D-dimer Threshold Research Articles

Utility of D-dimer in predicting pulmonary embolism in patients with COVID-19 presenting to the emergency department.

While our understanding of coronavirus disease 2019 (COVID-19) has evolved, uncertainty remains regarding utility of previously established pulmonary embolism (PE) screening guidelines in patients with COVID-19. Many studies have investigated the efficacy of D-dimer (DD) screenings for patients with COVID-19 admitted to inpatient services, but few have evaluated patients in the emergency department (ED). The purpose of this study was to investigate utility of DD threshold for PE screening in patients with COVID-19 presenting to the ED. This was a retrospective, multicenter cohort including patients presenting to three EDs between March 1, 2020 and February 1, 2021 who tested positive for COVID-19 during ED visit or in 60 days prior to presentation and had DD ordered in ED. Patients were grouped by those who underwent computed tomography pulmonary angiogram (CTPA) to evaluate for PE and those who did not, and descriptive statistics were performed. Those who underwent CTPA were further divided into PE-positive and PE-negative groups. The discriminative ability of DD in predicting PE in patients with COVID-19 was analyzed using the receiver operating characteristic (ROC) curve. A total of 570 patients with COVID-19 were included in the study, of which 107 underwent CTPA to evaluate for PE. History of diabetes, elevated glucose, elevated lactate dehydrogenase, elevated white blood cell count, elevated platelets, elevated respiratory rate, and lower temperature were associated with increased risk for PE. Compared to those without PE, patients with PE were significantly more likely to be hospitalized (100%vs. 82%, p=0.020) and admitted to the ICU (64%vs. 24%, p=0.002). Those with PE had a significantly higher median DD value (21,177ng/mL) compared to PE-negative group (952ng/mL, p<0.001). The ROC curve for DD in predicting PE had an area under the curve of 0.91 (95% confidence interval [0.84, 0.98]). In our study population, the optimal DD threshold for predicting PE was 1815ng/mL (sensitivity 93% and specificity 80%). A conservative threshold of 1089ng/mL could be used with sensitivity 100% and specificity 58%. DD is often elevated in patients with COVID-19, regardless of PE. While the classically used DD cutoff is 500ng/mL, our study demonstrated a threshold of 1089ng/mL safely predicted PE in patients withCOVID-19 .

Combining KRAS gene status with preoperative D‑dimer levels as a predictive marker of venous thromboembolism risk in patients with resectable colorectal cancer: A prospective cohort study.

Colorectal cancer (CRC), one of the most prevalent types of cancer, is accompanied by a notably high incidence of thrombotic complications. The present study aimed to elucidate the association between KRAS mutations and hypercoagulability in operable CRC. The prognostic value of preoperative D-dimer levels was also investigated, thus providing novel insights into the development of therapeutic strategies to enhance patient survival and diminish morbidity. Therefore, a prospective analysis of 333 CRC cases post-surgery at Yan'an Hospital Affiliated to Kunming Medical University, between May 2019 and October 2022 was performed. Data on demographics, tumor characteristics and D-dimer levels were compiled from the electronic health records. Venous thromboembolism (VTE) was diagnosed by doppler or computed tomography angiography, with D-dimer thresholds set at 550 and 1,650 µg/l. KRAS mutations at codons 12 and 13 were assessed in a subset of 56 cases. Subsequently, the factors affecting the hypercoagulable state in these patients were prospectively analyzed, focusing on the pivotal role of KRAS. The results showed that KRAS mutations were associated with elevated preoperative D-dimer levels, with 1,076 µg/l compared with 485 µg/l in the wild-type cohort, indicative of a hypercoagulable state. Increased D-dimer levels were also associated with vascular invasion, distant metastases and a heightened risk of postoperative VTE. Furthermore, multivariate analyses identified KRAS mutations, distant metastases and vascular invasion as independent predictors of elevated D-dimer levels, with relative risk values of 2.912, 1.884 and 1.525, respectively. Conversely, sex, age, tumor location, differentiation grade, Ki67 index and tumor stage could not significantly affect D-dimer levels, thus indicating a complex interplay between tumor genetics and coagulation dysfunction in CRC. The current study suggested that the KRAS mutation status, distant metastasis and vascular invasion could be considered as independent risk factors of blood hypercoagulability in patients with CRC, potentially serving as prognostic factors for VTE risk.

Contemporary approaches to pulmonary embolism diagnosis: a clinical review.

The optimal diagnosis strategy for pulmonary embolism (PE) in the emergency department (ED) remains complex. This review summarizes PE diagnosis with clinical presentation, decision rules and investigations for acute PE. This review was performed using studies published between January 1, 2010, and September 1, 2023. PE should be considered in ED in patients with chest pain, shortness of breath, syncope or signs of deep veinous thrombosis. Definitive diagnosis of PE relies on thoracic imaging, with the use of chest tomographic pulmonary angiogram or ventilation-perfusion lung scintigraphy. To limit the continuous increased use of chest imaging, the clinical probability should be the first step for PE workup. The pulmonary embolism rule-out criteria (PERC) can rule out PE at this stage. If not, for low or intermediate probability, several clinical decision rules have been validated, either by ruling out PE on clinical signs, or by raising D-dimer thresholds (YEARS or PEGeD [Pulmonary Embolism Graduated D-Dimer] criteria) or by combination of these different rules. It is recommended that patients with a high clinical probability of PE should undergo chest imaging without the need for D-dimer testing. The PE diagnostic approach can be tailored in specific populations such as pregnant, younger, COVID-19, or cancer patients. PE diagnosis workup illustrates the complexity of modern probabilistic-based approaches of decision-making in medicine. It is recommended to use a Bayesian approach with the evaluation of clinical probability, then order D-dimer if the PERC rule is positive, then adapt the D-dimer threshold for ordering chest imaging using clinical decision rules.

Distinct age-adjusted D-dimer threshold to rule out acute pulmonary embolism in outpatients and inpatients.

The diagnosis of acute pulmonary embolism (PE) is combinations of clinical probability assessments, plasma D-dimer (DD) test results, and/or computed tomographic pulmonary angiography (CTPA). The aim of this study is to explore the appropriate DD cutoff using the immunoturbidimetric method in outpatients and inpatients. We retrospectively enrolled 2689 patients with suspected PE between January 2014 and December 2019. All patients underwent clinical probability assessments, DD tests, and CTPA. We investigated the appropriate cutoff level for plasma DD tests in the correlation analysis and receiver operating characteristic (ROC) curves. Among all patients, 1263 were confirmed acute PE. The age-adjusted DD level was determined to be age × 10μg/L (for patients aged >50 years) in outpatients. This cutoff value resulted in a sensitivity of 96.75% and a specificity of 87.02%, with the area under the curve (AUC) of 0.908 and the number needed to treat (NNT) of 1.18. For inpatients, the age-adjusted cutoff values for the biomarker DD demonstrated poor specificity (13.34%) and NNT (9.88). However, when the DD cutoff was adjusted to 2 × the upper limit of normal (ULN), the sensitivity increased to 93.19%, while the specificity remained at 29.55%, with the AUC of 0.610 and the NNT of 4.76. The optimal DD cut-off value was 3010 μg/L (about 5 × ULN), resulting in a sensitivity of 75.22% and specificity of 61.72%, with the AUC of 0.727 and the NNT of 2.7. Using the immunoturbidimetric method to measure DD, an age-adjusted DD cutoff (age × 10μg/L, if aged >50 years) should be considered for outpatients with suspected PE. For inpatients, increasing the DD cutoff value to at least 2 × ULN yields the best test performance.

Cost-effectiveness of modified diagnostic strategy to safely rule-out pulmonary embolism in the emergency department: a non-inferiority cluster crossover randomized trial (MODIGLIA-NI)

BackgroundThe aim of this trial-based economic evaluation was to assess the incremental costs and cost-effectiveness of the modified diagnostic strategy combining the YEARS rule and age-adjusted D-dimer threshold compared with the control (which used the age-adjusted D-dimer threshold only) for the diagnosis of pulmonary embolism (PE) in the Emergency Department (ED).MethodsEconomic evaluation from a healthcare system perspective alongside a non-inferiority, crossover, and cluster-randomized trial conducted in 16 EDs in France and two in Spain with three months of follow-up. The primary endpoint was the additional cost of a patient without failure of the diagnostic strategy, defined as venous thromboembolism (VTE) diagnosis at 3months after exclusion of PE during the initial ED visit. Mean differences in 3-month failure and costs were estimated using separate generalized linear-regression mixed models, adjusted for strategy type, period, and the interaction between strategy and period as fixed effects and the hospital as a random effect. The incremental cost-effectiveness ratio (ICER) was obtained by dividing the incremental costs by the incremental frequency of VTE.ResultsOf the 1,414 included patients, 1,217 (86%) were analyzed in the per-protocol analysis (648 in the intervention group and 623 in the control group). At three months, there were no statistically significant differences in total costs (€-46; 95% CI: €-93 to €0.2), and the failure rate was non inferior in the intervention group (-0.64%, one-sided 97.5% CI: -∞ to 0.21%, non-inferiority margin 1.5%) between groups. The point estimate of the incremental cost-effectiveness ratio (ICER) indicating that each undetected VTE averted in the intervention group is associated with cost savings of €7,142 in comparison with the control group. There was a 93% probability that the intervention was dominant. Similar results were found in the as randomized population.ConclusionsGiven the observed cost decrease of borderline significance, and according to the 95% confidence ellipses, the intervention strategy has a potential to lead to cost savings as a result of a reduction in the use of chest imaging and of the number of undetected VTE averted. Policy-makers should investigate how these monetary benefits can be distributed across stakeholders.ClinicaltrialsTrial registration number ClinicalTrials.gov Identifier: NCT04032769; July 25, 2019.

Fast screening using attenuated total reflectance- fourier transform infrared (ATR-FTIR) spectroscopy of patients based on D-dimer threshold value

Attenuated Total Reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy is an emerging technology in the medical field. Blood D-dimer was initially studied as a marker of the activation of coagulation and fibrinolysis. It is mainly used as a potential diagnosis screening test for pulmonary embolism or deep vein thrombosis but was recently associated with COVID-19 severity. This study aimed to evaluate the use of ATR-FTIR spectroscopy with machine learning to classify plasma D-dimer concentrations. The plasma ATR-FTIR spectra from 100 patients were studied through principal component analysis (PCA) and two supervised approaches: genetic algorithm with linear discriminant analysis (GA-LDA) and partial least squares with linear discriminant (PLS-DA). The spectra were truncated to the fingerprint region (1800–1000 cm−1). The GA-LDA method effectively classified patients according to D-dimer cutoff (≤0.5 μg/mL and >0.5 μg/mL) with 87.5 % specificity and 100 % sensitivity on the training set, and 85.7 % specificity, and 95.6 % sensitivity on the test set. Thus, we demonstrate that ATR-FTIR spectroscopy might be an important additional tool for classifying patients according to D-dimer values. ATR-FTIR spectral analyses associated with clinical evidence can contribute to a faster and more accurate medical diagnosis, reduce patient morbidity, and save resources and demand for professionals.

Development and validation of a clinical prediction model for the diagnostic management of acute pulmonary embolism: an individual participant data meta-analysis

Abstract Background/Introduction Risk stratification is used for decisions about imaging in patients with clinically suspected acute pulmonary embolism (PE). Purpose To develop a clinical prediction model that provides an individualized, accurate probability estimate for acute pulmonary embolism (PE) based on readily available clinical items and D-dimer concentrations. Methods An individual participant data meta-analysis was performed based on sixteen studies with data from 28,305 adult patients with clinically suspected PE from various clinical settings. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict PE at baseline or during follow-up of 30-90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value &amp;lt; 0.10. Discrimination (c-statistic with 95% CI and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was compared to algorithms based on the Wells score and D-dimer testing. Results The final model included age (in years), sex, previous VTE, recent surgery/immobilization, hemoptysis, cancer, clinical signs of DVT, inpatient status, D-dimer (in μg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95%-CI, 0.85-0.89; 95%-PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). In the lower range of probabilities, the model slightly overestimated VTE probability. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c- statistic 0.73; 95%-CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95%-CI, 0.76- 0.81). Conclusion(s) The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study.Calibration plot of the new model

OC 11.4 Diagnosis of Deep Vein Thrombosis Using a D-Dimer Threshold Adjusted to Clinical Probability: Supportive Real-World Evidence for a Change in Clinical Practice

OC 11.4 Diagnosis of Deep Vein Thrombosis Using a D-Dimer Threshold Adjusted to Clinical Probability: Supportive Real-World Evidence for a Change in Clinical Practice

Diagnostic management of acute pulmonary embolism: a prediction model based on a patient data meta-analysis.

Risk stratification is used for decisions regarding need for imaging in patients with clinically suspected acute pulmonary embolism (PE). The aim was to develop a clinical prediction model that provides an individualized, accurate probability estimate for the presence of acute PE in patients with suspected disease based on readily available clinical items and D-dimer concentrations. An individual patient data meta-analysis was performed based on sixteen cross-sectional or prospective studies with data from 28 305 adult patients with clinically suspected PE from various clinical settings, including primary care, emergency care, hospitalized and nursing home patients. A multilevel logistic regression model was built and validated including ten a priori defined objective candidate predictors to predict objectively confirmed PE at baseline or venous thromboembolism (VTE) during follow-up of 30 to 90 days. Multiple imputation was used for missing data. Backward elimination was performed with a P-value <0.10. Discrimination (c-statistic with 95% confidence intervals [CI] and prediction intervals [PI]) and calibration (outcome:expected [O:E] ratio and calibration plot) were evaluated based on internal-external cross-validation. The accuracy of the model was subsequently compared with algorithms based on the Wells score and D-dimer testing. The final model included age (in years), sex, previous VTE, recent surgery or immobilization, haemoptysis, cancer, clinical signs of deep vein thrombosis, inpatient status, D-dimer (in µg/L), and an interaction term between age and D-dimer. The pooled c-statistic was 0.87 (95% CI, 0.85-0.89; 95% PI, 0.77-0.93) and overall calibration was very good (pooled O:E ratio, 0.99; 95% CI, 0.87-1.14; 95% PI, 0.55-1.79). The model slightly overestimated VTE probability in the lower range of estimated probabilities. Discrimination of the current model in the validation data sets was better than that of the Wells score combined with a D-dimer threshold based on age (c-statistic 0.73; 95% CI, 0.70-0.75) or structured clinical pretest probability (c-statistic 0.79; 95% CI, 0.76-0.81). The present model provides an absolute, individualized probability of PE presence in a broad population of patients with suspected PE, with very good discrimination and calibration. Its clinical utility needs to be evaluated in a prospective management or impact study. PROSPERO ID 89366.

Assessment of D-dimer levels in pregnant women diagnosed with COVID-19: A case-control study

Objective We aimed to evaluate D-dimer levels in pregnant women diagnosed with COVID-19. Methods This single-center study was carried out in a tertiary center hospital serving as a pandemic hospital. 151 pregnant women with COVID-19 diagnosis were included as the study group, and 70 healthy pregnant women as the control group. The data were analyzed separately in 3 different trimesters of pregnancy. Results Of the 221 pregnant women included in the study, 151 had a diagnosis of COVID-19. 70 healthy pregnant women were taken as the control group. It was observed that D-dimer values in pregnancy increased as the trimesters progressed. No significant difference was observed when this was compared with pregnant women with COVID-19 (p = .428, .75, .927 according to the 1st, 2nd and 3rd trimesters, respectively). Conclusion The diagnosis of pulmonary embolism is difficult due to the lack of reliable alternative D-dimer thresholds for pregnant patients. On the other hand, D-dimer elevation continues to be a sign of poor prognosis in patients with COVID-19. The situation remains uncertain in patients who are pregnant and have COVID-19. Maybe D-dimer value should be removed from being a poor prognosis criterion in pregnant women.

Diagnostic Approach for Venous Thromboembolism in Cancer Patients.

Venous thromboembolic disease (VTE) is a common complication in cancer patients. The currently recommended VTE diagnostic approach involves a step-by-step algorithm, which is based on the assessment of clinical probability, D-dimer measurement, and/or diagnostic imaging. While this diagnostic strategy is well validated and efficient in the noncancer population, its use in cancer patients is less satisfactory. Cancer patients often present nonspecific VTE symptoms resulting in less discriminatory power of the proposed clinical prediction rules. Furthermore, D-dimer levels are often increased because of a hypercoagulable state associated with the tumor process. Consequently, the vast majority of patients require imaging tests. In order to improve VTE exclusion in cancer patients, several approaches have been developed. The first approach consists of ordering imaging tests to all patients, despite overexposing a population known to have mostly multiple comorbidities to radiations and contrast products. The second approach consists of new diagnostic algorithms based on clinical probability assessment with different D-dimer thresholds, e.g., the YEARS algorithm, which shows promise in improving the diagnosis of PE in cancer patients. The third approach uses an adjusted D-dimer threshold, to age, pretest probability, clinical criteria, or other criteria. These different diagnostic strategies have not been compared head-to-head. In conclusion, despite having several proposed diagnostic approaches to diagnose VTE in cancer patients, we still lack a dedicated diagnostic algorithm specific for this population.

Does Performance of D-Dimer for Diagnosis of Periprosthetic Joint Infection Change With the Virulence of Infecting Organism?

BackgroundThe impact of the organism virulence on diagnostic accuracy of D-Dimer for periprosthetic joint infection (PJI) is unknown. Our objective was to assess if the performance of D-Dimer in PJI diagnosis changes with the virulence of the organism(s). MethodsWe retrospectively reviewed 143 consecutive revision total hip arthroplasties/total knee arthroplasties with D-Dimer ordered preoperatively. Operations were performed by 3 surgeons at a single institution (November 2017 through September 2020). There were 141 revisions with complete 2013-International Consensus Meeting-criteria initially included. This criteria was used to classify revisions as aseptic versus septic. Culture-negative septic revisions (n = 8) were excluded, and 133 revisions (47-hips/86-knees; 67-septic/66-aseptic) were analyzed. Based on culture results, septic-revisions were categorized into ‘low-virulence (LV/n = 40)’ or ‘high-virulence (HV/n = 27)’. The D-Dimer threshold (850-ng/mL) was tested against 2013-International Consensus Meeting-criteria (“standard”) in identifying septic-revisions (LV/HV) from aseptic-revisions. Sensitivity, specificity, and positive predictive values/negative predictive values (NPV) were determined. Receiver-operating-characteristic-curve-analyses were performed. ResultsPlasma D-Dimer showed high sensitivity (97.5%) and NPV (95.4%) in LV septic cases, which appeared to reduce by about 5% in HV septic cases (sensitivity = 92.5% and NPV = 91.3%). However, this marker had poor overall accuracy (LV = 57%; HV = 49.4%), low specificity (LV and HV = 31.8%), and positive predictive values (LV = 46.4%; HV = 35.7%) to diagnose PJI. The area under the curve was 0.647 and 0.622 in LV and HV versus aseptic revisions, respectively. ConclusionD-Dimer performs poorly to identify septic from aseptic revisions in the setting of LV/HV infecting organisms alike. However, it shows high sensitivity for PJI diagnosis in cases of LV organisms which might be missed by most diagnostic tests.

Utility and limitations of patient-adjusted D-dimer cut-off levels for diagnosis of venous thromboembolism-A systematic review and meta-analysis.

To systematically assess test performance of patient-adapted D-dimer cut-offs for the diagnosis of venous thromboembolism (VTE). Systematic review and analysis of articles published in PubMed, Embase, ClinicalTrials.gov, and Cochrane Library databases. Investigations assessing patient-adjusted D-dimer thresholds for the exclusion of VTE were included. A hierarchical summary receiver operating characteristic model was used to assess diagnostic accuracy. Risk of bias was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 score. A total of 68 studies involving 141,880 patients met the inclusion criteria. The standard cut-off revealed a sensitivity of 0.99 (95% confidence interval [CI] 0.98-0.99) and specificity of 0.23 (95% CI 0.16-0.31). Sensitivity was comparable to the standard cut-off for age-adjustment (0.97 [95% CI 0.96-0.98]) and YEARS algorithm (0.98 [95% CI 0.91-1.00]) but lower for pretest probability (PTP)-adjusted (0.95 [95% CI 0.89-0.98) and COVID-19-adapted thresholds (0.93 [95% CI 0.82-0.98]). Specificity was significantly higher across all adjustment strategies (age: 0.43 [95% CI 0.36-0.50]; PTP: 0.63 [95% CI 0.51-0.73]; YEARS algorithm: 0.65 [95% CI 0.39-0.84]; and COVID-19: 0.51 [95% CI 0.40-0.63]). The YEARS algorithm provided the best negative likelihood ratio (0.03 [95% CI 0.01-0.15]), followed by age-adjusted (both 0.07 [95% CI 0.05-0.09]), PTP (0.08 [95% CI 0.04-0.17), and COVID-19-adjusted thresholds (0.13 [95% CI 0.05-0.32]). This study indicates that adjustment of D-dimer thresholds to patient-specific factors is safe and embodies considerable potential for reduction of imaging. However, robustness, safety, and efficiency vary considerably among different adjustment strategies with a high degree of heterogeneity.

Age- versus clinical pretest probability-adjusted D-dimer to rule out lower-extremity deep vein thrombosis in ambulatory patients with active cancer

BackgroundIn patients with suspected deep vein thrombosis (DVT), D-dimer thresholds adjusted to age or clinical pretest probability (CPTP) increase the proportion of patients in whom DVT can be safely excluded compared to a standard approach using a fixed D-dimer threshold. Performance of these diagnostic strategies among cancer patients is uncertain. AimTo compare the performance of age- and CPTP-adjusted D-dimer approaches among cancer outpatients with clinically suspected DVT, and derive a cancer-specific CPTP rule. Patients and methodsConsecutive ambulatory patients with active cancer and clinically suspected DVT of the lower extremity underwent CPTP assessment using the Wells rule, D-dimer testing, and whole-leg compression ultrasonography. Patients with normal ultrasonography were followed-up for 3 months for the occurrence of symptomatic venous thromboembolism. ResultsUpon referral, DVT was diagnosed in 48 of 239 (20.1 %) patients. The age-adjusted approach showed higher specificity and efficiency than the standard approach. Compared to the standard and age-adjusted strategies, the CPTP-adjusted approach had 35 % and 21 % higher specificity, and 34 % and 21 % higher efficiency, respectively. Failure rate, sensitivity, and predictive values were similar across strategies. A simplified CPTP score derived from the Wells rule reduced unnecessary imaging with similar accuracy and efficiency, but higher failure rate. ConclusionsIn this prospective cohort of ambulatory cancer patients with clinically suspected DVT, the CPTP-adjusted D-dimer approach held the highest specificity and efficiency, potentially safely reducing unnecessary ultrasonography examinations compared to other approaches. Additional studies are warranted to evaluate the use of a simplified clinical prediction rule in this setting.

Strategies to safely rule out pulmonary embolism in COVID-19 outpatients: a multicenter retrospective study.

The objective was to define a safe strategy to exclude pulmonary embolism (PE) in COVID-19 outpatients, without performing CT pulmonary angiogram (CTPA). COVID-19 outpatients from 15 university hospitals who underwent a CTPA were retrospectively evaluated. D-Dimers, variables of the revised Geneva and Wells scores, as well as laboratory findings and clinical characteristics related to COVID-19 pneumonia, were collected. CTPA reports were reviewed for the presence of PE and the extent of COVID-19 disease. PE rule-out strategies were based solely on D-Dimer tests using different thresholds, the revised Geneva and Wells scores, and a COVID-19 PE prediction model built on our dataset were compared. The area under the receiver operating characteristics curve (AUC), failure rate, and efficiency were calculated. In total, 1369 patients were included of whom 124 were PE positive (9.1%). Failure rate and efficiency of D-Dimer > 500µg/l were 0.9% (95%CI, 0.2-4.8%) and 10.1% (8.5-11.9%), respectively, increasing to 1.0% (0.2-5.3%) and 16.4% (14.4-18.7%), respectively, for an age-adjusted D-Dimer level. D-dimer > 1000µg/l led to an unacceptable failure rate to 8.1% (4.4-14.5%). The best performances of the revised Geneva and Wells scores were obtained using the age-adjusted D-Dimer level. They had the same failure rate of 1.0% (0.2-5.3%) for efficiency of 16.8% (14.7-19.1%), and 16.9% (14.8-19.2%) respectively. The developed COVID-19 PE prediction model had an AUC of 0.609 (0.594-0.623) with an efficiency of 20.5% (18.4-22.8%) when its failure was set to 0.8%. The strategy to safely exclude PE in COVID-19 outpatients should not differ from that used in non-COVID-19 patients. The added value of the COVID-19 PE prediction model is minor. • D-dimer level remains the most important predictor of pulmonary embolism in COVID-19 patients. • The AUCs of the revised Geneva and Wells scores using an age-adjusted D-dimer threshold were 0.587 (95%CI, 0.572 to 0.603) and 0.588 (95%CI, 0.572 to 0.603). • The AUC of COVID-19-specific strategy to rule out pulmonary embolism ranged from 0.513 (95%CI: 0.503 to 0.522) to 0.609 (95%CI: 0.594 to 0.623).

Prognostic association between d-dimer thresholds and 30-day pulmonary embolism diagnosis among emergency department patients with suspected SARS-CoV-2 infection: a Canadian COVID-19 Emergency Department Rapid Response Network study.

The primary objective was to quantify the prognostic association between various D-dimer thresholds and 30-day PE diagnosis among emergency department (ED) patients with suspected SARS-CoV-2 infection. This was a retrospective study of patients enrolled in the Canadian COVID-19 ED Rapid Response Network (CCEDRRN) registry from March 1, 2020 to July 2, 2021. We included consecutive adults (≥ 18years) presenting to 49 EDs with chest pain, shortness of breath, hypoxia, syncope, presyncope, or hemoptysis who were tested for both SARS-CoV-2 and D-dimer at index ED visit. The primary outcome measure was the sensitivity, specificity, and negative predictive value of D-dimer test thresholds for the outcome of 30-day PE diagnosis. Among 10,837 patients included in our study, 404 (3.7%) were diagnosed with PE at 30-days. A standard D-Dimer threshold of 500ng/mL had a sensitivity of 97.8% (95% confidence interval [CI] 95.8-99.0%), specificity of 40.9% (95% CI 39.9-41.8%), and negative predictive value of 99.8% (95% CI 99.6-99.9%). An age-adjusted D-dimer threshold had a sensitivity of 96.0% (95% CI 93.6-97.7%), specificity of 48.5% (95% CI 47.5-49.4%), and negative predictive value of 99.7% (95% CI 99.5-99.8%). D-dimer testing had slightly lower prognostic performance among SARS-CoV-2 positive compared to SARS-CoV-2 negative patients in predicting 30-day PE diagnosis. Among ED patients with suspected SARS-CoV-2, the standard 500ng/mL and age-adjusted D-dimer thresholds were comparable for the prediction of PE at 30-days. The prognostic performance of D-dimer was lower among SARS-CoV-2 positive patients. Clinicaltrials.gov, NCT04702945.

High D-Dimer Level at First Incident Cancer-Associated Venous Thromboembolism is a Predictor for Recurrence

BACKGROUND: Cancer is considered a major risk factor of venous thromboembolism (VTE). Whether the D-dimer level at first incident cancer-associated VTE can predict recurrence is not fully elucidated. AIM: The aim of this study was to assess the association between D-dimer level measured at first incident cancer-associated VTE and risk of recurrence. METHODS: In this study, the electronic records of all patients with first incident cancer-associated VTE were retrospectively retrieved and followed up for a period of 36 months. The measured levels of D-dimer and clinical predictors for each patient prior intervention were collected. Univariate and multivariant Cox regressions were fitted to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: A total of 73 (34.3%) of 213 cancer-associated VTE patients had recurrent VTE. The crude recurrence rate was 11.4/100 person-years (95% CI, 9.2–14.2). The mean value of D-dimer was significantly higher seen in recurrent VTE patients than those without recurrence (14.8 ± 7.5 mg/L vs. 4.8 ± 5.7 mg/L, P &lt; 0.001). The highest positive likelihood ratio using area under the receiver operating characteristic (ROC) curve occurred when a D-dimer threshold of 8.67 mg/L was chosen. At this threshold, the D-dimer was 92% sensitive and 80% specific in predicting recurrent VTE. The area under the ROC curve was 0.924 (95% CI 0.887–0.960, P &lt; 0.001). Patients with a D-dimer ≥8.67 mg/L at first VTE in our study were 3.1-fold more likely to have a recurrence than those with lower D-dimer results. CONCLUSION: A D-dimer ≥8.67 mg/L measured at the first incident cancer-associated VTE was associated with a 3.1-fold increased hazard of recurrence events. Our finding suggests that a low D-dimer level at the time of first cancer-associated VTE is suitable in the clinical practice to avoid extended-duration anticoagulation.

Pulmoner Emboli ile D-dimer Düzeyinin Korelasyonu ve Yaşa Göre Eşik Değerlerinin Belirlenmesi

Aim: This study was conducted to determine the D-dimer threshold levels according to age in patients diagnosed with pulmonary embolism (PE) by pulmonary computed tomography (CT) angiography. Material and Methods: Patients who had pulmonary CT angiography performed and whose D-dimer test was obtained with the suspicion of pulmonary embolism (PE) in the emergency department of a tertiary university hospital between January 01, 2015, and December 30, 2019, were included in the study. The demographic characteristics of the patients, imaging reports, and 1-month mortality were evaluated retrospectively by examining the hospital information management system and patient files. Patients with missing records and patients who had diagnostic examinations other than the preliminary diagnosis of PE were excluded from the study. Results: Among the 6240 patients included in the study, 58.1% were female. The mean age of the patients was 43±17 years. Of the 1,507 patients who had a pulmonary CT angiogram, 9.8% were diagnosed with PE. When we looked at the 1-month mortality of 6240 patients, whose D-dimer assay was analyzed with the preliminary diagnosis of PE, we found that 0.3% of patients died. The monthly mortality rate was 0.7% in patients with high D-dimer levels while the mortality rate in patients with normal D-dimer levels was 0.1%. A positive and statistically significant correlation was found between the location of the pulmonary embolism in pulmonary CT angiography and the D-dimer level (spearman’s rho= 0.251, p&amp;lt;0.001). The cut-off D-dimer value in predicting the presence of PE in all age groups was calculated as 1.34 mg/L. The cut-off values of D-dimer to predict the presence of PE according to age ranges was calculated as 1.18 mg/L (&amp;lt;50 years), 1.19 mg/L (50-60 years), 1.58 mg/L (60-70 years) 1.79 mg/L (70-80 years), 2.83 mg/L (&amp;gt;80 years) respectively. Conclusion: As age increases, the D-dimer cut-off value for the diagnosis of PE also increases. There is a positive and significant relationship between D-dimer level and pulmonary embolism severity.

Noninvasive diagnostic work-up for suspected acute pulmonary embolism during pregnancy: a systematic review and meta-analysis of individual patient data

BackgroundFew studies evaluated the performance of noninvasive diagnostic strategies for suspected acute pulmonary embolism (PE) in pregnant women. ObjectivesThe aim of this study was to establish the safety and efficiency of the Wells rule with fixed and adapted D-dimer threshold, and the YEARS algorithm, combined with compression ultrasonography (CUS), in pregnant women with suspected PE in an individual patient data meta-analysis. MethodsWe performed a systematic review to identify prospective diagnostic management studies in pregnant women with suspected PE. Primary outcomes were safety, defined as the failure rate, ie, the 3-month venous thromboembolism (VTE) incidence after excluding PE without chest imaging, and efficiency, defined as the proportion of patients in whom chest imaging could be avoided. ResultsWe identified 2 relevant studies, of which individual patient-level data were analyzed in a fixed-effect meta-analysis, totaling 893 pregnant women. The Wells rule with fixed and adapted D-dimer threshold as well as the YEARS algorithm could safely rule out acute PE (failure rate, 0·37%-1·4%), but efficiency improved considerably when applying pretest probability-adapted D-dimer thresholds. The efficiency of bilateral CUS was limited (2·3% overall; number needed to test 43), especially in patients without symptoms of deep-vein thrombosis (efficiency 0·79%; number needed to test 127). ConclusionThis study supports the latest guideline recommendations (European Society of Cardiology 2019) to apply pretest probability assessment and D-dimer tests to rule out PE in pregnant women. From an efficiency perspective, the use of a strategy with pretest probability-adapted D-dimer threshold is preferred. The yield of CUS was very limited in patients without concomitant symptoms of deep-vein thrombosis.

The application of an age adjusted D-dimer threshold to rule out suspected venous thromboembolism (VTE) in an emergency department setting: a retrospective diagnostic cohort study

BackgroundVenous Thromboembolic disease (VTE) poses a diagnostic challenge for clinicians in acute care. Over reliance on reference standard investigations can lead to over treatment and potential harm.We sought to evaluate the pragmatic performance and implications of using an age adjusted D-dimer (AADD) strategy to rule out VTE in patients with suspected disease attending an emergency department (ED) setting. We aimed to determine diagnostic test characteristics and assess whether this strategy would result in proportional imaging reduction and potential cost savings.MethodsDesign: Single centre retrospective diagnostic cohort study.All patients > 50 years old evaluated for possible VTE who presented to the emergency department over a consecutive 12-month period between January and December 2016 with a positive D-dimer result. Clinical assessment records and reference standard imaging results were followed up by multiple independent adjudicators and coded as VTE positive or negative.ResultsDuring the study period, there were 2132 positive D-dimer results. One thousand two hundred thirty-six patients received reference standard investigations. A total increase of 314/1236 (25.1%) results would have been coded as true negatives as opposed to false positive if the AADD cut off point had been applied, with 314 reference standard tests subsequently avoided. The AADD cut off had comparable sensitivity to the current cut off despite this increase in specificity; sensitivities for the diagnosis of DVT were 99.28% (95% CI 96.06–99.98%) and 97.72% for PE (95% CI 91.94% to 97.72). There were 3 false negative results using the AADD strategy.ConclusionsIn patients with suspected VTE with a low or moderate pre-test probability, the application of AADD appears to increase the proportion of patients in which VTE can be excluded without the need for reference standard imaging. This management strategy is likely to be associated with substantial reduction in anticoagulation treatment, investigations and cost/time savings.