https://www.annemergmed.com/article/S0196-0644(02)00021-5/pdf

The accuracy of the enzyme-linked immunosorbent assay D -dimer test in the diagnosis of pulmonary embolism: A meta-analysis

Background
Pulmonary embolism (PE) can occur when a thrombus (blood clot) travels through the veins and lodges in the arteries of the lungs, producing an obstruction. People who are thought to be at risk include those with cancer, people who have had a recent surgical procedure or have experienced long periods of immobilisation and women who are pregnant. The clinical presentation can vary, but unexplained respiratory symptoms such as difficulty breathing, chest pain and an increased respiratory rate are common.

D-dimers are fragments of protein released into the circulation when a blood clot breaks down as a result of normal body processes or with use of prescribed fibrinolytic medication. The D-dimer test is a laboratory assay currently used to rule out the presence of high D-dimer plasma levels and, by association, venous thromboembolism (VTE). D-dimer tests are rapid, simple and inexpensive and can prevent the high costs associated with expensive diagnostic tests.

Objectives
To investigate the ability of the D-dimer test to rule out a diagnosis of acute PE in patients treated in hospital outpatient and accident and emergency (A&E) settings who have had a pre-test probability (PTP) of PE determined according to a clinical prediction rule (CPR), by estimating the accuracy of the test according to estimates of sensitivity and specificity. The review focuses on those patients who are not already established on anticoagulation at the time of study recruitment.

Search methods
We searched 13 databases from conception until December 2013. We cross-checked the reference lists of relevant studies.

Selection criteria
Two review authors independently applied exclusion criteria to full papers and resolved disagreements by discussion.

We included cross-sectional studies of D-dimer in which ventilation/perfusion (V/Q) scintigraphy, computerised tomography pulmonary angiography (CTPA), selective pulmonary angiography and magnetic resonance pulmonary angiography (MRPA) were used as the reference standard.

• Participants: Adults who were managed in hospital outpatient and A&E settings and were suspected of acute PE were eligible for inclusion in the review if they had received a pre-test probability score based on a CPR.

• Index tests: quantitative, semi quantitative and qualitative D-dimer tests.

• Target condition: acute symptomatic PE.

• Reference standards: We included studies that used pulmonary angiography, V/Q scintigraphy, CTPA and MRPA as reference standard tests.

Data collection and analysis
Two review authors independently extracted data and assessed quality using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). We resolved disagreements by discussion. Review authors extracted patient-level data when available to populate 2 × 2 contingency tables (true-positives (TPs), true-negatives (TNs), false-positives (FPs) and false-negatives (FNs)).

Main results
We included four studies in the review (n = 1585 patients). None of the studies were at high risk of bias in any of the QUADAS-2 domains, but some uncertainty surrounded the validity of studies in some domains for which the risk of bias was uncertain. D-dimer assays demonstrated high sensitivity in all four studies, but with high levels of false-positive results, especially among those over the age of 65 years. Estimates of sensitivity ranged from 80% to 100%, and estimates of specificity from 23% to 63%.

Authors' conclusions
A negative D-dimer test is valuable in ruling out PE in patients who present to the A&E setting with a low PTP. Evidence from one study suggests that this test may have less utility in older populations, but no empirical evidence was available to support an increase in the diagnostic threshold of interpretation of D-dimer results for those over the age of 65 years.

D-dimer test for excluding the diagnosis of pulmonary embolism.

Background: Predictors of hospital admissions for asthma in children and young adults in a general population are not well defined, because most studies have used selected subpopulations. Objective: The purpose of this investigation was to determine risk factors for single and multiple hospital admissions for asthma. Methods: The members of a population-based, unselected birth cohort of 1037 New Zealanders answered questionnaires and underwent lung function, airway responsiveness, and allergy testing on 7 occasions to the age of 26 years. Results: Among the 766 study members (74% of the cohort) who reported wheezing symptoms ever by the age of 26 years, 136 hospitalizations were reported by 62 individuals (8.3% of those at risk, 6.2% of the total cohort). Only 55 of these 136 admissions involved children less than 9 years of age; admissions continued to occur between the ages of 9 and 18 years (40 admissions) and at >18 years (41 admissions). Those admitted were predominantly male, had earlier ages of onset of symptoms, were more atopic, and had more airway hyperresponsiveness to methacholine than those not admitted. Frequent symptoms and low lung function were evident among the 45 study members with single admissions and even more evident among the 17 study members with multiple (2-10) admissions. Conclusions: A surprisingly large fraction of this unselected population experienced hospitalization for asthma during the 26-year follow-up, many being admitted in later childhood, adolescence, and early adulthood. Clinical characteristics and markers of severity, including frequent respiratory symptoms, airway hyperresponsiveness, atopy, and low lung function, identify those at high risk for hospitalization for asthma, particularly with respect to multiple admissions. (J Allergy Clin Immunol 2002;110:220-7.)

Risk factors for hospital admission for asthma from childhood to young adulthood: A longitudinal population study

Ablation and Coagulation Activation. Introduction: Although thromboembolism is an uncommon complication of radiofrequency (RF) ablation, some preliminary reports have suggested that RF ablation results in activation of the coagulation system, possibly increasing this risk. We hypothesized that the insertion of intravenous catheters and their prolonged intravenous placement rather than RF ablation activates the coagulation cascade.



Methods and Results: Thirty-seven patients, group 1 (n = 21) during RF ablation, and group 2 (n = 16) during routine electrophysiologic studies (EPS), were studied prospectively. Blood was drawn for coagulation and fibrinolytic studies following insertion of venous sheaths (TO), following catheter placement (T1), and 1 hour after completion of RF ablation or EPS {T2). Conversion of prothrombin to thrombin was measured using thrombin-antithrombin complex (TAT) and prothrombin activation peptide (F1+2). and fibrinolytic activity was assessed using D-dlmer concentration. Levels of D-dimer increased in group 1 from 823.52 ± 323.52 ng/mL at TO to 1,314.28 ± 297.63 ng/mL at T2 (P= 0.005), and in group 2 from 658.15 ± 161.70 ng/mL at T0 to 1625 641.45 ng/mL at T2 (P=±0.064). TAT levels increased from to 27.74 ± 5.6 μg/L at T0 to 52.99 ± 5.93 μg/L at T2 in group 1 (P= 0.09), and from 19.79 ± 5.14 μg/L at T0 to 73.5 ± 24.15 μg/L at T2 in group 2 (P= 0.05). F1+2 concentration increased from 1.52 ± 0.30 nmol/L at T0 to 3.06 ± 0.41 nmol/L at T2 in group 1 (P= 0.004), and from 1.32 ± 0.30 nmol/L at T0 to 3.11 ± 0.46 nmol/L at T2 in group 2 (P= 0.087). There was no significant difference in the concentration of the three coagulation variables between group 1 and group 2 at any given time point. No correlation was demonstrable between concentration of D-dimers, TAT, or F1+2 and variables of RF delivery such as cumulative energy, number of RF energy applications, or number of impedance rises. However, a significant positive correlation (r = 0.65, P < 0.01) was noted between the duration of the RF ablation procedure and the concentration of D-dimers.



Conclusion: We conclude that activation of the coagulation cascade in RF ablation procedures is not related to the delivery of RF energy, but is related to the placement of intravascular catheters and to the duration of the ablation procedure.

Does Radiofrequency Ablation Induce a Prethrombotic State? Analysis of Coagulation System Activation and Comparison to Electrophysiologic Study

Pulmonary embolism is a common, yet often unsuspected and unrecognised disease associated with a high mortality. New, objective, “user friendly” and cost eVective diagnostic strategies are being explored. D-Dimers, the fibrinolytic degradation products of crosslinked fibrin, have emerged as the most useful of the procoagulant activity and ongoing fibrinolysis markers. D-Dimer measurements are very sensitive in excluding a diagnosis of pulmonary embolism in the setting of normal values, a low clinical suspicion, and nondiagnostic lung scans. Several assays have been developed and are reviewed. (J Clin Pathol 2001;54:664‐668)

https://jcp.bmj.com/content/jclinpath/54/9/664.full.pdf

D-Dimer testing: the role of the clinical laboratory in the diagnosis of pulmonary embolism

The aim of this study is to evaluate the usefulness of plasma measurements of D-dimer using ELISA method and latex agglutination test in the diagnostic approach of venous thromboembolism. Among 126 patients suspected of pulmonary embolism (80 pat.) or deep venous thrombosis of the legs (46 pat.), the diagnosis of acute venous thromboembolism has been confirmed using gold standard invasive techniques (pulmonary angiography and/or contrast venography) in 49% of them. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimer plasma concentration above 500 ng/ml, on admission day, for the diagnosis of venous thromboembolism are 98%, 66%, 97%, 74% respectively when using the ELISA method, and 87%, 70%, 85%, 74% respectively when using the latex assay. In the 51 patients with a lung scan showing an indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method is very high (94%) but that of the latex assay is low (67%). The repetition of D-dimer measurement on days 2 and 4 following admission has no significant effect on the sensitivity of the ELISA and latex assays. Our results demonstrate that the measurement of plasma D-dimer concentration using latex assay should not be used in the diagnostic approach of venous thromboembolism because the sensitivity of this test is insufficient for ruling out the presence of the disease. On the opposite, a low concentration of plasma D-dimer measured by the ELISA method might be used to rule out acute venous thromboembolism, and avoid invasive radiological techniques, especially in patients with an indeterminate probability lung scan.

[Value of the determination of D-dimers in the diagnostic approach of venous thrombo-embolic disorders].

Objective
To evaluate bronchial hyperresponsiveness (BHR) early after recovery from acute severe asthma (ASA).Design: Prospective study including all patients admitted to the intensive care unit (ICU) for ASA over a 12-month period.

Bronchial hyperresponsiveness following acute severe asthma

The diagnostic usefulness of measuring plasma D-dimers using the ELISA method and the latex agglutination test has been prospectively evaluated in 117 patients hospitalized for suspicion of acute venous thrombo-embolism (AVTE): pulmonary embolism was suspected in 80 patients and the remaining 37 had a suspicion of deep vein thrombosis of the lower limbs. The diagnosis of AVTE was confirmed in 50% of the patients, all of whom underwent gold standard invasive investigation i.e. pulmonary angiography and/or contrast venography. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimers plasma concentration exceeding 500 ng/ml for the diagnosis of AVTE were respectively 98, 58, 97 and 70% when using the ELISA method, and 86, 71, 84 and 75% when using the latex assay. In 47 patients whose lung scans yielded abnormalities of indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method was very high (94%), but that of latex assay was low (67%). Our results demonstrate that measuring the plasma D-dimers by the latex assay should not be used in the diagnosis of AVTE. On the other hand, the ELISA method might be of great interest in the diagnostic strategy of AVTE, as a normal concentration of D-dimers rules out almost definitely the diagnosis of AVTE, and hence, spares from performing invasive investigations.

[Value of plasma D-dimer assays in the diagnosis of venous thromboembolism]

[Can the D-dimer assay predict the importance of pulmonary reperfusion in pulmonary embolism?].

Examen non invasif : L'angioscanner pulmonaire est un examen non invasif dont les seules contre-indications relatives sont l'insuffisance renale et l'allergie a l'iode. Embolie pulmonaire massive : En cas de suspicion d'une telle embolie, l'angioscanner est l'examen ideal en raison de son excellente performance pour le diagnostic d'embolie pulmonaire proximale et de son innocuite. Embolie pulmonaire non massive : Dans la strategie diagnostique, l'angioscanner pourrait, en raison de sa specificite elevee, etre l'examen de premiere intention a la place de la scintigraphie. Si l'angioscanner montre un thrombus, le diagnostic d'embolie pulmonaire est confirme et un traitement institue. Si l'angioscanner ne montre pas de thrombus, le diagnostic d'embolie pulmonaire peut etre ecarte dans la majorite des cas. En cas de doute, d'autres investigations non invasives doivent etre pratiquees. Le recours a l'angiographie devrait devenir exceptionnel.

Pulmonary embolism. The role of computed tomography angiography

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