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Purpose of Review: To discuss reports published in 2005 on the diagnosis of clinically suspected nonmassive pulmonary embolism., Recent Findings: Progress has been made in assessing the clinical probability of pulmonary embolism, in addressing diagnosis in the elderly, in evaluating the diagnostic performance of single-detector and multidetector row helical computed tomography, and in the role of D-dimer measurement and lower limb venous compression ultrasonography in the diagnostic work-up of pulmonary embolism., Summary: Diagnosing venous thromboembolism depends mainly on noninvasive diagnostic tools that are used sequentially. In most patients, a noninvasive work-up is feasible and the diagnostic algorithms are becoming simpler. This review focuses on developments in clinical probability assessment, pulmonary embolism in the elderly, potential new uses of D-dimer measurement, advent of multidetector row helical computed tomography, and utility of ultrasonography in detecting deep vein thrombosis in patients with suspected pulmonary embolism. With the development of potentially more sensitive diagnostic tests for pulmonary embolism, physicians are now facing the risk of overdiagnosis and hence overtreatment. The issue will no longer be just to detect clots but to identify patients who must be treated using anticoagulants, a complicated question.

To evaluate the performances of a new D-dimer assay, Stratus CS D-dimer (Dade Behring, Newark, Delaware, USA), for the exclusion of venous thromboembolism and to determine the best cut-off values. This test relies on a sandwich enzyme-linked immunosorbent assay with a fluorogenic substrate in a radial partition immunoassay system in a dedicated device. It does not require laboratory staff and the results are available within 18 min. Two hundred and ninety-one frozen samples from patients suspected of either deep venous thrombosis (n = 137) or pulmonary embolism (n = 154) were measured and the results compared with the VIDAS D-dimer New assay. There were 37 deep venous thrombosis (27%) and 49 pulmonary embolism (32%) samples. Receiver-operating characteristic curve analysis indicated that the cut-off value could be set at either 300 or 400 ng/ml Fibrinogen Equivalent Units (FEU). The coefficient of variation determined with a lyophilized low-level control plasma (305 ng/ml FEU) was 6%. With a cut-off at 300 ng/ml FEU, the sensitivity, the specificity and the negative predictive value were 100% [95% confidence interval (CI), 95.8-100], 33.1% (95% CI, 26.8-40) and 100% (95% CI, 94.7-100), respectively. Raising the cut-off to 400 ng/ml FEU, the corresponding figures were 96.5% (95% CI, 90.1-99.3), 46.3% (95% CI, 39.4-53.2) and 96.9% (95% CI, 91.3-99.4), respectively. At 400 ng/ml, three results were false-negative, one with both devices and two with the Stratus D-dimer only. Stratus D-dimer appears to be suitable for the exclusion of venous thromboembolism in the emergency room setting., (Copyright 2004 Lippincott Williams and Wilkins)

The performance of a new latex-enhanced turbidimetric assay, D-Dimer PLUS, has been evaluated with two analyzers performing various coagulation assays: the BCS Analyzer and the BCT Analyzer. A precision study showed total coefficients of variation ranging from 2.7 to 11.1% with the BCS Analyzer and from 2.5 to 6.6% with the BCT Analyzer. We investigated the ability of D-Dimer PLUS to exclude venous thromboembolism in 312 outpatients suspected of either pulmonary embolism or deep venous thrombosis. Three months follow-up was available for all patients. With the BCS Analyzer, we determined a cut-off value of 190 ng/ml, which gave a sensitivity of 97.9% [95% confidence interval (CI), 92.6-99.7%], a specificity of 37.9% (95% CI, 30.9-43.8%) and a negative predictive value of 97.6% (95% CI, 91.7-99.7%). With the BCT Analyzer, at a cut-off value of 130 ng/ml, sensitivity was 96.8% (95% CI, 91.0-99.3%), specificity was 45.2% (95% CI, 38.5-51.2%) and the negative predictive value was 97% (95% CI, 91.6-99.4). This new assay is fast and fully automated, and its performance is suitable to exclude venous thromboembolism. Management studies should be performed to assess its utility.

Fibrin monomer (FM) is a highly sensitive marker of venous thromboembolism and can be used to rule out deep venous thrombosis (DVT) and/or pulmonary embolism in symptomatic outpatients. The aim of the study was to investigate the usefulness of serial fibrin monomer determinations to predict or rule out DVT after total knee arthroplasty in asymptomatic patients. One hundred and thirty consecutive patients underwent total knee replacement. Blood samples were obtained in 104 of them the day before, at days 1, 3, 6 after surgery and at the day of phlebography. Phlebography was performed in all these patients between days 8 and 12 after surgery. There were 44 DVT (44/104, 42%). As compared with the patients without DVT, FM mean levels were 2 and 1.5 times higher in the DVT group at day 3 (P < 0.001) and day 6 (P < 0.01), respectively. However, no useful cut-off values for DVT prediction or exclusion could be determined due to the scattering of the values. Therefore, despite differences between patients with or without DVT, serial FM determinations are of no value for predicting or ruling out DVT in individual patients undergoing total knee arthroplasty.

Purpose: To evaluate the risk of major bleeding in unselected patients given anticoagulant treatment (heparin overlapped and followed by oral anticoagulants) because of deep vein thrombosis (DVT) or pulmonary embolism (PE)., Subjects and Methods: We screened the database of 1590 outpatients suspected of DVT and PE in prospective diagnostic studies conducted in Geneva between 1992 and 1998., Results: Four hundred and eleven of 1590 patients (26%) were anticoagulated for confirmed venous thromboembolism (PE, 300; DVT, 111). One patient was excluded because of concomitant thrombolytic therapy. Five (1.2%; 95% confidence interval, 0.4-2.8) of the remaining 410 patients experienced a major hemorrhagic event during the 3-month follow-up, including two fatal events. All bleedings occurred during the first month of therapy (heparin, two; oral anticoagulants, two; combined treatment, one) and the median age of the patients who bled was 80 years. At least one serious comorbid condition associated with higher bleeding risk was present in four patients and, in one case, the bleeding was clearly related to an excessive intensity of anticoagulation., Conclusion: The rate of bleeding events in this population of unselected outpatients is similar to that reported in controlled therapeutic trials. The hemorrhagic events occurred early in the course of anticoagulant therapy and concerned old patients mostly affected by at least one comorbid condition. Particular care should be used to avoid the risk of overtreatment.

Plasma D-dimer, a highly sensitive marker of venous thromboembolism, was measured using an enzyme-linked immunosorbent assay pre-operatively, on the third postoperative day, and at the time of phlebography in 118 patients undergoing elective total knee arthroplasty. Deep venous thrombosis (DVT) was detected using systematic bilateral phlebography between the eighth and 12th postoperative day in 47 (39.8%) patients. D-dimer plasma concentrations did not differ between patients who had DVT and those who had no DVT, either pre-operatively (n = 118, P = 0.63) or at the time of phlebography (n = 111, P = 0.70). On the third postoperative day, D-dimer concentration was significantly higher (P < 0.01) in the patients who had DVT (median 3270 microg/l, range 1156-9996, n = 47) than in those who did not (2287 microg/l, 685-7062, n = 64). However, receiver operating characteristics curve analysis did not provide any useful cutoff values that would allow individual diagnoses to be made. In conclusion, the results of the present study suggest that plasma measurement of D-dimer concentration is of no value for predicting, diagnosing or ruling out DVT in patients undergoing total knee arthroplasty.

Pneumatic intermittent compression is an effective method to prevent postoperative venous thromboembolism. Its efficacy has been ascribed to both a haemodynamic action (increase of blood flow velocity) and a stimulation of endogenous fibrinolytic activity [via the production of tissue-type plasminogen activator (t-PA) by the vascular endothelium]. The relative contribution of these two effects is still debated. In a randomized, cross-over study in ten healthy volunteers, we compared the haemodynamic and fibrinolytic effects of two different pneumatic intermittent compression devices: a classical, low-pressure, whole-leg boots system, and a novel, high-pressure, plantar compression system. The study was performed at rest, to compare haemodynamics and fibrinolytic activity modifications, and under induced venous leg stasis, in order to compare the two compression systems in experimental conditions mimicking laparoscopic surgery. Our data show that (1) a pneumatic compression device that exerts its compression on the plantar venous plexus only induced an increase of venous blood peak velocity and flow in the common femoral vein that is very similar to that induced by the classical whole-leg boots compression system; (2) the venous stasis induced by an external pressure mimicking the conditions of laparoscopic surgery further increased the absolute velocity and flow increase, with the two intermittent compression systems tested; (3) no changes of t-PA or plasminogen activator-inhibitor 1 antigens were observed with either pneumatic compression device. In conclusion, the present study indicates that the antithrombotic effect of mechanical prophylaxis is probably mainly due to its ability to increase venous peak velocity and flow, especially under venous stasis conditions.

Deep vein thrombosis of the lower limbs is usually treated with an initial course of heparin or low-molecular-weight heparin associated with oral anticoagulants which are started simultaneously, thereby allowing heparin to be stopped after 4-7 days. Although consensus conferences have proposed a uniform duration of oral anticoagulant therapy of 3 months, great uncertainties remain as to the optimal treatment duration in an individual patient. Two large-scale studies have recently demonstrated that short treatment durations (4 weeks or 6 weeks, respectively) are associated with about two-fold higher rates of thromboembolic recurrences over follow-up periods of 1-2 years compared with longer treatment durations (3 months or 6 months, respectively). However, because treatment duration is also a major determinant of the hemorrhagic risk on oral anticoagulants, it is essential to balance the protective effect of these agents against their bleeding risk. This paper reviews the literature on the antithrombotic effects and hemorrhagic risks of different durations of oral anticoagulant therapy following lower limb deep vein thrombosis and suggests tentative recommendations which range from a short anticoagulant course of 4 weeks in a patient with a low risk of thromboembolic recurrence and a high hemorrhagic risk (e.g. postoperative distal vein thrombosis) to 6 months or more in a patient with a low hemorrhagic risk and a high risk of thromboembolic recurrence (e.g. idiopathic proximal vein thrombosis in a patient with inherited thrombophilia or malignancy).

The performance of a new membrane ELISA for semi-quantitative determination of plasma D-dimer has been evaluated. Its cut-off is about 500 ng/ml FEU and this single test is completed within 10 min. D-dimer was measured in 301 patients suspected of pulmonary embolism by conventional microplate and membrane ELISA. For the latter, readings were made by eye and some differences were noticed between the readers for reactions in the grey zone. Sensitivity and negative predictive values were similar for the two ELISA (higher than 90%). The 95% confidence intervals of sensitivity and negative predictive values obtained with this membrane ELISA suggest that this new test may be used as a diagnostic tool to exclude the presence of pulmonary embolism.

The diagnosis of pulmonary embolism remains a difficult issue. In a previous study of patients submitted to ventilation--perfusion (V-P) scintigraphy we suggested that measurement of D-dimer might be of value for ruling out the diagnosis of pulmonary embolism if the plasma level was less than 500 micrograms/l (ELISA). In the present paper, this cut-off was validated in a consecutive series of 21 patients who were submitted to pulmonary angiography. Sensitivity and specificity were 100% and 36%, respectively. When these data were pooled with the results obtained following V-P scintigraphy (total number of patients = 67), sensitivity, specificity, and positive and negative predictive values were 100%, 70%, 59% and 100%, respectively. It is therefore worthwhile to further evaluate the value of the plasma measurement of D-dimers, especially in patients with inconclusive lung scintigraphy.