Moderate Clinical Pretest Probability Research Articles

External validation of the PEGeD diagnostic algorithm for suspected pulmonary embolism in an independent cohort.

Sequential diagnostic algorithms are used in the case of suspected pulmonary embolism (PE). The PEGeD study proposed a new diagnostic strategy to reduce the use of computed tomography pulmonary angiography (CTPA). We aimed to externally validate this diagnostic strategy in an independent cohort. We analyzed data from 3 prospective studies of outpatients with suspected PE. As per the PEGeD algorithm, patients were classified as having a low, moderate, or high clinical pretest probability (C-PTP). PE was excluded with a D-dimer <1000 ng/mL in case of low C-PTP and <500 ng/mL in case of moderate C-PTP. We assessed the yield and safety of this approach and compared them with those of previously validated algorithms. Among the 3308 evaluated patients, 1615 (49%) patients could have had PE excluded according to the PEGeD algorithm, without the need for imaging. Of these patients, 38 (2.3%; 95% confidence interval [CI], 1.7-3.2) were diagnosed with a symptomatic PE at initial testing or during the 3-month follow-up. On further analysis, 36 patients out ofthese 38 patients had a positive age-adjusted D-dimer. The risk of venous thromboembolic events among the 414 patients with a D-dimer <1000 ng/mL but above the age-adjusted D-dimer cut-off was 36 of 414 (8.7%; 95% CI, 6.4-11.8). We provide external validation of the PEGeD algorithm in an independent cohort. Compared with standard algorithms, the PEGeD decreased the number of CTPA examinations. However, caution isrequired in patients with a low C-PTP and a D-dimer <1000 ng/mL but above their age-adjusted D-dimer cut-off.

Diagnosis of deep vein thrombosis with D-dimer adjusted to clinical probability: prospective diagnostic management study

ObjectiveTo evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT.DesignProspective diagnostic management study.SettingUniversity based...

Pragmatic Evaluation of an Algorithm Using D-Dimer Adjusted to Clinical Probability in the Diagnosis of Pulmonary Embolism

BACKGROUNDDiagnosis of pulmonary embolism (PE) using clinical decision rules in combination with D-dimer (DD) values is a standard practice. The Wells score is the most commonly used rule, either in its original (3-category) or modified (2-category) versions, and in conjunction with a (DD) <500 ng/mL allows to exclude a PE in approximately 30% of patients. The recent PEGeD study (Kearon et al. 2019) concluded that a PE can be safely excluded by using a DD threshold adjusted to the clinical pre-test probability (C-PTP). In that study PE was excluded in patients with low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL In the present study we aimed to evaluate the performance of the PEGeD algorithm in daily practice. METHODSWe conducted a retrospective cohort study involving all adult patients who presented at London Health Sciences Centre or St. Joseph's Health Care Emergency Departments in London, Ontario, Canada between November 1, 2018 and December 31, 2020 with signs or symptoms suggestive of a pulmonary embolism and for whom a DD was ordered electronically. They were excluded if they did not have complete follow-up information for at least 90 days from the initial visit, they were pregnant, they were on long term anticoagulation for other indications, or had chest imaging prior to DD order. Using the electronic hospital chart, we extracted demographics, imaging results, and the Wells score with all its individual components. In our center, information about the Wells score and its components is routinely and prospectively collected when ordering DD. Since the PEGeD algorithm is not routinely used in our hospital, data of the C-PTP was utilized to determine which DD cut-off should be applied to the patient. Decision to perform imaging studies was taken by the ED physician at the time of assessment. The outcome of interest was the proportion of a PE or DVT at 90 days after the visit to the ED in patients with a low or intermediate C-PTP and who did not receive an initial diagnosis of PE and 99% confidence intervals (CI) were estimated using the Wilson's score method. RESULTSA total of 2769 patient charts were reviewed and 1070 were included (Table 1, Figure 1). Of the 1070 patients, 71 (7%) of patients had a pulmonary embolism on initial presentation to the emergency department. At 90 days of follow up none (99% CI 0, 0.84) of the 787 patients who had a low C-PTP or a moderate C-PTP score and a DD <1000 ng/mL or <500 ng/mL, respectively, were positive for a PE . This included 194 patients who had a low C-PTP and a DD level of 500-999 ng/mL and 26 patients who had an intermediate C-PTP and a DD level of <500 ng/mL. Notably, 8 (1.02%, 99% CI 0.42-2.43) PEs would have been missed using the PEGeD protocol when using DD cut-off levels of <1000 ng/mL in the low C-PTP group, or <500 ng/mL in the intermediate C-PTP. CONCLUSIONSIn this cohort we found that if the PEGeD algorithm had been used, it would have resulted in a low risk of VTE during follow up in patients without an initial diagnosis of PE and who had either a low C-PTP and a DD <1000 ng/mL or a moderate C-PTP and a DD <500 ng/mL. We also found it would have been associated with 194 (48%) less diagnostic imaging studies in the low C-PTP range and 2 (6%) less studies in the intermediate C-PTP range. Despite this, 1% of patients with PE (99% upper confidence limit 2.43%) would have been missed. This study is limited by its retrospective nature with an inherent risk of misclassification. Further studies are needed before recommending the use of this algorithm in clinical practice.Work CitedKearon, C., de Wit, K., Parpia, S., Schulman, S., Afilalo, M., Hirsch, A., Spencer, F. A., Sharma, S., D'Aragon, F., Deshaies, J.-F., Le Gal, G., Lazo-Langner, A., Wu, C., Rudd-Scott, L., Bates, S. M., & Julian, J. A. (2019). Diagnosis of Pulmonary Embolism with d -Dimer Adjusted to Clinical Probability. New England Journal of Medicine, 381(22), 2125-2134. https://doi.org/10.1056/NEJMoa1909159 [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Deep Vein Thrombosis Diagnosis with D-Dimer Adjusted to Clinical Probability

Introduction Diagnostic testing for deep vein thrombosis (DVT) is a multi-step and time-consuming process. Testing starts with clinical pretest probability (C-PTP) assessment. A negative D-dimer in combination with low C-PTP is widely used to exclude DVT; otherwise ultrasound imaging is required. When proximal vein ultrasound is used, a repeat ultrasound after a week is usually required to exclude DVT in moderate or high C-PTP patients. Ultrasound imaging is costly and can introduce delays. The goal of this study was to evaluate the safety and efficiency of a diagnostic algorithm for DVT that was designed to minimize the need for ultrasound imaging by using C-PTP-based D-dimer thresholds to exclude DVT (the 4D algorithm), rather than a standard fixed D-dimer cut-off value. Methods Consenting patients were enrolled in a Canadian prospective multicentre management study. Outpatients with symptoms or signs of DVT were eligible to be included in this study. Physicians used the 9-item Wells score to categorize the patient's C-PTP as low (Wells score, -2 to 0), moderate (1 or 2), or high (≥3). Patients with low C-PTP and a D-dimer &amp;lt;1,000 ng/mL or with a moderate C-PTP and a D-dimer &amp;lt;500 ng/mL underwent no further diagnostic testing for DVT and did not receive anticoagulant therapy. All other patients underwent proximal vein ultrasound. Patients with a single negative ultrasound but very high D-dimer (low or moderate C-PTP with D-dimer ≥3000 ng/mL, high C-PTP with D-dimer ≥1500 ng/mL) had a second proximal venous ultrasound one week later. The primary outcome was symptomatic, objectively verified, venous thromboembolism (VTE), which included proximal DVT or pulmonary embolism. All patients were followed for 90 days. A sample size of 1500 was required to establish 4D algorithm safety (90-day post-test probability of VTE &amp;lt;2%). Results From April 2014 through March 2020, a total of 1512 patients were enrolled and analyzed. The mean age was 60 years and 58% were female. Overall, 173 (11%) had DVT on initial or serial diagnostic testing (168 had DVT on ultrasound imaging on the day of presentation and 5 had DVT on repeat ultrasound imaging at one week). Of all 1298 patients (86% of total) who did not have DVT (at either initial presentation or at scheduled repeat ultrasound imaging) and who did not receive anticoagulant therapy, 7 had VTE during follow-up (0.5%, 95% confidence interval (CI): 0.3 to 1.1%). In the 579 patients who had low (378 patients) or moderate (201 patients) C-PTP and negative D-dimer results (i.e. &amp;lt;1000 or &amp;lt;500 ng/mL respectively) and who did not receive anticoagulant therapy, 2 had VTE during follow-up (0.4%, 95% CI: 0.1 to 1.3%). In the 572 patients with a single negative ultrasound who were low or moderate C-PTP with D-dimer &amp;lt;3000 ng/mL (423 patients), or high C-PTP with D-dimer &amp;lt;1500 ng/mL (149 patients) and who did not receive anticoagulant therapy, 3 had VTE during follow-up (0.5%, 95% CI: 0.2 to 1.5%). The difference in the mean number of ultrasound examinations with the 4D algorithm (0.72) compared with the conventional algorithm (1.36) was -0.64 (95% CI, -0.68 to -0.61), corresponding to a 47% relative reduction (1083 ultrasound scans performed with the 4D algorithm compared with 2053 ultrasound scans required for the conventional algorithm). Conclusions The 4D diagnostic algorithm ruled out DVT safely while substantially reducing the requirement for ultrasound imaging. Disclosures Wu: BMS-pfizer: Honoraria, Other: advisory board; leo pharma: Other: advisory board; Pfizer: Honoraria; Servier: Other: advisory board.

LO55: Comparison of the age-adjusted D-dimer, clinical probability-adjusted D-dimer, and Wells rule with D-dimer for diagnosing deep vein thrombosis in the emergency department.

Introduction: Diagnosing deep vein thrombosis (DVT) is of critical importance because of its associated morbidity and mortality. Diagnosing DVT can be challenging in the Emergency Department (ED) due to inconsistent adherence to, and utilization of the Wells rule. Both the age-adjusted and clinical probability adjusted D-dimer have been shown to decrease ultrasound (US) utilization rates. We aimed to compare the safety and efficacy of the Wells score with D-dimer to the age-adjusted and clinical probability-adjusted D-dimer in Canadian ED patients tested for DVT. Methods: This was a health records review of ED patients investigated for DVT at two EDs over a two-year period. Inclusion criteria were ED physician ordered duplex ultrasonography or D-dimer for investigation of lower limb DVT. Patients under the age of 18 were excluded. DVT was considered to be present during the ED visit if DVT was diagnosed on duplex ultrasonography and was treated for acute DVT, or if the patient was subsequently diagnosed with pulmonary embolism (PE) or DVT during the next 30 days. Trained researchers extracted anonymized data. The Wells D-dimer, age-adjusted D-dimer, and the clinical probability-adjusted D-dimer rules were applied retrospectively. The rate of duplex ultrasonography imaging and the false negative rate was calculated for each rule. Results: Between April 1st 2013 and March 31st 2015, there were 1,198 patients tested for DVT. Of the low and moderate clinical pretest probability patients (Wells score ≤ 2), only 436 had a D-Dimer test and were eligible for our analysis. The average age of the patients was 59, 56% were female, and 4% had a malignancy. 207/436 patients (47.4%, 95%CI 42.8-52.2%) would have had US imaging for DVT if the age-adjusted D-dimer rule was used. 214/436 patients (49.1%, 95%CI 44.4-53.8%) would have had imaging for DVT if the clinical probability-adjusted D-dimer was used. If the Wells rule was used with the standard D-dimer cutoff of 500, 241/436 patients (55.2%, 95%CI 50.6-59.9%) would have had imaging for DVT. The false-negative rate for the Wells rule was 1.5% (95%CI 0.5-4.4%). The false-negative rate for the age-adjusted D-dimer rule was 1.3% (95%CI 0.4-3.8%). The false-negative rate for the clinical-probability adjusted D-Dimer was 1.8% (95%CI 0.7-4.5%). Conclusion: In comparison with the approach of the Wells score and D-dimer, both the age-adjusted and clinical probability-adjusted D-dimer diagnostic strategies could reduce the proportion of patients who require US imaging.

In outpatients, low or moderate clinical pretest probability with probability-defined D-dimer cut points ruled out PE.

Source Citation Kearon C, de Wit K, Parpia S, et al. Diagnosis of pulmonary embolism with D-dimer adjusted to clinical probability. N Engl J Med. 2019;381:2125-34. 31774957

Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability

BackgroundRetrospective analyses suggest that pulmonary embolism is ruled out by a d-dimer level of less than 1000 ng per milliliter in patients with a low clinical pretest probability (C-PTP) and by a d-dimer level of less than 500 ng per milliliter in patients with a moderate C-PTP.MethodsWe performed a prospective study in which pulmonary embolism was considered to be ruled out without further testing in outpatients with a low C-PTP and a d-dimer level of less than 1000 ng per milliliter or with a moderate C-PTP and a d-dimer level of less than 500 ng per milliliter. All other patients underwent chest imaging (usually computed tomographic pulmonary angiography). If pulmonary embolism was not diagnosed, patients did not receive anticoagulant therapy. All patients were followed for 3 months to detect venous thromboembolism.ResultsA total of 2017 patients were enrolled and evaluated, of whom 7.4% had pulmonary embolism on initial diagnostic testing. Of the 1325 patients who had a low C-PTP (1285 patients) or moderate C-PTP (40 patients) and a negative d-dimer test (i.e., <1000 or <500 ng per milliliter, respectively), none had venous thromboembolism during follow-up (95% confidence interval [CI], 0.00 to 0.29%). These included 315 patients who had a low C-PTP and a d-dimer level of 500 to 999 ng per milliliter (95% CI, 0.00 to 1.20%). Of all 1863 patients who did not receive a diagnosis of pulmonary embolism initially and did not receive anticoagulant therapy, 1 patient (0.05%; 95% CI, 0.01 to 0.30) had venous thromboembolism. Our diagnostic strategy resulted in the use of chest imaging in 34.3% of patients, whereas a strategy in which pulmonary embolism is considered to be ruled out with a low C-PTP and a d-dimer level of less than 500 ng per milliliter would result in the use of chest imaging in 51.9% (difference, −17.6 percentage points; 95% CI, −19.2 to −15.9).ConclusionsA combination of a low C-PTP and a d-dimer level of less than 1000 ng per milliliter identified a group of patients at low risk for pulmonary embolism during follow-up. (Funded by the Canadian Institutes of Health Research and others; PEGeD ClinicalTrials.gov number, NCT02483442.)

Selectived-Dimer Testing for Diagnosis of a First Suspected Episode of Deep Venous Thrombosis

D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) 5 Canadian hospitals. Consecutive symptomatic patients with a first episode of suspected DVT. Selective testing (n = 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels <1.0 µg/mL [low C-PTP] or <0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels <0.5 µg/mL). The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT. Heart and Stroke Foundation of Ontario.

Positive Predictive Value of Progressively Elevated D-Dimer Levels in Patients with a Suspected First Deep Vein Thrombosis.

AbstractAbstract 2258 BackgroundD-dimer is nearly always increased in patients with acute venous thromboembolism (VTE) and, therefore, a low value (i.e., negative test) has high negative predictive value. A positive result indicates the need for further diagnostic testing (e.g. ultrasound imaging if deep vein thrombosis is suspected), but it is generally believed that the predictive value of a positive result is of no clinical value. While this is true if D-dimer values are dichotomized as positive or negative, D-dimer may have diagnostically useful positive predictive value when levels are markedly elevated (i.e., positive results are not considered as a single category). ObjectiveTo determine the prevalence of, and likelihood ratios for, deep vein thrombosis (DVT) associated with progressively elevated D-dimer levels in patients with a suspected first DVT. MethodsWe performed a retrospective analysis of D-dimer level from 1224 banked peripheral blood samples from participants enrolled at 4 of the 5 participating clinical centres in the recently competed SELECT study, which compared two diagnostic strategies in patients with a suspected first DVT. D-dimer levels were measured using the Triage® D-dimer assay. The clinical pretest probability (CPTP) was determined in all patients using the 9 point Wells score and categorized as low, moderate or high. Patients were categorized as DVT positive if DVT was diagnosed by lower limb ultrasound (US) at initial presentation or VTE was diagnosed during three months of follow-up. Patients were categorized as DVT negative if DVT was not diagnosed at initial assessment (patients with low CPTP and negative D-dimer results did not undergo US) and there was no VTE during three months of follow-up. The diagnosis or exclusion of DVT was made independently of the Triage® D-dimer measurements (a different D-dimer assay was used at presentation in the SELECT study, and D-dimer was not used to evaluate suspected VTE during the 3 month follow-up).The prevalence of DVT and likelihood ratios (LHR) for all patients, and according to CPTP (low, moderate or high), was determined for the following intervals of D-dimer level: <500ug/L, 500–1000ug/L, 1001–1500ug/L, 1501–2000ug/L, 2001–3000 ug/L, 3001–4000ug/L, 4001ug/L-5000ug/L and >5000ug/L. ResultsThe prevalence of DVT, and associated LHR, among all patients increased steadily with rising D-dimer levels (Table 1). At values of less than 1000ug/L, the prevalence of DVT among all patients was low (0.15% for D-dimer <500ug/L and 1.2% for 500–1000ug/L). However, at levels above 1500ug/L there was a progressive increase in the prevalence from 14.3% for 1500–2000ug/L to 64.0% at levels >5000ug/L. The associated likelihood ratios for DVT also increased according to D-dimer level from 2.6 for levels of 1500–2000ug/L to 28.0 for values >5000ug/L.The prevalence of DVT was 2.6% for patients with low CPTP, 6.0% among those with moderate CPTP and 22.0% among patients with high CPTP. The increase in prevalence and associated LHR for DVT with increasing D-dimer levels was consistent across all three CPTP groups. ConclusionIncreasing D-dimer levels are associated with a progressive increase in prevalence and LHR for DVT across all clinical pretest probability strata. The positive predictive value of markedly elevated D-dimer levels was high and may help to identify the subgroup of patients with an abnormal D-dimer level who require more intensive investigation after a normal imaging test.Table 1-Prevalence and Likelihood Ratio associated with different D-dimer levelsD-dimer (ug/L)All patientsLow CPTPModerate CPTPHigh CPTPPrev (%)LHRPrev (%)LHRPrev (%)LHRPrev (%)LHR<5000.150.02000.40.0600500-10001.20.20000.90.15110.441001-15005.00.824.61.74.40.738.30.321501-2000142.6145.6173.2002001-3000193.7156.2203.2251.23001-4000286.12311265.5503.44001-5000306.9209275.9432.7>50006428432756208928Prev, prevalence; LHR, likelihood ratio; CPTP, clinical pretest probability Disclosures:Bates:Trinity Biotech: Consultancy, consultation fees and in-kind support (D-dimer kits) Other. Kearon:Alere: Consultancy.

Differences in clinical presentation of deep vein thrombosis in men and women.

As assessment of clinical pretest probability is the first step in the diagnostic evaluation of deep vein thrombosis (DVT), it is important to know if the clinical features of DVT are the same in men and women. To compare the prevalence and clinical characteristics of DVT, and the accuracy of clinical pretest probability assessment, between men and women with suspected DVT. A retrospective analysis of individual patient data from three prospective studies by our group that evaluated diagnostic tests for a suspected first episode of DVT. Clinical characteristics, clinical pretest probability for DVT, and prevalence and extent of DVT was assessed in a total of 1838 outpatients. The overall prevalence of DVT was higher in men than in women (14.4% vs. 9.4%) (P = 0.001). The prevalence of DVT was higher in men than in women who were categorized as having a clinical pretest probability that was low (6.9% vs. 3.5%; P = 0.025) or moderate (16.9% vs. 8.7%; P = 0.04), but similar in patients in the high category (40.2% vs. 44.0%; P = 0.6). In patients diagnosed with DVT, swelling of the entire leg occurred more often (41.5% vs. 15.7%; P < 0.001), and thrombosis was more extensive (involvement of both popliteal and common femoral veins in 47.9% vs. 21.6%), in women than in men. In outpatients with suspected DVT, the overall prevalence of thrombosis and the prevalence of thrombosis in those with a low or a moderate clinical pretest probability were higher in men than in women.

Uses of different D-dimer levels can reduce the need for venous duplex scanning to rule out deep vein thrombosis in patients with symptomatic pulmonary embolism

This study investigated the prevalence and distribution of deep vein thrombosis (DVT) in patients with symptomatic pulmonary embolism (PE) to establish a screening protocol to reduce unnecessary venous duplex scanning using different D-dimer level rather than single cutoff point of 0.5 microg/mL in patients with low and moderate pretest clinical probability (PTP). The PTP score and D-dimer testing were used to evaluate 85 consecutive patients with symptomatically proven PE before venous duplex scanning. After calculating the PTP score, patients were divided into low (<or=0 points), moderate (1 to 2 points), and high (>or=3 points) PTP groups. The receiver operating characteristic (ROC) curves analysis was used to determine the appropriate D-dimer cutoff point in low and moderate PTP, with a negative predictive value of >98%. The study enrolled 81 patients. The prevalence of DVT was 63%, with 27 patients (33%) classified as low, 38 (47%) as moderate, and 16 (20%) as high PTP. DVT was detected in nine patients (33%) in the low PTP group, in 27 (71%) in the moderate group, and in 15 (94%) in the high group. In the low PTP patients, the difference in the value of D-dimer assay between positive-scan and negative-scan patients was statistically significant (9.99 +/- 7.33 vs 3.46 +/- 4.20, respectively; P = .008). Conversely, no significant difference in the D-dimer assay value between positive and negative scan results was found in the moderate PTP patients. ROC curves analysis were used to select D-dimer cutoff points of 2.0 microg/mL for the low PTP group and 0.7 microg/mL for the moderate PTP groups. For both groups, D-dimer testing provided 100% sensitivity and 100% negative predictive value in the diagnosis of DVT. In the low PTP group, specificity increased from 33% to 67% (P = .046). In the moderate PTP group, however, the determined D-dimer level did not improve the specificity. Overall, venous duplex scanning could have been reduced by 17% (14/81) by using different D-dimer cutoff points. A combination of specific D-dimer level and clinical probability score is most effective in the low PTP patients in excluding DVT. In the moderate PTP group, however, the recommended cutoff point of 0.5 microg/mL may be preferable. These results show that a different D-dimer level is more useful than single cutoff point of 0.5 microg/mL in excluding DVT in established PE patients.

Pulmonary embolism: Accuracy and safety of a negative CT pulmonary angiogram and value of a negative D‐dimer assay to exclude CT pulmonary angiogram‐detectable pulmonary embolism*

This is a retrospective study to determine the accuracy and safety of a negative CT pulmonary angiogram (CTPA) based on clinical outcome and to determine the usefulness of a negative D-dimer assay before CTPA. A total of 483 patients with a negative CTPA study were followed up for 3 months, with the aim of detecting episodes of venous thromboembolism and mortality. Three hundred and forty-nine patients had an immunochromatographic D-dimer assay called 'Simplify', carried out before a CTPA examination. Seventy-eight patients had a negative D-dimer assay and a negative CTPA. Three patients had a negative D-dimer assay and a positive CTPA. All three patients had a moderate pretest clinical probability. Of the 483 patients who had a negative CTPA and a 3-month follow up, 444 (92%) were alive and 39 (8%) had died. Of the 444 patients who were alive, none had any further suspected episode of thromboembolism or had received anticoagulation therapy within the follow-up period. Of those who died, none of the deaths was thought to be as a result of pulmonary embolism (PE). Single-detector helical CT can be used safely as the primary diagnostic test to evaluate PE. Negative Simplify D-dimer assay and low pretest clinical probability exclude CTPA-detectable PE, and a CTPA is unnecessary in this cohort of patients.

Objective Assessment of Pulmonary Embolism Can Be Deferred without Increased Risk.

Background. Management of patients with suspected Pulmonary Embolism (PE) is problematic if diagnostic imaging is not available. Pretest Clinical Probability (PCP) and D-dimer (D-d) assessment were shown to be useful to identify those high risk patients for whom empirical, protective anticoagulation is indicated (Siragusa S et al. Arch Intern Med 2004; 164:2477–82).Objective of the study. In consecutive patients with suspected PE, we evaluated whether PCP and D-d assessment, together with the use of low molecular weight heparins (LMWHs), allow objective appraisal of PE to be deferred for up to 72 hours.Methods. In case of deferment of diagnostic imaging for PE, patients identified at high-risk (those with high PCP and those with moderate PCP and a positive D-d), received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulants. All patients were scheduled to undergo objective tests for PE (ventilation/perfusion lung scanning or computed tomography lung scan) within 72 hours from the index visit (figure). Standard antithrombotic therapy was then administered when diagnostic tests confirmed Venous ThromboEmbolism (VTE).Results. 336 patients with suspected PE were included in this study. The prevalence of VTE was 6.1% (95% CI 2.7–9.3) in the “low-risk group” and 50.4% (95% CI 41.7–59.1) in the “high-risk group”. In total, VTE was confirmed in 76 (22.6%) of 336 patients (95% CI 18.2–27). Patients' characteristics, median time for deferral test and for LMWH administration are listed in table 1. Events at the short-term (72 hours) and long-term follow-up are listed in table 2. None of the patients had major bleeding events during the follow-ups.Conclusions. When objective diagnostic assessment of PE is not immediately available, management of symptomatic PE patients can prove highly unsatisfactory. This study demonstrates that a simple and reproducible approach allows a safe deferral of diagnostic imaging for PE for up to 72 hours.patients' characteristicsBaseline featuresLow risk group (n. 211)High-risk group (n. 125)p valueAge in years (range)59.3 (22–91)60.3 (23–91)n.s.Sex (F/M)98/11359/66n.s.Time since onset of symptoms (days)1.71.5n.s.Co-morbidity and16 (7.5)25 (19.2)0.03Median time of deferral test (hours)49.542.5n.s.Median time of protective anticoagulation (hours)not applicable35.5not applicablen.s.: not significantOutcome of Short- and Long-term FUCategories of patients (n)Events at the short-term FUEvents at the long -term FU*“Low-risk group” (211)0 (0%) [95% CI 1.4]0 (0%) [95% CI 1.4]“High-risk group” (125)1 (0.8%) [95% CI 2.3]3 (2.4%) [95% CI 3.2]FU indicates follow-up; CI indicates Confidence Intervals. *This refers to patients in whom Pulmonary Embolism has been previously ruled out (n. 260). [Display omitted]

Prospective Evaluation of a Screening Protocol to Exclude Deep Vein Thrombosis on the Basis of a Combination of Quantitative D-Dimer Testing and Pretest Clinical Probability Score

Clinical signs and symptoms such as swelling, pain, and redness are unreliable markers of deep vein thrombosis (DVT). Because of this venous duplex scanning (VDS) has been heavily used in DVT detection. The purpose of this study was to determine if a combination of D-dimer testing and pretest clinical score could reduce the use of VDS in symptomatic patients with suspected DVT. One hundred seventy-four consecutive patients with suspected DVT were prospectively evaluated using pretest clinical probability (PCP) score and D-dimer testing before VDS. After calculating clinical probability scores developed by Wells and associates, patients were divided into low risk (<or= 0 points), moderate risk (1 to 2 points), and high risk (>or=3 points) PCP. One hundred fifty-eight patients were enrolled. The prevalence of DVT in this study was 37%. Thirty-eight patients (24%) were classified as low risk, 64 (41%) as moderate risk, and 56 (35%) as high risk PCP. DVT was identified in only one patient (2.6%) with low risk PCP. In contrast, DVT was found in 22 (34%) with moderate risk, and 35 (63%) with high risk PCP. In the high and moderate risk PCP groups, positive scan patients had a markedly higher value of D-dimer assay than negative scan patients (p=0.0001 and p=0.0057, respectively). In the low risk PCP patients, D-dimer testing provided 100% sensitivity, 46% specificity, 4.8% positive predictive value, and 100% negative predictive value in the diagnosis of DVT. Similarly, in the moderate risk PCP, the D-dimer testing showed 100% sensitivity, 45% specificity, 49% positive predictive value, and 100% negative predictive value. In the high risk group, D-dimer testing achieved 100% sensitivity, 57% specificity, 80% positive predictive value, and 100% negative predictive value in the diagnosis of DVT. These results suggested that 36 of 158 patients who had a non-high PCP (low and moderate PCP) and a normal D-dimer concentration were considered to have no additional investigation, so VDS could have been reduced by 23% (36/158). A combination of D-dimer testing and clinical probability score may be effective in avoiding unnecessary VDS in suspected symptomatic DVT in the low and moderate PCP patients. The need for VDS could be reduced by 23% despite a relatively high prevalence of DVT.

Deferment of Objective Assessment of Deep Vein Thrombosis and Pulmonary Embolism Without Increased Risk of Thrombosis

Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-dose treatment of LMWH; the remaining patients were discharged without anticoagulant administration. However, all patients were scheduled to undergo objective tests for DVT or PE within 72 hours. Standard antithrombotic therapy was administered when deferred diagnostic tests confirmed venous thromboembolism. In total, 409 consecutive patients with suspected DVT and 124 with suspected PE were included in this study. A total of 23.8% (95% confidence interval [CI], 20.3%-27.3%) of patients had confirmed venous thromboembolism. At the short-term follow-up (72 hours), only a single thromboembolic event (0.2%; upper 95% CI, 0.6%) had occurred, whereas at the 3-month follow-up, 5 events (1.2%; 95% CI, 0.2%-2.1%) had occurred in patients in whom diagnosis of DVT or PE had previously been ruled out. None of the patients had major bleeding events. Ninety percent of patients were treated as outpatients. Our study demonstrates that this approach allows the safe deferral of diagnostic procedures for DVT and PE for up to 72 hours.

Use of different d‐dimer levels to exclude venous thromboembolism depending on clinical pretest probability

Currently, the same D-dimer cut-off point is used to define a positive result for all patients with suspected venous thromboembolism, regardless of their pretest probability. However, use of a relatively high D-dimer cut-off point (lower sensitivity) for those with a low clinical pretest probability, and a low D-dimer cut-off point (higher sensitivity) for those with a high clinical pretest probability, may be preferable. To determine if using three different D-dimer cut-off points according to low, moderate or high clinical pretest probability has greater utility for exclusion of venous thromboembolism than using the same single D-dimer cut-off point in all patients. Data from a previously published study of 571 patients was used to identify the highest D-dimer cut-off point with a negative predictive value of at least 98% for the subgroup of patients with low and high pretest probability. The D-dimer cut-off point for those with moderate clinical pretest probability remained unchanged [0.5 fibrinogen equivalent units (FEU) microgram mL(-1)]. Accuracy of D-dimer testing for venous thromboembolism using three cut-off points vs. one cut-off point was than determined. D-dimer cut-off points of 0.2 and 2.1 FEU microgram mL(-1) were selected for the high and low pretest probability groups, respectively. When three pretest probability-specific cut-off points were used instead of the previously determined single D-dimer cut-off point (0.5 FEU microgram mL(-1)), sensitivity and negative predictive value were unchanged (95 and 98%, respectively), but specificity increased from 44.7 to 60.4% (P < 0.001). This resulted in exclusion of venous thromboembolism in 80 additional patients. Use of three pretest probability-specific D-dimer cut-off points rather than a single D-dimer cut-off point for all patients, has the potential to increase the utility of D-dimer testing for the diagnosis of venous thromboembolism.