer blood test in the diagnostic work up of pulmonary embolism. Thromb Haemost. 1999;821588- 1592
Egermayer  PTown  GITurner  JGHeaton  DCMee  ALBeard  ME Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism. Thorax. 1998;53830- 834
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
Egermayer  PTown  GITurner  JGHeaton  DCMee  ALBeard  ME Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism. Thorax. 1998;53830- 834
Kline  JAIsrael  EGMichelson  EAO'Neil  BJPlewa  MCPortelli  DC Diagnostic accuracy of a bedside D-dimer assay and alveolar dead-space measurement for rapid exclusion of pulmonary embolism. JAMA. 2001;285761- 768
Kollef  MHZahid  MEisenberg  PR Predictive value of a rapid semiquantitative D-dimer assay in critically ill patients with suspected venous thromboembolic disease. Crit Care Med. 2000;28414- 420
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
Wildberger  JEVorwerk  DKilbinger  M  et al.  Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis: evaluation of 250 patients. Invest Radiol. 1998;33232- 235
Turkstra  Fvan Beek  EJten Cate  JWBuller  HR Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients. Thromb Haemost. 1996;769- 11
Ginsberg  JSWells  PSKearon  C  et al.  Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Intern Med. 1998;1291006- 1011
Farrell  SHayes  TShaw  M A negative SimpliRED D-dimer assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients. Ann Emerg Med. 2000;35121- 125
Goldstein  NMKollef  MHWard  SGage  BF The impact of the introduction of a rapid D-dimer assay on the diagnostic evaluation of suspected pulmonary embolism. Arch Intern Med. 2001;161567- 571
Perrier  ABounameaux  H Cost-effective diagnosis of deep vein thrombosis and pulmonary embolism. Thromb Haemost. 2001;86475- 487
Pieper  CFRao  KMCurrie  MSHarris  TBCohen  HJ Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol A Biol Sci Med Sci. 2000;55M649- M657
Currie  MSMurali Krishna Rao  KBlazer  DGCohen  HJ Age and functional correlations of markers of coagulation and inflammation in the elderly: functional implications of elevated cross-linked fibrin degradation products (D-dimers). J Am Geriatr Soc. 1994;42738- 742
Perrier  ADesmarais  SGoehring  C  et al.  D-dimer testing for suspected pulmonary embolism in outpatients. Am J Respir Crit Care Med. 1997;156492- 496
Tardy  BTardy-Poncet  BViallon  A  et al.  Evaluation of D-dimer ELISA test in elderly patients with suspected pulmonary embolism. Thromb Haemost. 1998;7938- 41
Pernod  GBarro  CSatger  B  et al.  Positive predictive value of D-dimers in the diagnosis of pulmonary embolism [abstract]. Thromb Haemost. 2001;86 (suppl) 728
Bounameaux  Hde Moerloose  PPerrier  AMiron  MJ D-dimer testing in suspected venous thromboembolism: an update. Q J Med. 1997;90437- 442
Sanson  BMeinders  AKraaijenhagen  Avan Beek  EJBuller  HR Requirements for appropriate evaluation of diagnostic tests in suspected pulmonary embolism. Haematologica. 1999;8478- 81
Hull  RHirsh  JSackett  DL  et al.  Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. Circulation. 1981;64622- 624
Novelline  RABaltarowich  OHAthanasoulis  CAWaltman  ACGreenfield  AJMcKusick  KA The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram. Radiology. 1978;126561- 567
Hull  RDRaskob  GECoates  GPanju  AA Clinical validity of a normal perfusion scan in patients with suspected pulmonary embolism. Chest. 1990;9723- 26
Wells  PSHirsh  JAnderson  DR  et al.  Accuracy of clinical assessment of deep vein thrombosis. Lancet. 1995;3451326- 1330
Wells  PSHirsh  JAnderson  DR  et al.  A simple clinical model for the diagnosis of deep vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process. J Intern Med. 1998;24315- 23
Miron  MJPerrier  ABounameaux  H Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment. J Intern Med. 2000;247249- 254
Wicki  JPerneger  TVJunod  AFBounameaux  HPerrier  A Assessing clinical probability of pulmonary embolism in the emergency ward. Arch Intern Med. 2001;16192- 97
Bernardi  EPrandoni  PLensing  AW  et al.  D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;3171037- 1040
Kraaijenhagen  RAKoopman  MMBernadi  E  et al.  Simplification of the diagnostic management of outpatients with symptomatic deep vein thrombosis with D-dimer measurements [abstract]. Thromb Haemost. 1997;159
Perone  NBounameaux  HPerrier  A Comparison of four strategies for diagnosing deep vein thrombosis: cost-effectiveness analysis. Am J Med. 2001;11033- 40
Perrier  ABounameaux  HMorabia  A  et al.  Diagnosis of pulmonary embolism by a decision analysis–based strategy including clinical probability, D-dimer levels and ultrasonography: a management study. Arch Intern Med. 1996;156531- 536
Perrier  ADesmarais  SMiron  M  et al.  Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet. 1999;353190- 195
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
Wells  PSAnderson  DRRodger  M  et al.  Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;13598- 107
Wells  PSAnderson  DRRodger  M  et al.  Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the model's utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83416- 420
Brandstater  MERoth  EJSiebens  HC Venous thromboembolism in stroke: literature review and implications for clinical practice. Arch Phys Med Rehabil. 1992;73S379- S391
Collins  RScrigeour  AYusuf  SPeto  R Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;3181162- 1173
Siragusa  SSerafini  SBeltrametti  CBarone  MPiovella  F The incidence of post-thrombotic syndrome after asymptomatic post-operative deep vein thrombosis: an inception cohort study [abstract]. Blood. 1998;92 (suppl 1) 47a
Estrada  CAMcElligott  JDolezal  JMCunningham  PR Asymptomatic patients at high risk for deep venous thrombosis who receive inadequate prophylaxis should be screened. South Med J. 1999;921145- 1150
Nurmohamed  NTRosendall  FRBuller  HR  et al.  Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992;340152- 155
Hull  RDPineo  GFFrancis  C  et al.  Low molecular weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients. Arch Intern Med. 2000;1602208- 2215
Gubitz  GCounsell  CSandercock  PSignorini  D Anticoagulants for acute ischaemic stroke [Cochrane Review on CD-ROM].  Oxford, England Cochrane Library, Update Software, issue 11999;
Harvey  RLRoth  EJYarnold  PRDurham  JRGreen  D Deep vein thrombosis in stroke: the use of plasma D-dimer level as a screening test in the rehabilitation setting. Stroke. 1996;271516- 1520
Bounameaux  HKhabiri  EHuber  O  et al.  Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery. Thromb Haemost. 1992;67603- 606
Roussi  JBentolila  SBoudaoud  L  et al.  Contribution of D-dimer determination in the exclusion of deep venous thrombosis in spinal cord injury patients. Spinal Cord. 1999;37548- 552
Crippa  LRavasi  FD'Angelo  S  et al.  Diagnostic value of compression ultrasonography and fibrinogen-related parameters for the detection of postoperative deep vein thrombosis following elective hip replacement: a pilot study. Thromb Haemost. 1995;741235- 1239
Bongard  OWicky  JPeter  R  et al.  D-dimer plasma measurement in patients undergoing major hip surgery: use in the prediction and diagnosis of postoperative proximal vein thrombosis. Thromb Res. 1994;74487- 493
Rowbotham  BJWhitaker  ANHarrison  JMurtaugh  PReasbeck  PBowie  EJ Measurement of cross-linked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis. Blood Coagul Fibrinolysis. 1992;325- 31
Lowe  GD Prediction of postoperative deep vein thrombosis. Thromb Haemost. 1997;7847- 52
Lowe  GDHaverkate  FThompson  SG  et al. for the ECAT DVT Study Group, Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT study. Thromb Haemost. 1999;81879- 886
Dunn  IDHui  ACTriffitt  PD  et al.  Plasma D-dimer as a marker of postoperative deep venous thrombosis: a study after total hip or knee arthroplasty. Thromb Haemost. 1994;72663- 665
Douketis  JDMcGinnis  JGinsberg  JS The clinical utility of a rapid bedside D-dimer assay for screening of deep vein thrombosis following orthopaedic surgery. Thromb Haemost. 1997;781300- 1301
Kearon  CJulian  JAMath  MNewman  TEGinsberg  JSfor the McMaster Diagnostic Imaging Practice Guidelines Initiative, Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med. 1998;128663- 677
Rathbun  SWRaskob  GEWhitsett  TL Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000;132227- 232
Stein  PDHull  RDPineo  GF The role of newer diagnostic techniques in the diagnosis of pulmonary embolism. Curr Opin Pulm Med. 1999;5212- 215
Gefter  WBHatabu  HHolland  GAGupta  KBHenschke  CIPalevsky  HI Pulmonary thromboembolism: recent developments in diagnosis with CT and MR imaging. Radiology. 1995;197561- 574
Remy-Jardin  MRemy  JArtaud  DDeschildre  FBeregi  JP Opinion response to acute pulmonary embolism: the role of computed tomographic imaging. J Thorac Imaging. 1997;1292- 95
Lorut  CGhossains  MHorellou  MAchkar  AFretault  JLaaban  J A noninvasive diagnostic strategy including spiral computed tomography in patients with suspected pulmonary embolism. Am J Respir Crit Care Med. 2000;1621413- 1418
Ost  DRozenshtein  ASaffran  LSnider  A The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans. Am J Med. 2001;11016- 21
Goodman  LRLipchik  RJKuzo  RSLu  YMcAuliffe  TLO'Brien  DJ Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram: prospective comparison with scintigraphy. Radiology. 2000;215535- 542
Polak  JFFox  LA MR assessment of the extremity veins. Semin Ultrasound CT MR. 1999;2036- 46
Fraser  DGMoody  ARMorgan  PSMartel  ALDavidson  I Diagnosis of lower limb deep venous thrombosis (DVT): prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med. 2002;13689- 98
Moody  ARLiddicoat  AKrarup  K Magnetic resonance pulmonary angiography and direct imaging of embolus for the detection of pulmonary emboli. Invest Radiol. 1997;32431- 440
Hull  RDRaskob  GEGinsberg  JS  et al.  A non-invasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154289- 297
Stein  PDHull  RDRaskob  GE Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial non-invasive leg tests. Am J Med. 2000;109301- 306
Dalen  JE When can treatment be withheld in patients with suspected pulmonary embolism? Arch Intern Med. 1993;1531415- 1418
ACCP Consensus Committee on Pulmonary Embolism, Opinions regarding the diagnosis and management of venous thromboembolic disease. Chest. 1996;109233- 237

Figures

Tables

Table Graphic Jump LocationTable 1. Characteristics of the Different Classes of D-Dimer Detection Techniques*
Table Graphic Jump LocationTable 2. Performance Characteristics of 13 D-Dimer (D-d) Assays in Suspected Deep Vein Thrombosis*
Table Graphic Jump LocationTable 3. Performance Characteristics of the Asserachrom Ddi ELISA (Diagnostica Stago, Inc, Parsippany, NJ) in Different Age Strata at a Cutoff Value of 500 ng/mL in 671 Outpatients Investigated for Suspected Pulmonary Embolism*
Table Graphic Jump LocationTable 4. Clinical Probability Score Used in Patients With Suspected Deep Vein Thrombosis*
Table Graphic Jump LocationTable 5. Clinical Probability Score Used in Patients With Suspected PE*

References

Kniffin  WDBaron  JABarrett  JBirkmeyer  JDAnderson  FA The epidemiology of diagnosed pulmonary embolism and deep vein thrombosis in the elderly. Arch Intern Med. 1994;154861- 866
Hansson  PWelin  LTibblin  GEriksson  H Deep vein thrombosis and pulmonary embolism in the general population. Arch Intern Med. 1997;1571665- 1670
Byrne  JJ Phlebitis: a study of 748 cases at the Boston City Hospital. N Engl J Med. 1955;253579- 586
Dalen  JEAlpert  JS Natural history of pulmonary embolism. Prog Cardiovasc Dis. 1975;17259- 270
Not Available, NIH Consensus Development: prevention of venous thrombosis and pulmonary embolism. JAMA. 1986;256744- 749
Sasahara  AASharma  GVBarsamian  EMSchoolman  MCella  G Pulmonary thromboembolism: diagnosis and treatment. JAMA. 1983;2492945- 2950
American Thoracic Society, The diagnostic approach to acute venous thromboembolism: clinical practice guideline. Am J Respir Crit Care Med. 1999;1601043- 1066
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. 1993;3291365- 1369
Cogo  ALensing  AWKoopman  MM  et al.  Compression ultrasonography for diagnostic management of patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;31617- 20
Birdwell  BGRaskob  GEWhitsett  TL  et al.  The clinical validity of normal compression ultrasonography in outpatients suspected of having deep venous thrombosis. Ann Intern Med. 1998;1281- 7
The Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) investigators, Value of the ventilation-perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED) investigators. JAMA. 1990;2632753- 2759
Hull  RDRaskob  GEGinsberg  JS  et al.  A noninvasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154289- 297
Dalen  JE When can treatment be withheld in patients with suspected pulmonary embolism? Arch Intern Med. 1993;1531415- 1418
Stein  PDHull  RDPineo  G Strategy that includes serial noninvasive leg tests for diagnosis of thromboembolic disease in patients with suspected acute pulmonary embolism based on data from PIOPED. Arch Intern Med. 1995;1552101- 2104
Hansson  POEriksson  HEriksson  EJagenburg  RLukes  PRisberg  B Can laboratory testing improve screening strategies for deep vein thrombosis at an emergency unit? J Intern Med. 1994;235143- 151
Kraaijenhagen  RALensing  AWLijmer  JG  et al.  Diagnostic strategies for the management of patients with clinically suspected deep vein thrombosis. Curr Opin Pulm Med. 1997;3268- 274
Kario  KMatsuo  TKobayashi  H Which factors affect D-dimer levels in the elderly? Thromb Res. 1991;62501- 508
Crippa  LD'Angelo  SVTomassini  LRizzi  BD'Alessandro  GD'Angelo  A The utility and cost-effectiveness of D-dimer measurements in the diagnosis of deep vein thrombosis. Haematologica. 1997;82446- 451
Hager  KPlatt  D Fibrin degeneration product concentrations (D-dimers) in the course of ageing. Gerontology. 1995;41159- 165
Sie  P The value of laboratory tests in the diagnosis of venous thromboembolism. Haematologica. 1995;80 (suppl) 57- 60
D'Angelo  AD'Alessandro  GTomassini  L Evaluation of a new rapid quantitative D-dimer assay in patients with clinically suspected deep vein thrombosis. Thromb Haemost. 1996;75412- 416
Chapman  CSAkhtar  NCampbell  SMiles  KO'Connor  JMitchell  VE The use of D-dimer assay by enzyme immunoassay and latex agglutination techniques in the diagnosis of deep vein thrombosis. Clin Lab Haematol. 1990;1237- 42
The DVTENOX Study Group, Markers of haemostatic system activation in acute deep venous thrombosis evolution during the first days of heparin treatment. Thromb Haemost. 1993;70909- 914
Fraser  DGMoody  ARMartel  AMorgan  P Determinants of D-dimer level in patients presenting with deep venous thrombosis: assessment using magnetic resonance thrombus imaging. Abstracts from the European Haematology Association 5th Congress; June 27, 2000; Birmingham, Ala. Abstract 513.
Speiser  WMallek  RKoppensteiner  R  et al.  D-dimer and TAT measurement in patients with deep venous thrombosis: utility in diagnosis and judgement of anticoagulant treatment effectiveness. Thromb Haemost. 1990;64196- 201
Estivals  MPelzer  HSie  PPichon  JBoccalon  HBoneu  B Prothrombin fragment 1 + 2, thrombin-antithrombin 3 complexes and D-dimers in acute deep vein thrombosis: effects of heparin treatment. Br J Haematol. 1991;78421- 424
Kruskal  JBCommerford  PJFranks  JJKirsch  RE Fibrin and fibrinogen related antigens in patients with stable and unstable coronary disease. N Engl J Med. 1987;3171361- 1365
Gustafsson  CBlomback  MBritton  M Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke. 1990;2147- 51
Becker  DMPhilbrick  JTBachhuber  TLHumphries  JE D-dimer testing and acute venous thromboembolism. Arch Intern Med. 1996;156939- 946
Giroud  MDutrillaux  FLemesle  M  et al.  Coagulation abnormalities in lacunar and cortical ischaemic stroke are quite different. Neurol Res. 1998;2015- 18
Raimondi  PBongard  Ode Moerloose  PReber  GWaldvogel  FBounameaux  H D-dimer plasma concentration in various clinical conditions: implication for the use of this test in the diagnostic approach of venous thromboembolism. Thromb Res. 1993;69125- 130
Whitaker  ANElms  MJMasci  PP  et al.  Measurement of cross linked fibrin derivatives in plasma: an immunoassay using monoclonal antibodies. J Clin Pathol. 1984;37882- 887
Elms  MJBunce  IHBundesen  PG  et al.  Measurement of cross-linked fibrin degradation products: an immunoassay using monoclonal antibodies. Thromb Haemost. 1983;50591- 594
Indik  JHAlpert  JS Detection of pulmonary embolism by D-dimer assay, spiral computed tomography and magnetic resonance imaging. Prog Cardiovasc Dis. 2000;42261- 272
Pittet  JLde Moerloose  PReber  G  et al.  VIDAS D-dimer: fast quantitative ELISA for measuring D-dimer in plasma. Clin Chem. 1996;42410- 415
de Moerloose  PDesmarais  SBounameaux  H  et al.  Contribution of a new, rapid, individual and quantitative automated D-dimer ELISA to exclude pulmonary embolism. Thromb Haemost. 1996;7511- 13
Scarano  LBernardi  EPrandoni  P  et al.  Accuracy of two newly described D-dimer tests in patients with suspected deep venous thrombosis. Thromb Res. 1997;8693- 99
Dale  SGogstad  GOBrosstad  F  et al.  Comparison of three D-dimer assays for the diagnosis of DVT: ELISA, latex and an immunofiltration assay (NycoCard D-dimer). Thromb Haemost. 1994;71270- 274
John  MAElms  MJO'Reilly  EJRylatt  DBBundesen  PGHillyard  CJ The SimpliRED D dimer test: a novel assay for the detection of crosslinked fibrin degradation products in whole blood. Thromb Res Suppl. 1990;58273- 281
Bounameaux  Hde Moerloose  P Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost. 1994;711- 6
Van der Graaf  Fvan den Borne  Hvan der Kolk  Mde Wild  PJJanssen  GWvan Uum  SH Exclusion of deep venous thrombosis with D-dimer testing. Thromb Haemost. 2000;83191- 198
Eisenberg  PR Does a negative D-dimer exclude thrombosis? Fibrinolysis. 1993;732- 35
Janssen  MCHeebels  AEde Metz  M  et al.  Reliability of five rapid D-dimer assays compared to ELISA in the exclusion of deep venous thrombosis. Thromb Haemost. 1997;77262- 266
Freyburger  GTrillaud  HLabrouche  S  et al.  D-dimer strategy in thrombosis exclusion. Thromb Haemost. 1998;7932- 37
Keeling  DMWright  MBaker  PSackett  D D-dimer for the exclusion of venous thromboembolism: comparison of a new automated latex particle immunoassay (MDA D-dimer) with an established enzyme-linked fluorescent assay (VIDAS D-dimer). Clin Lab Haematol. 1999;21359- 362
Shitrit  DHeyd  JRaveh  DRudensky  B Diagnostic value of the D-dimer test in deep vein thrombosis: improved results by a new assay method and by using discriminating methods. Thromb Res. 2001;102125- 131
Righini  MGoehring  CBounameaux  HPerrier  A Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med. 2000;109357- 361
Legnani  CPancani  CPalareti  GGuazzaloca  GCoccheri  S Contribution of a new rapid, quantitative and automated method for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis. 1999;1069- 74
Bonnin  FHadjikostova  HJebrak  G  et al.  Complementarity of lung scintigraphy and D-dimer test in pulmonary embolism. Eur J Nucl Med. 1997;24444- 447
Legnani  CPancani  CPalareti  G  et al.  Comparison of new rapid methods for D-dimer measurement to exclude deep vein thrombosis in symptomatic outpatients. Blood Coagul Fibrinolysis. 1997;8296- 302
Sijens  PEvan Ingen  HEvan Beek  EJBerghout  AOudkerk  M Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. Thromb Haemost. 2000;84156- 159
Elias  AAptel  IHuc  B  et al.  D-dimer test and diagnosis of deep vein thrombosis: a comparative study of 7 assays. Thromb Haemost. 1996;76518- 522
Le Blanche  AFSiguret  VSettegrana  C  et al.  Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old. Angiology. 1999;50873- 882
van Beek  EJvan den Ende  BBerckmans  RJ  et al.  A comparative analysis of D-dimer assays in patients with clinically suspected pulmonary embolism. Thromb Haemost. 1993;70408- 413
De Moerloose  P D-dimer assays for the exclusion of venous thromboembolism: which test for which diagnostic strategy? Thromb Haemost. 2000;83180- 181
Ginsberg  JSWells  PSBrill-Edwards  P  et al.  Application of a novel and rapid whole blood assay for D-dimer inpatients with clinically suspected pulmonary embolism. Thromb Haemost. 1995;7335- 38
Oger  ELeroyer  CBressollette  L  et al.  Evaluation of a new, rapid, and quantitative D-dimer test in patients with suspected pulmonary embolism. Am J Respir Crit Care Med. 1998;15865- 70
Bates  SMGrand'Maison  AJohnston  MNaguit  IKovacs  MJGinsberg  JS A latex D-dimer reliably excludes venous thromboembolism. Arch Intern Med. 2001;161447- 453
de Groot  MRvan Marwijk Kooy  MPouwels  JGEngelage  AHKuipers  BFBuller  HR The use of a rapid D-dimer blood test in the diagnostic work up of pulmonary embolism. Thromb Haemost. 1999;821588- 1592
Egermayer  PTown  GITurner  JGHeaton  DCMee  ALBeard  ME Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism. Thorax. 1998;53830- 834
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
Egermayer  PTown  GITurner  JGHeaton  DCMee  ALBeard  ME Usefulness of D-dimer, blood gas, and respiratory rate measurements for excluding pulmonary embolism. Thorax. 1998;53830- 834
Kline  JAIsrael  EGMichelson  EAO'Neil  BJPlewa  MCPortelli  DC Diagnostic accuracy of a bedside D-dimer assay and alveolar dead-space measurement for rapid exclusion of pulmonary embolism. JAMA. 2001;285761- 768
Kollef  MHZahid  MEisenberg  PR Predictive value of a rapid semiquantitative D-dimer assay in critically ill patients with suspected venous thromboembolic disease. Crit Care Med. 2000;28414- 420
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
Wildberger  JEVorwerk  DKilbinger  M  et al.  Bedside testing (SimpliRED) in the diagnosis of deep vein thrombosis: evaluation of 250 patients. Invest Radiol. 1998;33232- 235
Turkstra  Fvan Beek  EJten Cate  JWBuller  HR Reliable rapid blood test for the exclusion of venous thromboembolism in symptomatic outpatients. Thromb Haemost. 1996;769- 11
Ginsberg  JSWells  PSKearon  C  et al.  Sensitivity and specificity of a rapid whole-blood assay for D-dimer in the diagnosis of pulmonary embolism. Ann Intern Med. 1998;1291006- 1011
Farrell  SHayes  TShaw  M A negative SimpliRED D-dimer assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients. Ann Emerg Med. 2000;35121- 125
Goldstein  NMKollef  MHWard  SGage  BF The impact of the introduction of a rapid D-dimer assay on the diagnostic evaluation of suspected pulmonary embolism. Arch Intern Med. 2001;161567- 571
Perrier  ABounameaux  H Cost-effective diagnosis of deep vein thrombosis and pulmonary embolism. Thromb Haemost. 2001;86475- 487
Pieper  CFRao  KMCurrie  MSHarris  TBCohen  HJ Age, functional status, and racial differences in plasma D-dimer levels in community-dwelling elderly persons. J Gerontol A Biol Sci Med Sci. 2000;55M649- M657
Currie  MSMurali Krishna Rao  KBlazer  DGCohen  HJ Age and functional correlations of markers of coagulation and inflammation in the elderly: functional implications of elevated cross-linked fibrin degradation products (D-dimers). J Am Geriatr Soc. 1994;42738- 742
Perrier  ADesmarais  SGoehring  C  et al.  D-dimer testing for suspected pulmonary embolism in outpatients. Am J Respir Crit Care Med. 1997;156492- 496
Tardy  BTardy-Poncet  BViallon  A  et al.  Evaluation of D-dimer ELISA test in elderly patients with suspected pulmonary embolism. Thromb Haemost. 1998;7938- 41
Pernod  GBarro  CSatger  B  et al.  Positive predictive value of D-dimers in the diagnosis of pulmonary embolism [abstract]. Thromb Haemost. 2001;86 (suppl) 728
Bounameaux  Hde Moerloose  PPerrier  AMiron  MJ D-dimer testing in suspected venous thromboembolism: an update. Q J Med. 1997;90437- 442
Sanson  BMeinders  AKraaijenhagen  Avan Beek  EJBuller  HR Requirements for appropriate evaluation of diagnostic tests in suspected pulmonary embolism. Haematologica. 1999;8478- 81
Hull  RHirsh  JSackett  DL  et al.  Clinical validity of a negative venogram in patients with clinically suspected venous thrombosis. Circulation. 1981;64622- 624
Novelline  RABaltarowich  OHAthanasoulis  CAWaltman  ACGreenfield  AJMcKusick  KA The clinical course of patients with suspected pulmonary embolism and a negative pulmonary arteriogram. Radiology. 1978;126561- 567
Hull  RDRaskob  GECoates  GPanju  AA Clinical validity of a normal perfusion scan in patients with suspected pulmonary embolism. Chest. 1990;9723- 26
Wells  PSHirsh  JAnderson  DR  et al.  Accuracy of clinical assessment of deep vein thrombosis. Lancet. 1995;3451326- 1330
Wells  PSHirsh  JAnderson  DR  et al.  A simple clinical model for the diagnosis of deep vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process. J Intern Med. 1998;24315- 23
Miron  MJPerrier  ABounameaux  H Clinical assessment of suspected deep vein thrombosis: comparison between a score and empirical assessment. J Intern Med. 2000;247249- 254
Wicki  JPerneger  TVJunod  AFBounameaux  HPerrier  A Assessing clinical probability of pulmonary embolism in the emergency ward. Arch Intern Med. 2001;16192- 97
Bernardi  EPrandoni  PLensing  AW  et al.  D-dimer testing as an adjunct to ultrasonography in patients with clinically suspected deep vein thrombosis: prospective cohort study. BMJ. 1998;3171037- 1040
Kraaijenhagen  RAKoopman  MMBernadi  E  et al.  Simplification of the diagnostic management of outpatients with symptomatic deep vein thrombosis with D-dimer measurements [abstract]. Thromb Haemost. 1997;159
Perone  NBounameaux  HPerrier  A Comparison of four strategies for diagnosing deep vein thrombosis: cost-effectiveness analysis. Am J Med. 2001;11033- 40
Perrier  ABounameaux  HMorabia  A  et al.  Diagnosis of pulmonary embolism by a decision analysis–based strategy including clinical probability, D-dimer levels and ultrasonography: a management study. Arch Intern Med. 1996;156531- 536
Perrier  ADesmarais  SMiron  M  et al.  Non-invasive diagnosis of venous thromboembolism in outpatients. Lancet. 1999;353190- 195
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
Wells  PSAnderson  DRRodger  M  et al.  Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and D-dimer. Ann Intern Med. 2001;13598- 107
Wells  PSAnderson  DRRodger  M  et al.  Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the model's utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83416- 420
Brandstater  MERoth  EJSiebens  HC Venous thromboembolism in stroke: literature review and implications for clinical practice. Arch Phys Med Rehabil. 1992;73S379- S391
Collins  RScrigeour  AYusuf  SPeto  R Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin: overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med. 1988;3181162- 1173
Siragusa  SSerafini  SBeltrametti  CBarone  MPiovella  F The incidence of post-thrombotic syndrome after asymptomatic post-operative deep vein thrombosis: an inception cohort study [abstract]. Blood. 1998;92 (suppl 1) 47a
Estrada  CAMcElligott  JDolezal  JMCunningham  PR Asymptomatic patients at high risk for deep venous thrombosis who receive inadequate prophylaxis should be screened. South Med J. 1999;921145- 1150
Nurmohamed  NTRosendall  FRBuller  HR  et al.  Low molecular weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet. 1992;340152- 155
Hull  RDPineo  GFFrancis  C  et al.  Low molecular weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients. Arch Intern Med. 2000;1602208- 2215
Gubitz  GCounsell  CSandercock  PSignorini  D Anticoagulants for acute ischaemic stroke [Cochrane Review on CD-ROM].  Oxford, England Cochrane Library, Update Software, issue 11999;
Harvey  RLRoth  EJYarnold  PRDurham  JRGreen  D Deep vein thrombosis in stroke: the use of plasma D-dimer level as a screening test in the rehabilitation setting. Stroke. 1996;271516- 1520
Bounameaux  HKhabiri  EHuber  O  et al.  Value of liquid crystal contact thermography and plasma level of D-dimer for screening of deep venous thrombosis following general abdominal surgery. Thromb Haemost. 1992;67603- 606
Roussi  JBentolila  SBoudaoud  L  et al.  Contribution of D-dimer determination in the exclusion of deep venous thrombosis in spinal cord injury patients. Spinal Cord. 1999;37548- 552
Crippa  LRavasi  FD'Angelo  S  et al.  Diagnostic value of compression ultrasonography and fibrinogen-related parameters for the detection of postoperative deep vein thrombosis following elective hip replacement: a pilot study. Thromb Haemost. 1995;741235- 1239
Bongard  OWicky  JPeter  R  et al.  D-dimer plasma measurement in patients undergoing major hip surgery: use in the prediction and diagnosis of postoperative proximal vein thrombosis. Thromb Res. 1994;74487- 493
Rowbotham  BJWhitaker  ANHarrison  JMurtaugh  PReasbeck  PBowie  EJ Measurement of cross-linked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis. Blood Coagul Fibrinolysis. 1992;325- 31
Lowe  GD Prediction of postoperative deep vein thrombosis. Thromb Haemost. 1997;7847- 52
Lowe  GDHaverkate  FThompson  SG  et al. for the ECAT DVT Study Group, Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT study. Thromb Haemost. 1999;81879- 886
Dunn  IDHui  ACTriffitt  PD  et al.  Plasma D-dimer as a marker of postoperative deep venous thrombosis: a study after total hip or knee arthroplasty. Thromb Haemost. 1994;72663- 665
Douketis  JDMcGinnis  JGinsberg  JS The clinical utility of a rapid bedside D-dimer assay for screening of deep vein thrombosis following orthopaedic surgery. Thromb Haemost. 1997;781300- 1301
Kearon  CJulian  JAMath  MNewman  TEGinsberg  JSfor the McMaster Diagnostic Imaging Practice Guidelines Initiative, Noninvasive diagnosis of deep venous thrombosis. Ann Intern Med. 1998;128663- 677
Rathbun  SWRaskob  GEWhitsett  TL Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review. Ann Intern Med. 2000;132227- 232
Stein  PDHull  RDPineo  GF The role of newer diagnostic techniques in the diagnosis of pulmonary embolism. Curr Opin Pulm Med. 1999;5212- 215
Gefter  WBHatabu  HHolland  GAGupta  KBHenschke  CIPalevsky  HI Pulmonary thromboembolism: recent developments in diagnosis with CT and MR imaging. Radiology. 1995;197561- 574
Remy-Jardin  MRemy  JArtaud  DDeschildre  FBeregi  JP Opinion response to acute pulmonary embolism: the role of computed tomographic imaging. J Thorac Imaging. 1997;1292- 95
Lorut  CGhossains  MHorellou  MAchkar  AFretault  JLaaban  J A noninvasive diagnostic strategy including spiral computed tomography in patients with suspected pulmonary embolism. Am J Respir Crit Care Med. 2000;1621413- 1418
Ost  DRozenshtein  ASaffran  LSnider  A The negative predictive value of spiral computed tomography for the diagnosis of pulmonary embolism in patients with nondiagnostic ventilation-perfusion scans. Am J Med. 2001;11016- 21
Goodman  LRLipchik  RJKuzo  RSLu  YMcAuliffe  TLO'Brien  DJ Subsequent pulmonary embolism: risk after a negative helical CT pulmonary angiogram: prospective comparison with scintigraphy. Radiology. 2000;215535- 542
Polak  JFFox  LA MR assessment of the extremity veins. Semin Ultrasound CT MR. 1999;2036- 46
Fraser  DGMoody  ARMorgan  PSMartel  ALDavidson  I Diagnosis of lower limb deep venous thrombosis (DVT): prospective blinded study of magnetic resonance direct thrombus imaging. Ann Intern Med. 2002;13689- 98
Moody  ARLiddicoat  AKrarup  K Magnetic resonance pulmonary angiography and direct imaging of embolus for the detection of pulmonary emboli. Invest Radiol. 1997;32431- 440
Hull  RDRaskob  GEGinsberg  JS  et al.  A non-invasive strategy for the treatment of patients with suspected pulmonary embolism. Arch Intern Med. 1994;154289- 297
Stein  PDHull  RDRaskob  GE Withholding treatment in patients with acute pulmonary embolism who have a high risk of bleeding and negative serial non-invasive leg tests. Am J Med. 2000;109301- 306
Dalen  JE When can treatment be withheld in patients with suspected pulmonary embolism? Arch Intern Med. 1993;1531415- 1418
ACCP Consensus Committee on Pulmonary Embolism, Opinions regarding the diagnosis and management of venous thromboembolic disease. Chest. 1996;109233- 237

Correspondence

CME
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.
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.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Multimedia

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

Web of Science® Times Cited: 124

Related Content

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

Articles Related By Topic
Related Topics
PubMed Articles