Improving the Efficacy of Non-Radiologic Exclusion of Deep Venous Thrombosis in the Elderly Using the Thrombin Generation Assay

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3815-3815
Author(s):  
Fred JLM Haas ◽  
Roger EG Schutgens ◽  
Douwe Biesma
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Predictive Value ◽  
False Positive ◽  
Thrombin Generation ◽  
The Elderly ◽  
Thrombin Generation Assay ◽  
Additional Value ◽  
Positive Results ◽  
D Dimer

Abstract Background: Exclusion of deep venous thrombosis (DVT) using a pretest probability score (PTP) and a normal D-dimer concentration has proven to be safe and feasible. However, the high frequency of false positive D-dimer results in the elderly hampers its use, necessitating additional compression ultrasound (CUS) in these patients. We evaluated an alternative approach for the exclusion of DVT, especially in the elderly, using a thrombin generation assay (TGA) in combination with a PTP and a D-dimer assay. Patients and methods: In symptomatic outpatients suspected for DVT, the Endogenous Thrombin Potential (ETP) assay (Dade Behring Marburg GmBH, a Siemens Company, Germany) was tested. The results of this assay were expressed as ETP % NV (normalized value) [%], ETP AUC (area under the curve) [mE], ETP tlag (lagtime) [sec], ETP tmax (time to peak) [sec] and ETP Cmax (peak value) [mE/sec]. In all patients, a Tina-Quant D-dimer assay (Roche, Manheim, Germany) and a PTP according to Wells were performed. DVT was diagnosed or excluded using B-mode CUS. Results: A total of 443 patients were included (38% men, mean age 60 y). Total DVT prevalence was 39%. In the total group, the Tina-Quant D-dimer assay had a sensitivity (sens) of 98.9%, a negative predictive value (NPV) of 98.3% and a specificity (spec) of 41.9%. Combining D-dimer with a PTP < 2, these values were 100%, 100% and 52.2% respectively. With a spec of 51.8%, a large number of false positive results remain. All ETP parameters had a low AUC of the receiver operation curve (ROC), range 0.53–0.64. For all ETP parameters, there was a significant difference (p < 0.001) between patients with and without DVT, except ETP tmax. ETP parameters were tested for additional value to Tina-Quant and PTP. Only ETP tlag demonstrated an additional value, using an optimal cut-off value of 23.0 sec. In patients with a low PTP and an abnormal D-dimer value, that might be false positive, adding ETP tlag improved specificity to 87.5%, but sensitivity decreased to 26.5%. The percentage false positive results decreased from 38 to 8%, with an increase of false negative results. However, in the fourth age quartile cohort (patients >75 y), sensitivity reached 100% with a specificity of 94.1% and a decrease of false positive results from 58 to 5% (Table). Discussion and conclusion: In this study, a safe exclusion of DVT is possible with a low PTP and a normal D-dimer result as first step. Combining ETP tlag with a low PTP and an abnormal Tina-Quant D-dimer as second step (figure), the sens and NPV reached values of 100% in the fourth age quartile cohort. This algorithm should be confirmed by a new management study. Table. Performance of Tina-Quant (TQ) in relation to DVT, < 500 μg/l, low PTP + TQ < 500 μg/l and low PTP + TQ ≥ 500 μg/l + ETP tlag < 23.0 sec in the total cohort and the fourth age quartile; values (95% lower confidence limit) Sens Spec NPV false pos Sens = sensitivity, Spec = specificity, NPV = negative predictive value and false pos = false positive Total Tina-Quant < 500 98.9 (96.1) 41.9 (36.2) 98.3 (94.2) 35.4 PTP + TQ < 500 100 (92.6) 51.8 (43.8) 100 (94.9) 37.7 PTP + TQ > 500 + tlag 26.5 (12.9) 87.5 (76.8) 69.1 (57.9) 8.1 Elderly Tina-Quant < 500 100 (89.4) 23.9 (14.6) 100 (80.5) 51.9 PTP + TQ < 500 100 (15.8) 37.5 (18.8) 100 (66.4) 57.7 PTP + TQ > 500 + tlag 100 (15.8) 94.1 (65.3) 100 (84.6) 5.2 Figure. Algorithm for exclusion of DVT Figure. Algorithm for exclusion of DVT

Diagnostic Value of a New Sensitive Membrane Based Technique for Instantaneous D-Dimer Evaluation in Patients with Clinically Suspected Deep Venous Thrombosis

1997 ◽  
Vol 77 (04) ◽  
pp. 637-640 ◽  
Author(s):  
Christophe Leroyer ◽  
Martine Escoffre ◽  
Emmanuelle Le Moigne ◽  
Marc Grimaux ◽  
Olivier Cagnioncle ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Predictive Value ◽  
Clinical Signs ◽  
High Sensitivity ◽  
Diagnostic Value ◽  
Lower Sensitivity ◽  
Predictive Values ◽  
Study Results ◽  
D Dimer

SummaryBackground: Plasma D-Dimer analysis, using ELISA assays, has demonstrated in previous studies a high sensitivity, suggesting its utility in excluding deep venous thrombosis (DVT). Aim: To assess the performance of a new rapid plasma D-Dimer ELISA measurement in suspected DVT patients with recent clinical signs, not exceeding one week. Methods: A prospective study of patients admitted for a suspected recent DVT. Contrast venography or compression ultrasonography were performed within 24 h of admission. A new membrane based ELISA technique, which uses an immunofiltration and two complementary monoclonal antibodies was tested. Results were expressed as positive or negative. A standard plasma D-Dimer ELISA measurement was also performed. D-Dimer performances were assessed at the end of the study. Results: 265/448 patients had a proven DVT (72 distal, 193 proximal). The sensitivity of the instantaneous method in the diagnosis of overall DVT is 92 ± 3.4% (95% Cl), and specificity is 36.6 ± 6.9%. Positive predictive value is 67.7 ± 4.8% and negative predictive value is 76.1 ± 8.9%. Sensitivity and negative predictive values reach 97.9 and 94.3% in the diagnosis of proximal DVT, but only 76.3 and 79.7% in the diagnosis of distal DVT. Similar results are observed with the standard ELISA method. Conclusion: This new rapid plasma D-Dimer measurement appears highly sensitive, and could substitute the older ELISA methods. Both methods provide lower sensitivity in the case of a distal DVT location.

scholarly journals The D-Dimer Test for Deep Venous Thrombosis: Gold Standards and Bias in Negative Predictive Value

2003 ◽  
Vol 49 (4) ◽  
pp. 570-574 ◽  
Author(s):  
John T Philbrick ◽  
Steven Heim
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Gold Standard ◽  
English Language ◽  
False Negative ◽  
True Negative ◽  
Language Studies ◽  
D Dimer

Abstract Background: Because venous ultrasound (US) fails to fully image the calf veins, there is the potential for US gold standard studies to classify patients with calf deep venous thrombosis (DVT) in the nondiseased category, causing bias in test index calculations. A false increase in negative predictive value (NPV) is especially likely because calf DVT false-negative tests will be counted in the numerator along with the true-negative tests in NPV calculations. We verified the presence and magnitude of this bias for the d-dimer test. Methods: We abstracted data on overall (calf and thigh) and thigh-only test sensitivity, specificity, and NPV from the six English language studies published between March 1995 and October 2001 that compared d-dimer to a gold standard (GS) capable of imaging both thigh and calf veins and that also stratified results by thigh and calf location. Thigh specificity and NPV were calculated classifying calf DVT patients as free of disease. Results: The six studies included 81–214 participants and provided 26 comparisons of 16 different d-dimer assays to the GS. Thigh sensitivity was higher than overall sensitivity in 22 of 26 comparisons (range, −0.3 to 8.6); thigh specificity was lower than overall specificity in all comparisons (range, −0.7 to −7.8); and thigh NPV was higher than overall NPV in 22 of 26 comparisons and unchanged in 4 comparisons (range, 0.0–9.2). NPV was &gt;95% in 20 of the thigh results but &gt;95% in only 8 of the overall results. Conclusions: Different GS can produce clinically significant differences in test indices. Care must be taken in interpreting DVT studies that evaluate d-dimer as a rule-out test and that use US as a GS, because missed calf DVT can falsely increase the NPV.

scholarly journals D‐dimer, thrombin generation, and risk of a first venous thrombosis in the elderly

2021 ◽  
Vol 5 (5) ◽  
Author(s):  
Huijie Wang ◽  
Frits R. Rosendaal ◽  
Mary Cushman ◽  
Astrid Hylckama Vlieg
Keyword(s):  
Venous Thrombosis ◽  
Thrombin Generation ◽  
The Elderly ◽  
D Dimer

scholarly journals Age-Adjusted D-Dimer Cutoffs for DVT and Pulmonary Embolism: A Comparison of Five Assays

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1419-1419 ◽  
Author(s):  
Maria Farm ◽  
Anwar Siddiqui ◽  
Liselotte Onelöv ◽  
Roza Chaireti ◽  
Margareta Holmström ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Plasma Concentration ◽  
Venous Thrombosis ◽  
False Positive ◽  
Older Patients ◽  
Research Funding ◽  
Imaging Techniques ◽  
Increased Risk ◽  
Positive Results ◽  
D Dimer

Abstract Background: Venous thromboembolism (VTE) is a common but underdiagnosed condition constituted primarily by deep venous thrombosis (DVT, 2/3) and pulmonary embolism (PE, 1/3).Diagnosis of VTE is based on the biomarker D-dimer for excluding low probability VTE, and imaging techniques to verify mid/high probability VTE. D-dimer assays generally have excellent sensitivity, but specificity is kept low by the physiology of the measurand. The plasma concentration of D-dimer increases in thrombosis and activated coagulation, but also in several other conditions such as pregnancy, cancer, trauma, inflammation, infection and with age. Many of these conditions are especially prevalent in VTE-patients, because they are also linked to an increased risk of venous thrombosis. Haase et al. showed that the plasma concentration of D-dimer in a healthy population increases with age, 50% of those ≥70 years old had a positive D-dimer (>0.5 mg/L FEU)1. Age-adjusted decision thresholds have subsequentially been recommended and validated, to increase specificity and reduce the rate of false positive D-dimer results in older patients without decreasing sensitivity. Aims: The study compares age-adjusted D-dimer decision thresholds for different assays in Swedish out-patients with suspected DVT or PE. Methods: Patients (n=940) with clinically suspected PE or DVT in a lower limb were recruited from the medical emergency department (ED) of Karolinska University Hospital, and fresh citrated plasma samples were analyzed for D-dimer within 30 minutes. D-dimer concentrations were measured by four immunoturbidimetric assays using the instruments Sysmex CS2100i and Stago CompactMax. VTE was verified by imaging techniques (ultrasonography, computed tomography or ventilation/perfusion lung scintigraphy, as appropriate) and classified into segmental or subsegmental PE and proximal or distal DVT. Non-VTE was identified by imaging techniques or absence of VTE in a three month follow up of medical records. Age adjusted cutoff values were calculated if age was ≥50 years according to Douma et al.2, as age x 0.01 for assays measured in mg/L FEU (Siemens INNOVANCE® D-dimer and STA®-Liatest® D-Di) and as age x 0.005 for Roche Tina-quant D-dimer and as age x 0.004 for MediRox D-dimer. Results: VTE was found in 125 patients (13.3%), PE in 35 (3.7%; 3.0% segmental and 0.7% subsegmental) and DVT in 90 (9.6%; 6.3% proximal and 3.4% distal). The diagnostic performances of the assays are displayed below, see table 1. All assays had excellent areas under the ROC-curve (AUC) and all except MediRox D-dimer fulfilled the FDA requirements of sensitivity > 95% and a NPV > 97%, at the cutoff recommended by the manufacturer. When age adjusted cutoffs were applied, all assays maintained their sensitivities, whereas specificities increased by 6-7%. The rate of false positive results decreased by 6% overall, but 10-20% for patients older than 70, see table 2. Conclusion: D-dimer is still the only biomarker used for suspected VTE, even though low specificity with false positive results presents a significant problem due to an elderly patient population burdened with co-morbidity. The examined age-adjusteddecision thresholds increase specificity for VTE without decreasing sensitivity and can thus be used to improve diagnosis of VTE. With fewer false positives, diagnosis will be faster, cheaper and will result in decreased health risks from intravenous contrast, radiation and unnecessary hospital admissions. References 1. Haase C, et al. Age- and sex-dependent reference intervals for D-dimer: evidence for a marked increase by age. Thromb Res. 2013;132(6):676-80. 2. Douma RA, et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. BMJ. 2010;340:c1475. Disclosures Farm: Leo Pharma: Research Funding; Triolab: Honoraria; Siemens: Honoraria. Chaireti:Baxalta: Research Funding. Antovic:Siemens: Honoraria; Roche: Honoraria; Baxter Healthcare Corporation: Honoraria, Research Funding; Novo Nordisk: Honoraria; Sysmex: Honoraria; Stago: Honoraria.

scholarly journals The Diagnostic Efficacy of Age-Adjusted D-Dimer Cutoff Value and Pretest Probability Scores for Deep Venous Thrombosis

2019 ◽  
Vol 25 ◽  
pp. 107602961982631 ◽  
Author(s):  
Junxun Li ◽  
Fan Zhang ◽  
Chujia Liang ◽  
Zhuangjian Ye ◽  
Shaoqian Chen ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Negative Predictive Value ◽  
Predictive Value ◽  
Diagnostic Efficacy ◽  
Predictive Values ◽  
Cutoff Value ◽  
Wells Score ◽  
D Dimer

This study seeks to evaluate the diagnostic value of D-Dimer Plus and Innovance D-Dimer as well as the age-adjusted cutoff value for D-dimer detection in combination with 4 pretest probability (PTP) scores for deep venous thrombosis (DVT). A total of 688 patients referred for lower extremity vascular compression venous ultrasonography for suspected DVT from January 2016 to May 2018 in the First Affiliated Hospital of Sun Yat-sen University underwent D-dimer tests combining with 4 PTP scores. The diagnostic efficacy of the Wells score was the highest of the 4 PTP scores. The diagnostic efficacy of Innovance D-Dimer for DVT was greater than that of D-Dimer Plus, with better sensitivity and negative predictive value, which were both greater than 98%. If the cutoff values were adjusted by age, the Innovation D-Dimer could further improve both the specificity and the positive predictive value, providing better diagnostic performance. When the 2 D-dimer detections were used in combination with 4 PTP scores for DVT diagnosis, separately, both the positive predictive value and the negative predictive value significantly improved for D-Dimer Plus, and the positive predictive values significantly improved for Innovance D-Dimer. However, the sensitivity, specificity, and negative predictive values did not obviously change. For our patients, Wells score had the best diagnostic efficacy for our patients with suspected DVT among the 4 PTP scores. Innovance D-Dimer in combination with age-adjusted cutoff values exhibited increased sensitivity and negative predictive value for DVT diagnosis and was equivalent to the diagnostic efficacy of the Innovance D-Dimer in combination with PTP scores.

scholarly journals Reliability of Five Rapid D-Dimer Assays Compared to ELISA in the Exclusion of Deep Venous Thrombosis

1997 ◽  
Vol 77 (02) ◽  
pp. 262-266 ◽  
Author(s):  
M C H Janssen ◽  
A E Heebels ◽  
M de Metz ◽  
H Verbruggen ◽  
H Wollersheim ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Negative Predictive Value ◽  
Degradation Product ◽  
Predictive Value ◽  
Clinical Management ◽  
Screening Test ◽  
Latex Agglutination ◽  
Fibrin Degradation Product ◽  
D Dimer

SummaryStudies measuring the fibrin degradation product D-Dimer (DD) using enzyme-linked immunosorbent assays (ELISA) in patients with venographically proven deep venous thrombosis (DVT) suggest that it is possible to exclude DVT when DD level is below a certain cut-off level. However, ELISA methods are time-consuming and not available in all laboratories. Different rapid latex-agglutination assays have been investigated, but their sensitivity is considerably lower.In the present study we compared the value of four novel latex DD tests (Tinaquant®, Minutex®, Ortho® and SimpliRed®) and one rapid ELISA (VIDAS®) to a classical ELISA DD assay (Organon Mab Y18®) in 132 patients suspected of DVT.The VIDAS®, a new quantitative automated ELISA, had a sensitivity of 100% and a negative predictive value of 100% for both proximal and distal DVT at a cut-off level of 500 ng/ml. The Tinaquant® assay, a new quantitative latex method, had a sensitivity of 99% and a negative predictive value of 93% for both proximal and distal DVT at a cut-off level of 500 ng/ml. For proximal DVT only, both assays had a sensitivity and negative predictive value of 100%. VIDAS® and Tinaquant® correlated well with ELISA (correlation of r = 0.96 and r = 0.98 respectively). Sensitivities of the semi-quantitative latex assays Minutex®, Ortho® and SimpliRed® were considerably lower (77%, 51 % and 61 % respectively).These results suggest that VIDAS® and Tinaquant® may be used instead of ELISA DD in the exclusion of DVT. Tinaquant® can be performed within 20 min and VIDAS® within 35 min. Both assays might be used as a routine screening test and should be evaluated in large clinical management studies.

Value of Liquid Crystal Contact Thermography and Plasma Level of D-Dimer for Screening of Deep Venous Thrombosis Following General Abdominal Surgery

1992 ◽  
Vol 67 (06) ◽  
pp. 603-606 ◽  
Author(s):  
H Bounameaux ◽  
E Khabiri ◽  
O Huber ◽  
P-A Schneider ◽  
D Didier ◽  
...  
Keyword(s):  
Liquid Crystal ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Predictive Value ◽  
Virus Transmission ◽  
Alternative Methods ◽  
Roc Curve Analysis ◽  
Sequential Approach ◽  
Crystal Contact ◽  
D Dimer

SummaryBecause the use of radioactive fibrinogen uptake test (FUT) has become questionable both for ethical (risk of virus transmission) and technical (lack of sensitivity) reasons, we investigated the potential value of two alternative methods for screening of asymptomatic deep venous thrombosis following elective digestive surgery: liquid crystal contact thermography (LCCT) and measurement of plasma concentration of D-dimer (DD), as compared with bilateral ascending phlebography. Out of 194 patients, 185 underwent phlebography on the 8th (0-19, median and range) postoperative day. Despite prophylaxis with low-molecular-weight heparin and elastic stockings, DVT was detected on phlebography in 58 legs of 45 patients. Sensitivity of LCCT with respect to the presence of DVT was 55% (n = 184 patients) or 28% (n = 368 legs) with a specificity of 67% and 82%, respectively. These poor performances were obtained despite a good interobserver agreement for the LCCT assessments (overall kappa coefficient of 0.66 between three experts). The most accurate cut-off of DD for discriminating patients with or without DVT was 3,000 pg/1, as determined by ROC curve analysis. Sensitivity of a DD level of more than 3,000 pg/1 for the presence of phlebographically documented DVT on the 8th postoperative day was 89% for a specificity of 48%.Thus, LCCT cannot be used for screening of postoperative, mainly asymptomatic DVT following general surgery. On the other hand, measurement of plasma DD may be useful for initial screening, a negative result (level less than 3,000 pg/1) allowing to exclude DVT (negative predictive value of 93%) and a positive result (positive predictive value of 35%) requiring confirmation by phlebography. This sequential approach might be useful in studies of the efficacy of antithrombotic regimens for prophylaxis of DVT in patients at risk.

Sign in / Sign up

Export Citation Format

Share Document