Diagnostic value of the D-dimer test in deep vein thrombosis: improved results by a new assay method and by using discriminate levels

Previous studies have suggested that D-dimer testing reliably selects patients for whom duplex sonography should be performed for diagnosis of deep vein thrombosis (DVT). However, the interassay correlation is poor. Therefore, we tested four D-dimer methods for their ability to rule out DVT, including the Miniquant test, a new D-dimer assay method. Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated vs. duplex sonography. Twenty-nine of 108 (27%) patients with suspected DVT were diagnosed as having DVT by sonography. The Vidas enzyme-linked immunoabsorbent assay (ELISA) test, the Miniquant turbidimetric test and the latex agglutination test for D-dimer all provided discriminate values for achieving 100% sensitivity and 100% NPV. D-dimer results demonstrated higher specificity and PPV in the outpatient vs. the inpatient group. This probably reflects the higher proportion of inpatients with comorbid conditions, such as malignancy and postsurgery status, in whom D-dimer results show very poor specificity and PPV. The new Miniquant turbidimetric assay performed as well as the more established ELISA method. We conclude that the D-dimer tests were shown to possess the necessary sensitivity and NPV to be useful in screening patients with suspected DVT. A negative D-dimer test in selected patients could be helpful in reducing the number of sonograms performed for diagnosis of DVT.     

Performance of the automated and rapid STA Liatest D-dimer on the STA-R analyzer

OBJECTIVE: The aim of the present study was to investigate the accuracy indices of the new automated and rapid microlatex D-dimer assay, STA Liatest D-Di, on the STA-R analyzer and to compare it with established D-dimer assays. METHODS: D-dimer testing has been performed in 103 consecutive outpatients with suspected deep venous thrombosis (DVT). Diagnosis of DVT was established by contrast venography or color-coded duplex ultrasonography. D-dimers plasma concentrations were measured with the STA Liatest D-Di on the STA-R coagulation analyzer, with a reference ELISA technique (Asserachrom), with an automated quantitative latex-based immunoassay (Tinaquant) and with the VIDAS D-dimer test. RESULTS: In total, 103 eligible outpatients entered the current study and DVT was detected in 46 patients (44.6%). Two duplicate D-dimer measurement with the STA Liatest D-Di revealed excellent correlation (r(S)=0.996) and almost identical sensitivity (each 98%), specificity (49% and 50%), negative predictive value (NPV; each 97%), positive predictive value (PPV; 61% and 62%) and exclusion rate (27% and 28%), respectively. Comparison of the STA Liatest D-Di with the other D-dimer tests revealed highly significant correlations (r(S)=0.951-0.979), highly comparable regression and excellent agreement in clinical interpretation of the test results (kappa coefficients 0.812-0.856). Moreover, sensitivity, specificity, NPV, PPV and exclusion rate at a cut-off level of 500 ng/ml were in the same range for the STA Liatest D-Di when compared with the other D-dimer tests. CONCLUSION: The Liatest D-Di performed on the coagulation analyzer STA-R compares favorable with the VIDAS, Tinaquant and Asserachrom D-dimer tests and is suitable for the safe exclusion of DVT in symptomatic outpatients. The test can be included in an algorithm for DVT diagnosis including other diagnostic tools.     

Exclusion of venous thromboembolism: evaluation of D-Dimer PLUS for the quantitative determination of D-dimer

The objective of this study was to evaluate if D-Dimer PLUS (Dade Behring, USA), a rapid fully automated assay, could be used as an initial screening test in the diagnosis of venous thromboembolism (VTE). Samples from 274 consecutive symptomatic patients with suspected pulmonary embolism (n=229; 79% outpatients, 21% inpatients), deep venous thrombosis (n=37; 84% outpatients, 16% inpatients) or suspected for both complications (n=8) were tested with this D-dimer assay with a Sysmex CA-1500 Coagulation Analyzer. Clinical probability for pulmonary embolism (PE) or deep venous thrombosis (DVT) was staged according to a pretest risk score proposed by Wells. Final diagnosis of PE and/or DVT was established by spiral-computed tomography of the pulmonary arteries or compression ultrasonography, respectively. PE was diagnosed in 13.5% of the patients, whereas DVT was confirmed in 17.7% of the patients. The optimal cut-off value for exclusion of venous thromboembolism was 130 mug/l, and sensitivity, specificity and negative predictive value (NPV) were 95.0% (95% CI: 92.4-97.6), 30.4% (95% CI: 25.0-35.8) and 97.2% (95% CI: 95.2-99.2), respectively. In fact, two patient with PE were missed using D-Dimer PLUS; both cases were outpatients. In conclusion, this assay appears to be safe when implemented in an algorithm based on clinical assessment, D-dimer concentration, and radiological diagnostic techniques to stratify the risk for PE or DVT. However, higher sensitivities and negative predictive values were claimed in the scarce published reports for the D-Dimer PLUS assay than found in this study.     

Results of a new rapid d-dimer assay (cardiac d-dimer) in the diagnosis of deep vein thrombosis.

The objective was to evaluate the accuracy of a new full blood rapid D-dimer assay in the diagnosis of suspected deep vein thrombosis (DVT). In 100 consecutive patients with suspected DVT, clinical probability was staged according to a pretest score proposed by Wells. For the determination of plasma D-dimer, heparin and citrate blood samples were drawn, and Cardiac D-dimer, STA-LIA, and Tina-quant tests were performed. Final diagnosis was confirmed either by duplex sonography or ascending venography. DVT was diagnosed in 37%, thrombophlebitis in 10%, and no venous thromboembolism was diagnosed in 52%. In 2% pulmonary embolism was detected and one patient was dismissed before final diagnosis. Cardiac D-dimer assay from citrate tubes showed a sensitivity of 88.6%, a specificity of 54%, a positive predictive value of 57.4%, and a negative predictive value of 87.1%. Nearly identical results were observed with heparin tubes. Corresponding results were 88.6%, 48%, 52.5%, and 85.7% for STA-LIA and 88.6%, 46%, 53.4%, and 85.2% for Tina-quant, respectively. In conclusion, we can say that Cardiac D-dimer is a rapid, whole blood assay with a great potential for clinical use. It can help in diagnosing DVT from citrate as well as heparin tubes with comparable sensitivity, specificity, positive and negative predictive values as STA-LIA and Tina-quant tests.     

D-dimer,other markers of haemostasis activation and soluble adhesion molecules in patients with different clinical probabilities of deep vein thrombosis

Two automated turbidimetric D-dimer assays (BC D-dimer Plus, Dade Behring, Marburg, Germany and Auto-Dimer, Biopool, Ume?, Sweden) were compared to two enzyme-linked immunosorbent assays (ELISAs) (Enzygnost D-dimer micro, Dade Behring and Asserachrome D-dimer, Diagnostica Stago, Asnières, France) and two rapid D-dimer assays (SimpliRed, Agen Biomedical, Brisbane, Australia and Minutex, Biopool) in out-patients with suspected deep vein thrombosis (DVT). In addition, the performance of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), and soluble adhesion molecules VCAM-1 and P-selectin for DVT diagnosis was assessed. One hundred and thirty-five consecutive out-patients with suspected DVT of the lower limb were included, and in 52 (39%), DVT was confirmed by compression ultrasound. All D-dimer assays investigated reliably excluded DVT in those patients without DVT irrespective of their pre-test clinical probability of DVT. One D-dimer ELISA (Dade Behring) gave the highest area under the receiver operating characteristic (ROC) curve compared to other assays, and therefore, this was the most accurate assay in differentiating patients with from patients without DVT. The diagnostic performance of one automated turbidimetric assay (Auto Dimer, Biopool) was similar to ELISA and its convenience close to rapid latex agglutination assays. Most patients with a high pre-test clinical probability of DVT had positive D-dimer regardless of the presence or absence of DVT, which decreased the specificity of the tests and made D-dimer determination less useful for this group of patients. Because the diagnostic accuracy [sensitivity, specificity, negative (NPV) and positive predictive value (PPV)] of F1+2, TAT, VCAM-1 and P-selectin was inferior to D-dimer assay, these assays could not substitute or supplement D-dimer testing in diagnosis of DVT. Levels of VCAM-1 and P-selectin were increased in patients with DVT and should therefore be investigated further to clarify their role in DVT.     

Multicenter evaluation of a new quantitative highly sensitive D-dimer assay, the Hemosil® D-dimer HS 500, in patients with clinically suspected venous thromboembolism

Introduction

D-dimer testing is widely used in conjunction with clinical pretest probability (PTP) for venous thromboembolism (VTE) exclusion. We report on a multicenter evaluation of a new, automated, latex enhanced turbidimetric immunoassay [HemosIL® D-Dimer HS 500, Instrumentation Laboratory (IL)].

Materials and Methods

747 consecutive outpatients with suspected proximal deep vein thrombosis (DVT, n = 401) or pulmonary embolism (PE, n = 346) were evaluated at four university hospitals in a management study with a 3 month follow-up. Samples were tested at each center using the new D-dimer assay on an automated coagulation analyzer [ACL TOP (IL)], with clinical cut-off for VTE at 500 ng/mL (FEU).

Results

The sensitivity and negative predictive value (NPV) were 100% for all PTP subgroups (no false negative results); for both sensitivity and NPV the lower limit of the 95% CI in patients with moderate/low PTP was higher than 95%. The overall specificity was 45.1% (95%CI: 41.1-49.3%). Higher specificity value was recorded in the low PTP subgroup [49.2% (95%CI: 41.7-56.7)]. No significant differences were found between patients suspected of having DVT or PE; sensitivity and NPV were 100%. The reproducibility of the assay was good, being the total CVs% less than 10% for D-dimer concentration near the clinical cut-off.

Conclusions

The new, highly sensitive D-dimer assay proved to be accurate when used for VTE diagnostic work-up in outpatients. Based on 100% sensitivity and NPV and lower limit of the 95% CI higher than 95%, the assay can be used as a stand-alone test in patients with non high PTP.     

A rapid and quantitative D-Dimer assay in whole blood and plasma on the point-of-care PATHFAST analyzer

The objective of this study was to evaluate the accuracy indices of the new rapid and quantitative PATHFAST D-Dimer assay in patients with clinically suspected deep-vein thrombosis (DVT). Eighty two consecutive patients (34% DVT, 66% non-DVT) with suspected DVT of a lower limb were tested with the D-Dimer assay with a PATHFAST analyzer. The diagnostic value of the PATHFAST D-Dimer assay (which is based on the principle of a chemiluminescent enzyme immunoassay) for DVT was evaluated with pre-test clinical probability, compression ultrasonography (CUS). Furthermore, each patient underwent contrast venography and computed tomography, if necessary. The sensitivity and specificity of the D-Dimer assay using 0.570 mug/mL FEU as a clinical cut-off value was found to be 100% and 63.2%, respectively, for the diagnosis of DVT, with a positive predictive value (PPV) and negative predictive value (NPV) of 66.7% and 100%, respectively. The correlation between the results of PATHFAST D-Dimer and VIDAS D-Dimer was acceptable (y=1.134x+0.003, r=0.902). The test reproducibility was good (CV%: from 4.0% to 5.0% for plasma and from 7.1% to 7.5% for whole blood) and the total imprecision was very good (CV%: 3.6-5.7%). Whole blood as well as plasma can be used as samples in this assay (y=1.013x-0.010, r=0.971 for heparinized specimens; y=1.068x+0.003, r=0.989 for citrated specimens). Because of its high sensitivity and NPV PATHFAST D-Dimer assay can be useful for the rapid rule out of DVT in patients admitted with suspected thrombosis.     

Analytical and clinical validation of a new point-of-care testing system for determination of D-Dimer in human blood

D-Dimer testing is used for exclusion of deep venous thrombosis (DVT). AQT90 FLEX D-Dimer (AQT D-Dimer) is a novel time-resolved fluorescence based point-of-care test for quantification of D-Dimer in whole blood or plasma. Presently we have determined the analytical and clinical performance of AQT D-Dimer and compared it with four routine D-Dimer assays.The within-run CV of AQT D-Dimer was 3.8-7.2% and the between-run CV was 5.7- 9.7%. Excellent agreement was found between the D-Dimer concentrations recorded in citrate-, heparin- and EDTA stabilised blood. The plasma concentration of D-Dimer was determined with AQT D-Dimer, AxSYM, Biopool Auto-Dimer, STA-Liatest and Vidas New in 170 consecutive patients suspected for DVT. Phlebograms were positive in 64 patients (22 distal, 42 proximal). ROC-curves (ROC), the negative and positive predictive values (NPV, PPV), the sensitivity and specificity of the tests were compared. The area under ROC was comparable for all tests. NPV for all DVT was 87-88%, the sensitivity was 88-92% and the PPV was 45-55%. For proximal DVT the NPV and sensitivity were 100% for all tests, whereas the PPV was 37-48%. For distal DVT we obtained a NPV of 87-88%. The sensitivity was 64-77%, the PPV was 19-24% whereas a specificity of 32-58% was observed.The AQT D-Dimer demonstrates excellent analytical and diagnostic performance. The test is rapidly performed and the measuring range of the assay is wide. The NPV, PPV, specificity, sensitivity and AUC of AQT D-Dimer for both proximal and distal DVT are comparable to routine D-Dimer assays.     

Rapid ELISA assay for plasma D-dimer in the diagnosis of segmental and subsegmental pulmonary embolism. A comparison with pulmonary angiography

STUDY OBJECTIVE: To assess the accuracy of a rapid ELISA D-dimer assay for the exclusion of pulmonary embolism (PE) in patients suspected of PE, using pulmonary angiography alone as reference method rather than a diagnostic strategy including lung scintigraphy and leg vein ultrasonography. METHODS: In 342 patients who were examined by pulmonary angiography to diagnose or exclude PE, the accuracy of the quantitative rapid VIDAS D-dimer test for the exclusion of PE was evaluated retrospectively. D-dimer levels were assayed in frozen samples collected during the diagnostic work-up at the time of pulmonary angiography while on treatment with unfractionated heparin for 1-2 days. RESULTS: Mean plasma D-dimer concentrations were increased in patients with angiographic evidence of PE (P <0.0001). The sensitivity of D-dimer for segmental PE was 98%, its accuracy in excluding segmental PE was 99%, higher than the respective figures for subsegmental PE (76% and 94%; P <0.01, both). For both forms of PE combined the sensitivity was 90% and the negative predictive value 94%. DISCUSSION: The sensitivity and negative predictive values reported here, are low compared with previous studies using the same rapid ELISA D-dimer assay. This probably reflects an overlooking of mild cases of subsegmental PE in previous studies, although a reduction of D-dimer levels by the heparin pretreatment may have contributed to part of the discrepancy. Prospective studies are needed to clarify this issue.     

The role of fibrin monomers in optimizing the diagnostic work-up of deep vein thrombosis

Despite the use of a clinical score and D-dimers to exclude deep vein thrombosis (DVT), the majority of patients still need repeated ultrasound (US). The aim of the study was to investigate whether fibrin monomers (FMs), as markers of thrombin generation, have additional value in the diagnosis of DVT. This is a posthoc analysis of 464 outpatients, participants in a management study using D-dimers (Tina-Quant and a clinical score in the exclusion of DVT. Two new FM assays (Auto LIA-FM and IATRO SF, Japan) were performed. Overall sensitivity, negative predictive value (NPV) and specificity of the D-dimer test were 98%, 98% and 42%. The optimal cut-off point for the Auto LIA-FM test was 相似文献   

D-dimer testing in the diagnosis of acute venous thromboembolism

Patients with acute VTE require clinical assessment and objective testing to be accurately diagnosed. Almost all patients with acute VTE have an elevated D-dimer level. An elevated D-dimer is associated with many illnesses, and therefore, is not specific for VTE. D-dimer tests can have a high sensitivity, however, which is useful because a normal test excludes the diagnosis of VTE. D-dimer testing is most appropriate in the assessment of outpatients because the prevalence of disease and the likelihood of comorbid conditions are lower than in inpatient populations, making a test of exclusion particularly valuable. Accuracy studies using conventional ELISA assays have confirmed that a test with a high sensitivity can be used to exclude a diagnosis of VTE, but conventional ELISA testing is not practical. Studies of more practical D-dimer testing indicate that, for patients with suspected DVT or PE, the need for serial testing or further investigation can be reduced if normal results are obtained using assays with a high sensitivity. There are, however, many sources of variation in the test characteristics of D-dimer assays. Therefore there is no reassurance that results from one manufacturer's test are applicable to other tests and different investigators may obtain varied results when using the same manufacturer's product. In addition, the results of D-dimer accuracy studies lack generalizability. This lack of generalizability has led to the recommendation that clinicians await the results of management studies before adopting the routine use of D-dimer assays in the diagnosis of VTE. Further, it may be reasonable to perform an accuracy study when planning to adopt a specific D-dimer assay from a published management trial, to be confident of its characteristics can be reproduced. In the management of patients with suspected DVT, rapid ELISA tests show promise as a practical D-dimer test, in that they have a sensitivity similar to that of the conventional ELISA assay. Two management studies have recently confirmed that a normal D-dimer result (using the SimpliRED whole-blood assay or the Instant IA rapid ELISA) in combination with a noninvasive test or a clinical model can reliably exclude DVT in outpatients. Use of a clinical model can reduce the need for VU, and the combination of a clinical model and D-dimer testing could further reduce the number of VU procedures required. As noted by Wells et al, who recently published a clinical model, however, a normal D-dimer result was most accurate in the patients with a low pretest likelihood (NPV = 99.5%) and least accurate in patients with a high pretest likelihood (NPV = 85.7%) Patients with a low pretest likelihood and a normal D-dimer are the largest proportion of outpatients referred for testing, and considerable resources may be saved if additional management studies confirm the usefulness of D-dimer testing in such patients. In patients with suspected PE, there is a lack of published management trials despite a number of accuracy studies indicating that D-dimer testing may be useful as a method of PE diagnosis exclusion. Recent results, however, from an accuracy study of patients with suspected PE who had D-dimer testing complement the findings of Wells et al in patients with suspected DVT. Using a standardized clinical model of PE in combination with a SimpliRED D-dimer assay, Ginsberg and colleagues found that the combination of a low pretest likelihood and a normal D-dimer had a negative predictive value of 99%, whereas the negative predictive value was only 78% in patients with a high pretest likelihood and a normal D-dimer. Similar to the findings in DVT, these results indicate that D-dimer testing is most useful in patients with a low pretest likelihood for PE and raise the possibility that such patients may not require lung scans. This finding is currently being evaluated in a prospective management trial.     

Exclusion of pulmonary embolism using C-reactive protein and D-dimer. A prospective comparison

Our goal was to evaluate the diagnostic utility of C-reactive protein (CRP) alone or combined with clinical probability assessment in patients with suspected pulmonary embolism (PE), and to compare its performance to a D-dimer assay. We conducted a prospective study in which we performed a common immuno-turbidimetric CRP test and a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer test in 259 consecutive outpatients with suspected PE at the emergency department of a teaching hospital. We assessed clinical probability of PE by a validated prediction rule overridden by clinical judgment. Patients with D-dimer levels > or = 500 microg/l underwent a work-up consisting of lower-limb venous ultrasound, spiral computerized tomography, ventilation-perfusion scan, or pulmonary angiography. Patients were followed up for three months. Seventy-seven (30%) of the patients had PE. The CRP alone had a sensitivity of 84% (95% confidence interval [CI).: 74 to 92%) and a negative predictive value (NPV) of 87% (95% CI: 78 to 93%) at a cutpoint of 5 mg/l. Overall, 61 (24%) patients with a low clinical probability of PE had a CRP < 5 mg/l. Due to the low prevalence of PE (9%) in this subgroup, the NPV increased to 97% (95% CI: 89 to 100%).The D-dimer (cutpoint 500 micro g/l) showed a sensitivity of 100% (95% CI: 95 to 100%) and a NPV of 100% (95% CI: 94 to 100%) irrespective of clinical probability and accurately rule out PE in 56 (22%) patients. Standard CRP tests alone or combined with clinical probability assessment cannot safely exclude PE.     

Preliminary evaluation of two new rapid immunoturbidimetric D-dimer assays in patients with clinically suspected venous thromboembolism (VTE)

The practical utility and diagnostic accuracy of two new rapid, automated and quantitative immunoturbidimetric D-dimer methods have been evaluated in a population of 123 randomly selected patients with suspected VTE. The STA Liatest D-dimer and MDA D-dimer methods are based on the photo-optical measurement of the rate of agglutination of antibody-coated latex particles. The VIDAS D-dimer automated Elisa was used as the reference method. Diagnosis was confirmed in 51 patients (29 PE, 19 DVT, 3 DVT+PE). The immunoturbidimetric methods compared favorably with the VIDAS Elisa as judged from the correlation coefficients of linear regression lines (r = 0.82, MDA vs VIDAS; r = 0.75, STA vs VIDAS) and areas under the curve of ROC plots (VIDAS 0.83; STA 0.83; MDA 0.81). At a discriminant value of 500 ng/mL, all three D-dimer assays showed high sensitivity (96-98%), high NPV (93-97%) and moderate specificity (39-42%). Reproducibility of results around the cut-off is an important aspect of the diagnostic utility of D-dimer assays. CV's of duplicate determinations in this critical zone showed average values of 5.4% and 17.0% for MDA and STA, respectively. These data demonstrate that such rapid and automated latex-based methods for the quantitative measurement of D-dimer hold promise as reliable and cost-efficient approaches for the exclusion of VTE. Prospective patient management studies will be required to confirm this.     

Performance of two relatively new quantitative D-dimer assays (Innovance D-dimer and AxSYM D-dimer) for the exclusion of deep vein thrombosis

Introduction

D-dimer assays are now widely used as the first-line test in the diagnostic algorithm of suspected deep vein thrombosis (DVT). The aim of this study was to evaluate the performance of two relatively new quantitative D-Dimer assays (Innovance™ and AxSYM®) by comparison with a clinical gold standard.

Patients and methods

311 samples from outpatients with clinical suspicion of DVT, included in a prospective management study, was analysed (prevalence of DVT 23%). The diagnostic workup included estimation of pre-test probability, D-dimer determination, objective imaging as well as 3 month clinical follow up of negative patients.

Results

No significant differences were seen in sensitivity and negative predictive values between Innovance, AxSYM and the reference assays. The area under the ROC curve was slightly lower for the AxSYM assay and the correlation to the reference assays was only moderate (r < 0.8) whereas the agreement with the Vidas assay was near excellent (κ = 0.8). The Innovance assay reached the highest AUC, showed a strong correlation with the reference assays (r ≥ 0.9) and a good agreement with the Vidas assay (κ = 0.76). In combination with a low pre-test probability score the Innovance assay reached a NPV of 100% (95% CI, 92-100) and the AxSYM assay 98% (95% CI, 87-100).

Conclusion

The Innovance and AxSYM assays show an overall good and comparable performance for the exclusion of DVT when compared to the established assays. Our results for the AxSYM assay indicate that the optimal cut-off value needs to be further evaluated.     

Combined use of clinical pre-test probability and D-dimer test in the diagnosis of preoperative deep venous thrombosis in colorectal cancer patients

The preoperative prevalence of deep venous thrombosis (DVT) in patients with colorectal cancer may be as high as 8%. In order to minimize the risk of pulmonary embolism, it is important to rule out preoperative DVT. A large study has confirmed that a negative D-dimer test in combination with a low clinical pre-test probability (PTP) can be safely used to rule out the tentative diagnosis of DVT in cancer patients. However, the accuracy in colorectal cancer patients is uncertain. This study assessed the diagnostic accuracy of a quantitative D-dimer assay in combination with the PTP score in ruling out preoperative DVT in colorectal cancer patients admitted for surgery. Preoperative D-dimer test and compression ultrasonography for DVT were performed in 193 consecutive patients with newly diagnosed colorectal cancer. Diagnostic accuracy indices of the D-dimer test were assessed according to the PTP score. The negative predictive value, positive predictive value, sensitivity and specificity were 99% (95% confidence interval (CI), 95-100%), 17% (95% CI, 9-26), 93% (95% CI, 68-100%) and 61% (95% CI, 53-68%), respectively. In conclusion, the combined use of pre-test probability and D-dimer test may be useful in ruling out preoperative DVT in colorectal cancer patients admitted for surgery.     

Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis

D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis (DVT) in patients without severe concomitant diseases. We have determined diagnostic sensitivity and specificity of a new point-of-care rapid assay for quantitative determination of D-dimer in heparinized whole blood in outpatients with suspected DVT. In 19 participating centers, 637 patients were included in the study, of which 77 were excluded, the majority because of inadequate documentation of analytical quality control measures. DVT was diagnosed in 223 of the remaining 560 patients by duplex ultrasound examination. The POC D-dimer assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D-dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879 +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina-quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences were not statistically significant. The new whole blood POC D-dimer assay is a reliable tool for exclusion of DVT in symptomatic outpatients, displaying a comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.     

Diagnostic performance of complete lower limb venous ultrasound in patients with clinically suspected acute pulmonary embolism

A limited ultrasound (US) confined to the popliteal and femoral veins is usually performed to detect deep vein thrombosis (DVT) in patients with clinically suspected acute pulmonary embolism (PE). Our objective was to assess the diagnostic accuracy of complete lower limb US examining both the proximal and distal veins in this setting. In this prospective study, 210 consecutive patients were included. Complete US was performed by independent operators and compared blindly with a reference strategy combining clinical probability, ventilation perfusion scan and pulmonary angiography to a three-month clinical follow-up. Simultaneously, VIDAS D-dimer (DD) assay and helical computed tomography (HCT) of the lungs were assessed independently and blindly. PE was present in 74 patients (35%). Complete US detected DVT in 91 patients (43%), proximal in 51 and distal in 40. Sensitivity and specificity with a 0.95 confidence interval were respectively 0.93 [0.85 - 0.97] and 0.84 [0.77 - 0.89]. Limited US detected DVT in only 46 patients (22%). Sensitivity and specificity were respectively 0.55 [0.44 - 0.66] and 0.96 [0.92 - 0.98]. For DD they were 0.92 [0.83 - 0.96] and 0.24 [0.17 - 0.32] and for HCT 0.84 [0.73 - 0.90] and 0.87 [0.80 - 0.92]. Complete lower limb US has higher sensitivity and capacity to exclude PE than limited US, but a slightly lower specificity. Complete US results also compared favourably with those of HCT and DD. The utility of including this method in diagnostic strategies for PE needs to be assessed in cost-effectiveness analysis and in outcome studies.     

A new rapid bedside assay for quantitative testing of D-Dimer (Cardiac D-Dimer) in the diagnostic work-up for deep vein thrombosis

The accuracy of a new bedside, rapid and quantitative D-Dimer assay (Cardiac D-Dimer) was evaluated in outpatients with clinically suspected deep vein thrombosis (DVT); VIDAS test was used as reference method. Eighty consecutive outpatients with suspected DVT of a lower limb were included in the study. Patients were classified as DVT positive or negative according to results of objective test (serial CUS), pretest clinical probability and 3-month follow-up. DVT was diagnosed in 32/80 patients (40%). The performance of the two D-Dimer assays was comparable, as indicated by the areas under the ROC curves (0.89 and 0.88, for Cardiac D-Dimer and VIDAS, respectively) and the coefficient of correlation (r=0.91). The reproducibility of the test was acceptable (from 6.2% to 12.0%). The sensitivity and negative predictive values were 100% for both tests. The specificity (SP) and positive predictive values (PPV) were similar (SP: 50.0% and 52.0%, PPV: 57.1% and 58.2%, for Cardiac D-Dimer and VIDAS, respectively). The Cardiac D-Dimer test proved to be very accurate and produced results fully comparable to those obtained with the VIDAS test. Since the test can be directly performed in the emergency room within a few minutes, it seems to have great clinical potential. The place of this assay in the diagnostic strategy of DVT remains to be determined in prospective management studies.     

Performances of the fibrin monomer test for the exclusion of pulmonary embolism in symptomatic outpatients

Many studies have shown that D-dimer determinations can be used for the exclusion of venous thromboembolism in symptomatic outpatients, depending however on the method of D-dimer measurement. Another related assay, the Fibrin Monomer test which measures soluble fibrin levels in plasma by ELISA, is now available. We have evaluated the performances of this assay for the exclusion of pulmonary embolism (PE) in 426 consecutive outpatients presenting at the emergency ward of our institution. Diagnosis of PE was made by D-dimer measurement, compression ultrasonography, lung scintigraphy, venography and pulmonary angiography. With a cut-off of 3 microg/ml. the sensitivity and the negative predictive value were both 100% (95% CI: 97.1-100 and 96.3-100 respectively) and the specificity 33% (95 % CI: 25.7-38.1). With 4 microg/ml, the corresponding figures were 98.4 (95% CI: 94.4-99.8), 98.3 (95% CI: 94.1-99.8) and 39% (95% CI: 33.6-44.7) respectively. The prevalence of PE was 30%, the exclusion rates were 23 and 27% for either cut-off. When compared with a reference D-dimer assay (Asserachrom D-Di), a good correlation was observed. In conclusion, this is the first study suggesting the interest of this Fibrin Monomer test to rule out PE; these results, however, need to be confirmed by other studies.     

Accuracy of the ice test in the diagnosis of myasthenia gravis in patients with ptosis

Introduction: Several studies have reported high diagnostic sensitivity and specificity for the ice test in myasthenia gravis. All of the studies employed a case–control design, in which the diagnosis was already known at the time of the test for both patients and controls, leading to case selection bias. This suggests that the available literature substantially overestimates the diagnostic utility of these tests. Methods: A retrospective cohort study without selection bias was performed to examine the sensitivity and specificity of the ice test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the ice test were determined by means of a 2 × 2 table. Results: The ice test has a sensitivity of 0.92 (95% CI 0.62–1.00), specificity of 0.79 (95% CI 0.56–1.00), PPV of 0.73 (95% CI 0.48–0.90), and NPV of 0.94 (95% CI 0.70–1.00). Conclusions: Due to its high negative predictive value the ice test is still a reliable and useful bed‐side test. Muscle Nerve 48 : 902–904, 2013