Negative D-dimer Result Research Articles

Avoidable Overuse of Computed Tomography Pulmonary Angiography (CTPA) in Patients with Suspected Acute Pulmonary Thromboembolism (PTE): The Role of Clinical Prediction Rules and D-Dimer Assay

Background: Computed tomography pulmonary angiography (CTPA) is an imaging technique widely used in the diagnosis of acute pulmonary thromboembolism (PTE). Despite its disadvantages and potential risks, the overuse of CTPA has been a growing concern over the past decades. Objectives: The objective of this study was to investigate the rate of avoidable overuse of CTPA in patients with suspected PTE and to identify factors contributing to this overuse. The study aimed to highlight the importance of proper training for physicians in using validated diagnostic algorithms to minimize the overuse of CTPA and improve patient outcomes. Methods: In a cross-sectional study conducted between April 2016 and March 2019 at Shariati Hospital at Tehran University of Medical Sciences (TUMS), 1058 patients underwent CTPA due to suspected PTE. Wells scores were calculated retrospectively for all patients. The study defined avoidable overuse of CTPA as an imaging request without prior D-dimer testing or ignoring a negative D-dimer result in patients with low clinical pre-test probability. Results: Two hundred and seventy-three patients were excluded from the study due to unavailable documentation or pregnancy. Among the included 785 patients, 139 (17.7%) revealed PTE on CTPA. Based on the Wells scores, 480 patients were identified as the “PTE-unlikely” group. In this group, 299 patients (62.3%) underwent CTPA directly despite recommendations to order a D-dimer test first. Of these patients, 281 (94%) cases showed negative results. Moreover, CTPA was performed inappropriately in 52 “PTE-unlikely” cases despite negative D-dimer serum levels, and only one patient was diagnosed with PTE. Conclusions: The study revealed that 44.7% of the CTPA requests for patients with suspected PTE were avoidable, indicating the need for better adherence to current diagnostic guidelines to reduce unnecessary radiologic investigations and improve patient care.

Analysis of clinical characteristics and imagological features of the aortic dissection patients with negative D-dimer results.

D-dimer (DD) is a vital biomarker to rule out the diagnosis of aortic dissection (AD). However, the DD level in some patients with AD is not high in clinical practice, which often leads to missed diagnosis; therefore, understanding the characteristics of patients with AD and negative DD is of great clinical value. From May 2015 to October 2020, 286 patients with AD who visited the first medical contact (FMC) within 24 h of symptom onset and were hospitalized in the Xiamen Cardiovascular Hospital of Xiamen University were enrolled in this study. Clinical characteristics and outcomes of patients were assessed. Among them, 13 cases (approximately 4.5%) had negative DD results. Compared to patients with positive DD results, patients with negative DD results had significantly higher platelet counts and lower aortic dissection detection risk scores (ADD-RS). The imagological analysis showed that patients with AD and negative DD had lower extension scores and milder damage to the mesenteric artery and three branches of the aortic arch. Furthermore, the results of the multivariable analysis showed that white blood cell count (WBC) [odds ratio (OR): 1.379, P = 0.028], FMC (OR: 0.904, P = 0.028), and extension score (OR: 1.623, P = 0.046) were associated with negative DD result. Patients with AD and negative DD results had longer FMC and lower WBC. Imaging showed a smaller tear extension range and less damage to the mesenteric artery and three branches of the aortic arch. A negative DD result could not completely rule out AD even if the ADD-RS was zero.

Diagnostic Challenge of d-dimer Negative Upper Extremity DVT

Studies suggest D-Dimer has a high sensitivity with negative predictive value for upper extremity DVT (UEDVT). Sensitivity is around 92% with a negative predictive value of 98%. UEDVT is an uncommon presentation with an incidence rate of 4-10%. Risk factors for UEDVT include thrombophilia, central venous catheters, malignancy, pacemakers and upper limb surgery and/or immobilisation. The use of scoring systems for assessing UEDVT risk is less well known and therefore poorly utilised. A scoring system similar to a Wells' score, known as Constans criteria, is a 2 level scoring system developed and first published in 2008. The Criteria considers, venous material in-situ, localised pain, unilateral oedema and plausibility of alternative cause. Score interpretation; -1 to 0 points (low probability of UEDVT 12%), 1 point (intermediate probability 20%), 2 to 3 points (high probability 70%). Kleinjan, et al., sought further improved upon this scoring tool by incorporating D-dimer results in the stratification of intermediate risk patients, asserting that its use can safely and effectively exclude venous thrombosis of the upper extremity. This case series shows 2 patients diagnosed with UEDVT. both patients had a Constans score of 1 therefore prompting use of D-Dimer results to stratify risk. Irrespective of negative D-dimer results, ultrasound doppler scans where performed and appropriate treatment given. The authors of this case series reviewed the limitations/interference factors of HemosIL HS D-Dimer reagent, along with 2 other D-Dimer reagents and subsequently developed recommendations which may be useful in interpretation of D-Dimers in clinical practice. Additionally, recommendation for cautious intrepretation of D-Dimer results in conjunction the Constans scoring tool with scores of 1 or less

Rationale and design of a study on D-dimer use to stratify patients after a first unprovoked venous thromboembolism for their risk of recurrence: extended low-dose Apixaban given only to patients with positive D-dimer results

Optimal duration of anticoagulation in patients with a first venous thromboembolism (VTE) is still uncertain. Extended anticoagulant treatment beyond the first 3 to 6 months is recommended in patients with unprovoked VTE for their high risk of recurrence, provided the risk of bleeding during anticoagulation is not high. Recent meta-analyses indicated that only one-third of these patients have a recurrence 10 years after anticoagulation is stopped, whereas the risk of major bleeding is consistent and persistent during anticoagulation. We designed the prospective, multicenter Apidulcis study to test whether serial D-dimer measurements, using commercial assays with predefined sex-specific cutoffs (350 ng/mL and 500 ng/mL for men and women, respectively, for assays expressing results as fibrinogen equivalent units), may be useful to stratify patients for the risk of recurrence. Those presenting positive D-dimer results, considered at higher risk, will receive low dose Apixaban, 2.5 mg tablets BID for 18 months, whereas those with persistently negative D-dimer results, considered at lower risk, will remain without anticoagulant treatment. Outpatients with a first VTE (unprovoked or associated with weak risk factors), aged 18 to 74 years, who have already received anticoagulation for at least 12 months are eligible for the study.

Adjusted D-dimer cutoff levels to rule out pulmonary embolism in patients hospitalized for COPD exacerbation: results from the SLICE trial

BackgroundFor patients with suspected pulmonary embolism (PE), age- or clinically-adjusted D-dimer threshold level can be used to define a negative test that safely excludes PE and reduces the use of imaging. However, the utility of this approach in patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbation is undefined.MethodsWe ran an analysis of the patients hospitalized for COPD exacerbation and randomized to the intervention in the SLICE trial. Using the conventional strategy as the reference, we compared the proportion of patients with a negative D-dimer result, and the negative predictive value and sensitivity of three D-dimer threshold strategies for initial PE or subsequent diagnosis of venous thromboembolism (VTE): the age-adjusted strategy, the Wells-adjusted strategy, and the YEARS-adjusted strategy.ResultsWe included 368 patients. Using a conventional threshold, 182 (49.5%) patients had negative D-dimer values, of whom 1 (0.6%) had PE (sensitivity, 94.1%). The use of an age-adjusted threshold increased the number of patients in whom PE could be excluded from 182 to 233 patients (63.3%), and the proportion of false-negative findings increased from 0.5% to 1.7% (sensitivity, 76.5%). With the use of the Wells or YEARS strategies, 64.4% and 71.5% had negative values, and the proportion of false-negative findings was 2.5% (sensitivity, 64.7%) and 2.7% (sensitivity, 58.8%), respectively.ConclusionsIn patients hospitalized for COPD exacerbation, compared with the conventional strategy, age- or clinically-adjusted strategies of D-dimer interpretation were associated with a larger proportion of patients in whom PE was ruled out with a higher failure rate.Trial RegistrationClinicalTrials.gov number: NCT02238639.

Evaluation of the diagnostic management of deep vein thrombosis in the emergency department of a tertiary hospital in Santa Catarina, Brazil: a cross-sectional study.

Venous thromboembolism is an entity that encompasses both deep vein thrombosis and pulmonary thromboembolism. Although protocols for the diagnosis of these diseases are well defined, there is evidence of inappropriate use of diagnostic resources. To define the epidemiological profiles of patients admitted to the emergency department with suspected deep vein thrombosis, to determine rates of inappropriate ordering of D-dimer assays and color venous Doppler echocardiography of the lower limbs, and to identify whether these requests followed the recommendations contained in the 2015 Brazilian Society of Angiology and Vascular Surgery guidelines. We conducted a cross-sectional observational study that retrospectively evaluated 168 patients with suspected deep vein thrombosis for whom D-dimer assays were requested. The most common risk factors were measured and the pretest probability was calculated with the Wells score. The epidemiological profile of these patients and the rates of inappropriate D-dimer testing were assessed using descriptive statistics. The D-dimer requests were inadequate in 55 (32.7%) patients. Venous color Doppler ultrasound was used to examine the lower limbs of 14 (8.3%) of the patients with a low probability according to the Wells score and a negative D-dimer result. No additional diagnostic methods were used in 19 (11.3%) of those with a low probability according to the Wells score and a high D-dimer result. There was unnecessary use of CDUS in 35 (20.8%) cases. The overall rate of inappropriate workup was 53.5%. Differences were found between clinical practice and the recommendations for diagnostic evaluation of patients with suspected deep vein thrombosis, with inappropriate use of diagnostic tests.

Avaliação do manejo diagnóstico de trombose venosa profunda no departamento de emergência de um hospital terciário em Santa Catarina: um estudo transversal

BackgroundVenous thromboembolism is an entity that encompasses both deep vein thrombosis and pulmonary thromboembolism. Although protocols for the diagnosis of these diseases are well defined, there is evidence of inappropriate use of diagnostic resources.ObjectivesTo define the epidemiological profiles of patients admitted to the emergency department with suspected deep vein thrombosis, to determine rates of inappropriate ordering of D-dimer assays and color venous Doppler echocardiography of the lower limbs, and to identify whether these requests followed the recommendations contained in the 2015 Brazilian Society of Angiology and Vascular Surgery guidelines.MethodsWe conducted a cross-sectional observational study that retrospectively evaluated 168 patients with suspected deep vein thrombosis for whom D-dimer assays were requested. The most common risk factors were measured and the pretest probability was calculated with the Wells score. The epidemiological profile of these patients and the rates of inappropriate D-dimer testing were assessed using descriptive statistics.ResultsThe D-dimer requests were inadequate in 55 (32.7%) patients. Venous color Doppler ultrasound was used to examine the lower limbs of 14 (8.3%) of the patients with a low probability according to the Wells score and a negative D-dimer result. No additional diagnostic methods were used in 19 (11.3%) of those with a low probability according to the Wells score and a high D-dimer result. There was unnecessary use of CDUS in 35 (20.8%) cases. The overall rate of inappropriate workup was 53.5%.ConclusionsDifferences were found between clinical practice and the recommendations for diagnostic evaluation of patients with suspected deep vein thrombosis, with inappropriate use of diagnostic tests.

Recommended D-Dimer Use in Suspected Pulmonary Embolism Is Insufficient to Curb the Long-Term Overutilization of CT Pulmonary Angiography.

The aim of this study was to determine whether the authors' emergency medicine department has seen a significant change in CT pulmonary angiography (CTPA) utilization or positive rates for pulmonary embolism (PE) over a 10-year period for the 2 years before and 8 years after the implementation of patient population-specific D-dimer recommendations. A retrospective chart review was performed among all patients belonging to a geographically isolated health maintenance organization who underwent CTPA for the evaluation of acute PE in the emergency department between 2010 and 2019. The positive rate for acute PE among these studies was calculated and stratified by serum D-dimer value collected within 48 hours previously. A total of 6,013 CT pulmonary angiographic studies were reviewed, of which 40.2% had serum D-dimer ≥ 1.0 μg/mL (positive rate 10.6%), 42.5% did not have serum D-dimer drawn (positive rate 7.3%), and 17.2% had serum D-dimer < 1.0 μg/mL (positive rate 0.6%). There was a significant increase in positivity on CTPA in 2012 with the health group's formal recommendation of a D-dimer cutoff of 1.0 μg/mL. This improvement also corresponded with fewer orders for CTPA after a negative D-dimer result. However, in the following years, CTPA utilization and percentage positivity were found to be reverting to the prerecommendation statistics. The failure to mandate the use of serum D-dimer with a higher threshold value for patients who are to undergo CTPA for possible PE has resulted in poor lasting compliance despite promising early results. A firmer approach is likely necessary to yield positive long-term outcomes.

D-dimer level for ruling out peripherally inserted central catheter-associated upper extremity deep vein thrombosis and superficial vein thrombosis.

AimsTo examine the effectiveness of D‐dimer values to be used as an independent diagnostic marker for excluding peripherally inserted central catheter‐associated upper extremity deep vein thrombosis and superficial vein thrombosis.DesignThis was a retrospective case–cohort study.MethodsRecords were reviewed for 281 patients who underwent peripherally inserted central catheter insertion between 1 October 2017 and 1 October 2019. According to the modified Wells score after peripherally inserted central catheter insertion, the patients who had low vein thrombosis risk underwent a D‐dimer test and colour Doppler ultrasound.ResultsAmong 281 patients, 180 patients (64%, 95% CI: 58.2%–69.4%) had negative D‐dimer results and 39 of 180 patients had vein thrombosis despite having a negative D‐dimer result, resulting in a failure rate of 21.7% (95% CI: 16.3%–28.3%). The negative predictive value of peripherally inserted central catheter‐associated vein thrombosis in the cancer group (80.0%, 95% CI: 73.2%–85.4%) was higher than that of the non‐cancer group (60.0%, 95% CI: 35.7%–80.2%). The negative predictive value of peripherally inserted central catheter‐associated deep venous thrombosis (84.9%, 95% CI: 78.7%–89.6%) was lower than that of the PICC‐associated superficial venous thrombosis (91.0%, 95% CI: 85.4%–94.6%).ConclusionThe D‐dimer levels maybe should not be used as a diagnostic index to rule out peripherally inserted central catheter‐associated upper extremity vein thrombosis.

A Retrospective Review of the Appropriateness of D-Dimer Ordering and Interpretation Using Wells' Clinical Probability Criteria

Introduction The D-dimer has been validated in diagnostic venous thromboembolism (VTE) algorithms. The high sensitivity of the assay allows for safe exclusion of VTE in patients with low clinical pre-test probability and a negative D-dimer. The Wells score for Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) are validated pre-test probability tools which help guide physicians on when to order a D-dimer in patients with suspected VTE. However, we suspect these scoring tools are often under-utilized by physicians leading to inappropriate D-dimer ordering and subsequent interventions. We sought to explore the landscape of D-dimer ordering at our institution. Methods We conducted a retrospective chart review of 482 patients in whom a D-dimer had been ordered over a 3-month period at the University of Alberta Hospital, a tertiary care teaching hospital in Edmonton, Canada. Charts were reviewed for patient demographics, specialty of ordering physician, apparent indication for ordering, patient risk factors for VTE and evidence of a pre-test probability (PTP) calculation. WIf no PTP score was documented, we retrospectively calculated Wells DVT or PE scores. VTE was deemed likely with a calculated Wells score for DVT ≧2 or Wells score for PE &amp;gt;4. In the case of high PTP for PE, patients should go directly to imaging and a D-dimer should not be performed. A cut off of ≥ 0.50 mg/L was deemed a positive D-dimer (STA-LIATEST). We also reviewed subsequent investigations thought to be influenced by interpretation of the D-dimer including: ventilation/perfusion (V/Q) and pulmonary angiography (CTPA) scans, and upper and lower extremity doppler ultrasound studies. We then used multivariable logistic regression analysis to evaluate the proportion of patients who received imaging despite a low PTP and negative D-dimer. Results Seventy eight percent of D-dimers were ordered by Emergency physicians while 15.3% were drawn on admitted patients, and 5.8% in the outpatient setting. The indication for ordering was unknown in 87 (17.5%) of cases. Pre-test probability scores were documented in only 8 (1.6%) of cases. All of those documented were the Wells PE score. When Wells DVT and PE scores were calculated retrospectively, 30.0% and 17.1% (87 cases) were deemed 'likely' for VTE, respectively. However, imaging was performed in 172 cases (34.6%), including in 36 cases despite a negative D-dimer result and low PTP. In contrast, 68 cases (17.2%) had a D-dimer performed with a high Wells PTP for PE despite the recommendation to proceed directly to imaging. VTE (either DVT or PE) was confirmed by imaging in 32 (18.6%) of cases, the majority (53.1%) had a high retrospective PTP. Conclusions Inappropriate ordering and interpretation of D-dimers remains a significant problem despite the implementation of clinical guidelines and pre-test probability algorithms, namely the Wells score for DVT and PE meant to guide physicians. This leads to unnecessary cost, radiation exposure, and prolonged contact with the health care system for patients. This suggests the need for quality improvement initiatives which draw physician's attention to pre-test probability tools which can curbing subsequent inappropriate investigations and improve patient care. Disclosures Wu: Servier: Other: advisory board; BMS-pfizer: Honoraria, Other: advisory board; leo pharma: Other: advisory board; Pfizer: Honoraria.

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.

Characteristics and prognosis of acute type A aortic dissection with negative D-dimer result

BackgroundEvidence regarding the characteristics and prognosis in acute type A aortic dissection (AAD) patients with negative D-dimer result is limited. We aimed to investigate the characteristics and prognosis in AAD patients with negative D-dimer result. Methods and results370 AAD patients within 24 h of symptom onset were enrolled in a hospital in China from January 2014 to December 2018. Nine (2.43%) and 361 (97.57%) exhibited negative and positive D-dimer results, respectively. The average age of nine negative D-dimer result participants was 47.67 ± 10.95 years old, and about seven (77.78%) of them were male. The negative group showed a significantly lower blood pressure, white blood cell, hemoglobin, activated partial thromboplastin, ejection fraction and symptom with pain than the positive group. Multivariate analysis showed white blood cell (×109/L) (P = 0.008; odds ratio, 0.566) and symptom with pain (P < 0.001; odds ratio, 0.013) were significantly related to a negative result. The result of the fully-adjusted model showed negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients after adjusting confounders (OR = 0.34, 95%CI 0.01 to 10.82). ConclusionsNegative D-dimer result is strongly influenced by white blood cell and symptom with pain. Negative D-dimer result was negatively associated with in-hospital mortality compared with positive group in AAD patients.

D-dimer: A role in ruling out pulmonary embolism in an emergency care department

Background/Aim: Pulmonary embolism (PE) is a diagnostic challenge, particularly in prehospital care. The aim of this study was to determine to what extent the evaluation of D-dimer value helps physicians with differentiation of PE and whether D-dimer values are in correlation with the values of revised Geneva score. Methods: Data have been collected for the patients whose D-dimer has been evaluated at the Emergency Care Department of the City of Banja Luka in 2018. Gender, age, symptoms, working diagnosis and D-dimer value have all been recorded and also the fact whether the patient was referred to hospital treatment or not. For each patient the revised Geneva score was determined. Results: Sixty-eight tests were done in 2018. Out of 68 tests, 41 were negative (60.3 %). D-dimer results helped in making decisions about referring patients to the hospital or not (ch2 = 36.32, p < 0.001). Patients with elevated D-dimer levels, especially where the values were four times higher than the reference ones typically were referred to hospital treatment, whereas 67.5% patients with negative D-dimer results were sent home after giving a treatment and advice. In the elderly patients D-dimer was statistically more positive (F = 10.82, p < 0.001). Values of D-dimer were not significantly different regarding gender (ch2 = 2.19, p = 0.33). According to the results of the revised Geneva score, 5.1 % of patients had high risk of PTE, while moderate and low risk had 47.5 % each. Although it has been found that the values of D-dimer were slightly more elevated at higher values of the revised Geneva score and that the difference was not statistically significant (ch2 = 7.71, p = 0.10). Conclusion: Values of D-dimer considerably helped in differentiation of PE in the Emergency Care Department. D-dimer has a high negative predictive value and should be used to exclude PE diagnosis for patients with low clinical probability of PE.

Value of revised Geneva criteria and d-dimer levels in reducing overuse of pulmonary CT angiography in the diagnosis of pulmonary thromboembolism

Aim: To investigate the applicability of modified Geneva score which is used to evaluate the clinical probability, with the d-dimer results, to reduce the overuse of pulmonary CT angiography, on patients with suspicion of pulmonary thromboembolism. Material and Methods: A total of 400 patients who had performed pulmonary CT angiography, with the suspicion of pulmonary thromboembolism, in the emergency department, were included in this retrospective study. The clinic and demographic datas of the patients were classified according to the modified Geneva score, and d-dimer values were recorded. Presence of pulmonary thromboembolism was investigated on the pulmonary CT angiography images accessed from Picture Archiving Communication Systems.Results: In a 33 (%8.25) of 400 patients, thromboembolism was detected in the pulmonary CT angiography. 20% (n=1), 8.8% (n=25), and 6.4% (n=7) of the patients, have been diagnosed pulmonary thromboembolism by CT, with the high, intermediate, and low clinical probability, respectively. One hundred ninety-seven (49.25%) out of 400 patients had d-dimer results. One (2.9%) out of 34 patients with a negative d-dimer value had thromboembolism in CT. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated, as 78.8%, 28.1%, 9%, 93.6% of the modified Geneva score, and as 94.7%, 18.5%, 11%, and 97.1% of the d-dimer, respectively.Conclusion: In the diagnosis of pulmonary thromboembolism, modified Geneva score, and d-dimer test have high negative predictive values. Other clinic diagnoses can be considered primarily, in patients have low modified Geneva scores with negative d-dimer results. This may contribute to the reduction of the overuse of pulmonary CT angiography.

Review of Clinical Utility of Age-Adjusted D-Dimer Assay

Background: Diagnosis of venous thromboembolism (VTE) uses biomarker D-dimer to exclude low probability VTE and imaging techniques to verify mid/high probability VTE. Plasma concentration of D-dimer increases with age in over 50 years and age-adjusted thresholds have been recommended and validated. Age-adjusted D-dimer reporting was introduced in Our Lady's Hospital (OLH) Navan in October 2018. By increasing the cut-off D-dimer values in older patients, a reduction in request for radiological investigations to out-rule VTE was anticipated. Aims: To establish the clinical utility of using age-adjusted D-dimer reporting to our-rule VTE in clinical practice. Methods: This retrospective analysis examined consecutive D-dimer results for individuals over age 50 during 5 months (May 2018 to September 2018) before and 5 months (October 2018 to February 2019) after introduction of age-adjusted D-dimer reporting. Data was collected from OLH Navan Laboratory information system and NIMIS (National Integrated Medical Imaging System). Results: Five months prior to introduction of age-adjusted D-dimer reporting, 422 D-dimer tests were processed for patients over 50 years, of which 273(65%) were positive and 149(35%) were negative. In positive D-dimer group, 82 patients (30%) with positive results did not undergo radiological investigations. In remaining 191 patients with positive D-dimers, 21 patients (11%) had VTE (7 patients with Pulmonary Embolism (PE) and 4 patients with Deep Vein Thrombosis (DVT)). Over next 5 months following introduction of new D-dimer reporting, 290 D-dimer tests were performed for patients over 50 years, of which 65 (22%) had positive results and 225 (78%) had negative D-dimer. Five patients in positive group did not undergo further radiological tests. In the remaining 115 patients, 25 patients were diagnosed with VTE (22%), 4 patients with PE and 21 with DVT. Notably, 97 patients (33%) had negative D-dimer results that previously would have been positive with the old method. This resulted in reduction in request for number of radiological investigations. However, 20 individuals with negative age-adjusted D-dimer results had radiological investigations but reported negative for VTE. Only 15 patients in the negative group had results low enough that it would have been negative using non-age adjusted assay. Conclusion: Proportion of patients with positive D-dimer results had significantly reduced using age-adjusted reporting. Total number of VTE cases was comparable between the two periods but diagnostic yield from radiological investigations increased from 11% to 22% following introduction of age-adjusted assay. Our audit did not reveal any VTE diagnosis being missed with new reporting method in negative D-dimer group. From our experience, clinical utility of D-dimer was enhanced following introduction of age-adjusted assay with subsequent increase in its specificity and reduction in radiological investigations requested to out-rule VTE. The new method also prevents patients from having unnecessary investigations with potential cost-saving benefits. The study did not find any evidence of compromising clinical efficacy in out-ruling VTE. Disclosures No relevant conflicts of interest to declare.

D-dimer testing, with gender-specific cutoff levels, is of value to assess the individual risk of venous thromboembolic recurrence in non-elderly patients of both genders: a post hoc analysis of the DULCIS study

Male patients, especially the young, are at a higher risk of recurrent venous thromboembolism (RVTE) than females. Recent scientific reports show the use of D-dimer does not help predict RVTE risk in males. In the present report, we reviewed the data obtained in the DULCIS study (main report published in Blood 2014), focusing on D-dimer results recorded in non-elderly patients of both genders included in the study, and their relationship with RVTE events occurring during follow-up. Using specifically designed cutoff values for positive/negative interpretation, serial D-dimer measurements (performed during warfarin treatment and up to 3 months after discontinuation of anticoagulation) in 475 patients (males 57.3%) aged ≤ 65 years were obtained. D-dimer resulted positive in 46.3% and 30.5% of males and females, respectively (p = 0.001). Following management procedure, anticoagulation was stopped in 53.7% of males and 69.5% of females, who had persistently negative D-dimer results. The rate of subsequent recurrent events was 1.7% (95% CI 0.5–4.5%) and 0.4% (95% CI 0–2.5%) patient-years in males and females, respectively, with upper limits of confidence intervals always below the level of risk considered acceptable by international scientific societies for stopping anticoagulation (< 5%). In conclusion, using sensitive quantitative assays with specifically designed cutoff values and serial measurements during and after discontinuation of anticoagulation, D-dimer testing is useful to predict the risk of RVTE and is of help in deciding the duration of anticoagulation in both male and female adult patients aged up to 65 years.

Oncologic Emergencies: Too Much Clotting-Venous Thromboembolism in Malignancy.

Malignancy predisposes patients to higher risk of venous thromboembolism (VTE), which is the second leading cause of death in patients with cancer. This narrative review evaluates VTE in malignancy and the emergency medicine investigation and management of this patient population. Patients with malignancy are at higher risk of VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE). Risk factors include the underlying cancer, other hematologic disorders, cancer therapies, and underlying comorbidities. While patients with malignancy and VTE can present similarly to those without malignancy, incidental VTE is more common in cancer patients. Existing scores such as the Wells and Revised Geneva score can assist in risk stratification in patients with malignancy. A negative D-dimer result in the appropriately risk-stratified patient can be used to exclude VTE, though D-dimer is more commonly elevated at baseline in patients with malignancy. Several scoring systems may be useful to predict recurrent risk of VTE, including the Khorana and Ottawa scores. Treatment includes anticoagulation with direct oral anticoagulants (DOACs) or low molecular weight heparin (LMWH). Outpatient therapy may be appropriate in select patients. This narrative review provides key updates in the assessment and management of cancer patients with VTE.

Overuse of Lower Extremity Venous Duplex by the Emergency Department for Detection of DVT: Pilot Study to Evaluate Use of D-Dimers as a Screening Tool in Low-Risk Patients

As the cost of health care remains a major concern for patients, providers, and payers, it has become increasingly important to evaluate resource utilization behaviors. The purpose of this study was to evaluate the utilization patterns of the emergency department in the ordering of lower extremity venous duplex ultrasound examinations for detection of acute deep venous thrombosis (DVT) and the use of D-dimer as a screening test in low-risk (by Wells criteria) patients. Estimated cost at our institution is $15 for the D-dimer test and $300 for the venous duplex ultrasound scan. All venous duplex ultrasound examinations that were ordered by the emergency department during the course of 10 days were evaluated. After-hours duplex ultrasound examinations were those ordered between the hours of 9 pm and 7 am on weekdays and between the hours of 4 pm and 7 am on weekends. Studies were evaluated for the patient’s presenting complaint, indication for duplex ultrasound as documented in the provider’s notes, results of the duplex ultrasound examination (positive vs negative for DVT), D-dimer studies, and Wells criteria scores. During this 10-day period, 68 lower extremity venous duplex ultrasound examinations were performed for emergency department patients, 28% of which were performed after hours (n = 19). Only 13% (n = 9) of these patients received concomitant D-dimer serum tests, of which 56% (5/9) of results were positive; 26 studies were bilateral, and only 5 studies were positive for acute DVT in one (n = 4) or both (n = 1) legs. Of 42 unilateral studies, only 9% (n = 4) were positive for acute DVT. Among patients with Wells criteria score <2, only 5 of 63 (8%) had a D-dimer sample sent. Among these, one had a positive duplex ultrasound scan. Five (8%) other positive duplex ultrasound scans occurring in the low-risk population did not have concomitant D-dimer samples sent. No patients with negative D-dimer results had acute DVT on duplex ultrasound examination. Based on the preliminary results of our pilot study, it appears there is significant overutilization of venous duplex ultrasound imaging by the emergency department for DVT screening with underutilization of D-dimer in low-risk patients. Use of D-dimer tests instead of duplex ultrasound scan in low-risk (Well criteria score <2) patients would have potentially saved $16,359 during a 10-day period, which would be approximately $597,104 per annum. Larger studies are recommended to examine the overuse of duplex ultrasound in the emergency department setting.

Safety of D‐dimer testing as a stand‐alone test for the exclusion of deep vein thrombosis as compared with other strategies

Essentials The aim of deep vein thrombosis (DVT) diagnostic work-up is to maximize both safety and efficiency. We explored whether D-dimer is safe and efficient as a stand-alone test to exclude DVT. Our findings suggest it is a safe, efficient and simplified diagnostic strategy. The safety of age-adjusted D-dimer as a stand-alone test requires further investigation. SUMMARY: Background Several strategies for safely excluding deep vein thrombosis (DVT) while limiting the number of imaging tests have been explored. Objectives To determine whether D-dimer testing could safely and efficiently exclude DVT as a stand-alone test, and evaluate its performance as compared with strategies that incorporate the Wells score and age-adjusted D-dimer. Patients/Methods We included consecutive outpatients referred with suspected DVT to the Emergency Department at Østfold Hospital, Norway. STA-Liatest D-Di PLUS D-dimer was analyzed for all patients. Patients with a D-dimer level of ≥0.5μgmL-1 were referred for compression ultrasonography (CUS). In patients with a D-dimer level of <0.5μgmL-1 , no further testing was performed and anticoagulation was withheld. Patients were followed for 3months for venous thromboembolism (VTE). Results Of the 913 included patients, 298 (33%) had a negative D-dimer result. One hundred and seventy-three patients (18.9%) were diagnosed with DVT at baseline. One of 298 patients had DVT despite having a negative D-dimer result, resulting in a failure rate of 0.3% (95% confidence interval [CI]0.1-1.9%). Adding the modified Wells score would have yielded a failure rate of 0.0% (95%CI0.0-1.8%) while necessitating 87 more CUS examinations. Age-adjusted D-dimer as a stand-alone test would have necessitated 80 fewer CUS examinations than fixed D-dimer as a stand-alone test, at the cost of a failure rate of 1.6% (95%CI0.7-3.4%). Conclusions This outcome study shows that a negative high-sensitivity D-dimer result safely excludes DVT in an outpatient population, and necessitates fewer CUS than if used in combination with Wells score. The safety of stand-alone age-adjusted D-dimer needs further assessment in prospective outcome studies.

Diagnosis of Pulmonary Embolism During Pregnancy: A Multicenter Prospective Management Outcome Study.

Data on the optimal diagnostic management of pregnant women with suspected pulmonary embolism (PE) are limited, and guidelines provide inconsistent recommendations on use of diagnostic tests. To prospectively validate a diagnostic strategy in pregnant women with suspected PE. Multicenter, multinational, prospective diagnostic management outcome study involving pretest clinical probability assessment, high-sensitivity D-dimer testing, bilateral lower limb compression ultrasonography (CUS), and computed tomography pulmonary angiography (CTPA). (ClinicalTrials.gov: NCT00740454). 11 centers in France and Switzerland between August 2008 and July 2016. Pregnant women with clinically suspected PE in emergency departments. Pulmonary embolism was excluded in patients with a low or intermediate pretest clinical probability and a negative D-dimer result. All others underwent lower limb CUS and, if results were negative, CTPA. A ventilation-perfusion (V/Q) scan was done if CTPA results were inconclusive. Pulmonary embolism was excluded if results of the diagnostic work-up were negative, and untreated pregnant women had clinical follow-up at 3 months. The primary outcome was the rate of adjudicated venous thromboembolic events during the 3-month follow-up. 441 women were assessed for eligibility, and 395 were included in the study. Among these, PE was diagnosed in 28 (7.1%) (proximal deep venous thrombosis found on ultrasonography [n= 7], positive CTPA result [n= 19], and high-probability V/Q scan [n= 2]) and excluded in 367 (clinical probability and negative D-dimer result [n= 46], negative CTPA result [n= 290], normal or low-probability V/Q scan [n= 17], and other reason [n= 14]). Twenty-two women received extended anticoagulation during follow-up, mainly for previous venous thromboembolic disease. The rate of symptomatic venous thromboembolic events was 0.0% (95% CI, 0.0% to 1.0%) among untreated women after exclusion of PE on the basis of negative results on the diagnostic work-up. There were several protocol deviations, reflecting the difficulty of performing studies in pregnant women with suspected PE. A diagnostic strategy based on assessment of clinical probability, D-dimer measurement, CUS, and CTPA can safely rule out PE in pregnant women. Swiss National Foundation for Scientific Research, Groupe d'Etude de la Thrombose de Bretagne Occidentale, and International Society on Thrombosis and Haemostasis.