The use of a fixed high sensitivity to evaluate five D-dimer assays' ability to rule out deep venous thrombosis: a novel approach

Abstract Background: The use of D-dimer assays as a rule-out test for deep venous thrombosis (DVT) is controversial. To clarify this issue we performed a systematic review of the relevant literature. Methods: We identified eligible studies, using MEDLINE entries from February 1995 through October 2003, supplemented by a review of bibliographies of relevant articles. Studies reporting accuracy evaluations comparing D-dimer test results with lower extremity ultrasound or venography in symptomatic patients with suspected acute DVT were selected for review. Two reviewers critically appraised each study independently according to previously established methodologic standards for diagnostic test research. Those studies judged to be of highest quality were designated Level 1. Results: The 23 Level 1 studies reported data on 21 different D-dimer assays. There was wide variation in assay sensitivity, specificity, and negative predictive values, and major differences in methodology of reviewed studies. A multivariate analysis of assay performance, controlling for sample size, DVT prevalence, reference standard, and patient mix, found few differences among the assays in effect on test performance as measured by diagnostic odds ratio. Increasing prevalence of DVT was associated with poorer test performance (P = 0.01), whereas the choice of venography as the reference standard was associated with better test performance (P <0.005). Conclusions: Explanations for the wide variation in assay performance include differences in biochemical and technical characteristics of the assays, heterogeneity and small size of patient groups, and bias introduced by choice of reference standards. Assay sensitivity and negative predictive value were frequently <90%, uncharacteristic of a good rule-out test. General use of D-dimer assays as a stand-alone test for the diagnosis of DVT is not supported by the literature.

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Diagnostic Value of a New Sensitive Membrane Based Technique for Instantaneous D-Dimer Evaluation in Patients with Clinically Suspected Deep Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656025 ◽

1997 ◽

Vol 77 (04) ◽

pp. 637-640 ◽

Cited By ~ 22

Author(s):

Christophe Leroyer ◽

Martine Escoffre ◽

Emmanuelle Le Moigne ◽

Marc Grimaux ◽

Olivier Cagnioncle ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Predictive Value ◽

Clinical Signs ◽

High Sensitivity ◽

Diagnostic Value ◽

Lower Sensitivity ◽

Predictive Values ◽

Study Results ◽

D Dimer

SummaryBackground: Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). Aim: To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. Methods: A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. Results: 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 ± 3.4% (95% Cl), and specificity is 36.6 ± 6.9%. Positive predictive value is 67.7 ± 4.8% and negative predictive value is 76.1 ± 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. Conclusion: This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.

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The cost–effectiveness of point-of-care D-dimer tests compared with a laboratory test to rule out deep venous thrombosis in primary care

Expert Review of Molecular Diagnostics ◽

10.1586/14737159.2015.976202 ◽

2014 ◽

Vol 15 (1) ◽

pp. 125-136 ◽

Cited By ~ 8

Author(s):

Janneke MT Hendriksen ◽

Geert-Jan Geersing ◽

Suzanne C van Voorthuizen ◽

Ruud Oudega ◽

Arina J ten Cate-Hoek ◽

...

Keyword(s):

Primary Care ◽

Cost Effectiveness ◽

Laboratory Test ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Point Of Care ◽

The Cost ◽

D Dimer ◽

Rule Out

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Can a D-dimer assay, alone or combined with structured clinical risk assessment, rule out deep venous thrombosis in symptomatic patients?

Western Journal of Medicine ◽

10.1136/ewjm.174.4.255 ◽

2001 ◽

Vol 174 (4) ◽

pp. 255-255 ◽

Cited By ~ 1

Author(s):

M Aschwanden

Keyword(s):

Risk Assessment ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Clinical Risk ◽

Clinical Risk Assessment ◽

D Dimer ◽

Rule Out

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Investigations into the Clinical Utility of Latex D-Dimer in the Diagnosis of Deep Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651178 ◽

1993 ◽

Vol 69 (01) ◽

pp. 008-011 ◽

Cited By ~ 22

Author(s):

Cedric J Carter ◽

D Lynn Doyle ◽

Nigel Dawson ◽

Shauna Fowler ◽

Dana V Devine

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Lower Limb ◽

Clinical Utility ◽

Rapid Test ◽

Fibrin Degradation Product ◽

Current Form ◽

Non Invasive ◽

Clinically Significant ◽

D Dimer

SummaryThe serial use of non-invasive tests has been shown to be a safe method of managing outpatients who are suspected of having lower limb deep venous thrombosis (DVT). Objective testing has shown that the majority of these outpatients do not have venous thrombosis. A rapid test to exclude DVT in these patients, without the need for expensive and inconvenient serial non-invasive vascular testing, would have practical and economic advantages.Studies measuring the fibrin degradation product D-dimer using enzyme-linked immunoassays (EIA) in patients with veno-graphically proven DVT suggest that it should be possible to exclude this condition by the use of one of the rapid latex bead D-dimer tests.We have examined 190 patients with suspected DVT using both a latex and an EIA D-dimer assay. The latex D-dimer test used in this study was negative in 7 of the 36 proven cases of DVT. This sensitivity of only 80% is not sufficient to allow this type of assay, in its current form, to be used as an exclusion test for DVT. The same plasma samples were tested with an EIA assay. This information was used to mathematically model the effects of selecting a range of D-dimer discriminant cut off points for the diagnosis of DVT. These results indicate that 62% of suspected clinically significant DVT could have this diagnosis excluded, with a 98% sensitivity, if the rapid latex or equivalent D-dimer test could be reformulated to measure less than 185 ng/ml of D-dimer.

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Faculty Opinions recommendation of A red blood cell agglutination D-dimer test to exclude deep venous thrombosis in pregnancy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1090530.543802 ◽

2007 ◽

Author(s):

Ibrahim Bildirici

Keyword(s):

Blood Cell ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Red Blood Cell ◽

Cell Agglutination ◽

D Dimer ◽

In Pregnancy

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Evaluating the Use of a Negative D-Dimer and Modified Low Wells Score in Excluding above Knee Deep Venous Thrombosis in an Outpatient Population, Assessing Need for Diagnostic Ultrasound

ISRN Radiology ◽

10.1155/2014/519875 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5 ◽

Cited By ~ 3

Author(s):

Maryam Rahiminejad ◽

Anshul Rastogi ◽

Shirish Prabhudesai ◽

David Mcclinton ◽

Peter MacCallum ◽

...

Keyword(s):

Risk Factor ◽

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Lower Limb ◽

Clinical Risk Factor ◽

Diagnostic Pathway ◽

Clinical Diagnostic ◽

Retrospective Audit ◽

Wells Score ◽

D Dimer

Aims. Colour doppler ultrasonography (CDUS) is widely used in the diagnosis of deep venous thrombosis (DVT); however, the number of scans positive for above knee DVT is low. The present study evaluates the reliability of the D-dimer test combined with a clinical probability score (Wells score) in ruling out an above knee DVT and identifying patients who do not need a CDUS. Materials and Method. This study is a retrospective audit and reaudit of a total of 816 outpatients presenting with suspected lower limb DVT from March 2009 to March 2010 and from September 2011 to February 2012. Following the initial audit, a revised clinical diagnostic pathway was implemented. Results. In our initial audit, seven patients (4.9%) with a negative D-dimer and a low Wells score had a DVT. On review, all seven had a risk factor identified that was not included in the Wells score. No patient with negative D-dimer and low Wells score with no extra clinical risk factor had a DVT on CDUS (negative predictive value 100%). A reaudit confirmed adherence to our revised clinical diagnostic pathway. Conclusions. A negative D-dimer together with a low Wells score and no risk factors effectively excludes a lower limb DVT and an ultrasound is unnecessary in these patients.

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Performance of five D-dimer assays for the exclusion of symptomatic distal leg vein thrombosis

Thrombosis and Haemostasis ◽

10.1160/th11-07-0511 ◽

2012 ◽

Vol 107 (02) ◽

pp. 369-378 ◽

Cited By ~ 14

Author(s):

Jan Schwonberg ◽

Carola Hecking ◽

Marc Schindewolf ◽

Dimitrios Zgouras ◽

Susanne Lehmeyer ◽

...

Keyword(s):

High Sensitivity ◽

Diagnostic Value ◽

Vein Thrombosis ◽

Clinical Probability ◽

Wells Score ◽

Deep Vein ◽

Test Result ◽

D Dimer ◽

Rule Out ◽

Compression Ultrasonography

SummaryThe diagnostic value of D-dimer (DD) in the exclusion of proximal deep-vein thrombosis (DVT) is well-established but is less well-known in the exclusion of distal (infrapopliteal) DVT. Therefore, we evaluated the diagnostic abilities of five DD assays (Vidas-DD, Liatest-DD, HemosIL-DD, HemosIL-DDHS, Innovance-DD) for excluding symptomatic proximal and distal leg DVT. A total of 243 outpatients whose symptoms were suggestive of DVT received complete compression ultrasonography (cCUS) of the symptomatic leg(s). The clinical probability of DVT (PTP) was assessed by Wells score. Thirty-eight proximal and 31 distal DVTs (17 tibial/fibular DVTs, 14 muscle DVTs) were diagnosed by cCUS. Although all assays showed high sensitivity for proximal DVT (range 97–100%), the sensitivity was poor for distal DVT (range 78–93%). None of the assays were individually able to rule out all DVTs as a stand-alone test (negative predictive value [NPV] 91–96%). However, a negative DD test result combined with a low PTP exhibited a NPV of 100% for all DVTs (including proximal, tibial/fibular, and muscle DVTs) with the HemosIL-DDHS and Innovance-DD. All proximal and tibial/fibular DVTs, but not all muscle DVTs, could be ruled out with this strategy using the Liatest-DD and Vidas-DD. The HemosIL-DD could not exclude distal leg DVT, even in combination with a low PTP. The combination of a negative DD with a low PTP showed a specificity of 32–35% for all DVTs. In conclusion, our study shows that when used in conjunction with a low PTP some DD assays are useful tools for the exclusion of distal leg DVT.

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D-Dimer Determination to Assess Regression of Deep Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657631 ◽

1997 ◽

Vol 78 (02) ◽

pp. 799-802 ◽

Cited By ~ 12

Author(s):

M C H Janssen ◽

H Verbruggen ◽

H Wollersheim ◽

B Hoogkamer ◽

H van Langen ◽

...

Keyword(s):

Venous Thrombosis ◽

Deep Venous Thrombosis ◽

Odds Ratio ◽

Initial Treatment ◽

Heparin Therapy ◽

Duplex Scanning ◽

Fibrinolytic Parameters ◽

The Relationship ◽

Insight Into ◽

D Dimer

SummaryA number of studies evaluating deep venous thrombosis (DVT) have demonstrated that plasma levels of thrombotic and fibrinolytic parameters change during treatment, but the relationship between thrombus regression and evolution of these markers remains unknown. The objective of the present study was to correlate levels of D-Dimer (DD) with thrombus regression as assessed by duplex scanning.From 44 patients treated for acute DVT, DD were determined at diagnosis and at the end of initial heparin therapy of at least 5 days. Thrombus regression was measured by repeated duplex scanning at diagnosis and after 1 and 3 months.DD significantly decreased during heparin treatment as compared with values at presentation. DD levels were significantly higher in the group of patients without normalization of the DVT after 3 months (p = 0.003). A ninefold excess tendency was seen for DD levels > 1200 ng/ml at the end of initial treatment to be associated with poor resolution of the DVT [odds ratio 9.0, 0.95 confidence interval (CI) 2.3-35.4]. When the patients with an established malignancy were excluded, the differences were even more significant (p = 0.0004 for DD levels after initial treatment and an odds ratio of 17.5, 0.95 CI 3.3-92.5).These results suggest that increased DD levels after the initial phase of treatment are related to poor resolution of DVT after 3 months. These findings contribute to further insight into the process of thrombus regression. Furthermore high DD levels might help to identify the patients with a poor prognosis and could be useful to judge the efficacy of anticoagulant treatment.

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