D-dimer Assay Research Articles

Utilidade clínica de analisadores de ensaio D- dímero Point-of-Care para exclusão de tromboembolismo pulmonar em pacientes com COVID-19

The aim was to evaluate the clinical utility of D-dimer POC assay analyzers to rule out the diagnosis of PTE in adult patients diagnosed with COVID-19. Systematic review and meta-analysis. The evaluated technology was the Point-of-Care D-dimer assay analyzer. To combine the effect estimates whose measure was the difference between the means, the random effect model was used. We included 10 studies that evaluated 14 Point-of-Care analyzers compared to the Enzyme Linked Immunosorbent Assay assay. All Point-of-Care analyzers evaluated showed sensitivity and NPV greater than 95 and 97%, respectively, with an average return time of 95 minutes. Evidence suggests that the use of Point-of-Care analyzers for D-dimer is clinically useful to rule out cases of pulmonary thromboembolism and other thromboembolic complications in patients with COVID-19 treated in the emergency room or in primary care units.

Influence of hemolysis, icterus and lipemia on coagulation tests as performed on Cobas t511 new analyzer.

: In the coagulation laboratory, spurious hemolysis, icterus and lipemia (HIL) in test samples represent by far the leading diagnostic prenalytical challenges. The aim of this study was to assess the performance of the preanalytical module on the new hemostasis analyser Cobas Roche t511. We assessed the influence of HIL on prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), antithrombin and D-dimer on plasma pools aliquots with different interference degrees. Moreover, we evaluated spontaneous hemolysis by comparing results on 50 paired samples (hemolysed versus nonhemolysed). Spurious hemolysis interference studies highlight the absence of a clinical significant impact on PT, APTT and antithrombin test results at all hemoglobin concentration investigated. For Fib and D-dimer assays a clinically significant difference was observed in the most hemolysed aliquot for Fib and in the two most hemolysed aliquots for D-dimer. Spontaneous hemolysis interference studies showed no clinical significant differences for PT and antithrombin assays, instead for APTT, Fib and D-dimer we found significant statistical and clinical differences between hemolysed and non hemolysed specimens. Bilirubin interference studies and lipemic samples interference studies enable us to confirm that the differences in the results obtained between the different aliquots and reference pool is not clinically significant for all assays. HIL check preanalytical module of Cobas Roche t511 analyzer displaied excellent performance for routine use in clinical laboratories. Regardless of analytical considerations, the type of interference encountered with spurious HIL is substantially different and requires different approaches.

Estimation of lipemia interference with automated HIL-test on d-dimer ACL TOP 50 series analysis – reveals a higher cut-off than manufacturer’s recommendations

Fibrin-d-dimer (d-dimer) is essential for the diagnosis and treatment of thrombosis patients. The new ACL TOP 50- series used for d-dimer determination, integrates a preanalytical interference check for hemolysis, icterus and lipemia (HIL-test). Using earlier versions of ACL TOP, HIL was evaluated by visual inspection by the biomedical laboratory scientist. With the new integrated HIL-test, lipemia is determined by measuring turbidity in the sample at 671 nm, reflecting the lipid content in the sample. Using the new ACL TOP 50- series, we observed more samples being rejected for d-dimer analysis due to lipemia-interference evaluated by the integrated HIL-test suggesting a discrepancy between the former triglyceride-based cut-off and the new turbidity-based cut-off. Therefore, to re-evaluate the lipemia interference cut-off with the turbidimetric measurement, we did a spike-in experiment, using intralipid as lipemia simulation. Three × six different patient pools were prepared from sodium-citrate plasma. We observed no interference in the d-dimer assay by intralipid concentrations resulting in milli absorbances (mAbs) below 3000 mAbs. Thus, the cut-off for lipemia interference using the integrated HIL-test on ACL TOP 550 should be 3000 mAbs. This cut-off will reduce the number of samples rejected due to false positive interference and at the same time reduce ‘hands on’ time for the biomedical laboratory scientists and minimize the risk of subjective evaluation by a visual inspection.

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

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

Inappropriate use of D-dimer and impact on the test characteristics for deep vein thrombosis exclusion

This study aimed to investigate the prevalence of the inappropriate use of D-dimer testing for deep vein thrombosis (DVT) exclusion, and to evaluate the diagnostic value of D-dimer testing compared between testing in appropriate and inappropriate conditions. A retrospective chart review of patients with D-dimer requests at Siriraj Hospital, Bangkok, Thailand during January–September 2017 was performed. Data relating to D-dimer requests, Wells score, imaging investigations, and coexisting conditions that cause elevated D-dimer without correlation to DVT were analyzed. From 2196 cases, there were 300 D-dimer requests for DVT diagnosis. Of those, 5 (1.7%) and 158 (53.6%) requests were considered to be absolutely inappropriate D-dimer test requests due to the absence of pre-test Wells score evaluation and testing in DVT-likely patients, respectively. One-hundred and forty-eight (49.3%) requests were considered to be the relatively inappropriate D-dimer test requests due to testing in patients with coexisting conditions that included malignancies, sepsis, surgery, trauma, arterial thrombosis, and pregnancy. Three patients had more than one of these conditions. Comparatively higher negative predictive values (NPVs) of D-dimer assay for DVT exclusion were observed when used in DVT-unlikely (100% versus 80%), and in patients without coexisting conditions (100% versus 66.7%). The present study revealed the rate of inappropriate D-dimer testing for DVT exclusion to be high and this may lead to missed DVT diagnosis, overuse of imaging study, and unnecessary cost of D-dimer testing. Appropriate patient selection before test request can improve the NPV of D-dimer for DVT exclusion.

D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with non-vitamin K anticoagulants.

BackgroundD-dimer levels measured during and after vitamin K antagonist withdrawal may be used in clinical practice to assess the individual risk of recurrent venous thromboembolism. Currently, direct oral anticoagulants (DOACs) are frequently used in venous thromboembolism treatment; however, their pharmacokinetics and pharmacodynamics characteristics are completely different than vitamin K antagonists. The present study aimed at comparing the results of D-dimer levels during and after anticoagulation withdrawal in patients with venous thromboembolism treated with DOACs or warfarin.Material and methodsD-dimer levels were measured in 527 patients (“cases”) during DOACs treatment (T0) and after 15 (T15), 30 (T30), 60 (T60) and 90 (T90) days after their discontinuation and in 527 patients (“controls”) enrolled in the DULCIS study (all treated with warfarin), matched for sex, age (+/-3 y), type of D-dimer assay and site of venous thromboembolism. Both cases and controls received anticoagulant treatment after a first venous thromboembolism event that was unprovoked or associated with weak risk factors.ResultsThe rate of positive D-dimer results was significantly higher in cases than in controls at T0 (10.8% vs 5.1%, p = 0.002) and at T30 (18.8% vs 11.8%, p = 0.019), as well as at the other time-points, though not statistically significant.ConclusionD-dimer levels during and after stopping an anticoagulant treatment for a venous thromboembolism episode differ between patients treated with a DOAC than in those treated with warfarin. Specifically designed prospective studies are warranted to reassess the use of D-dimer as predictor of the risk of recurrent venous thromboembolism in patients treated with DOACs.

Prospective Study of Pulmonary Embolism Presenting as Syncope.

Syncope represents a common condition among the general population. It is also a frequent complaint of patients in the emergency department (ED). Pulmonary embolism (PE) considers a differential diagnosis, particularly in a case of syncope without chest pain. What is the prevalence of PE among patients who presented an episode of syncope to the ED and among those hospitalized for syncope in a tertiary care hospital? From January 2012 to December 2017, we conducted a prospective observational study among adult patients presenting themselves to the ED consecutively or admitted for syncope. Syncope and PE were defined by professional guidelines. PE was ruled out in patients who had a low pretest clinical probability, as per Wells score and a negative D-dimer assay. In other patients, computed tomography pulmonary angiography was performed. Seventeen thousand eight-two patients (mean age 71.3 ± 13.24 years) visited the ED for syncope. PE was detected in 45 patients (mean age 65.75 ± 9.45 years): 4 with low risk, 26 with intermediate risk, and 15 with high risk. The prevalence of PE in those hospitalized with syncope was 11.47%, which is 45 of 392 (confidence interval 95% 8.48-15.04), and was 2.52%, 45 of 1782 (confidence interval 95% 1.8-3.3), in patients presenting with syncope to the ED. The location of the embolus was bilateral in 24 patients (53.33%), in a main pulmonary artery in 10 (22.22%), in a lobar artery in 10 (22.22%), and in a segmental artery in 1 (2.22%). The occurrence of syncope, if not explained otherwise, should alert one to consider PE as a differential diagnosis. PE rate, presenting as syncope, is the highest in patients with large thrombi, which is responsible for bilateral or proximal obstruction in a main or lobar pulmonary artery.

Comparative study to establish significance of D-dimer, lipid profile and homocysteine level in cases of deep vein thrombosis

Background: The purpose of the study was to establish the relationship of D-dimer, lipid profile and homocysteine level in deep-vein thrombosis (DVT). The purpose of this study was to assess the value of D-dimer in the detection of early DVT.Methods: A hospital based comparative study was conducted at Dr. D.Y. Patil Medical College, Hospital and Research Centre, Pimpri, Pune with 100 patients to compare the level of D-dimer and lipid profile in cases of Deep Vein Thrombosis (DVT) with healthy controls. The study was carried out with following two groups of 50 patients each: study group : 50 cases with DVT; control group: 50 healthy controls.Results: The D-Dimer levels was significantly higher in study group as compared to control group (748.44±93.17 vs. 426.06±78.11 ng/ml) and statistically significant as per student t-test (p<0.05). It was observed that total cholesterol (r=0.714; p<0.05), triglyceride (r=0.534; p<0.05), LDL (r=0.662; p<0.05), HDL (r=0.655; p<0.05), homocysteine (r=0.285; p<0.05) and D-dimer (r=0.368; p<0.05) were strongly and directly correlated with DVT.Conclusions: In our study most sensitive test for early diagnosis of DVT is D-dimer as it is considered to be useful as a screening test for DVT in hospitalized patients with acute medical diseases/episodes. D-dimer assay is an important preliminary test to detect deep vein thrombosis in post-operative cases. Its extreme sensitivity and high negative predictive value make it an ideal single test to screen patients suspected of having deep vein thrombosis. A negative test rules out deep vein thrombois and a positive test report needs further investigation for its confirmation. In case of increased lipid profile levels, patients are more prone to develop DVT hence there should be regular screening for DVT.

Acute venous thromboembolism in Indian patients of isolated proximal femur fractures

IntroductionVenous Thromboembolism (VTE) has a variable incidence in trauma patients and fatal embolism can be the very first manifestation. Proximal femur fractures result from high velocity trauma in younger age groups and could require prolonged immobilisation, which is associated with increased risk of VTE. Therefore we sought to determine the occurrance of VTE in patients with proximal femur fractures. ObjectivesThe present study was initiated to assess the occurrance of deep vein thrombosis (DVT) or pulmonary embolism in isolated proximal femur fractures and identify the requirement of routine thromboprophylaxis in such patients. MethodsIt was a prospective study conducted over a period of one and a half years. All patients, presenting with isolated proximal femur fractures were included. Patients having any other known risk factors for DVT were excluded, so that the proximal femur fracture remained their only acquired risk for DVT. All the patients were evaluated clinically and with help of diagnostic modalities like Color Doppler with compression ultrasound, D-dimer assays and CT venogram, if indicated. Patients were followed up till 8 weeks post-operatively. ResultsA total of 66 patients with fractures of proximal femur were assessed, out of which there were 42 males with mean age of 48.1 years and 24 females with mean age of 58.3 years. A total of 9 cases of radiologically proved DVT were observed. Clinical DVT was seen in 5 of these cases (54%). Complete resolution of thrombus was noted in all the patients, evaluated by Color Doppler at 6 weeks, post diagnosis. Although the majority of the cases (6) occurred in patients beyond 50 years of age, this was not statistically significant. ConclusionDVT is common in patients with proximal femur fractures and the provision for screening both clinically and radiologically, should be made routine in all such patients. In case of delay in surgery and patient being bed ridden, we recommend thromboprophylaxis in this subset of trauma patients.

Generation and characterization of D-dimer specific monoclonal antibodies for use in latex agglutination test.

The commercially available D-dimer assays used in the clinical practice often show differences in the results, and their specificity and sensitivity are rather unsatisfactory. Our aim was to develop a new monoclonal antibody against D-dimer with a proper specificity, and estimating its suitability using in a latex agglutination diagnostic test. Monoclonal antibodies were generated using hybridoma technology. Their titer was determined by a self-developed ELISA method. The cross-reactions of the antibodies were tested. Characterization of the epitope specificity of a selected antibody was performed through digestion of D-dimer followed by Western blotting. The amino acid sequences of the active antigen fragments were determined. According to the ELISA results, 38 cell groups were constated as antibody-producing hybridomas, among them 7 gave raised titer of antibody and were cloned. Based on the cross-reaction analysis, none of the antibodies gave cross-reaction with fibrin-E and fibrinogen-E fragments but reacted with fibrin D and fibrinogen D fragments. A low cross-reaction was showed with fibrinogen and fibrin X and Y. Contrary to the others, antibody 2B9 gave no cross-reaction with fibrinogen and reacted weakly with fibrin X and Y fragments. According to the epitope analysis the antibody 2B9 binds to amino acids 94–99 and to amino acids 140–147 on the beta chain and it recognizes the amino acids 23–32 and 93–98 on the gamma chain of D-dimer. Considering the characteristics of the above mentioned monoclonal antibody 2B9, we found that it is suitable to be a basis for a D-dimer diagnostic test with proper specificity.

The diagnostic efficacy of cardiac CTA combined with D-dimer assay for the detection of left atrial thrombus in patients with atrial fibrillation

PurposeWe aimed to evaluate a combination diagnostic method of single-phased, single-contrast injection cardiac computed tomography angiography CTA combined with age-adjusted D-dimer assay for diagnosis of left atrial/left atrial appendage (LA/LAA) thrombus in comparison to transesophageal echocardiography (TEE) in patients with atrial fibrillation. The addition of D-dimer to the CTA is to increase specificity, since CTA is part of the combined method. Materials and methodsBetween October 2016 and December 2017, 113consective patients with non-valvular or valvular AF (male: 72.6%; mean age: 57.9 ± 11.5 y) underwent diagnostic work-up, included TEE, single-phased, single contrast injection cardiac CTA, and age-adjusted D-dimer assay, for the evaluation of LA/LAA thrombus formation. ResultsCardiac CTA identified 32 patients with filling defects in LA or LAA. Of these patients, 17 had an elevated D-dimer value according to age-adjusted cut-off. TEE detected definitive thrombus formation in 15 patients. Using TEE as the reference standard, the combination diagnostic method had a sensitivity of 100.0%, specificity of 97.9%, positive predictive value (PPV) of 88.2, and negative predictive value of 100.0%. Further, compared to cardiac CTA alone, the combination diagnostic method had significantly better specificity (82.7% vs. 97.9%, respectively; p < 0.01) and PPV (46.9% vs. 88.2%, respectively; p < 0.01). ConclusionThe combination diagnostic method comprising single-phase, single-contrast injection cardiac CTA and age-adjusted D-dimer assay had good diagnostic efficacy for the detection of LA/LAA thrombus in patients with AF. The combination diagnostic method had significantly better specificity and PPV than cardiac CTA alone.The presented diagnostic approach could potentially facilitate rapid diagnosis or exclusion of left atrial thrombus under emergency situation or when TEE is un-available, with good diagnostic efficacy and no TEE related risks.

Application of D-Dimer in Prognosis of Pulmonary Embolism

Abstract Introduction Pulmonary embolism (PE) is a relatively common cardiovascular emergency. It can lead to a variety of outcomes, from potentially reversible right ventricular failure (by occluding the pulmonary arterial bed) to eventual death. The diagnosis of PE is often missed due to its nonspecific clinical presentation. Materials and Methods This is a descriptive cross-sectional study conducted at tertiary care center in India from October 1, 2016 to September 30, 2018, which includes 36 cases of PE. Institutional ethics committee clearance was obtained before start of the study. Written and informed consent was obtained from all patients. Patients were informed regarding purpose, procedures, risks, and benefits of the study in their own vernacular language. Results The age-wise distribution of patients in this study showed that most patients were up to 40 years amounting to 58.4% of cases. Sex-wise distribution also showed that most patients were male (66.7%). Fifty percent of the patients had no thrombosis on Color Doppler findings of the involved limb, and 31.25% had superficial venous thrombosis. Blood investigation revealed that 94.4% patients had troponin negative and 94.4% had D-dimer positive. This study also attempted to correlate the D-dimer findings and Well's score. It can be seen that as per Well's score, 13 patients were with high probability, 18 with moderate probability, and 5 with low probability. Conclusion This study states that D-dimer assays are highly sensitive and have a low rate of false-negative results. The assays have been found safe and effective when the clinical probability of PE is low. When the D-dimer result is negative in patients with low clinical probability of having PE, the presence of acute PE can be safely ruled out without diagnostic imaging.

Highly Elevated Quantitative D-Dimer Assay Values Increase the Likelihood of Venous Thromboembolism.

Objectives In patients with suspected venous thromboembolism (VTE), the D-dimer assay is commonly utilized as part of the workup. The assay is primarily used to determine whether to proceed with radiographic imaging. We compared D-dimer levels in patients suspected of having VTE. We hypothesized that higher D-dimer values predict a higher likelihood of subsequent VTE diagnosis. Methods We conducted a secondary analysis of a multinational, prospective observational study of low- to intermediate-risk adult patients presenting to the emergency department with suspicion of VTE. Demographic and clinical data were collected in a structured manner. Advanced imaging including ultrasound, computed tomography (CT) pulmonary angiography, and ventilation/perfusion scanning was obtained at the discretion of the treating physicians. Imaging was evaluated by board-certified radiologists in real time. D-dimer values' bins were evaluated using a logistic regression model. Results We evaluated 1,752 patients for suspected deep vein thrombosis (DVT), with 191 (10.4%) DVT positive. We evaluated 1,834 patients for suspected pulmonary embolism (PE), with 108 (5.9%) PE positive. Higher D-dimer values in both groups were associated with higher likelihood of subsequent VTE diagnosis, with D-dimer values > 3,999 ng/mL in both groups having the highest incidence of VTE. More than 50% of those patients were VTE positive. Conclusions Increasing D-dimer values predict increased likelihood of being found VTE positive in this patient population. Among those in the highest D-dimer category, > 3,999 ng/mL, over half of patients were VTE positive. Further research could determine additional nuance in D-dimer as a tool to work up suspected VTE.

Diagnostic Accuracy of Age-Adjusted D-Dimer Cutoff in Suspected Cases of Pulmonary Embolism

IntroductionCurrent guidelines recommend use of clinical pretest probability scores, d-dimer assay, and imaging studies in the diagnosis of pulmonary embolism (PE). Studies have shown that normal d-dimer levels with low-intermediate probability in Wells score can safely exclude PE in most cases. Usually, d-dimer level of less than 500 µg/L is used to decide that no further imaging studies such as computed tomography pulmonary angiography (CTPA) or ventilation perfusion (V/Q) scan) are required. However, the conventional cutoff of 500 µg/L may not be as specific in all patients as d-dimer levels increase with age. Thus, use of age-adjusted d-dimer cutoff has been advocated which is defined as (age × 10) µg/L in patients 50 years or older.ObjectiveTo study if age-adjusted d-dimer is helpful in decreasing imaging studies without missing the diagnosis of PE in suspected cases.MethodsWe did an observational retrospective study of all consecutive adult patients who presented to the emergency department from January 2014 to December 2016. The patients who were clinically suspected with PE and underwent subsequent workup along with d-dimer assays were included for analysis. The number of imaging studies performed for PE diagnosis were recorded.ResultsWe included 3,197 patients in the study. Median age was 55 years, and 67% were females (Table 1). Total 2,937 (92%) patients had elevated d-dimer levels based on conventional d-dimer cutoff compared to 2,526 (79%) patients based on age-adjusted d-dimer cutoff. The age-adjusted d-dimer cutoff was more specific (21% vs 8%, p-value<0.0001) but less sensitive (100% vs 95%, p-value= 0.15) than conventional cutoff (Table 2). The use of age-adjusted d-dimer cutoff would have avoided 409 (13% of total) imaging studies (Table 3). However, 2 cases (0.7% of total) with PE, which would have underwent imaging study with conventional cutoff, would have been missed with age-adjusted d-dimer cutoff. The Wells score was 3, intermediate pretest probability, for both cases of PE.ConclusionAge-adjusted d-dimer cutoff can significantly decrease the number of imaging studies performed in cases of suspected PE. However, as shown in our study, there is a chance of missing cases with actual PE. Thus, clinicians should always be aware of a rare probability of false negative result with age-adjusted d-dimer levels. Further stratification of the probability risk or the prompt use of imaging studies in cases with higher clinical suspicion can help in accurate diagnosis of PE. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Safety of D-Dimer As a Stand-Alone Test for the Exclusion of Deep Vein Thrombosis Compared to Other Strategies

BackgroundTogether with clinical decision rules, D-dimer testing has long been the mainstay of diagnostic work-up of suspected deep vein thrombosis (DVT). Advantages of D-dimer measurement include wide availability, low costs and high sensitivity. Age-adjusted D-dimer cut-off values have been suggested to improve specificity of D-dimer testing, defining a positive D-dimer as age multiplied by 0.01 mg/L at or over fifty years of age. Age-adjusted cut-off values have been found to increase specificity without compromising safety in the setting of acute pulmonary embolism, but have not been extensively evaluated in DVT.In this study, we aimed to evaluate and compare the diagnostic performance of fixed versus age-adjusted D-dimer thresholds in patients with suspected DVT, as a stand-alone test or in combination with pre-test probability assessment.MethodsWe included 973 consecutive outpatients referred to Østfold Hospital, Norway, with suspected first or recurrent lower extremity DVT, between 2015 and 2017. STA®-Liatest® Plus D-Dimer assay was performed and Wells clinical score assessed in all patients. Patients with positive fixed D-dimer (≥0.5 mg/L) were referred for whole-leg compression ultrasonography (CUS), whereas patients with negative D-dimer were not, irrespective of the clinical pre-test probability. Failure rate was defined as patients with negative D-dimer at baseline remaining untreated and diagnosed with symptomatic venous thromboembolism during 3-month follow-up. We compared diagnostic indices of both D-dimer thresholds with or without initial pre-test probability assessment.ResultsDVT was diagnosed in 177 out of 973 patients (18%).The fixed D-dimer cut-off was associated with a sensitivity of 99.4% (95% CI 96.9 to 99.9%) for one diagnostic failure (0.3%) (not adjudicated as of print). Adding the Wells score would have detected this one case at a cost of 90 additional CUS examinations. Age-adjusted D-dimer as a stand-alone test was associated with 6 diagnostic failures (1.5%) for a sensitivity of 96.6% (95% CI 92.8 to 98.8%). Age-adjusted D-dimer combined with Wells score yielded a sensitivity of 99.4% (95% CI 96.9 to 99.9%), with one diagnostic failure (0.4%) and 714 patients referred for CUS.ConclusionOur results suggest that the fixed D-dimer as a stand-alone test without Wells score is a safe and efficient diagnostic strategy. Combining age-adjusted D-dimer with Wells score was equally safe, but was not associated with a lower number of necessary CUS examinations. DisclosuresFronas:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant in conducting the study. Tøvik Jørgensen:Bayer AG: Other: Bayer AG contributed with financial support in conducting the study; South-Eastern Norway Regional Health Authority: Other: Grant for conducting the study. Ghanima:Bayer, BMS, Novartis: Research Funding; Amgen, Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees.

2323. Unexpected Pediatric Presentation Patterns of Toxic Shock Syndrome

BackgroundA subcategory of severe septic shock, toxic shock syndrome (TSS) represents up to 20% of pediatric septic shock in the United States. Diagnostic criteria for streptococcal TSS (STSS) and non-streptococcal TSS (NSTSS) were first published by the CDC in the early 1990s, with updates, respectively, in 2010 and 2011.MethodsThe Nationwide Children’s Hospital electronic medical record was queried for inpatient hospitalizations with ICD-9/10 codes of interest between 1/1/2010 and 8/31/2017. The query returned 579 hospitalizations which were assessed for adherence to STSS and NSTSS criteria published by the CDC. 61 cases of TSS were identified: 27 STSS, 32 NSTSS. The prevalence of organ system involvement was quantified, and organ system involvement unanticipated by CDC criteria was examined for prevalence, quality and chronology.ResultsTSS patients were predominately female (62%) with an average age of 12. The most common presentation of TSS was with hypotension (93%), fever (82%) and rash (72%). Findings unanticipated by CDC criteria include: pyuria in STSS (41%), pulmonary involvement in NSTSS (66%) and coagulation abnormalities in NSTSS (92%). Pyuria in STSS was commonly accompanied by protein (73%) and leukocyte esterase (55%) on urinalysis. Pyuria also commonly presented with hematuria (45%). Radiographic evidence of pulmonary involvement in NSTSS was typically described as bilateral/diffuse airspace disease, presenting simultaneously with pulmonary edema and pleural effusions. Abnormalities in PT/PTT associated with NSTSS were commonly found within the first few hours of admission and began normalizing by the next day; d-dimer assays were abnormal in the six instances in which they were assessed.ConclusionThis study suggests that early signs and symptoms of pediatric TSS may exist beyond those described by existing guidelines. The organ systems found to be involved in this review are often found early in the clinical course and can be assessed by noninvasive methods. Contextualization of these findings within the narrative of TSS might help clinicians better detect and diagnose a disease associated with significant patient morbidity and mortality. They may also aid in understanding the results of toxic shock surveillance efforts.Disclosures All authors: No reported disclosures.

What makes D-dimer assays suspicious-heterophilic antibodies?

Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article. Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature. The D-dimer values were normal (0.49 and 0.15μg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody. The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.

Usefulness of plasma D-dimer level for monitoring development of distant organ metastasis in colorectal cancer patients after curative resection.

PurposeTo investigate the usefulness of plasma D-dimer level for monitoring the development of distant organ metastasis in colorectal cancer (CRC) patients after curative resection.Patients and methodsOne hundred and seventy-eight CRC patients after curative resection were enrolled in the study. Ninety-two patients developed distant organ metastasis during follow-up (metachronous metastasis), and blood was collected on the day metastasis was confirmed. Eighty-six patients had no evidence of metastasis yet, and their blood samples were evaluated at last return visit. The levels of D-dimer, carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH) between two patient groups were compared. The agreement between D-dimer and CEA (or LDH) was examined. The receiver operator characteristic (ROC) curve was used to evaluate the performance of D-dimer, CEA, LDH, and their combination in detection of distant organ metastasis.ResultsThe level of D-dimer in CRC patients with metachronous metastasis was higher than that in non-metastasis patients (P<0.0001). Agreement between D-dimer and CEA was fair (κ=0.416, P<0.0001). D-dimer had a larger area under ROC (AUC) (0.85) compared to CEA (0.72) or LDH (0.68). The specificity of D-dimer (73.3%) was lower than that of CEA (74.4%), but the sensitivity (88.0%) of D-dimer assay was superior to that of CEA assay (65.2%). LDH showed the lowest sensitivity (42.4%) and highest specificity (95.3%) among the three bio-markers. The sensitivity and negative predictive value (NPV) of a combination assay (either D-dimer elevation or CEA elevation) were 94.6% and 91.1%, respectively, and the specificity and positive predictive value of another combination assay (both D-dimer elevation and LDH elevation) were 97.7% and 94.9%, respectively. Parallel test of the three markers improved the sensitivity and NPV to 95.7% and 92.7%, respectively.ConclusionCombining with CEA and/or LDH, D-dimer could be a useful surveillance marker for distant organ metastasis in CRC patients after curative resection.

Investigation of age-adjusted D-dimer using an uncommon assay

BackgroundUse of an age-adjusted D-dimer for the evaluation of acute pulmonary embolus (PE) has been prospectively validated in the literature and has become a practice recommendation from major medical societies. Most research on this subject involves the most common D-dimer assays reporting in Fibrinogen Equivalent Units (FEU) with a non-age-adjusted manufacturer-recommended cutoff of 500 ng/ml FEU. Limited research to date has evaluated age-adjustment in assays that report in D-Dimer Units (D-DU), which use a manufacturer-recommended cutoff of 230 ng/ml D-DU. Despite scant evidence, an age-adjusted formula using D-DU has been recently endorsed by the American College of Emergency Physicians (ACEP). This formula seems arbitrary in its derivation and unnecessarily deviates from existing thresholds, thus prompting the creation of our novel-age adjustment formula. The goal of this study was to retrospectively evaluate the test characteristics of our novel age-adjusted D-dimer formula using the D-DU assay in comparison to existing traditional and age-adjusted D-dimer thresholds for the evaluation of acute PE in the ED. MethodsThis was a retrospective chart review at an academic quaternary health system with three EDs and 195,000 combined annual ED visits. Only patients with D-dimer testing and CT PE protocol (CTPE) imaging were included. Admission and discharge diagnosis codes were used to identify acute PE. Outcome measures were sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of an unadjusted traditional threshold (230) compared with both novel and ACEP-endorsed age adjusted thresholds, (Age × 5) − 20 and Age × 5 if >50, respectively. Estimates with their exact 95% threshold were performed. Results4846 adult patients were evaluated from January 2012 to July 2017. Group characteristics include a mean age of 52 and a frequency of acute PE diagnosis by CTPE of 8.25%. Traditional D-dimer cutoff demonstrated a sensitivity of 99.8% (95% CI 98.6–100), specificity of 16.7% (95% CI 15.6–17.8) and NPV of 99.9% (95% CI 99.3–100). Our novel age-adjusted D-dimer thresholds had a sensitivity of 97.0% (95% CI 94.8–98.4), specificity of 27.9% (95% CI 26.6–29.2) and NPV of 99.0% (95% CI 98.3–99.5) with the ACEP-endorsed formula demonstrating similar test characteristics. ConclusionUse of an age-adjusted D-dimer on appropriately selected patients being evaluated for acute PE in the ED with a D-DU assay increases specificity while maintaining a high sensitivity and NPV. Both our novel formula and the ACEP-endorsed age-adjusted formula performed well, with our novel formula showing a trend towards improved testing characteristics.

Significance of D-dimer assay in the diagnosis of acute pulmonary embolism after deep second-degree burn in rabbits

Objective: To explore the significance of D-dimer assay in the diagnosis of acute pulmonary embolism (APE) after deep seconddegree burn by detecting the changes of plasma D-dimer in rabbits with deep second-degree burn and in different phases of burn with concomitant pulmonary embolism. Methods: 48 healthy male or female Chinese white rabbits, were randomly divided into: control group, burn group, burn shock group, burn shock + pulmonary embolism group, burn infection group and burn infection + pulmonary embolism group, with 8 rabbits in each group. By use of the ELISA method, the plasma D-dimer was determined on 1 d, 3 d, 5 d, 7 d, 14 d and 21 d after modeling in the burn group and the control group, and the plasma D-dimer in other groups was detected in 30 min, 1 h, 3 h, 6 h, 24 h after modeling. Results: The expression of D-dimer in the burn group was higher than that in the control group on 1 d, 3 d, 5 d and 7 d ( p &lt; .05). There were significant differences in the expression of D-dimer in the burn shock + pulmonary embolism group in comparison to the burn shock group ( p &lt; .05). There were also some significant differences in the expression of D-dimer in the burn infection + pulmonary embolism group in comparison with the burn shock + pulmonary embolism group ( p &lt; .05). Conclusions: There were some differences in the expression of D-dimer in each group. D-dimer can be used as one of diagnostic indexes for deep second-degree burn with pulmonary embolism.