D‐dimer assays are commonly used in clinical practice to exclude a diagnosis of deep vein thrombosis or pulmonary embolism. More recently, they have been also been used to guide patients with ...unprovoked venous thromboembolism (VTE) when faced with the decision to continue or stop anticoagulation after initial treatment is complete. D‐dimer assays vary widely with respect to the antibody used, method of capture, instrumentation required, and calibration standard. These differences have an important influence on the operating characteristics of the assays. Consequently, the evidence available in the literature for one assay cannot simply be extrapolated to another. In this review, we will outline the general properties of D‐dimer assays, discuss the concept of raising the D‐dimer threshold used in diagnosis of VTE according to pretest probability and age, and provide clinical perspective on the role of D‐dimer testing in the diagnosis and prognosis of VTE.
The risk of bleeding on anticoagulation varies between patients. It is uncertain whether sex influences this risk.
To determine if the risk of major bleeding differs between men and women receiving ...anticoagulation for atrial fibrillation or venous thromboembolism(VTE).
We searched MEDLINE, EMBASE, and Cochrane databases, and relevant conference proceedings, until February 2013. We included randomized controlled trials and prospective cohort studies of patients on therapeutic anticoagulation for atrial fibrillation or VTE. Two reviewers independently extracted data. The relative risk of bleeding in men compared to women was pooled using a random-effects model.
Forty-two studies including 94 293 patients were eligible; 78 044 patients (83%) had atrial fibrillation; 16 156 patients (17%) had VTE; 37 250 patients were women (40%); and there were 4147 major bleeds. The relative risk of major bleeding for men vs. women was 1.02(95% CI 0.95–1.10; P = 0.27 for heterogeniety). The relative risk was 1.02 (95% CI 0.95–1.09) in patients with atrial fibrillation and 0.80 (95% CI 0.65–0.98) in patients with VTE (P = 0.03 for subgroup effect). Type of anticoagulant,intensity of anticoagulation, and whether patients began or were already established on anticoagulants at enrollment did not influence the relative risk of major bleeding in men compared to women.
The risk of major bleeding on anticoagulation appears to be the same in men and women, particularly if patients have atrial fibrillation. This finding is less certain for patients with VTE, in whom the risk of bleeding may be marginally lower in men compared to in women.
SUMMARY POINTS Assessment of clinical pre-test probability (CPTP) is the first step in the diagnosis of pulmonary embolism Combinations of CPTP and test results are usually needed to identify ...patients who require, and do not require, anticoagulant therapy Thrombolytic therapy is usually reserved for patients with hypotension and without major risk factors for bleeding Pulmonary embolism associated with a reversible risk factor is usually treated for three months Pulmonary embolism associated with active cancer, or a second unprovoked pulmonary embolism, is usually treated indefinitely The decision to treat an unprovoked pulmonary embolism for three months or indefinitely is sensitive to an individual patient's preference and risk of bleeding
Essentials It is unclear if raising the D-dimer level to exclude venous thrombosis in older patients is valid. We compared this 'age-adjusted' strategy with other ways of interpreting D-dimer ...results. A non-age adjusted increase, and using higher thresholds in younger patients, was just as accurate. Age-adjustment of D-dimer thresholds does not appear to be appropriate. Click to hear Prof. le Gal's presentation on controversies in venous thromboembolism diagnosis SUMMARY: Background Using a progressively higher D-dimer level to exclude venous thromboembolism (VTE) with increasing age has been proposed but is not well validated. Objective To determine whether it is appropriate to use a progressively higher D-dimer level to exclude VTE with increasing age. Patients/methods We analyzed clinical data and blood samples from 1649 patients with a first suspected deep vein thrombosis or pulmonary embolism. We compared the negative predictive values (NPVs) for VTE, and the proportions of patients with a negative D-dimer result, by using three D-dimer interpretation strategies: a progressively higher D-dimer threshold with increasing age (age-adjusted strategy); the same higher D-dimer threshold in all patients (mean D-dimer strategy); and a progressively higher D-dimer threshold with decreasing age (inverse age-adjusted strategy). Results The NPV with the age-adjusted strategy (99.6%; 95% confidence interval CI 99.0-99.9%) was not different from that with the mean D-dimer strategy (99.7%; 95% CI 99.0-99.9%) or that with the inverse age-adjusted strategy (99.8%; 95% CI 99.1-99.9%). The proportion of patients with a negative result with the age-adjusted strategy (50.9%; 95% CI 48.5-53.4%) was not different from the proportion of patients with a negative result with the mean D-dimer strategy (51.7%; 95% CI 49.3-54.1%) or with the inverse age-adjusted strategy (49.5%; 95% CI 47.1-51.9%). Conclusions Our analysis does not support the use of a progressively higher D-dimer level to exclude VTE with increasing age.
ESSENTIALS: It is not known if D-dimer testing alone can safely exclude pulmonary embolism (PE). We studied the safety of using a quantitative latex agglutination D-dimer to exclude PE in 808 ...patients. 52% of patients with suspected PE had a negative D-dimer test and were followed for 3 months. The negative predictive value of D-dimer testing alone was 99.8%, suggesting it may safely exclude PE.
Strategies are needed to exclude pulmonary embolism (PE) efficiently without the need for imaging tests. Although validated rules for clinical probability assessment can be combined with D-dimer testing to safely exclude PE, the rules can be complicated or partially subjective, which limits their use.
To determine if PE can be safely excluded in patients with a negative D-dimer without incorporating clinical probability assessment.
We enrolled consecutive outpatients and inpatients with suspected PE from four tertiary care hospitals. All patients underwent D-dimer testing using the MDA D-dimer test, a quantitative latex agglutination assay. PE was excluded in patients with a D-dimer less than 750 μg FEU L(-1) without further testing.
with D-dimer levels of 750 μg FEU L(-1) or higher underwent standardized imaging tests for PE. All patients in whom PE was excluded had anticoagulant therapy withheld and were followed for 3 months for venous thromboembolism (VTE). Suspected events during follow-up were adjudicated centrally.
Eight hundred and eight patients were enrolled, of whom 99 (12%) were diagnosed with VTE at presentation. Four hundred and twenty (52%) patients had a negative D-dimer level at presentation and were not treated with anticoagulants; of these, one had VTE during follow-up. The negative predictive value of D-dimer testing for PE was 99.8% (95% confidence interval, 98.7-99.9%).
A negative latex agglutination D-dimer assay is seen in about one-half of patients with suspected PE and reliably excludes PE as a stand-alone test.
Autologous peripheral blood stem cell transplantation (PBSCT) for Hodgkin lymphoma (HL) is curative for many patients with relapsed or refractory disease. Relapsing disease, however, remains a major ...problem. Neoplastic transformation of B-lymphocytes probably underlies the development of classical HL. Whether clonal B cells are critical for disease evolution and response to therapy in HL remains uncertain. We investigated the impact of clonal B cells detected in peripheral blood stem cell (PBSC) collections on the outcome of patients with HL undergoing transplant. Qualitative semi-nested PCR was carried out on genomic DNA from mononuclear cells from PBSCs to determine the presence of clonal immunoglobulin heavy chain (IgH) complementary-determining region 3 (CDR3) gene rearrangements. Clinical factors were assessed for their association with relapse, overall survival (OS) and progression-free survival (PFS). Among 39 patients undergoing PBSCT, 12 grafts (31%) were PCR positive for clonal IgH rearrangements. OS was better in the PCR-negative group (logrank test, P=0.041). The OS at 5 years was 81% in PCR-negative versus 39% in PCR-positive patients; hazard ratio was 3.23 (95% confidence interval: 0.98-10.63). There was a trend towards better PFS (logrank test, P=0.12), estimated as 71% at 5 years in PCR-negative versus 41% in PCR-positive patients. Clonal B-lymphocytes in PBSC collections of patients with HL identify patients at risk of poor outcome. Larger series are needed to confirm our observations. Insight regarding the role of monoclonal B cells may lead to improved therapies.
We have implemented a cost-effective design for the readout electronics of both the anode wires and the cathode pads of large area proportional wire chambers for the HERA-B muon system based on the ...ASD-08 integrated circuit. To control and monitor the large number of readout channels, we have built a distributed control system based on Philips Semiconductors' I/sup 2/C bus and microcontrollers. To date we have installed about 10800 channels of muon chambers and electronics. The average single channel noise occupancy is less than 10/sup -5/, and the detectors have been operated with target interaction rates as high as 70 MHz.
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