D-dimer Results Research Articles

Anticoagulation in COVID-19

Anticoagulation in COVID-19

Autoimmune Thrombocytopenia in SLE and COVID-19.

Thrombocytopenia and hypercoagulopathy are haematological abnormalities commonly seen in individuals with coronavirus disease 2019 (COVID-19) and systemic lupus erythematosus (SLE). The difficulty arises when the patient has both diseases concurrently. The clinician should be able to comprehend the pathophysiology of these patient abnormalities in order to provide the best treatment possible. We present a case of a 20-year-old female COVID-19 patient with a history of SLE who had thrombocytopenia but normal D-dimer results. Our analysis revealed that the thrombocytopenia may have been caused by a relapse of lupus, not by COVID-19 infection. In this case, glucocorticoids were the primary therapy and produced excellent results.LEARNING POINTSThe pathophysiology of thrombocytopenia in a patient with concurrent COVID-19 and SLE should not always be associated with platelet consumption.Low-dose glucocorticoids should be administered, with infection risk and comorbidities taken into consideration.Glucocorticoid therapy may result in a delay in viral clearance.

Patient values and preferences in pulmonary embolism testing in the emergency department.

Patient-centered care is concordant with patient values and preferences. There is a lack of research on patient values and preferences for pulmonary embolism (PE) testing in the emergency department (ED), and a poor physician understanding of patient-specific goals. Our aim was to map patient-specific values, preferences, and expectations regarding PE testing in the ED. This qualitative study used constructivist grounded theory to identify patient values and expectations around PE testing in the ED. We conducted semi-structured interviews with ED patients who were being tested for PE in two EDs. Patients who were waiting for PE imaging or D-dimer results were approached and consented to take part in a 30-minute audio-recorded interview. Each interview was transcribed verbatim and analyzed using constant comparative coding. The interview script was modified to maximize information on emerging themes. Major themes and subthemes were derived, each representing an opportunity, barrier, or value to address with patient-centered PE testing. From 30 patient interviews, we mapped four major themes: patient satisfaction comes from addressing the patient's primary concern (for example, their pain); patients expect individualized care; patients prefer imaging over clinical examination for PE testing; and patients expect 100% confidence from their emergency physician when given a diagnosis. Subthemes included symptomatic relief, finding a diagnosis, receiving tests, rapid progression through their care, perception of highly accurate CT scans, willingness to seek a second opinion, direct physician communication, and expectation of case-specific testing with cognitive reassurance. Addressing each of these four themes by realigning ED processes could provide patient-centered PE testing.

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.

Impact of D-Dimer Assays Performed at Local Labs Vs. Central Laboratory in the Evaluation of Apex Trial Outcomes

Introduction: Elevated D-dimer levels are expected to represent both patients at high risk for venous thromboembolism (VTE), and those benefiting from extended-duration antithrombotic therapy. Using D-dimer testing as a method for enrichment strategy, the APEX trial compared the clinical benefit of extended-duration betrixaban therapy with enoxaparin standard of care (NEJM 375:534, 2016). D-dimer test results from the local laboratories at the enrollment sites were used for study outcome analyses based on a ≥ 2xULN value to identify subjects with elevated D-dimer (Cohort 1).Methods: Bloodsamples were collected from hospitalized medically ill patients (n=7,513) enrolled in the APEX study for D-dimer level analysis. A total of 27 differentD-dimer tests were used for D-dimer testing at the local laboratories. A duplicate sample was analyzed independently by a central laboratory using a single, quantitative method (STA-LITA-D-Di test). APEX study data are further analyzed using D-dimer test results obtained from the central laboratory and then compared with the D-dimer results obtained from the local laboratories.Results: Analysis of APEX D-dimer results from local vs central labs was performed in randomized subjects in the modified intention to treat (mITT) population (which consists of all subjects who were administered at least one dose of study drug) (n=7441).In this population 1,365 D-dimer results (18.3%) were discordant. The percent discordance of central and local lab D-dimer results in the betrixaban (670/3721) and enoxaparin (695/3720) arms were 18.0% and 18.7%, respectively. The event rates using ≥ 2X ULN D-dimer cutoff value showed significant differences between the two treatments when central lab D-dimer value was used (5.3% vs 7.6%, p=0.002) and with the local D-dimer (5.7% vs 7.2%, p=0.038), but less so with the latter test. Event rates in subjects designated as positive by central lab but negative by local lab (false negatives) in enoxaparin (21/302, 7%) vs betrixaban (9/313, 2.9%) groups were significantly different while in subjects identified as negative by central lab and positive by local lab (false positives), there were no differences in the overall event rates for enoxaparin (18/393, 4.6%) and betrixaban (17/357, 4.8%) groups. Further analysis of the data based on the type of local D-dimer method utilized suggested that 9/27 tests resulted in false negatives more than false positives.Conclusions: Variability in D-dimer testing as a prognostic indicator for VTE can significantly impact outcome evaluation in clinical trials. Standardization of D-dimer testing is necessary when utilizing the test for predictive enrichment of patient population. DisclosuresJennings:Portola Pharmaceuticals: Consultancy, Research Funding. Cohen:Portola: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Curnutte:Portola Pharmaceuticals, Inc.: Employment, Equity Ownership.

The Usefulness of the Combination of D-Dimer and Soluble Fibrin Monomer Complex for Diagnosis of Venous Thromboembolism in Psychiatric Practice: A Prospective Study.

PurposeD-dimer has the advantage of excluding venous thromboembolism (VTE) due to its high sensitivity but is disadvantageous for diagnosing VTE due to its low specificity. A method to increase the usefulness of D-dimer in the diagnosis of VTE is warranted. This study aimed to investigate the usefulness of the combination of D-dimer and soluble fibrin monomer complex (SFMC), which has been suggested as a new candidate marker for VTE, in VTE diagnosis.Patients and MethodsThis prospective study in 109 subjects was performed at a psychiatric department between August 1, 2017 and December 31, 2019. Subjects’ levels of D-dimer and SFMC were measured simultaneously. Plasma levels of D-dimer and SFMC were measured using NANOPIA® D-dimer and NANOPIA® SF. Subjects with positive D-dimer (≥1.0 µg/mL) results underwent contrast computed tomography for confirmation of VTE within 12 hours of D-dimer measurement. A receiver operating characteristic curve analysis was performed to examine the usefulness of SFMC for the diagnosis of VTE.ResultsOnly 109 of the 783 subjects without symptoms suggestive of VTE participated in the study. Out of 41 subjects with positive D-dimer results, 17 subjects were diagnosed with VTE. A receiver operating characteristic curve analysis was performed to determine cutoff values. The area under the curves was 0.848 for SFMC (p<0.001, 95% CI 0.722 to 0.974), and the optimal cutoff value was 10.0 µg/mL (sensitivity 58.8%, specificity 100%, positive predictive value 100%, negative predictive value 77.4%).ConclusionSFMC was useful for diagnosing VTE in the psychiatric patients with positive D-dimer results.

Impact of low molecular weight heparin administration on the clinical course of the COVID-19 disease

BackgroundLymphopenia is the most important criterion of mortality and discharging feature for patients infected with coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical impact of a low molecular weight heparin (LMWH) treatment on the clinical course of COVID-19.Materials and methodsPatients’ clinical symptoms, radiologic outcomes, hematologic, biochemical, D-dimer, and C-reactive protein (CRP) results were obtained from their medical records. Participants were separated into 2 groups: one was treated with LMWH and the other was not. Improvement in the patients was compared before and after treatment.ResultsNinety-six patients who were diagnosed with COVID-19 between April and May 2020 were retrospectively analyzed. The multivariable analysis showed that the count of lymphocytes, D-dimer, and CRP levels were significantly improved in the LMWH group, as compared to the control group (OR, (95% CI) 0.628 (0.248–0.965), P < 0.001); OR, (95% CI) 0.356 (0.089–0.674), P < 0.001, respectively). The area under the receiver operating characteristic (ROC) curve analysis was AUC: 0.679 ± 0.055, 0.615 ± 0.058, and 0.633 ± 0.057, respectively; the β-value was found to be –1.032, –0.026, and –0.465, respectively.ConclusionThe LMWH treatment group demonstrated better laboratory findings, including recovery in the lymphocyte count, CRP, and D-dimer results.

Effectiveness of Clinical Decision Tools in Predicting Pulmonary Embolism.

Objective The Wells criteria and revised Geneva score are two commonly used clinical decision tools (CDTs) developed to assist physicians in determining when computed tomographic angiograms (CTAs) should be performed to evaluate the high index of suspicion for pulmonary embolism (PE). Studies have shown varied accuracy in these CDTs in identifying PE, and we sought to determine their accuracy within our patient population. Methods Patients admitted to the Emergency Department (ED) who received a CTA for suspected PE from 2019 Jun 1 to 2019 Aug 31 were identified. Two CDTSs, the Wells criteria and revised Geneva score, were calculated based on data available prior to CTA and using the common D-Dimer cutoff of >500 μg/L. We determined the association between confirmed PE and CDT values and determined the association between the D-Dimer result and PE. Results 392 CTAs were identified with 48 (12.1%) positive PE cases. The Wells criteria and revised Geneva score were significantly associated with PE but failed to identify 12.5% and 70.4% of positive PE cases, respectively. Within our cohort, a D-Dimer cutoff of >300 μg/L was significantly associated with PE and captured 95.2% of PE cases. Conclusions Both CDTs were significantly associated with PE but failed to identify PE in a significant number of cases, particularly the revised Geneva score. Alternative D-Dimer cutoffs may provide better accuracy in identifying PE cases.

A 10-fold and greater increase in D-dimer at admission in COVID-19 patients is highly predictive of pulmonary embolism in a retrospective cohort study.

Background:COVID-19 patients present with both elevated D-dimer and a higher incidence of pulmonary embolism (PE). This single-centre retrospective observational study investigated the prevalence of early PE in COVID-19 patients and its relation to D-dimer at presentation.Methods:The study included 1038 COVID-19-positive patients, with 1222 emergency department (ED) attendances over 11 weeks (16 March to 31 May 2020). Computed tomography pulmonary angiogram (CTPA) for PE was performed in 123 patients within 48 h of ED presentation, of whom 118 had D-dimer results. The remaining 875 attendances had D-dimer performed.Results:CTPA performed in 11.8% of patients within 48 h of ED presentation confirmed PE in 37.4% (46/123). Thrombosis was observed at all levels of pulmonary vasculature with and without right ventricular strain. In the CTPA cohort, patients with PE had significantly higher D-dimer, prothrombin time, C-reactive protein, troponin, total bilirubin, neutrophils, white cell count and lower albumin compared with non-PE patients. However, there was no difference in the median duration of inpatient stay or mortality. A receiver operator curve analysis demonstrated that D-dimer could discriminate between PE and non-PE COVID-19 patients (area under the curve of 0.79, p < 0.0001). Furthermore, 43% (n = 62/145) of patients with D-dimer >5000 ng/ml had CTPA with PE confirmed in 61% (n = 38/62), that is, 26% of >5000 ng/ml cohort. The sensitivity and specificity were related to D-dimer level; cutoffs of 2000, 3000, 4000, and 5000 ng/ml, respectively, had a sensitivity of 93%, 90%, 90% and 86%, and a specificity of 38%, 54%, 59% and 68%, and if implemented, an additional 229, 141, 106 and 83 CTPAs would be required.Conclusion:Our data suggested an increased PE prevalence in COVID-19 patients attending ED with an elevated D-dimer, and patients with levels >5000 ng/ml might benefit from CTPA to exclude concomitant PE.

Lower mortality rate in health workers and their families infected with COVID-19 associated pneumonia in Quetta, Baluchistan.

Objectives:A bunch of pneumonia cases in Wuhan, China, was caused by a novel beta-corona virus, (COVID-19) in December 2019 from where it spread rapidly across the globe. The aim of the study was to find out relevant reasons and offered suggestions to reduce the risk of infection and check clinical outcomes of the infected healthcare workers.Methods:This study was conducted in COVID-19 Real Time Polymerase Chain Reaction (RT-PCR) laboratory, Bolan Medical Complex Hospital Quetta, Baluchistan from May to June 2020. Eight hundred (n=800) health workers and their families were included in this study. Data were obtained with standardized data collection forms shared by the WHO. Nasopharyngeal samples were collected following the WHO protocols. RNA was extracted and amplified using real time reverse transcriptase polymerase chain reaction (RT-PCR). Serum ferritin level, C-reactive protein, D-dimer and radiological results of the RT-PCR confirmed individuals were also recorded and analyzed.Results:Among (n=800) health workers and their families 457 (57.1%) were COVID-19 PCR negative, 332 (41.5%) positive and 11 (1.4%) individuals were PCR positive but asymptomatic carriers, 234 (29.5%) were male and 103 (12.9%) were female. Mortality rate in our study was very low, only three patients (0.87%) died of this COVID-19 pneumonia.Conclusion:Our results showed increased rate of positive cases with fortunately lower mortality rate, although this novel pneumonia was associated with acute respiratory distress syndrome ARDS and intensive care unit (ICU) admission. Timely decisions, risk awareness knowledge and supply of necessary equipments are inevitable for the control of such epidemics.

Diagnostic management of inpatients with a positive D-dimer test: developing a new clinical decision-making rule for pulmonary embolism.

BackgroundA positive D-dimer test has high sensitivity but relatively poor specificity for the diagnosis of pulmonary embolism, causing difficulty for clinicians unskilled in pulmonary embolism diagnosis in determining whether a patient with a positive D-dimer test needs to undergo computed tomographic pulmonary angiography.ObjectivesWe sought to develop a new clinical decision-making rule based on a positive D-dimer result to predict the probability of pulmonary embolism and to guide clinicians in making decisions regarding the need for computed tomographic pulmonary angiography.MethodsWe conducted a prospective, multicenter study in three hospitals in China. A total of 3014 inpatients with positive D-dimer results were included. In the derivation group, we built a multivariate logistic regression model and deduced a regression equation from which our score was derived. Finally, we validated the score in an independent cohort.ResultsOur score included nine variables (points): chest pain (1.4), chest tightness (2.3), shortness of breath (3.6), hemoptysis (3.4), heart rate ≥100 beats/min (3.6), blood gas analysis (2.9), electrocardiogram presenting a typical S1Q3T3 pattern (4.1), electrocardiogram findings (2.4), and ultrasonic cardiogram findings (3.7). The sensitivities and specificities were 100% and 86.94%, respectively, in the derivation group and 100% and 90.82%, respectively, in the validation group. Additionally, the observed and predicted proportions of patients who underwent computed tomographic pulmonary angiography were 16.82% and 10.76%, respectively, in the derivation group and 18.72% and 11.40%, respectively, in the validation group.ConclusionsThe new score can categorize inpatients with a positive D-dimer test as pulmonary embolism-likely or pulmonary embolism-unlikely, thus reducing unnecessary computed tomographic pulmonary angiography examinations.

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.

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.

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.

Serum D-dimer should not be used in the diagnosis of venous thromboembolism within 28\u2009days of total knee replacement surgery

BackgroundSerum D-dimer is frequently used to rule out a diagnosis of venous thromboembolism (VTE), a recognised complication following total knee replacement (TKR). TKR is known to cause a rise in D-dimer levels, reducing its specificity. Previous studies have demonstrated that D-dimer remains elevated within 10 days of TKR and therefore should be avoided. The aim of this study was to determine whether serum D-dimer tests are clinically appropriate in identifying VTE when performed within 28 days of TKR.MethodsCase notes for patients who had a serum D-dimer test performed for clinically suspected VTE at ≥ 28 days following TKR were retrospectively reviewed for a 6-year period. Demographics, D-dimer result, time after surgery and further radiological investigations were recorded.ResultsFifty patients underwent D-dimer tests at ≥ 28 days following surgery (median 60 days, range 29–266); 48 of these patients had a positive result. Of these, five had confirmed VTE on radiological investigations. Serum D-dimer was raised in 96% of the patients. Only 10.42% of these patients had confirmed VTE. No patients with negative D-dimers had confirmed VTE.ConclusionsThese findings suggest that serum D-dimer remains raised for at least 28 days and possibly considerably longer following TKR. Serum D-dimer should not be used in patients with clinically suspected VTE within this period because of its unacceptably low specificity of 4.44% and positive predictive value of 10.42%, which can lead to a delay in necessary further radiological investigations, waste of resources and unnecessary exposure to harm.

Predictive value of the Wells score combined with D-dimer level in identifying acute pulmonary embolism in patients with coronary heart disease with chest pain.

Predictive value of the Wells score combined with D-dimer level in identifying acute pulmonary embolism in patients with coronary heart disease with chest pain.

D-Dimer Varies Widely Across Instrument Platforms and is Not a Reliable Indicator of Periprosthetic Joint Infections

The D-dimer test is a component of the modified scoring criteria for periprosthetic joint infection (PJI). The performance of the D-dimer test varies greatly among laboratories because of the lack of standardization. Laboratories may use different assays and will produce widely varying results for the same sample. This study used published proficiency testing data from 3903 laboratories to demonstrate the variability in D-dimer results and estimate the misclassification rate of patients using the proposed cutoff for the test as a component of PJI criteria. Given the variability in D-dimer results, a clinically significant percentage of patients are likely to be misclassified. The data illustrate that a universal cutoff for this marker in the context of assessment for PJI is not appropriate. Each site must conduct a study to determine an appropriate cutoff for their unique testing platform.

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.