D-dimer Assay Research Articles

Deep vein thrombosis - the review

Deep vein thrombosis impacts between 2.5% and 5% of a population. It mostly affects lower-extremity veins and presents itself as pain, swelling, tenderness, and erythema of an affected region. Thrombus forms when at least one factor from the Virchow's triad is present - vascular damage, venous stasis or hypercoagulability. A range of clinical manifestations is very wide, from asymptomatic to life-threatening course of the disease. Post-thrombotic syndrome is a frequent complication that results in venous hypertension, which leads to tissue edema, subcutaneous fibrosis, and subsequent ulceration. In the diagnostic process, predominantly D-dimer assay and ultrasonographic compression test are performed. Noninvasive treatment relies on anticoagulation therapy which is based on direct oral anticoagulants, parenteral anticoagulants, and vitamin K antagonists. In specific cases, there is an option of invasive treatment, which involves inserting a catheter into a vein with a thrombus. Afterward, a thrombus can be mechanically fragmented and aspired or dissolved with the use of a thrombolytic agent.

Type of D-dimer assay determines the diagnostic yield of Computed Tomography in patients suspected for pulmonary embolism

ImportancePulmonary embolism (PE) is a life-threatening condition with high morbidity and mortality. The diagnosis of PE is challenging due to nonspecific symptoms, making reliable diagnostic tools essential. This study addresses the clinical impact of inter-assay variability in D-dimer measurements on the utilization and diagnostic yield of computed tomography pulmonary angiography (CTPA). ObjectiveTo investigate the effect of different D-dimer assays on the decision to perform CTPA and the subsequent diagnostic yield in patients with suspected PE. DesignThis retrospective cohort study analyzed data from three teaching hospitals in the Netherlands, covering the years 2018, 2019, 2022, and 2023. SettingMulticenter study involving three teaching hospitals in the south-west region of the Netherlands. ParticipantsThe study included data from 40,096 clinically requested D-dimer results and 11,372 CTPA records of patients with suspected PE. The D-dimer assays used were the Roche Tinaquant and Siemens Innovance. ResultsThe study found significant differences in CTPA utilization and diagnostic yield based on the D-dimer assay used. Hospitals using the Roche Tinaquant assay ordered 21% fewer CTPAs and had an 7% higher positivity rate compared to those using the Siemens Innovance assay. Conclusion and relevanceThe findings highlight the necessity for assay-specific cut-off values or, ideally, the standardization of the D-dimer assay to optimize the accuracy and efficiency of PE diagnosis. This study demonstrates that the choice of D-dimer assay significantly influences the clinical management of suspected PE, affecting both the number of CTPAs performed and the positivity rate of these scans. Implementing assay-specific cut-off values or standardization of the D-dimer assay could reduce unnecessary CTPA scans, minimize patient exposure to radiation, and lower healthcare costs. These results advocate for enhanced collaboration between clinicians and laboratory specialists to accurately interpret D-dimer results within the context of the specific assay used. Future research should validate these findings in prospective studies and explore standardized protocols that account for inter-assay variability.

Lecturer

COVID-19 is a highly contagious viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It primarily affects the respiratory system but can also impact other significant organs. Its rapid spread has heightened interest in biomarkers for screening and early diagnosis. This study evaluated D-dimer, C-reactive protein (CRP), and complete blood count (CBC) levels in patients with COVID-19 compared to healthy individuals. A total of 50 healthy individuals and 50 COVID-19 patients, aged 20 to 65, were included in the study, excluding individuals with conditions such as leukemia, thalassemia, or pregnancy. Whole blood and plasma samples were collected for CBC and D-dimer assays and stored at 2-4°C. The COVID-19 patients had significantly higher levels of D-dimer, CRP, white blood cells (WBC), granulocytes, and granulocyte percentage as compared with the healthy individuals (p<0.01), lower levels of lymphocyte percentage, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) (p<0.01), as shown. The severe COVID-19 cases often show elevated D-dimer levels, indicating a higher risk of thrombosis. Increased CRP levels correlate with more severe conditions and help assess inflammation severity. A CBC provides insights into blood components, like RBC and WBC, and platelets. During COVID-19, CBC results may reveal lymphopenia, a low lymphocyte count linked to increased severity. For the most accurate and current information, consult healthcare professionals, reliable health organizations, or recent scientific studies on COVID-19.

D-dimer-An International Assessment of the Quality of Laboratory Testing: Implications for D-dimer Use in the Real World.

D-dimer assessment has several established roles in venous thromboembolism (VTE) and disseminated intravascular coagulation diagnosis, and recently the risk stratification of coronavirus disease 2019 (COVID-19). D-dimer assays are neither standardized nor harmonized, use varying methodologies, and use different reporting units, all resulting in a lack of interchangeability and generalizability of assays. Using large multiyear datasets from an international laboratory quality assurance program, we assessed (1) common D-dimer assays in use worldwide, (2) differences in analytical performance between different methods, and (3) interlaboratory variability between positive samples. External proficiency testing results from laboratories participating in the External Quality Control for Assays and Tests (ECAT) Foundation were analyzed from 2017 to 2023. Annually, between 578 and 690 laboratories participated in the D-dimer sample surveys with response rates ranging from 88 to 97%. The three most common assays in use in 2023 were the Siemens Innovance D-dimer (42%), the IL HemosIL D-dimer HS 500 (20%), and the Diagnostica Stago (Stago) Liatest D-dimer Plus (10%)-all these are automated, quantitative, latex immunoassays expressed in fibrinogen equivalent units (FEU). The highest interlaboratory variability was observed around the typical VTE exclusion threshold of 0.5 mg/L FEU. Lower interlaboratory variability was observed at values above 0.8 mg/L FEU. Our study provides recent, international performance data on currently used D-dimer assays and describes the significant variability between assays and across D-dimer concentrations. We demonstrate that assays are not interchangeable and that using them interchangeably has the potential to result in clinically important errors. There is an urgent need to educate users about these issues and to work towards harmonizing D-dimer units and reporting.

Interfering antibodies may contribute to elevated d-dimer: a case report

BackgroundPlasma levels of d-dimer are elevated in patients with thromboembolisms. Here we investigated the existence of interfering antibodies as a potential cause for elevated d-dimer levels.Case presentationA 42-year-old white Caucasian woman with a prior history of pulmonary embolism during her first pregnancy (treated with heparin therapy for 6 weeks postnatally) and hypothyroidism had a persistent elevated d-dimer without any clinical or ultrasound-based signs of thromboembolic conditions during her second pregnancy. We obtained informed consent and plasma was obtained from the patient. d-dimer levels were measured using two different assays. We also tested for the presence of rheumatoid factor, performed dilution series, and finally used an antibody depletion strategy. The two d-dimer assays performed similarly. Using our antibody depletion technique, we observed that ~ 1/3 of the increased plasma levels of d-dimer may be attributed to interfering antibodies.ConclusionsOur results identify interfering antibodies as a potential contributor to an increased d-dimer in this patient. Our case highlights the potential of heterophilic interference for increased d-dimer and provides a procedure to determine this analytically.

The performance of quantitative D-dimer assays in Chinese clinical laboratories by analyzing data from National External quality Assessment Scheme

Background and aimsTo investigate performance of D-dimer assays in China and address analytical quality issues. Materials and methodsD-dimer assays data were collected from China National External Quality Assessment Scheme (China NEQAS) from 2014 to 2022. We analyzed reagents, assay results, reporting unit and cutoffs in 2022 China NEQAS. Interlaboratory coefficient variations (CVs) and influence of modified/unmodified test systems on CVs were investigated over 9 years. ResultsThere were 82 reagent brands in China NEQAS, but 55 reagent instructions did not indicate expression unit (DDU or FEU). Up to 7-fold of the ratio of max-to-min mean results was shown among different assays with same unit on the same sample. A prevalence of FEU (63.4%) over DDU (17.1%) was observed. Although 669 laboratories (37.9%) among 1766 laboratories used reagents without VTE exclusion claim, they also reported cutoffs. The CVs of only two assays were decreasing over years. CVs of modified test systems were higher than those of unmodified systems before improvement. ConclusionsExpression unit should be required to label in package inserts by regulatory authority. Laboratory professionals should follow instructions for use and prefer unmodified test systems for clinical safely application. Harmonization of reporting units through collaborative efforts is the promising step.

Comparison of four D-dimer assays in the context of venous thromboembolism in the emergency department.

This observational study conducted across seven emergency care units compares the efficacy of four D-dimer detection methods, namely HemosIL D-dimer HS (HS), HemosIL D-dimer HS-500 (HS-500), VIDAS D-dimer (VIDAS), and HemosIL AcuStar D-dimer (ACUSTAR). The primary focus is on patients with a clinical suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE). A total of 149 samples were collected from patients with suspected DVT or PE. The confirmation of DVT/PE was based on calf ultrasound or computed tomography-Angiography. Direct comparisons were made between the different detection methods, considering both their analytical performance and clinical utility. Additionally, the impact of an age-adjusted cut-off on the diagnostic accuracy of each method was assessed. The results revealed comparable negative predictive value, sensitivity, and specificity across the methods, with a notable exception of increased specificity for HS compared with HS-500 (50.8% vs. 41.5%, p = 0.03). Further analysis incorporating an age-adjusted cut-off demonstrated a significant improvement in specificity for HS. When using the age-adjusted cut-off, HS exhibited a substantial increase in specificity compared with HS-500 (63.1% vs. 49.2%, p = 0.004) and demonstrated significantly higher specificity compared with VIDAS (63.1% vs. 53.8%, p = 0.04). The study emphasizes the nonuniversal effect of an age-adjusted cut-off and discusses the potential necessity for different cut-off values, particularly in the case of HS-500. These findings contribute to the understanding of D-dimer detection methods in the context of DVT and PE, providing insights into their relative performances and the potential optimization through age-adjusted cut-offs.

Prevalence and Risk Factors of Deep Venous Thrombosis in Intensive Inpatient Neurorehabilitation Unit.

ABI patients were screened for DVT on admission to the intensive rehabilitation unit (IRU) with compression ultrasonography and basal D-dimer assay and were daily clinically monitored until discharge. A total of 127 consecutive ABI patients (mean age: 60.1 ± 17.6 years; 63% male; time from event: 30.9 ± 22.1 days; rehabilitation time in IRU: 84.6 ± 58.4 days) were enrolled. On admission to the IRU, the DVT prevalence was about 8.6%. The mean D-dimer level in patients with DVT was significantly higher than in patients without DVT (6 ± 0.9 vs. 1.97 ± 1.61, p-value = 0.0001). ABI patients with DVT did not show any significant clinical characteristics with respect to ABI without DVT, although a prevalence of hemorrhagic strokes and patients originating from the Intensive Care Unit and Neurosurgery ward was revealed. During the rehabilitation period, patients with DVT showed a significant difference in pharmacological DVT prophylaxis (high prevalence of nadroparin with 27.3% vs. 1.7%, p-value = 0.04) and a prevalence of transfers in critical awards (36% versus 9.5% of patients without DVT, p-value = 0.05). The mortality rate was similar in the two groups. Our research offers a more comprehensive view of the clinical development of DVT patients and confirms the prevalence rate of DVT in ABI patients as determined upon IRU admission. According to our findings, screening these individuals regularly at the time of rehabilitation admission may help identify asymptomatic DVT quickly and initiate the proper treatment to avoid potentially fatal consequences. However, to avoid time-consuming general ultrasonography observation, a more precise selection of patients entering the rehabilitation ward is required.

D-dimer and risk of venous thromboembolism recurrence: Comparison of two studies with similar designs but different laboratory and clinical results

BackgroundD-dimer testing may help deciding the duration of anticoagulation in subjects at high risk of venous thromboembolism (VTE) recurrence. Two management studies on this issue have been published (DULCIS in 2014 and APIDULCIS in 2022). They had similar designs but had important different results. Aim of this article is to compare their results. MethodsBoth studies were finalized to extend anticoagulation [with vitamin K anticoagulants (VKAs) in DULCIS or apixaban 2.5 mg BID (kindly provided by BMS-Pfizer Collaboration) in APIDULCIS] only in patients with positive D-dimer results. ResultsMore D-dimer assays resulted positive in APIDULCIS than in DULCIS (61.1 % vs 47.7 %, respectively; p < 0.0001). While only 4 (0.5 %) refused low dose apixaban in APIDULCIS, the 22.6 % of patients with positive D-dimer refused to resume VKAs in DULCIS; their rates of recurrence were 187 and 8.8 per 100 person-years, respectively (incidence rate ratio [IRR]: 21.2). The incidence of bleeding was low in those receiving apixaban vs those who resumed VKAs (0.4 vs 2.3 per 100 person-years, respectively; IRR 0.17;). While the recurrence rate was low and similar in the studies in subjects who resumed anticoagulation, it was significantly higher in APIDULCIS than in DULCIS in those who stopped anticoagulation for negative D-dimer (5.6 vs 3.0 per 100 person-years, respectively; IRR 1.9). ConclusionThe low dose Apixaban for extended VTE treatment is effective and safe, and well accepted by patients. Why subjects who stopped anticoagulation for negative D-dimer had a higher recurrence rate in APIDULCIS than in DULCIS remains to be explained.

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

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

Advances in D-dimer testing: progress in harmonization of clinical assays and innovative detection methods.

The D-dimer is a sensitive indicator of coagulation and fibrinolysis activation, especially valuable as a biomarker of intravascular thrombosis. Measurement of plasma D-dimer levels plays a crucial role in the diagnosis and monitoring of conditions such as deep vein thrombosis, pulmonary embolism, and disseminated intravascular coagulation. A variety of immunoassays, including enzyme-linked immunosorbent assays, latex-enhanced immunoturbidimetric assays, whole-blood aggregation analysis, and immunochromatography assays, are widely used in clinical settings to determine D-dimer levels. However, the results obtained from different D-dimer assays vary significantly. These assays exhibit intra-method coefficients of variation ranging from 6.4% to 17.7%, and the measurement discrepancies among different assays can be as high as 20-fold. The accuracy and reliability of D-dimer testing cannot be guaranteed due to the lack of an internationally endorsed reference measurement system (including reference materials and reference measurement procedures), which may lead to misdiagnosis and underdiagnosis, limiting its full clinical application. In this review, we present an in-depth analysis of clinical D-dimer testing, summarizing the existing challenges, the current state of metrology, and progress towards harmonization. We also review the latest advancements in D-dimer detection techniques, which include mass spectrometry and electrochemical and optical immunoassays. By comparing the basic principles, the definition of the measurand, and analytical performance of these methods, we provide an outlook on the potential improvements in D-dimer clinical testing.

Discrepancies between two D-dimer assays and impact on clinical decisions; a retrospective analysis of samples tested in community and hospital-based laboratories in Auckland.

In patients with suspected venous thromboembolism, an elevated D-dimer level provides an important branch-point in the management pathway. This study compared two D-dimer assays, INNOVANCE® DDimer (Innovance) and STA®-Liatest® D-Di Plus (Liatest), to assess potential impact on clinical management. Reflecting current practice in Waitematā, Auckland, we compared paired samples from 805 patients referred to hospital following a community D-dimer test. Samples were determined to be positive or negative using a 500μg/L fibrinogen equivalent units (FEU), and age-adjusted cut-offs. In the Innovance assay, 2% of samples had a result <500μg/L FEU. In contrast, by Liatest, 18% were below 500μg/L. This positive bias of Innovance was amplified with use of age-adjusted cut-offs; 23% of samples with an elevated Innovance result showed a normal result by Liatest. On average, the Innovance values were 22% higher than Liatest. Results suggestive of interference from heterophile antibodies were seen in 6% of sample-pairs. Innovance D-dimer test yielded higher values than Liatest and experienced interference from suspected heterophile antibodies. Discrepancies in nearly a quarter of patients may be leading to substantial under or over investigation, inefficient use of resources and clinical confusion.

Abbott D-dimer assay: analytical performance and diagnostic accuracy in management of venous thromboembolism

This study aimed to assess analytical characteristics and diagnostic accuracy in management of venous thromboembolism (VTE) in the Emergency Department (ED) of the Abbott D-dimer assay applied on the Alinity c clinical chemistry analyzer (Abbott Laboratories, Chicago, IL) compared to the INNOVANCE D-dimer assay (Siemens Healthineers, Marburg, Germany). Precision was determined at three concentration levels following the CLSI EP15-A3 protocol. Method comparison and diagnostic accuracy were assessed using samples obtained from 85 patients who were referred for diagnostic imaging and D-dimer testing due to clinically suspected VTE. Within-run coefficients of variation (CVs) were 3.0%, 0.5% and 0.5% at D-dimer concentrations of 0.54, 1.42 and 2.68 mg/L FEU, while respective between-run CVs were 2.0%, 3.4% and 2.7%, hence fulfilling the desirable biological variation criteria for imprecision (<12.6%). Passing–Bablok regression analysis yielded a small proportional difference between the two compared assays (y = 1.09 (95% confidence interval (CI): 1.01–1.18) x + 0.09 (95%CI: –0.09 to 0.16)), while Bland–Altman analysis showed significant negative absolute (–0.6 mg/L FEU, 95%CI: –0.9 to −0.3) and relative mean bias (–14.1%, 95%CI: –20.3 to −7.9). Spearman’s ρ was 0.979 (95%CI: 0.967–0.986). Inter-assay agreement relative to the cut-off was 92% (kappa coefficient = 0.547 (95%CI: 0.255–0.839)). Diagnostic sensitivity, specificity, positive and negative predictive values of the Abbott assay were 100%, 9.2%, 25.3% and 100%, respectively, compared to the following data for the INNOVANCE assay: 95.0%, 15.4%, 25.7% and 90.9%. Abbott D-dimer assay has shown excellent analytical precision, high comparability with the INNOVANCE D-dimer and high NPV at manufacturer’s cut-off.

Pregnancy-adapted YEARS Algorithm: A Retrospective Analysis.

Pulmonary embolism (PE) is an imperative diagnosis to make given its associated morbidity. There is no current consensus in the initial workup of pregnant patients suspected of a PE. Prospective studies have been conducted in Europe using a pregnancy-adapted YEARS algorithm, which showed safe reductions in computed tomography pulmonary angiography (CTPA) imaging in pregnant patients suspected of PE. Our objective in this study was 1)to measure the potential avoidance of CTPA use in pregnant patients if the pregnancy-adapted YEARS algorithm had been applied and 2)to serve as an external validation study of the use of this algorithm in the United States. This study was a single-system retrospective chart analysis. Criteria for inclusion in the cohort consisted of keywords: pregnant; older than 18; chief complaints of shortness of breath, chest pain, tachycardia, hemoptysis, deep vein thromboembolism (DVT), and D-dimer-from January 1, 2019- May 31,2022. We then analyzed this cohort retrospectively using the pregnancy-adapted YEARS algorithm, which includes clinical signs of a DVT, hemoptysis, and PE as the most likely diagnosis with a D-dimer assay. Patients within the cohort were then subdivided into two categories: aligned with the YEARS algorithm, or not aligned with the YEARS algorithm. Patients who did not receive a CTPA were analyzed for a subsequent diagnosis of a PE or DVT within 30 days. A total of 74 pregnant patients were included in this study. There was a PE prevalence of 2.7% (two patients). Of the 36 patients who did not require imaging by the algorithm, seven CTPA were performed. Of the patients who did not receive an initial CTPA, zero were diagnosed with PE or DVT within a 30-day follow-up. In total, 85.1% of all the patients in this study were treated in concordance with the pregnancy-adapted YEARS algorithm. The use of the pregnancy-adapted YEARS algorithm could have resulted in decreased utilization of CTPA in the workup of PE in pregnant patients, and the algorithm showed similar reductions compared to prospective studies done in Europe. The pregnancy-adapted YEARS algorithm was also shown to be similar to the clinical rationale used by clinicians in the evaluation of pregnant patients, which indicates its potential for widespread acceptance into clinical practice.

A one-step process for multi-gradient wettability modification on a polymer surface.

The surface modification technique is applied in microfluidic devices to modify wettability and achieve different flow velocities. Currently available methods for poly(dimethylsiloxane) (PDMS) surfaces may reliably induce wettability changes, but only one area can be altered at a time. This work introduces the controlled gradient oxygen plasma modification (CGPM) technique, which layers several resin masks with varying porosities on top of the PDMS surface. Selective wettability of the PDMS surface can be achieved by varying the oxygen plasma density above the modified material's surface by manipulation of the porosity value. Through the implementation of the COMSOL plasma module, the impact of the mask's porosity, through-hole size, distribution, and distance from the PDMS surface on wettability was studied. The suggested CGPM approach was characterized by contact angle measurements. During the 25-second CGPM procedure, the PDMS surface's contact angle continually changed from 8.77° to 76.98°. An integrated microfluidic device was created and manufactured to identify D-dimers to illustrate this method. In comparison with standard oxygen plasma treatment, the D-dimer assay was finished in 10 minutes and had a dynamic range of 1-1000 ng mL-1, with a peak fluorescence signal augmentation of 78.3% and an average fluorescence intensity enhancement of 31.1%.

Performance verification and clinical application evaluation of D-dimer assay

Objective: To evaluate the clinical application performance of a domestic D-dimer assay reagent (ADX D-dimer). Methods: A total of 546 residual sodium citrate anticoagulated plasma samples (530 of which were used for comparability validation and 16 for sample preparation of other validation components) were selected after the completion of clinical testing at Peking Union Medical College Hospital from Jun 2022 to May 2023. According to the American Clinical Laboratory Standards Institute (CLSI) guidelines, national health industry standards and relevant references, the performance of ADX D-dimer used in Sysmex CS 5100 fully automated coagulation analyzer which included accuracy, precision, linear range, carryover rate, interference resistance capability and reference interval were validated and the agreement compared with two mainstream imported detection reagents (reagent A: Vidas D-dimer reagent; reagent B: Innovance D-dimer detection reagent) was evaluated. The clinical diagnostic efficacy of the ADX D-dimer was evaluated using the ELISA D-dimer (reagent A) test results as criteria. Results: The linear correlation coefficient of the 6-point calibrated absorbance and target value was 0.998, the bias of accuracy met the requirements (-2.8%-8.4%), and the coefficient of variation (CV) of within-run and between-day precision of the two levels were 1.0%-2.7% and 2.7%-4.1%, respectively, which were less than the requirements of the manufacturer's statement and the national health industry standard. The linear range within 0.33-9.69 mg/L FEU was verified and the carryover rate was 0. There was no significant interference with the assay results at bilirubin F≤0.22 g/L, bilirubin C≤0.22 g/L, hemoglobin≤5.5 g/L and celiac≤2 800 FTU. The manufacturer's reference interval≤0.5 mg/L FEU was verified suitable for this laboratory. For 358 samples without suspicious heterophilic antibody whose D-dimer levels range from 0.06 to143.63 mg/L FEU, the correlation between ADX D-dimer and another two assay was good, with r values being 0.968 and 0.975, respectively, the percentage of deviation and relative deviation beyond the 95% confidence interval was 3.4%-4.5% and 5.3%-7.0%. The correlation between ADX D-dimer and ELISA D-dimer was better than that of reagent B in the concentration range of 0.06-1.00 mg/L FEU (r=0.858, 0.134). For 172 samples with heterophilic antibody, the correlation between ADX D-dimer and ELISA D-dimer was still good(r=0.827), with the percentage of deviation and relative deviation being 6.4% (11/172). The diagnostic efficacy was evaluated using 530 samples, and the sensitivity, specificity, positive predictive value, negative predictive value of ADX D-dimer was 97.4%, 77.6%, 91.9%, 91.9%. The area under the curve was 0.976 (95%CI: 0.964-0.987, P<0.001). Conclusion: The ADX D-dimer reagent has superior assay and diagnostic performance, and can meet the needs of clinical laboratories.

Use of Fibrinogen and D-Dimer to Predict Platelet Recovery in Heparin-Induced Thrombocytopenia

Introduction Heparin-induced thrombocytopenia (HIT) occurs in approximately 0.5-1.0% of patients treated with unfractionated heparin, though true incidence is hard to quantify due to difficulties in recognition and diagnosis. The mainstay of treatment is the initiation of non-heparin anticoagulants until platelet recovery and for one to three months thereafter. There is no available model to predict platelet recovery. A predictive model may help identify (1) patients who are improving even if not reflected in platelet count, particularly in refractory cases; and (2) those who may require adjunctive therapies for treatment. It has been previously proposed that in a distinct subset of HIT, termed “autoimmune HIT,” the fibrinogen and d-dimer may be helpful markers to assess treatment response. Anecdotally, in complex HIT cases at our institution, we have observed improvements in fibrinogen and d-dimer preceding the resolution of thrombocytopenia. In this study, our aim was to establish a correlation between the fibrinogen, d-dimer, and the platelet count. Fibrinogen and d-dimer assay accessibility make them alluring for widespread use, if informative. We hypothesized that the fibrinogen and d-dimer trends would correlate with improvements in platelets. Methods This study design was reviewed and approved by the Vanderbilt University Medical Center (VUMC) Institutional Review Board. All inpatients admitted to VUMC between August 2022 and March 2023 with a positive HIT immunoassay (ELISA) were identified. Venous blood aliquots in sodium citrate used for anticoagulation management were collected daily. Patients with confirmed HIT based on a positive serotonin release assay were included in the analysis. Samples were collected until resolution of HIT, discharge, and/or death. Fibrinogen and d-dimer were measured on stored samples and compared to the daily platelet counts for each patient. Statistical Analysis To determine how baseline platelet count, time, fibrinogen and d-dimer relate to longitudinal measurements of platelet counts (assessed between 1- and 22-days post-baseline) we used a generalized least squares model with an AR1 within-patient correlation pattern, determined using AIC and variograms assessing fit with the data. Results In total, samples from 10 patients with HIT were collected. Baseline characteristics are presented in Table 1. Longitudinal regression analysis presented in the ANOVA plot in Figure 1 suggested that d-dimer ( X2 3.72, p=0.71) and fibrinogen ( X2 9.29, p=0.16) had no statistically significant correlation with platelet recovery, and the only strong variable was time ( X2 30.46, p=0.0002), indicating non-flat trajectories. Baseline platelet count showed signal for positive effect ( X2 3.34, p=0.07). Other effects were assessed, but not significant. Discussion The results of our exploratory laboratory correlation study suggest that fibrinogen and d-dimer values were not reliably correlated with platelet counts in patients with HIT, despite anecdotal experience suggesting benefit in monitoring fibrinogen and d-dimer in difficult HIT cases. The best correlation and strongest association with the improvement in platelet counts was time. Our study has several limitations. First is our small patient sample size. In addition, 4 patients (40%) died due to unrelated complications, therefore limiting the number of data points available for interpretation. Lastly, mean and median fibrinogen values are within the normal range in our data set; d-dimer mean and median are only mildly abnormal. Future prospective studies should be considered to further explore the relationship between fibrinogen and d-dimer with platelet trajectory when markedly abnormal at time of HIT diagnosis, as we have observed in severe HIT cases.

Commercial human frozen plasmas for local, cross-site and long-term comparability of coagulation analysers.

Laboratory compliance implies to correlate instruments for coagulation parameter with a wide range of measure using patient samples or commercialized sets of frozen plasmas. The aim of this study was to evaluate the intra, inter-reproducibility and long-term stability of ExpertCor Routine (ECR) plasma sets (Stago) on different parameters. The study was realized in two laboratories on four different instruments. Inter-site and intra-site correlation of ECR sets for PT, aPTT, Fibrinogen, INR, factor V (FV) UFH and LMWH anti-Xa and intra-reproducibility of DDimer (DDI), factor VIII (FVIII:C) and antithrombin (AT) assays were tested. To evaluate ECR long-term stability, samples were tested until 180 after delivery in one laboratory. Intra-site evaluation correlation coefficients is around 1. All predefined criteria to fulfil good comparability between inter-site instruments are met with Passing slopes between 0.9 and 1.1 and intercepts ranging from -0.62 to 2.83%. Long-term stability evaluation does not show any deviation over 180 days for aPTT, fibrinogen, DDI, UFH, LMWH but a drift for FV with STA-NeoPTimal reagent. On contrary, AT and FVIII:C are not stable. PT in second has an excellent stability unlike PT in percentage. Our study validates the use of ECR sets for correlation between instruments and inter-sites agreement, as for parameters claimed on the products than for factor V and FVIII:C. The evaluation of stability confirming the possible extension of use for 180 days after delivery except for FVIII:C and AT. These plasmas sets are an excellent alternative to local plasma patient use to perform instrument comparison.

Unreliability of Serum- or Plasma-based Assays of D-dimer or Fibrin (Fibrinogen) Degradation Product for Diagnosing Periprosthetic Joint Infection: A Prospective Parallel Study.

The ability of D-dimer to diagnose periprosthetic joint infection (PJI) before revision hip or knee arthroplasty is still controversial, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and fibrin (fibrinogen) degradation product (FDP) are uncertain. The prospective parallel study was performed to determine the ability of D-dimer to diagnose PJI before revision hip or knee arthroplasty, and the differences in diagnostic ability between serum- or plasma-based assays of D-dimer and FDP. Patients undergoing knee or hip arthroplasty at our institution were prospectively enrolled into the following groups: those without inflammatory diseases who were undergoing primary arthroplasty ("Prim" group), those with inflammatory arthritis who were undergoing primary arthroplasty ("Prim/Inflam"), those undergoing revision arthroplasty because of aseptic failure ("Rev/Asept"), or those undergoing revision arthroplasty because of PJI ("Rev/PJI"). The ability of preoperative levels of D-dimer or FDP in serum or plasma to diagnose PJI in each group was assessed using areas under receiver operating characteristic curves (AUCs) and other diagnostic performance indicators. The diagnostic performance of these assays was compared with that of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). In the final analysis, Prim included 42 patients; Prim/Inflam, 40; Rev./Asept, 62; and Rev./PJI, 47. D-dimer assays led to AUCs of 0.635 in serum and 0.573 in plasma, compared to 0.593 and 0.607 for FDP. Even in combination with CRP or ESR, these assays failed to perform as well as the combination of CRP and ESR for diagnosing PJI. Levels of D-dimer or FDP in serum or plasma, whether used alone or together with CRP or ESR, are unreliable for diagnosing PJI before revision arthroplasty.

Immunoreactivity of canine, feline, and equine D-dimer with antibodies to human D-dimer.

Commercially available D-dimer assays use antibodies against human D-dimer, with limited sensitivity and specificity data in companion animals. To evaluate the immunoreactivity of D-dimer in plasma of dogs, horses, and cats with commercially available antibodies to human D-dimer. Plasma samples were collected from healthy dogs and horses, and from surplus feline plasma submitted for diagnostic purposes. Descriptive research study. A cross-linked fibrin lysate was prepared from plasma samples, and SDS-PAGE and immunoblotting were performed with a variety of commercially available antibodies to human D-dimer. The selected antibodies demonstrated variable reactivity with D-dimer of each species. The monoclonal antibody DD44 bound canine D-dimer with good specificity and sensitivity, but this antibody did not react with feline or equine D-dimer. The polyclonal antibody D2D bound putative D-dimer in dogs, cats, and horses with good specificity, and higher sensitivity compared to human D-dimer. The variable performance of commercially available human D-dimer assays between species is, in part, because of inter-species variation in D-dimer immunoreactivity. The use of these assays should follow validation studies. Monoclonal antibody DD44 could be a focus for the development of a canine-specific assay.