Age-adjusted D-dimer Cutoff Research Articles

Age-Adjusted D-Dimer Cutoff in Ruling Out Pulmonary Embolism among Saudi Arabians in Riyadh Province

Objective. The study aimed to investigate the effectiveness of an age-adjusted D-dimer (AADD) cutoff in ruling out pulmonary embolism (PE) among the Saudi population, addressing the lack of data on AADD utility in this demographic. Methods. This single-centre retrospective cohort study conducted at Department of Medicine, King Abdulaziz Medical City in Riyadh, Saudi Arabia, between 2010 and 2018 analysed the data from patients suspected of PE who underwent computed tomography pulmonary angiography (CTPA). Age-adjusted D-dimer (AADD) levels were calculated for patients over 50 years of age [(age×10) µg/L], and AADD cutoffs were compared for diagnostic accuracy. Results. Among 277 subjects meeting inclusion criteria, a significant association between D-dimer levels and PE presence was observed. The AADD criteria showed a specificity of 94.7% and a sensitivity of 25%, with a Youden index of 0.2. The high negative predictive value of 90.62% supported the use of AADD in confirming the absence of PE in patients. Conclusions. Based on the study findings, the AADD cutoff [(age×10) µg/L] can be efficiently and safely used as an exclusionary tool for patients over 50 years of age suspected of having PE. This study supports the clinical utility of AADD, particularly in older Saudi patient populations.

Age-Adjusted and Clinical Probability Adapted D-Dimer Cutoffs to Rule Out Pulmonary Embolism: A Narrative Review of Clinical Trials.

Diagnosis of pulmonary embolism remains a challenge for clinicians as its differential diagnosis is wide. The use of sequential diagnostic strategies based on the assessment of clinical probability, D-dimer measurement, and computed tomography pulmonary angiography have been validated in large prospective outcome studies. D-dimer measurement at a standard cutoff of 500 μg/L has gained wide acceptance to rule out pulmonary embolism in around 20 to 30% of patients with a clinically suspected pulmonary embolism. To improve the efficiency of D-dimer measurement, different ways of selecting a higher, albeit safe cutoff were explored: the age-adjusted D-dimer cutoff and the clinical adapted D-dimer cutoff. While both have been prospectively validated in large studies, some differences do exist. In particular, the prevalence of pulmonary embolism in these different validation studies was very different. Overall, the age-adjusted cutoff seems to be safer and less efficient, while the clinical probability adapted cutoff seems more efficient and less safe. Here, we report the available data regarding these two different ways to increase the diagnostic yield of D-dimer. Also, well beyond the accuracy of these adjusted/adapted cutoffs, some external factors, such as the prevalence of pulmonary embolism in the tested population and the clinical setting, have an important impact of the negative predictive value and on the overall efficiency of these cutoffs. Therefore, we also discuss which cutoff should be used according to the expected prevalence of the disease and according to the clinical setting.

Diagnostic Strategies in Pulmonary Embolism

AbstractKey to the diagnosis of pulmonary embolism (PE) is a careful bedside evaluation. After this, there are three further diagnostic steps. In all patients, estimation of the clinical probability of PE is performed. The other two steps are measurement of D-dimer when indicated and chest imaging when indicated. The clinical probability of PE is estimated at low, moderate, or high. The prevalence of PE is less than 15% among patients with low clinical probability, 15 to 40% with moderate clinical probability, and >40% in patients with high clinical probability. Clinical gestalt has been found to be very useful in estimating probability of PE. However, clinical prediction rules, such as Wells criteria, the modified Geneva score, and the PE rule out criteria have been advocated as adjuncts. In patients with high clinical probability, the high prevalence of PE can lower the D-dimer negative predictive value, which could increase the risk of diagnostic failure. Consequently, patients with high probability for PE need to proceed directly to chest imaging, without prior measurement of D-dimer level. Key studies in determining which low to moderate probability patients require chest imaging are the Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism (ADJUST-PE), the Simplified diagnostic management of suspected pulmonary embolism (YEARS), and the Pulmonary Embolism Graduated D-Dimer trials. In patients with low clinical probability, PE can be excluded without imaging studies if D-dimer is less than 1,000 ng/mL. In patients in whom there is not a low likelihood for PE, this can be excluded without imaging studies if the D-dimer is below the age-adjusted threshold.

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.

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.

Accuracy and Prediction of D-Dimers for Pulmonary Embolism in Patients with COVID-19 Infection

Background: D-dimer values in patients with SARS-2 COVID-19 infection are known to be elevated and have been shown to be a predictor for disease severity, mortality, and venous thromboembolism (VTE). Patients presenting with COVID-19 infection may endorse many of the same symptoms as patients with pulmonary emboli (PE) and the associated elevation of the d-dimer as a component of the inflammatory state has led to unanswered questions regarding the diagnostic utility of d-dimer testing. Methods: Computed tomography (CT) scans of the chest with intravenous contrast were searched from a unified data platform between 1/1/2020 and 5/31/2022 across the Mayo Clinic enterprise. Imaging was matched to patients with COVID-19 if it occurred between 10 days before and 30 days after the laboratory confirmed COVID-19 infection. Next, patients were matched to laboratory records of d-dimer testing within 1 day of the imaging. D-dimer testing was performed using the HemosIL D-dimer HS 500 kit on the Instrumentation Laboratory ACL TOP instrument. A negative result is ≤500ng/ml fibrinogen equivalent units (FEU) with a lower limit of detection of 220ng/ml. The primary outcome was acute PE on the imaging study as determined by a validated natural language processing algorithm. Results: A total of 6,747 d-dimer/CT pairs were examined in 5,971 unique patients with COVID-19. Pulmonary emboli were identified on 7.7% of CTA of the pulmonary arteries (n=6,222), 6.6% of CTA-other (n=241), and 3.9% of CTs with IV contrast (n=284). Patients diagnosed with PE were older (median age 67 vs 61, p<0.001), more likely to be male (60.0% vs 53.8%, p=0.03), white (91.3% vs 87.3%, p=0.02), and have dementia, cancer, hyperlipidemia, or ischemic stroke (Table 1). Median d-dimer values in patients found to have PE was 5432ng/ml compared 941ng/ml in those without PE. A prior history of VTE (by ICD-10 codes) was seen more frequently in the group diagnosed with PE (41.4% vs 6.8%, p =0.03). In the overall group of patients with CT imaging of the chest with some form of intravenous contrast, the sensitivity at the standard d-dimer threshold was 99.2% [negative predictive value (NPV) 99.3%], decreased to 98.0% with the age-adjusted cutoff (NPV 99.0%), and decreased further with an increased d-dimer threshold of 1000ng/ml (NPV 98.5%) (Table 2). Due to the strong association seen between patients with a history of VTE and positive findings of PE with COVID-19 infection, we performed additional sensitivity and specificity testing after excluding patients with prior VTE. Within this group and among CTA of the pulmonary arteries only, the sensitivity of the d-dimer was 99.0% using the standard threshold of 500ng/ml, was 98.4% using the age-adjusted d-dimer cutoff, and was 92.1% at an elevated threshold of 1000ng/ml. The NPV of d-dimer was high irrespective of the threshold used: 1000ng/ml (99.2%), age-adjusted cutoff (99.4%) and standard cutoff (99.3%). Conclusion: This study of COVID-19 positive patients more than doubles the number of patients examining the diagnostic utility of d-dimer in PE diagnosis compared to recent meta-analyses and with a consistent d-dimer methodology performed in close proximity to diagnostic imaging. D-dimer was highly predictive of PE with strong and expected NPVs at standard thresholds and using age-adjusted thresholds. We demonstrate that a higher d-dimer threshold of 1000ng/ml would maintain a very high NPV and overall AUC. A fixed and higher d-dimer threshold in patients with COVID-19 infection with possible PE would significantly reduce the need for CT angiography (by 42%). Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Is it possible to reduce overutilization of computed tomographic pulmonary angiography in a real-world population with suspected acute pulmonary embolism?

Introduction: Computed tomographic pulmonary angiography (CTPA) is the basic examination in the diagnosis of acute pulmonary embolism (PE), however, it is overused many times in emergency units. The aim of this study was to assess the percentage of CTPA which is possible to avoid in patients considered for radiological imaging due to suspected PE. Material and methods: The retrospective analysis of clinical data and the calculation of PE probability rules (Wells score, Geneva score, blood D-dimer concentration, ECG) were performed in 700 consecutive patients who underwent CTPA due to suspected PE in a single university center between January 2017 and January 2020. Results: Suspected PE was confirmed by CTPA in 22.7% of considered patients. The independent risk factors for PE diagnosis in CTPA were: history of DVT, diagnosis of DVT on admission, and “PE-likely” score according to simplified Wells scale. Blood D-dimer concentration was associated with the lowest diagnostic accuracy of PE. The combination of simplified Geneva “PE-likely” score with standard or age-adjusted D-dimer cut-offs achieved 100% negative predictive value for PE. In relation to studied PE pre-test probability rules, use YEARS algorithm was associated with the greatest number of CTPAs which could be avoided (9.3%) with the risk &lt; 1% of false-negative categorization. Conclusions: The combination of simplified Geneva “PE-likely” score with age-adjusted D-dimer cut-offs and YEARS algorithm were more effective than the PERC, original and simplified Wells and Geneva rules in safe exclusion of PE, which might reduce the absolute number of unnecessary CTPA.

Thrombotic burden, D-dimer levels and complete compression ultrasound for diagnosis of acute symptomatic deep vein thrombosis of the lower limbs

BackgroundDiagnostic algorithms for deep vein thrombosis (DVT) include D-dimer for its high negative predictive value, thus reducing the need for imaging. Small thrombi may be associated with low D-dimer levels, increasing false negatives. AimTo assess the sensitivity and thus the false negative rates of standard and age-adjusted D-dimer cut offs for isolated distal DVT (IDDVT) in outpatients. Materials and methodsWe enrolled consecutive outpatients with suspected DVT of the lower limbs referring to our vascular emergency department from 2009 to 2018. Patients underwent D-dimer testing (STA, Stago, cut-off: 500 μg/L), pretest clinical probability (PTP) evaluation and complete compression ultrasonography. Follow-up was 3 months. ResultsAmong 3948 patients (M:1554–39%, median age 69), 486 proximal DVTs (12.3%) and 348 IDDVTs (8.8%) were diagnosed. Median D-dimer was higher in proximal than IDDVT (3960 vs 1400 μgr/L; p = 0.001). The false negative rate of the standard D-dimer cut-off was 2% (95%CI: 0.8–3.2%) for proximal DVT and 14.7% (95% CI: 11–81%) for IDDVT. The false negative rate of the age-adjusted cut-off was 4.9% (3–7%) for proximal DVT and 19.5% (95% CI: 15.4–24.7%) for IDDVT. Conclusions: Small calf thrombi are associated with low D-dimer levels, and age-adjusted D-dimer may be below the cut-off more frequently in subjects with IDDVT than standard cut-off D-dimer, although such D-dimer levels might exclude IDDVT that require treatment.

Age-Adjusted D-Dimer in Ruling Out Acute Aortic Syndrome.

Background Recently, D-dimer has been suggested as a biomarker to rule out acute aortic syndrome (AAS). Since it increases with age, this study was conducted to reveal whether an age-adjusted D-dimer can increase diagnostic accuracy in ruling out AAS. Method A retrospective observational study design was used. Consecutive adult patients who visited an emergency room between January 2015 and September 2020 and who underwent a D-dimer test and computed tomography angiography for suspected AAS were enrolled. We calculated the diagnostic accuracy of both the conventional (0.5 μg/ml) and age-adjusted (age × 0.01 in patients >50 years) D-dimer cut-offs. Result D-dimer was higher in the AAS group (n = 82) than in the non-AAS group (n = 122) (10.85 (3.61–33.12) vs. 0.40 (0.23–1.07), OR: 1.139 (CI: 1.085 – 1.195), p < 0.001). The D-dimer plasma level had an area under the ROC curve of 0.915 (CI: 0.873–0.956) with AAS. At the age-adjusted cutoff point compared to a 0.5 μg/ml cutoff, the sensitivity of 97.6% and the NLR of 0.04 did not change, but the specificity increased by 5.7% to 65.6%, the PPV increased by 3.6% to 65.6%, and the NPV slightly increased by 0.2% to 97.6%. Conclusion Compared with a conventional method, the age-adjusted D-dimer cutoff may have higher specificity and PPV while maintaining high sensitivity for ruling out AAS.

Prognostic Value of Age-Adjusted D-Dimer Cutoff Thresholds in Patients with Acute Coronary Syndrome Treated by Percutaneous Coronary Intervention.

BackgroundAssociations between D-dimer and outcomes of patients with acute coronary syndrome (ACS) remain controversial. Using age-adjusted D-dimer cutoff thresholds improve the diagnostic accuracy for thrombotic diseases. This study aimed to investigate the prognostic value of age-adjusted D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).MethodsA total of 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The basal age-adjusted D-dimer threshold was 500 ng/mL and was calculated as age × 10 in patients older than 50 years. Cox regression was used for outcome analysis. C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the additional prognostic value of age-adjusted D-dimer when combined with established clinical risk factors. The primary outcome was all-cause death.ResultsDuring a median follow-up of 720 days, a total of 225 deaths occurred. High D-dimer level, as defined by age-adjusted thresholds, was an independent predictor for all-cause death (hazard ratio [HR]: 1.75, 95% confidence interval [CI]: 1.32–2.31, P < 0.001), cardiac death (HR: 1.84, 95% CI: 1.30–2.60, P = 0.001), and MACE (HR: 1.48, 95% CI: 1.19–1.83, P < 0.001). Sensitivity and subgroup analysis showed that high D-dimer levels were constantly associated with worse outcomes across common risk factors and comorbidities. Besides, age-adjusted elevation of D-dimer significantly improved the risk predictions for all-cause death when added to the model of established risk factors (C-index: 0.846 vs 0.838, Δ C-index: 0.008, 95% CI: 0.001–0.015, Pdifference = 0.027; NRI: 0.645, 95% CI: 0.464–0.826, P < 0.001; IDI: 0.008, 95% CI: 0.001–0.017, P = 0.048).ConclusionIn ACS patients treated by PCI, age-adjusted elevation of D-dimer was an independent predictor for adverse outcomes and improved the risk predictions for long-term mortality.

D-Dimer as a Prognostic Factor in a Tertiary Center Intensive Coronary Care Unit.

IntroductionD-dimer is a small protein fragment produced during fibrinolysis. High D-dimer levels were shown to have prognostic impact in critically ill patients. Nevertheless, data regarding D-dimer's prognostic impact among tertiary care intensive coronary care unit (ICCU) patients is scarce.Material and methodAll patients admitted to the ICCU between 1-12/2020 were prospectively included. Based on admission D-dimer level, patients were categorized into low and high D-dimer groups (< 500 ng/ml and ≥ 500 ng/ml) and also to age-adjusted D-dimer cutoff (500 ng/ml for ages ≤ 50 years old and age*10 for ages>50 years old).Results and discussionA total of 959 consecutive patients were included, including 296 (27.4%) and 663 (61.3%) patients with low and high D-Dimer levels, respectively. Patients with high D-dimer level were older compared with patients with low D-dimer level (age 70.4 ± 15 and 59 ± 13 years, p = 0.004) and had more comorbidities. The most common primary diagnosis on admission among the low D-dimer group was acute coronary syndrome (ACS) (74.3%), while in the high D-dimer group it was a combination of ACS (33.6%), cardiac structural interventions (26.7%) and various arrhythmias (21.1%). High D-dimer levels were associated with increased mortality rate, even after adjustment for age, gender, comorbidities and left ventricular ejection fraction (LVEF). High D-dimer levels were independently associated with increased overall 1-year mortality rate (HR = 5.8; 95% CI; 1.7-19.1; p = 0.004).ConclusionElevated D-dimer levels on admission in ICCU patients is an independently poor prognostic factor for in-hospital morbidity and 1-year overall mortality rate following hospitalization.

Role of a new age-adjusted D-dimer cutoff value for preoperative deep venous thrombosis exclusion in elderly patients with hip fractures

ObjectiveThis study aimed to describe the characteristics of plasma D-dimer level with increasing age and establish a new age-adjusted D-dimer cutoff value for excluding preoperative lower limb deep vein thrombosis (DVT) in elderly patients with hip fractures.MethodsThis was a retrospective study of elderly patients who presented with acute hip fracture in our institution between June 2016 and June 2019. All patients underwent D-dimer test and duplex ultrasound. Patients were divided into six 5-year-apart age groups. The optimal cutoff value for each group was calculated by using receiver operating characteristic (ROC) curves, whereby the new age-adjusted D-dimer cutoff value was determined. The sensitivity, specificity, positive predictive values (PPV) and negative predictive values (NPV) were calculated and compared when different D-dimer cutoff values were applied, i.e., conventional 0.5 mg/L, previously well-established age-adjusted cutoff value (age × 0.01 mg/L) and the new age-adjusted D-dimer cutoff value herein.ResultsThere were 2759 patients included, 887 males and 1872 females, with an average age of 78 years. In total, 280 patients were diagnosed with preoperative DVT. The optimal cutoff values for the six age groups were 0.715 mg/L, 1.17 mg/L, 1.62 mg/L, 1.665 mg/L, 1.69 mg/L and 1.985 mg/L, respectively, and the calculated age-adjusted coefficient was 0.02 mg/L. With this new coefficient applied, the specificity was 61%, clearly higher than those for conventional threshold (0.5 mg/L, 37%) or previously established age-adjusted D-dimer threshold (age × 0.01 mg/L, 22%). In contrast, the sensitivity was lower than that (59% vs 85% or 77%) when D-dimer threshold of 0.5 mg/L or age-adjusted cutoff value (age × 0.01 mg/L) was used. The other indexes as PPV (15%, 11% and 12%) and NPV (93%, 93% and 94%) were comparable when three different D-dimer thresholds were applied.ConclusionsWe developed a new age-adjusted D-dimer cutoff value (age × 0.02 mg/L) for a specified high-risk population of patients aged 65 years or older with hip fractures, and demonstrated the improved utility of the D-dimer test for exclusion of DVT. This formula can be considered for use in elderly hip fracture patients who meet the applicable standards as preoperative DVT screening, after its validity is confirmed by more well-evidenced studies.

CT pulmonary angiography appropriateness in a single emergency department: does the use of revised Geneva score matter?

PurposeTo assess the percentage of computed tomography pulmonary angiography (CTPA) procedures that could have been avoided by methodical application of the Revised Geneva Score (RGS) coupled with age-adjusted D-dimer cut-offs rather than only clinical judgment in Emergency Department patients with suspected pulmonary embolism (PE).Material and methodsBetween November 2019 and May 2020, 437 patients with suspected PE based on symptoms and D-dimer test were included in this study. All patients underwent to CTPA. For each patient, we retrospectively calculated the age-adjusted D-dimer cut-offs and the RGS in the original version. Finally, CT images were retrospectively reviewed, and the presence of PE was recorded.ResultsIn total, 43 (9.84%) CTPA could have been avoided by use of RGS coupled with age-adjusted D-dimer cut-offs. Prevalence of PE was 14.87%. From the analysis of 43 inappropriate CTPA, 24 (55.81%) of patients did not show any thoracic signs, two (4.65%) of patients had PE, and the remaining patients had alternative thoracic findings.ConclusionThe study showed good prevalence of PE diagnoses in our department using only physician assessment, although 9.84% CTPA could have been avoided by methodical application of RGS coupled with age-adjusted D-dimer cut-offs.

Age-Adjusted D-Dimer in the Prediction of Pulmonary Embolism: Systematic Review and Meta-analysis.

Background:Pulmonary embolism (PE), depending on the severity, carries a high mortality and morbidity. Proper evaluation, especially in patients with low probability for PE, is important to avoid unnecessary diagnostic testing.Objective:To review the diagnostic utility of conventional versus age-adjusted D-dimer cutoff values in patients 50 years and older with suspected pulmonary embolism.Methods:Systematic review with univariant and bivariant meta-analysis.Data sources:We searched PubMed, MEDLINE, and EBSCO for studies published before September 20th, 2020. We cross checked the reference list of relevant studies that compares conventional versus age-adjusted D-dimer cutoff values in patients with suspected pulmonary embolism.Study selection:We included primary published studies that compared both conventional (500 µg/L) and age-adjusted (age × 10 µg/L) cutoff values in patients with non-high clinical probability for pulmonary embolism.Results:Nine cohorts that included 47 720 patients with non-high clinical probability were included in the meta-analysis. Both Age-adjusted D-dimer and conventional D-dimer have high sensitivity. However, conventional D-dimer has higher false positive rate than age-adjusted D-dimer.Conclusion:Age-adjusted D-dimer cutoffs combined with low risk clinical probability assessment ruled out PE diagnosis in suspected patients with a decreased rate of false positive tests.

Multi-center implementation of automated age-adjusted D-dimer results reduces unnecessary PE imaging.

Several previous studies have investigated the clinical utility of age-adjusted D-dimer cutoffs for diagnosing pulmonary embolism (PE). We performed a pre/post implementation study, using data from a mid-Atlantic healthcare system comprising 6 hospitals and 400,000 ED visits to determine whether implementing age adjusted D-dimer cutoffs reduced the number of imaging tests performed. Retrospective study of all patients who had a D-dimer performed during ED visits between September 2015 to September 2018. On March 21, 2017, the D-dimer upper limit of normal system-wide was increased for patients over 50 to: Age (years) x 0.01μg/mL. D-dimer results were displayed as normal or high based on automated age adjustment. EHR Chart review was performed 1.5years prior to implementation of age-adjusted D-dimer cutoffs, as well as 1.5years after to evaluate mortality and test accuracy characteristics such as false negative rates. Comparisons were made using chi-square testing. 22,302 D-dimers were performed pre-implementation of which 10,837 (48.6%) were positive resulting in 7218 (32.3%) imaging studies. After implementation of age-adjusted d-dimer, 25,082 were performed of which 10,851 (43.2%) were positive resulting in 7017 (28.0%) imaging studies. (pre: 48.6%, post: 43.2%; p<0.01). A significantly lower proportion of patients had a positive d-dimer (pre: 48.6%, post: 43.2%; p<0.01) and underwent imaging post-implementation (pre: 32.3%, post: 28.0%; p<0.05) a relative risk reduction of 13.3. This absolute risk reduction of 4.4% is associated with 1104 less scans in the post-implementation group while still increasing test accuracy from 53.7% to 59.2% (p<0.05). Implementation of an automated age-adjusted D-dimer positive reference value reduced CT and V/Q imaging in this population by 4.4% while increasing test accuracy in a regional, heterogeneous six-hospital system.

Management of Venous Thromboembolisms: Part II. The Consensus for Pulmonary Embolism and Updates.

Pulmonary embolism (PE) is a potential life-threatening condition and risk-adapted diagnostic and therapeutic management conveys a favorable outcome. For patients at high risk for early complications and mortality, prompt exclusion or confirmation of PE by imaging is the key step to initiate and facilitate reperfusion treatment. Among patients with hemodynamic instability, systemic thrombolysis improves survival, whereas surgical embolectomy or percutaneous intervention are alternatives in experienced hands in scenarios where systemic thrombolysis is not the best preferred thromboreduction measure. For patients with suspected PE who are not at high risk for early complications and mortality, the organized approach using a structured evaluation system to assess the pretest probability, the age-adjusted D-dimer cut-offs, the appropriate selection of imaging tools, and proper interpretation of imaging results is important when deciding the allocation of treatment strategies. Patients with PE requires anticoagulation treatment. In patients with cancer and thrombosis, low-molecular-weight heparin (LMWH) used to be the standard regimen. Recently, three factor Xa inhibitors collectively show that non-vitamin K oral anticoagulants (NOACs) are as effective as LMWH in four randomized clinical trials. Therefore, NOACs are suitable and preferred in most conditions. Finally, chronic thromboembolic pulmonary hypertension is the most disabling long-term complication of PE. Because of its low incidence, the extra caution should be given when managing patients with PE.

Prognostic value of age-adjusted d-dimer cutoff thresholds in patients with myocardial infarction treated by percutaneous coronary intervention

Abstract Introduction The association between D-dimer and outcomes of patients with myocardial infarction (MI) remains controversial. Using age-adjusted D-dimer cutoff thresholds significantly improves the accuracy of diagnosis for thrombotic diseases. This study aimed to investigate the prognostic value of age-adjusted D-dimer in MI patients treated by percutaneous coronary intervention (PCI). Methods In this observational study, 3614 consecutive patients with MI treated by PCI were retrospectively recruited. The baseline age-adjusted D-dimer threshold was 500 ng/mL, and was calculated as age × 10 in patients older than 50 years. Cox regression was used for outcome analysis. The primary outcome was all-cause death. Discrimination and reclassification were calculated to assess the additional prognostic value of D-dimer when combined with established clinical risk factors and the Global Registry of Acute Coronary Events (GRACE) risk score. Results During a median follow-up of 652 days, a total of 194 deaths occurred. High D-dimer level, as defined by age-adjusted thresholds, was an independent predictor for all-cause death (hazard ratio:1.67, 95% confidence interval: 1.23–2.27, P=0.001). Addition of D-dimer level (high or low) significantly improved risk classification for death when combined with established clinical risk factors (net reclassification index [NRI]: 0.601, P&amp;lt;0.001; integrated discrimination improvement [IDI]: 0.011, P=0.046) and GRACE score (NRI: 0.618, P&amp;lt;0.001; IDI: 0.015, P=0.011). Conclusions In patients with MI treated by PCI, D-dimer elevation defined by age-adjusted thresholds was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and GRACE score. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Chinese Academy of Medical Sciences

Evidence for Age-Adjusted D-Dimer to Rule out Pulmonary Embolism: An Institutional Study

Abstract The diagnostic approach for ruling out suspected acute pulmonary embolism (PE) in the ED setting includes several tests: ultrasound, plasma d-dimer assays, ventilation-perfusion scans and computed tomography pulmonary angiography (CTPA). Importantly, a pretest probability scoring algorithm is highly recommended to triage high risk cases while also preventing unnecessary testing and harm to low/moderate risk patients. The d-dimer assay (both ELISA and immunoturbidometric) has been shown to be extremely sensitive to rule out PE in conjunction with clinical probability. In particularly, d-dimer testing is recommended for low/moderate risk patients, in whom a negative d-dimer essentially rules out PE sparing these patients from CTPA radiation exposure, longer hospital stay and anticoagulation. However, an unspecific increase in fibrin-degradation related products has been seen with increase in age, resulting in higher false positive rate in the older population. This study analyzed patient visits to the ED of a large academic institution for five years and looked at the relationship between d-dimer values, age and CTPA results to better understand the value of age-adjusted d-dimer cut-offs in ruling out PE in the older population. A total of 7660 ED visits had a CTPA done to rule out PE; out of which 1875 cases had a d-dimer done in conjunction with the CT and 5875 had only CTPA done. Out of the 1875 cases, 1591 had positive d-dimer results (&amp;gt;0.50 µg/ml (FEU)), of which 910 (57%) were from patients older than or equal to fifty years of age. In these older patients, 779 (86%) had a negative CT result. The following were the statistical measures of the d-dimer test before adjusting for age: sensitivity (98%), specificity (12%); negative predictive value (98%) and false positive rate (88%). After adjusting for age in people older than 50 years (d-dimer cut off = age/100), 138 patients eventually turned out to be d-dimer negative and every case but four had a CT result that was also negative for a PE. The four cases included two non-diagnostic results and two with subacute/chronic/subsegmental PE on imaging. None of these four patients were prescribed anticoagulation. The statistical measures of the d-dimer test after adjusting for age showed: sensitivity (96%), specificity (20%); negative predictive value (98%) and a decrease in the false positive rate (80%). Therefore, imaging could have been potentially avoided in 138/779 (18%) of the patients who were part of this older population and had eventual negative or not clinically significant findings on CTPA if age-adjusted d-dimers were used. This data very strongly advocates for the clinical usefulness of an age-adjusted cut-off of d-dimer to rule out PE.

Role of an age-adjusted D-dimer cutoff level in the diagnosis algorithm of lower limb deep venous thrombosis in outpatients

ObjectiveOur goal was to analyze the utility of the age-adjusted D-dimer cutoff value in patients with clinically suspected deep venous thrombosis (DVT) in an ambulatory care setting, including distal DVTs. MethodsThis was an observational cohort study of 606 outpatients older than 18 years presenting with low or moderate clinical suspicion of lower limb DVT (measured by Wells scale). D-dimer levels were obtained, and duplex ultrasound was performed (including femoropopliteal and below-knee veins). We calculated sensitivity, specificity, and positive and negative predictive D-dimer values and when to apply the age-adjusted D-dimer cutoff value (D-dimer threshold = age × 10 μg/L). We split patients older than 50 years into 10-year age groups. We constructed receiver operating characteristic curves of the D-dimer test for each group to find the best threshold (defined as the value of D-dimer that gives more specificity, maintaining the maximum possible sensitivity). ResultsThere were 249 men and 357 women with a mean age of 69.3 years; 41 patients were diagnosed with DVT. At a D-dimer threshold of 250 μg/L, sensitivity was 93%, specificity was 8%, positive predictive value was 7%, and negative predictive value was 94%. When the age-adjusted cutoff level was applied, global sensitivity was 76% and specificity 61%; positive predictive value was 12%, and negative predictive value was 97%. False-negative rate was 24%. We split patients older than 50 years into 10-year age groups: 50 to 60 years, 60 to 70 years, 70 to 80 years, and >80 years. The optimum thresholds were, respectively, 526 μg/L, 442.5 μg/L, 475 μg/L, and 549. μg/L. ConclusionsIn our series, the age-adjusted D-dimer cutoff level is not useful in the diagnostic algorithm of DVT.

The Burden of Unnecessary Testing From a Regularly Ordered Laboratory Assay: Age-Adjusted d-Dimer Quality Improvement Study.

Diagnosing acute pulmonary embolism (PE) involves clinical suspicion in combination with sequential diagnostic tests including d-dimer laboratory assays. Although the sensitivity of this assay is well validated and thoroughly tested, a false-positive result can lead to unnecessary and costly testing. The age-adjusted d-dimer (AADD) has been suggested in the literature to improve the usefulness of d-dimer cutoffs and safely decrease iodine and radiation exposure associated with definitively ruling out PE with computed tomographic angiography (CTA).1 We present an internal retrospective review utilizing the novel AADD cutoff to rule out PE and evaluate the potential extent of unnecessary testing with CTA. Using the AADD cutoff would have led to a 21.2% reduction in computerized tomography pulmonary embolus protocol. This internal quality improvement study suggests that changing our institutional conventional d-dimer to the novel AADD would provide a superior quality and cost–benefit.