SimpliRED D-dimer Assay Research Articles

The Inappropriate Use of the SimpliRed D-Dimer Assay in the Diagnosis of Venous Thromboembolism,

Abstract 4207 Introduction: Multiple diagnostic tests are available to evaluate patients with suspected venous thromboembolism (VTE). The diagnosis of VTE involves combining a clinical pre-test probability using validated scoring systems such as the Wells score (Wells, 2000) with laboratory testing and/or diagnostic imaging. The D-dimer assay is a highly sensitive screening test for VTE that has been shown to safely exclude VTE in patients with low pre-test probability (Kearon, 2006). This project was aimed at determining if the SimpliRed D-dimer assay is used appropriately at our institution. More specifically, we wanted to determine if it is being used in patients with low clinical probability of pulmonary embolism (PE) or deep vein thrombosis (DVT) based on the Wells score and in the absence of other variables which could falsely elevate the D-dimer as determined by expert opinion. Methods: A retrospective review of 199 charts from St. Joseph's Hospital in Hamilton, Ontario from March 2007 to April 2007 was performed. Information was obtained on a standardized data collection form. Duplicate data extraction of the first 20 charts was undertaken to ensure concordance. Results: Of the 199 SimpliRed D-dimer assays ordered during this time period, 84 (42%) were inappropriate. Forty (48%) were considered inappropriate because they were ordered in patients with a moderate to high pre-test probability for VTE while 44 (52%) were ordered in patients with a co-existing medical condition that should have precluded the use of the assay including sepsis, pregnancy, active malignancy, and recent major surgery. The D-dimer assay was positive in 51 (61%) of the 84 inappropriate tests and 31 of these patients underwent further testing. Twelve patients were eventually diagnosed with VTE. The remaining 20 patients with a positive D-dimer ordered in an inappropriate context did not undergo further testing to investigate the positive result. Thirty-three (41%) patients with an inappropriately ordered D-dimer had a negative result and did not undergo further investigation. For patients with an appropriately ordered D-dimer assay (115 out of 199 or 58%), 96 had a negative D-dimer result. Of the 96, 28 patients went on to further testing including Doppler ultrasounds, ventilation/perfusion scans, or CT scans. One of the 28 patients had VTE. Conclusions: This retrospective review revealed that 42% of the SimpliRed D-dimer assays ordered at our institution are inappropriate. Thirty three patients identified in this review who had a non-low pretest probability and negative D-dimer did not undergo further testing. A negative D-dimer result in these patients is not sufficient to rule out VTE – the lack of further appropriate testing could have led to missed VTE events. D-dimer assays, including the one used at our institution, have been shown to reliably rule out both DVT and PE in patients with a low pre-test probability (Kearon, 2006). At our institution 28 patients with an appropriately ordered, negative D-dimer underwent further testing that would not be recommended based on current diagnostic algorithms. These investigations are costly and expose the patient to possible unnecessary harm (such as radiation exposure from CT scans or use of anticoagulants until testing can be arranged). Of the patients with a negative D-dimer who went on to have further investigations, 1 was found to have VTE. This patient may have had a higher clinical pre-test probability than was assigned retrospectively from limited chart records. If the pre-test score assigned was accurate, this suggests that the failure rate of the D-dimer for ruling out VTE in a patient with a low pre-test probability is 3.6% (0.1% to 18.3%) in our series, higher than previously reported (Kearon, 2006). Disclosures: Crowther: Pfizer: Consultancy, Research Funding; Leo Pharma: Consultancy, Research Funding; Bayer: Consultancy; CSL: Consultancy; BI: Consultancy, Research Funding; Behring: Consultancy; Octapharma: Consultancy; Artisan: Consultancy.

Use of SimpliRED D-dimer assay and computerised tomography in the diagnosis of acute pulmonary embolism

Background: The utility of D-dimer in the diagnostic workup of pulmonary embolism has been established. Several D-dimer tests are available with different sensitivities and specificities. SimpliRED D-dimer is a rapid qualitative whole blood D-dimer assay suitable for bedside use. Objective: To assess the utility of the SimpliRED D-dimer test in patients with suspected acute pulmonary embolism in the absence of formal ‘risk scoring’. Design: A prospective study measuring SimpliRED D-dimer in unselected patients undergoing computed tomographic pulmonary angiography (CTPA) examination for suspected acute pulmonary embolism. Main outcome measures: D-dimer and CTPA results were compared. Sensitivity, specificity, and positive and negative predictive values of SimpliRED D-dimer were calculated for the unselected patient group. Results: Forty-seven patients underwent D-dimer testing and CTPA. SimpliRED D-dimer was positive in 23 and negative in 24 patients. D-dimer was positive in only 6 (50%) of the 12 patients with positive CTPA. Of the 35 with negative CTPA, 17 had positive D-dimer. The positive predictive value of the D-dimer was 26.1 % and the negative predictive value 75.0%. Conclusion: SimpliRED D-dimer should not be used in the diagnosis of pulmonary embolism in the absence of risk scoring.

Is pretest probability assessment on emergency department patients with suspected venous thromboembolism documented before SimpliRED D-dimer testing?

The SimpliRED D-dimer assay is commonly ordered by emergency physicians for suspected pulmonary embolus or deep venous thrombosis. A pretest probability (PTP) assessment is required for the results of this diagnostic test to be interpreted correctly and applied appropriately. Without this assessment, the physician may misinterpret the test results and proceed to unnecessary diagnostic imaging (DI) or inappropriate discharge. Our objectives were to measure the documentation rate of PTP for emergency department (ED) patients on whom a SimpliRED D-dimer assay was performed for suspected venous thromboembolism (VTE) and to determine if the clinical management decisions that followed were in keeping with current recommendations. In this medical record review, we used a random number generator to select 100 charts from all 760 patients who had a SimpliRED D-dimer performed during a 3-month period at an academic tertiary care centre with 3 EDs. Trained data abstractors, blinded to the study hypothesis, abstracted explicitly defined data from each chart. An independent abstractor assessed the reliability of 15 of the charts that were randomly chosen. Suspicion of VTE was documented in 97 of the 100 charts. There was no documentation of PTP assessment for 62 of the 97 cases. Ten had a positive D-dimer but 5 of these had no evidence of subsequent DI. Of the 97 charts reviewed, 24 documented decisions were in discordance with published clinical management recommendations for VTE. In the majority of ED cases of suspected VTE, PTP assessment was not documented and approximately one-quarter of these documented decisions were in discordance with established recommendations for the given test results. This suggests that PTP assessments are not being conducted in a significant proportion of cases and the diagnostic test results are misinterpreted, applied incorrectly or both.

A Red Blood Cell Agglutination D-dimer Test to Exclude Deep Venous Thrombosis in Pregnancy: Chan W-S, Chunilal S, Lee A, et al. Ann Intern Med 2007;147:165–70

This prospective cohort study was designed to determine the sensitivity, specificity, negative predictive value, and false-positive rates of the SimpliRED (latex agglutination) D-dimer assay for the diagnosis of deep venous thrombosis (DVT) in pregnant women. The authors enrolled 149 consecutive pregnant women with suspected DVT over a 5-year period. All patients had the SimpliRED D-dimer assay performed at presentation along with compression ultrasonography (US). All patients also had a minimum of 3 months of clinical follow-up. Twelve cases of DVT were diagnosed by US at initial presentation, and 1 patient developed pulmonary embolism within the follow-up period, yielding an overall prevalence of venous thromboembolic disease of 8.7% (95% confidence interval [CI] 5.2–14.4%). The sensitivity of the D-dimer assay was 100% (95% CI 77–100%) and the specificity was 60% (95% CI 52–68%). The negative predictive value of the assay was 100% (95% CI 95–100%). False-positive rates were 0% (95% CI 0–60%), 24% (95% CI 14–37%) and 51% (95% CI 40–61%) in the first, second, and third trimesters, respectively. The authors conclude that the SimpliRED D-dimer assay may be clinically useful in pregnancy, and a negative result effectively excludes DVT.

A Red Blood Cell Agglutination d-Dimer Test to Exclude Deep Venous Thrombosis in Pregnancy

Along with compression ultrasonography of the legs, widely viewed as the preferred test for diagnosing deep venous thrombosis (DVT), d-dimer testing frequently is carried out because it is highly sensitive and a negative result may preclude the need for further testing. The latter test has, however, not been evaluated for diagnosing DVT in pregnancy because of its relatively low specificity. This study sought to determine the utility of the easily performed SimpliRED assay for diagnosing DVT in pregnant women. A prospective cohort study, conducted at university-affiliated Canadian hospitals, enrolled 149 consecutive pregnant women suspected of having DVT. They underwent compression ultrasonography on days 0, 3, and 7, and were followed up clinically after 3 months to determine the presence or absence of DVT. Whole blood samples were obtained at initial presentation for the SimpliRED assay. In this rapid test, blood is mixed with a conjugate of monoclonal antibody to d-dimer linked to a monoclonal antibody that binds to the red cell surface. High levels of d-dimer cause agglutination. DVT was diagnosed in 13 of the 149 participants (8.7%). All cases but one were diagnosed from initial compression ultrasonography. The SimpliRED assay was 100% sensitive and 60% specific, and had a negative predictive value of 100%. When stratifying the results of d-dimer testing by the presence or absence of patient risk factors, women having positive d-dimer test results in the first trimester of pregnancy had a high prevalence of DVT (62.5%) regardless of whether or not risk factors were present. Among pregnant women in whom DVT was not diagnosed, the assay was positive in no women in the first trimester, 24% of second-trimester pregnancies, and 51% of women in the third trimester. These findings indicate that the SimpliRED d-dimer assay is clinically useful in pregnant women suspected of having DVT. A negative result effectively excludes this diagnosis. The test appears to be useful for at least the first 2 trimesters of pregnancy.

Doubts and certainness in diagnosis of pulmonary embolism in the elderly

We have read with much interest the article of Punukollu et al. [1] recently published in your Journal and focused on differences in clinical presentation and treatment of pulmonary embolism (PE) in elderly compared with younger patients. This article arises important reflections on clinical picture and diagnostic approach to PE in the elderly that it should be important to highlight. Diagnosis of PE in fact is difficult in the elderly because of the nonspecificity of the clinical picture and the instrumental and laboratory tests, making this disease one of the main misdiagnoses in geriatric patients [2]. It is actually accepted in literature and widespread in guidelines [3–5] or recommendations [6] that suspicion of PE is based on history, analysis of risk factors for venous thromboembolic diseases, symptoms and signs together with first level instrumental examinations such as 12-leads electrocardiography (ECG), chest X-ray and blood arterial gas analysis (BGA). Once that clinical suspicion exists a clinical pre-test probability should be performed based on one of the available and validated test [7–10]. Low, moderate or high pre-test probability of PE should be integrated with immunoturbidimetric, simpli-RED or ELISA D-Dimer assay [11]. PE could reasonably be excluded when low pre-test probability and negative DDimer (<500 ng/mL) exist. In the other cases PE should be

Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review

Objective To summarise the evidence supporting the use of rapid D-dimer testing combined with estimation of clinical probability to exclude the diagnosis of deep venous thrombosis among outpatients.Data sources Medline...

Emergency department investigation of deep vein thrombosis

Objectives: To apply a previously validated clinical model for predicting pre-test probability of deep vein thrombosis (DVT) to patients attending an emergency department with symptoms suggestive of DVT and assess...

Diagnostic Accuracy of Triage Tests to Exclude Pulmonary Embolism

We performed a study in 403 prospectively included patients with suspected pulmonary embolism to compare the accuracy of a combination of the SimpliRED D-dimer assay and an intuitive clinical probability estimate with either one alone. Based on a conjoint diagnostic refer, ence standard, including ventilation-perfusion lung scintigraphy and pulmonary angiography, the prevalence of pulmonary embolism was 31%. We demonstrated a high sensitivity (98%, 95% CI 95-100) and negative predictive value (94%, 95% CI 79-99) for the combination of the two tests. These figures were more favorable than for either test alone. The specificity of the combination was lower (11%, 95% CI 9-12) and consequently the proportion of patients in whom further diagnostic tests would have been avoided was only 8%. We conclude that the combined use of the SimpliRED test and the clinical probability estimate attains a higher sensitivity than either test alone. However, there remains a risk of false negatives and the exclusion efficiency is limited.

SimpliRED D-dimer assay did not rule out venous thromboembolism in the emergency department

Source Citation Farrell S, Hayes T, Shaw M. A negative SimpliRED D-dimer assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients. A...

A negative simpliRED D-Dimer Assay result does not exclude the diagnosis of deep vein thrombosis or pulmonary embolus in emergency department patients

Study objective: To determine whether a negative SimpliRED D -dimer assay result excludes the diagnosis of deep vein thrombosis (DVT) or pulmonary embolus (PE) in emergency department patients. Methods: This prospective, institutional review board–approved, clinical trial enrolled consecutive adult ED patients with the suspected diagnosis of venous thromboembolism (VTE) (DVT or PE). Initial ED evaluation included the SimpliRED D -dimer assay (American Diagnostica Inc, Greenwich, CT). Physicians were blinded to assay results. The diagnosis of DVT was made with positive findings on lower-extremity ultrasonography. PE was confirmed by a high-probability ventilation/perfusion (V/Q) scan, a positive pulmonary angiogram, or a positive finding on lower-extremity ultrasonography. A presumptive diagnosis of VTE was made in patients who had VTE at follow-up or unexplained death during the study period. Results: One hundred ninety-eight patients were enrolled during the study period. Twenty-five patients were excluded from data analysis; 9 had no diagnostic testing and 16 were lost to follow-up. Of the 173 patients analyzed, 57 (33%) had VTE—16 of 48 evaluated for DVT and 41 of 125 for suspected PE. The SimpliRED assay had a sensitivity of 65% and a negative predictive value of 81% for detection of VTE. In patients evaluated for DVT alone, the sensitivity was 56% and the negative predictive value was 77%. For patients with suspected PE, the sensitivity and negative predictive value were 68% and 83%, respectively. Conclusion: In contrast to earlier reports on the SimpliRED D -dimer assay, a negative result failed to exclude the diagnosis of VTE in our ED population. [Farrell S, Hayes T, Shaw 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. February 2000;35:121-125.]

Observer Dependency of the SimpliRed D-dimer Assay in 81 Consecutive Patients with Suspected Pulmonary Embolism

The SimpliRed D-dimer assay is a whole blood agglutination test for the exclusion of pulmonary embolism (PE) and has been advocated as a reliable rapid bedside alternative to more time-consuming quantitative assays. However, widely differing negative predictive values (77–100%) are reported. This study assessed the intra- and interobserver variability as a possible cause for this wide accuracy range and evaluated the accuracy of the SimpliRed test in 81 consecutive patients with clinically suspected PE. Absolute D-dimer concentration was measured using the Tinaquant (Roche Diagnostics GmbH, Mannheim, Germany) assay. Every assay was immediately scored by one observer and then photographed. Photos were randomised and read twice by two other independent observers. The intraobserver reproducibility was good: kappa=0.81 and 0.73. However, we found poor interobserver reproducibility with kappa= 0.47. This seems due to the fact that the SimpliRed test proved difficult to interpret in the 0.3–1.3 μg/mL plasma concentration D-dimer range, which contained 32/81 (40%) patients, 8 of whom had PE. Using pulmonary angiograms and ventilation perfusion lung scans with a concurrent spiral computed tomography scan as a gold standard (25 patients had PE), SimpliRed's accuracy to exclude PE was moderate, with negative predictive values of 0.78 and 0.84. In particular, the two observers scored the SimpliRed test as normal in 12 of 25 and 5 of 25 patients with proven PE. We conclude that SimpliRed is strongly observer-dependent. This explains the varying sensitivities for the detection of venous thromboembolism as reported in previous studies.

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.

Application of a Diagnostic Clinical Model for the Management of Hospitalized Patients with Suspected Deep-vein Thrombosis

The purpose of this study was to evaluate whether the determination of pretest probability using a simple clinical model and the SimpliRED D-dimer could be used to improve the management of hospitalized patients with suspected deep-vein thrombosis. Consecutive hospitalized patients with suspected deep-vein thrombosis, had their pretest probability determined using a clinical model and had a SimpliRED D-dimer assay. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound one week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed for three months for the development of venous thromboembolic complications. Overall, 28% (42/150), and 10% (5/50), 21% (14/71) and 76% (22/29) of the low, moderate and high pretest probability patients. respectively, had deep vein thrombosis. Two of 111 (1.8%; 95% CI = 0.02% to 6.4%) patients considered to have deep vein thrombosis excluded had events during three-month follow-up. Overall 13 of 150 (8.7%) required venography and serial testing was limited to 58 of 150 (38.7%) patients. The negative predictive value of the SimpliRED D-dimer in patients with low pretest probability was 96.2%, which is not statistically different from the negative predictive value of a negative ultrasound result in low pretest probability patients (97.8%). Management of hospitalized patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible.

Observer and Biological Variation of a Rapid Whole Blood D-Dimer Test

In consecutive patients with suspected venous thromboembolism the interobserver variability of the SimpliRED D-dimer test was evaluated by two observers who independently scored one plate, the between assay variation was performed simultaneously by a third independent observer, who assessed a second plate. The biological variation was studied, 1-4 hours later by an independent evaluation. A total of 155 patients entered the study, venous thromboembolism was present in 42 patients (28%). The interobserver variability was 2/83 samples, with a kappa of 0.95 (95% confidence interval 0.88-1.0). The between assay variation was 2/98, with a kappa value of 0.96 (95% confidence interval 0.90-1.0). When testing the biological variation the observers disagreed in 2 of 69 patients (3%). The SimpliRED D-dimer assay has a good to excellent interobserver variability, between assay variation and reproducibility.

SimpliRED D-dimer Assay: Comparability of Capillary and Citrated Venous Whole Blood, Between-assay Variability, and Performance of the Test for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients

SimpliRED D-dimer Assay: Comparability of Capillary and Citrated Venous Whole Blood, Between-assay Variability, and Performance of the Test for Exclusion of Deep Vein Thrombosis in Symptomatic Outpatients -

Application of a bedside whole blood D-dimer assay in the diagnosis of deep vein thrombosis

Cross-linked fibrin degradation products have been used to detect venous thrombosis. While the sensitivity of plasma D-dimer measured by ELISA in the diagnosis of deep vein thrombosis (DVT) is high, the utility of ELISA methods is limited in a clinical setting. This study analysed the diagnostic value of a rapid D-dimer assay performed on whole blood samples (SimpliRed D-dimer) compared with latex and ELISA in 86 patients suspected of having DVT. SimpliRed D-dimer was positive in 47/50 of patients with DVT established by Doppler ultrasound (DU; sensitivity 94%). SimpliRed D-dimer was positive in 35/37 of patients with proximal DVT, nine out of nine with popliteal DVT and three out of four with superficial thrombophlebitis. The specificity of SimpliRed D-dimer in the diagnosis of DVT was 61%. The sensitivity of the SimpliRed D-dimer assay was at least comparable with the ELISA (87%) and superior to the latex assay (80%). The positive predictive value (77%), the negative predictive value (88%) and the overall accuracy (80%) of the SimpliRed assay were better than the ELISA and latex methods. It is concluded that SimpliRed D-dimer is a rapid useful assay for screening of patients suspected of having deep vein thrombosis.

A Novel and Rapid Whole-Blood Assay for D-Dimer in Patients With Clinically Suspected Deep Vein Thrombosis

The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Application of a Novel and Rapid Whole Blood Assay for D-Dimer in Patients with Clinically Suspected Pulmonary Embolism

To determine the clinical utility of a novel whole blood assay for D-dimer (SimpliRED) in patients with clinically suspected pulmonary embolism (PE). Prospective cohort. Eighty-six consecutive patients with clinically suspected PE. All patients had the SimpliRED D-dimer assay performed and underwent ventilation/perfusion (V/Q) lung scanning and bilateral impedance plethysmography (IPG); pulmonary angiography was performed in two patients. Patients were classified as: 1) PE-positive; positive pulmonary angiography or high probability V/Q scan or non-high probability V/Q scan and either abnormal IPG (either at presentation or upon serial testing and confirmed by contrast venography) or symptomatic thromboembolic event within three months of presentation or 2) PE-negative; normal V/Q scan or normal pulmonary angiography or non-high probability V/Q scan and normal serial IPG and absence of symptomatic venous thromboembolism within three months of follow up. Sixteen (19%) patients were classified as PE-positive and 70 (81%) patients were classified as PE-negative. MEASUREMENTS AND RESULT: The sensitivities, specificities, positive predictive values, and negative predictive values of the D-dimer assay were calculated for all patients and for the subgroup of patients without comorbid conditions that independently can cause elevated D-dimer levels. The D-dimer showed a sensitivity of 94%, a negative predictive value of 98%, a specificity of 66%, and a positive predictive value of 38%. In the subgroup of patients without comorbid conditions, the specificity increased to 98% and the positive predictive value to 83%, but because only six patients had an abnormal D-dimer level, the 95% confidence interval on the observed positive predictive value is wide (36-100%). This study demonstrates that the SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within five minutes, has potential clinical utility as an exclusionary test in patients with clinically suspected PE. The assay should be evaluated in large clinical management studies.