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.

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

Background Established risk factors, including deficiencies of protein C, protein S or antithrombin and the factor V Leiden and prothrombin mutation, are present in about one third of unselected patients with venous thromboembolism. In addition to these inherited thrombophilic defects, elevated plasma levels of factor VIIIc have been suggested to be important in the pathogenesis of (recurrent) venous thromboembolism. The objective of this study was to assess the relevance of factor VIIIc plasma concentration in consecutive patients with venous thromboembolism. Methods We studied the prevalence of elevated plasma levels of factor VIIIc in 65 patients with a proven single episode and in 60 matched patients with documented recurrent venous thromboembolism. The reference group consisted of 60 ageand sexmatched patients who were referred for suspected venous thromboembolism, which was refuted by objective testing and longterm clinical follow-up. To minimalize the influence of the acute phase, blood was obtained at least 6 months after the thromboembolic event and results were adjusted for fibrinogen and C-reactive protein. Factor VIIIc was re-determined several years after the first measurement in a subset of patients to evaluate the variability over time. To study a possible genetic cause, a family study was done. Results In the control, single and recurrent episode group, the prevalences of plasma levels of factor VIIIc above 175 IU/dl (90 percentile of controls) were 10% (95% CI: 4 to 21%), 19% (95 % CI: 10 to 30%) and 33% (95% CI: 22 to 47%), respectively. For each 10 IU/dl increment of factor VIIIc, the risk for a single and recurrent episode of venous thrombosis increased by 10% (95% CI: 0.9 to 21%) and 24% (95% CI: 11 to 38%), respectively. Both low and high plasma levels of factor VIIIc were consistent over time (R = 0.80, p=0.01). A family study indicated a high concordance for elevated factor VIIIc plasma concentrations among first degree family members. Adjustment for fibrinogen, C-reactive protein and known thrombophilic risk factors did not change the observed association of elevated factor VIIIc with thromboembolism. Conclusion Elevated plasma levels of factor VIIIc are a significant, prevalent, independent and

/pdf/the-etiology-diagnosis-and-treatment-of-venous-30uvzr4k0i.pdf

The etiology, diagnosis and treatment of venous thromboembolism

FLIGHT RELATED deep vein thrombosis (DVT) is a potentially life threatening condition. It is more commonly known as the 'economy class syndrome' as it has been linked to the lack of space within the economy class cabin. Millions ofpeople travel by air each year and yet relatively very few people are aware of its aetiology and methods of prevention. This review article aims to provide background information on DVT and its relationship with flight travel. It also highlights the current available methods of diagnosis, treatment and prevention.

Flight related deep vein thrombosis.

Background: The performance of rapid D-dimer ELISA assay has been validated as a part of various diagnostic work-ups in tertiary care hospitals for the exclusion of acute thromboembolism in the medical emergency department. In order to measure the performance of this test outside of predetermined protocols and in a different medical setting, we retrospectively analysed a cohort of adult patients admitted to the emergency department of a regional hospital with a suspicion of acute venous thromboembolism. Methods: All D-dimer assays performed during an 18-month period were retrieved. The patients' data were collected from hospital charts. Six-month follow-up was determined either by a written or telephone questionnaire or after contact with the patient's physician. The patients for whom this process was completed were included in the study and a retrospective diagnostic assessment was performed using a combination of clinical probability and objective testing. The diagnosis was then compared to the result of the initial D-dimer assay. Results: During the study period 494 patients were included with 110 venous thromboembolic episodes. The sensitivity and negative predictive value of the D-dimer assay were respectively 94.5% (95% CI 88.4 to 97.7%) and 96.8% (95% CI 93.2 to 98.7%). Conclusions: The yield of the rapid D-dimer assay in this study is comparable to the results of management studies performed in tertiary centres. D-dimer ELISA assay can be used to exclude venous thromboembolism, particularly in cases with a low clinical probability, in the emergency department and for larger populations in various clinical settings, even in the absence of a formal diagnostic work-up. False negative results can occur, particularly in the presence of a high clinical probability of acute thromboembolism.

The use of the rapid D-dimer test for the exclusion of acute venous thromboembolism in a regional hospital.

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]

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