Serial Compression Ultrasonography Research Articles

Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: The X-COVID-19 Randomized Trial.

It is uncertain whether higher doses of anticoagulants than recommended for thromboprophylaxis are necessary in COVID-19 patients hospitalized in general wards METHODS: This is a multicentre, open-label, randomized trial performed in 9 Italian centres, comparing 40mg b.i.d. versus 40mg o.d. enoxaparin in COVID-19 patients, between April 30 2020 and April 25 2021. Primary efficacy outcome was in-hospital incidence of venous thromboembolism (VTE): asymptomatic or symptomatic proximal deep vein thrombosis (DVT) diagnosed by serial compression ultrasonography (CUS), and/or symptomatic pulmonary embolism (PE) diagnosed by computed tomography angiography (CTA). Secondary endpoints included each individual component of the primary efficacy outcome and a composite of death, VTE, mechanical ventilation, stroke, myocardial infarction, admission to ICU. Safety outcomes included major bleeding. The study was interrupted prematurely due to slow recruitment. We included 183 (96%) of the 189 enrolled patients in the primary analysis (91 in b.i.d., 92 in o.d.). Primary efficacy outcome occurred in 6 patients (6.5%, 0 DVT, 6 PE) in the o.d. group and 0 in the b.id. group (ARR 6.5, 95% CI: 1.5-11.6). The absence of concomitant DVT and imaging characteristics suggests that most pulmonary artery occlusions were actually caused by local thrombi rather than PE. Statistically nonsignificant differences in secondary and safety endpoints were observed, with two major bleeding events in each arm. No DVT developed in COVID-19 patients hospitalized in general wards, independently of enoxaparin dosing used for thromboprophylaxis. Pulmonary artery occlusions developed only in the o.d. group. Our trial is underpowered and with few events.

Outcomes of isolated distal thrombosis managed with serial compression ultrasonography

BackgroundIsolated distal deep vein thrombosis (IDDVT) is a common subtype of deep vein thrombosis (DVT). Consensus guidelines provide conflicting recommendations for IDDVT management; some recommend anticoagulant treatment, while others suggest serial compression ultrasonography (CUS) monitoring for patients not at “high risk” of proximal extension. The purpose of this study was to describe outcomes of serial CUS-monitored IDDVT and identify risk factors for proximal thrombus extension or anticoagulant treatment initiation. MethodsA retrospective descriptive study was conducted using electronic data from University of Utah Health. Adult subjects with objectively confirmed, serial CUS-monitored IDDVT were included. Subjects were followed for 30 days for occurrence of a composite outcome of proximal thrombus extension or anticoagulant treatment initiation. Descriptive statistics were used to summarize characteristics of the study population. Characteristics were compared across outcome groups using inferential statistics. ResultsA total of 182 subjects were included, with 53 subjects (29.1%) experiencing the composite outcome. Of these, 12 (22.6%) experienced proximal thrombus extension and 41 (77.4%) initiated anticoagulant treatment. A prior history of venous thromboembolism (VTE) was significantly higher in those who experienced the composite outcome than in those who did not. ConclusionsOur results suggest that 70% of patients with serial CUS-monitored IDDVT did not experience thrombus extension or require anticoagulant treatment within 30 days of diagnosis, regardless of risk factors for proximal extension. Serial CUS monitoring may be a useful management strategy for IDDVT. A history of VTE may identify patients more likely to experience proximal thrombus extension or require anticoagulation.

C0454: Accuracy of Nurse-Performed Compression Ultrasonography in the Diagnosis of Proximal Symptomatic Deep Vein Thrombosis: A Prospective Cohort Study

Summary. Background: Compression ultrasonography(CUS) has been recognized as the diagnostic procedure ofchoice for the investigation of patients with suspecteddeep vein thrombosis (DVT); the aim of this study was toassess the diagnostic accuracy of nurse-performed CUSfor symptomatic proximal DVT of the lower limb. Mate-rial and Methods: We prospectively evaluated all consecu-tive outpatients referred for suspected DVT from January2011 to December 2012. All patients underwent bilateralproximal lower limb CUS, first by trained nurses andthen by physicians expert in vascular ultrasonography,with every group blinded with respect to each other. Thistest was repeated after 5–7 days in all negative or unclearexaminations. Interobserver agreement and accuracy ofnurse-performed CUS were calculated, considering thephysician’s final diagnosis as the reference test. Results:Six hundred ninety-seven patients were included in thestudy. DVT was diagnosed in 122 patients by expertultrasound physicians with an overall prevalence of17.5% (95% confidence interval [CI] 15.8%–20.6%).Nurse agreement with the physician in DVT diagnosiswas excellent (Cohen’s j 0.82, 95% CI 0.79–0.85). Nurse-performed CUS had a sensitivity of 84.4% (95% CI81.7%–87.1%) and a specificity of 97.0% (95% CI95.8%–98.3%) with a diagnostic accuracy of 94.8% (95%CI 93.2%–96.5%). Conclusion: Our results suggest thatnurse-performed CUS may be a potential useful alterna-tive to physician performed CUS with a good accuracy.However, sensibility of nurse-performed CUS appearedsuboptimal and future studies should incorporate in theevaluation of this technique other pretest tools that mayincrease its accuracy.Keywords: diagnostic tests; Doppler ultrasonography;nurses; vascular diseases; venous thrombosis.IntroductionPrompt diagnosis of deep vein thrombosis (DVT) isessential to decrease the risk of potentially fatal pulmo-nary embolism and postthrombotic syndrome inuntreated patients [1,2]. Diagnostic strategies in DVTshould be accurate, simple to apply, and cost effective.Currently, compression ultrasonography (CUS) is consid-ered the method of choice for the diagnosis of DVT insymptomatic patients, and its use has been validated inseveral prospective studies [2–4]. The potential advantagesof this technique are the ease of performance by manyoperators and the availability in many hospitals with vir-tually all ultrasound scanners, regardless of generation,model, and even probe frequency [5].Although CUS has shown good accuracy for the diag-nosis of symptomatic proximal DVT, its specificity andsensitivity for calf vein thrombi are much lower [2,4]. Forthis reason, CUS may be limited to the proximal veinsand repeated within 1 week when negative (serial proxi-mal CUS) or extended to both proximal and distal veinsand performed on a single occasion with color-Dopplersupport (whole-leg ultrasonography) [2,5]; both strategiesare reliable diagnostic options for the management ofthese patients [2,5].

Safety of withholding anticoagulation in pregnant women with suspected deep vein thrombosis following negative serial compression ultrasound and iliac vein imaging

Compression ultrasonography performed serially over a 7-day period is recommended for the diagnosis of deep vein thrombosis in symptomatic pregnant women, but whether this approach is safe is unknown. We evaluated the safety of withholding anticoagulation from pregnant women with suspected deep vein thrombosis following negative serial compression ultrasonography and iliac vein imaging. Consecutive pregnant women who presented with suspected deep vein thrombosis underwent compression ultrasonography and Doppler imaging of the iliac vein of the symptomatic leg(s). Women whose initial test results were negative underwent serial testing on 2 occasions over the next 7 days. Women not diagnosed with deep vein thrombosis were followed for a minimum of 3 months for the development of symptomatic deep vein thrombosis or pulmonary embolism. In total, 221 pregnant women presented with suspected deep vein thrombosis. Deep vein thrombosis was diagnosed in 16 (7.2%) women by initial compression ultrasonography and Doppler studies; none were identified as having deep vein thrombosis on serial testing. One patient with normal serial testing had a pulmonary embolism diagnosed 7 weeks later. The overall prevalence of deep vein thrombosis was 7.7% (17/221); of these, 65% (11/17) of cases were isolated to the iliofemoral veins and 12% (2/17) were isolated iliac deep vein thromboses. The incidence of venous thromboembolism during follow-up was 0.49% (95% confidence interval [CI] 0.09%-2.71%). The sensitivity of serial compression ultrasonography with Doppler imaging was 94.1% (95% CI 69.2%-99.7%), the negative predictive value was 99.5% (95% CI 96.9%-100%), and the negative likelihood ratio was 0.068 (95% CI 0.01-0.39). Serial compression ultrasonography with Doppler imaging of the iliac vein performed over a 7-day period excludes deep-vein thrombosis in symptomatic pregnant women.

Serial Limited versus Single Complete Compression Ultrasonography for the Diagnosis of Lower Extremity Deep Vein Thrombosis

The diagnostic approach to deep vein thrombosis (DVT) has evolved during the last 3 decades. Contrast venography has been replaced by noninvasive tests. Compression ultrasonography (CUS) is currently the most widely used diagnostic test. Whereas CUS has a high accuracy for proximal DVT (thrombosis of the popliteal and more proximal veins), it has been shown to lack sensitivity and specificity for distal DVT. Ultrasonography can either be limited to the proximal veins and repeated within 1 week (serial limited CUS) or extended to both proximal and distal veins and performed on one occasion (single complete CUS). Both strategies are reliable diagnostic options for the management of patients with suspected DVT. The main limitation of proximal CUS is the need to repeat the test once in patients with initial negative findings. Conversely, complete CUS detects many distal DVTs for which systematic anticoagulation therapy is debatable and exposes patients to potentially unnecessary anticoagulation. Incorporation of D-dimer testing and clinical pretest probability assessment in the diagnostic algorithm is beneficial because it allows excluding DVT without the need for diagnostic imaging in about a third of patients.

Outcomes for Inpatients with Normal Findings on Whole-leg Ultrasonography: A Prospective Study

Background Ultrasonography is used routinely for ruling out suspected deep vein thrombosis in hospitalized patients, although most evidence supporting this strategy is derived from the outpatient setting. This study aimed to estimate the rate of venous thromboembolism when anticoagulant therapy was withheld from inpatients with normal findings on whole-leg ultrasonography. Methods As part of a prospective multicenter cohort study, 1926 medical and surgical inpatients with clinically suspected deep vein thrombosis during their stay were enrolled. Ultrasonography of all lower extremities was performed by board-certified vascular medicine physicians using a standardized examination protocol. Deep vein thrombosis was detected in 395 patients (20%). Anticoagulant therapy was withheld from patients with normal findings, and 523 of them were randomly selected for follow-up. The main outcome measure was 3-month incidence of symptomatic venous thromboembolism. Results A total of 513 patients with normal findings on ultrasonography successfully completed 3 months of follow-up, 9 patients were lost to follow-up, and 1 patient received anticoagulant therapy during follow-up. Three patients (0.6%) experienced nonfatal symptomatic venous thromboembolic events confirmed by objective testing. The cause of death was judged to be possibly related to pulmonary embolism for 7 other patients (1.3%). Overall, the 3-month rate of venous thromboembolism was 1.9% (10/513; 95% confidence interval, 0.9-3.5). Conclusion Although withholding anticoagulant therapy after a single negative whole-leg ultrasonography seems to be safe, up to 3.5% of inpatients may nevertheless develop venous thromboembolism in the next 3 months. Further study is warranted to determine whether this strategy is equivalent to serial compression ultrasonography limited to proximal veins.

Evolution of untreated calf deep-vein thrombosis in high risk symptomatic outpatients: The blind, prospective CALTHRO study

The natural history of calf deep-vein thrombosis (DVT) is still uncertain and it is debated whether it warrants to be diagnosed and treated. We aimed to investigate the complication rate of untreated isolated calf DVT (ICDVT). Symptomatic outpatients were prospectively managed with serial compression ultrasonography (SCUS). Those without proximal DVT and with likely pre-test clinical probability (PCP) or altered D-dimer received immediate subsequent complete examination of calf deep veins (CCUS) by a different operator. The result of CCUS was kept blind both to the managing doctor and the patient and disclosed after three months. Primary outcome was the rate of venous thromboembolism at three months. We examined 431 subjects (196 males; median age 68.0 years) in whom five outcomes were recorded (1.2%; 95% confidence intervals [CI]: 0.4-2.7). If CCUS results had been available, outcomes would have been recorded in 3/424 patients (0.7%; 95% CI: 0.2-2.1) with two events in subjects negative at both serial and complete CUS. ICDVT was diagnosed in 65 subjects (15.3%; 95% CI: 12-19); of whom 59 remained uneventful (one was lost to follow-up). A significant higher rate of outcomes was recorded in subjects with than without ICDVT (5/64; 7.8%; 95% CI: 3-17 vs. 3/351; 0.8%; 95% CI: 0-2; p=0.003). However, after excluding two events picked at serial CUS in subjects with ICDVT, the difference became barely significant (3/64; 4.7%; 95% CI: 1-13; p=0.049). Thrombotic evolution of untreated ICDVT in high-risk subjects may be relevant. Larger studies are needed to address this issue.

Safety of Excluding Suspected Deep Vein Thrombosis with a Single Whole-Leg Compression Ultrasound: Systematic Review and Meta-Analysis.

Abstract 243 Background:In patients with suspected lower extremity deep vein thrombosis (DVT), compression ultrasonography (CUS) is typically used as the initial test to confirm or exclude DVT. Patients with a negative CUS and either a moderate-to-high probability and/or a positive D-dimer usually require repeat CUS testing after 5–7 days to exclude proximal propagation of distal DVT, reducing diagnostic efficiency. Whole-leg compression ultrasound may safely exclude proximal and distal DVT in a single evaluation. Purpose:To assess the safety of withholding anticoagulation in patients presenting with suspected lower extremity DVT following a single negative whole-leg CUS. Methods:MEDLINE, EMBASE, CINAHL, LILACS, Cochrane, Health Technology Assessments databases were searched from January 1970 to April 2009 without language restrictions. This search was supplemented by reviewing Google, Google Scholar, clinicaltrials.gov, meeting abstracts, conference proceedings, reference lists, and by contacting content experts. Study Selection and Data Extraction:Randomized controlled trials and prospective cohort studies of patients with suspected DVT with a negative whole-leg CUS, not treated with anticoagulation, and followed at least 90 days for occurrence of venous thromboembolism (VTE). Studies required objective confirmation of VTE events during follow-up. Two authors independently reviewed articles and extracted data. Results:Six studies were included totaling 4,229 patients with negative whole-leg CUS exams and not receiving anticoagulation. VTE or suspected VTE-related death occurred within the follow-up period in 24 (0.6%) patients. Of these 24 events, 9 (37.5%) were distal DVT, 7 (29.2%) were proximal DVT, 6 (25.0%) were non-fatal pulmonary embolism, and 2 (8.3%) were deaths, possibly related to VTE. Combined VTE event rate at 3 months was 0.46% (95% CI 0.22, 0.70). Limitations:Pretest probability assessment was not available for all analyzed patients. Conclusions:Withholding anticoagulation in patients with suspected DVT based on a single whole-leg CUS is associated with a low risk of VTE (0.46%) during 3 months of follow-up. This strategy represents a safe and efficient alternative to serial CUS testing in patients with suspected DVT. Disclosures:No relevant conflicts of interest to declare.

A Negative D-dimer Excludes Recurrent Deep Vein Thrombosis: Results of a Multicentre Management Study.

The high frequency of residual radiologic abnormalities after initial deep vein thrombosis (DVT) makes management of patients with suspected recurrence difficult. D-dimer (DD) and serial compression ultrasonography (CUS) of the proximal veins have a high sensitivity and negative predictive value (NPV) in suspected first DVT. We hypothesized that it would be safe to withhold anticoagulation in patients with suspected recurrence who had a negative sensitive DD or negative serial CUS when DD testing was positive. In a multicentre prospective cohort study, patients underwent DD testing with an immunoturbidometric assay (MDA DD). If the DD was negative (<0.5 ug fibrinogen equivalent units [FEU]/mL), patients had no further testing. If the DD was positive, CUS was performed and, if normal, repeated after 1–3 and 7–10 days. Patients with a positive DD and abnormal CUS at presentation were managed as per their treating physician. Patients were followed for 3 months to detect venous thromboembolism (VTE) and suspected VTE were adjudicated centrally. Of the 504 patients enrolled in this study, 14 were subsequently deemed ineligible and 2 patients were lost to follow-up. The overall prevalence of confirmed recurrent DVT at presentation or during follow-up was 17%. 230 patients had a negative DD at presentation and, of the 227 evaluable patients, 4 had definite confirmed VTE (NPV of DD = 98%; 95% Confidence Interval [CI], 96–99%). Of the 135 patients with a positive DD and normal initial CUS, serial CUS was negative in 129 cases. Of these patients, 3 had definite VTE during follow-up (NPV of serial CUS in patients with positive DD = 98%; 95% CI, 93–99%). These results suggest that a negative MDA DD result excludes clinically significant recurrent DVT and that anticoagulants can also be safely withheld in patients with negative serial CUS, even if their DD is positive. This simple diagnostic approach can be used to safely manage approximately 70% of patients with suspected recurrent DVT.

Screening for Deep Vein Thrombosis and Pulmonary Embolism in Outpatients with Suspected DVT or PE by the Sequential Use of Clinical Score: A Sensitive Quantitative D-Dimer Test and Noninvasive Diagnostic Tools

The requirement for a safe diagnostic strategy should be based on an overall posttest incidence of venous thromboembolism (VTE) of less than 1% during 3-month follow-up. The negative predictive value (NPV) during 3 months of follow-up is 98.1 to 99% after a normal venogram, 97 to 98% after a normal compression ultrasonography (CUS), and > 99% after serial CUS testing. Serial CUS testing is safe but 100 CUS must be repeated to find one or two CUS positive for deep vein thrombosis (DVT), which is not cost-effective and indicates the need to improve the diagnostic workup of DVT by the use of clinical score assessment and D-dimer testing. The NPV varies from 97.6 to 99.4% for low clinical score followed by a negative SimpiRED test, indicating the need for a first CUS. The NPV is 98.4 to 99.3% for a normal rapid enzyme-linked immunosorbent assay (ELISA) VIDAS D-dimer test result (< 500 ng/mL) irrespective of clinical score. The NPV is more than 99% for a negative CUS followed by either a negative SimpiRED test or an ELISA VIDAS test result of < 1000 ng/mL without the need to repeat a second CUS within 1 week. The sequential use of a sensitive, rapid ELISA D-dimer and clinical score assessment will safely reduce the need for CUS testing by 40 to 60%. Large prospective outcome studies demonstrate that with one negative examination with complete duplex color ultrasonography (CCUS) of the proximal and distal veins of the affected leg with suspected DVT, it is safe to withhold anticoagulant treatment, with a negative predictive value of 99.5%. This may indicates that CCUS is equal to serial CUS or the combined use of clinical score, D-dimer testing, and CUS. Pulmonary angiography is the gold standard for segmental pulmonary embolism (PE) but not for subsegmental PE. A normal perfusion lung scan and a normal rapid ELISA VIDAS D-dimer test safely excludes PE. Helical spiral computed tomography (CT) detects all clinically relevant PE and a large number of alternative diagnoses in symptomatic patients with suspected PE and can replace both the ventilation perfusion scan and pulmonary angiography to safely rule in PE and to rule out PE with an NPV of > 99%. The combination of clinical assessment, a rapid ELISA VIDAS D-dimer, followed by CUS will reduce the need for helical spiral CT by 40 to 50%.

A diagnostic strategy involving a quantitative latex d-dimer assay reliably excludes deep venous thrombosis

Bates SM, Kearon C, Crowther M, et al(McMaster University, Hamilton, Ontario, Canada)BackgroundClinical diagnosis of deep venous thrombosis (DVT) can be inaccurate. Thus, objective testing is usually considered mandatory in patients with suspected DVT. Whether a negative finding on a quantitative latex d-dimer assay precludes further testing in patients with a low or moderate pretest probability of DVT was determined.MethodsFive hundred fifty-six consecutive outpatients with suspected first DVT seen at 3 Canadian hospitals were enrolled in the prospective study. Before d-dimer testing, patients were classified as having low, moderate, or high pretest probability of DVT. Those with low or moderate pretest probability and a negative d-dimer result did not receive further testing or anticoagulant treatment. All other patients underwent serial compression ultrasonography. Patients who did not receive a diagnosis of DVT were followed up for symptomatic venous thromboembolism.FindingsFifty-one percent of the patients had low or moderate pretest probability and a negative d-dimer test. One of these patients subsequently received a diagnosis of DVT. Overall, the negative likelihood ratio of the d-dimer test was 0.03.ConclusionsA negative finding on a quantitative latex d-dimer assay precludes additional evaluation in patients with a low or moderate pretest probability of DVT. Patients with an abnormal finding on d-dimer testing can be managed safely with serial compression ultrasonography.CommentWith the use of a latex immunoassay technique, the authors of this prospective study confirm the usefulness of d-dimer assays to exclude DVT. The latex technique appears to have a higher sensitivity than the whole-blood agglutination assay, a key parameter of a test used to exclude disease. Although bedside risk stratification is the critical starting point for determination of the likelihood of this entity, there may be some situations where the added reassurance of a negative d-dimer result may be helpful. The authors offer a model for bedside risk assessment adapted from Wells et al.1Wells PS Hirsh J Anderson DR et al.Value of assessment of pretest probability of deep-vein thrombosis in clinical management.Lancet. 1997; 350: 1795-1798Abstract Full Text Full Text PDF PubMed Scopus (977) Google Scholar Bates SM, Kearon C, Crowther M, et al (McMaster University, Hamilton, Ontario, Canada) BackgroundClinical diagnosis of deep venous thrombosis (DVT) can be inaccurate. Thus, objective testing is usually considered mandatory in patients with suspected DVT. Whether a negative finding on a quantitative latex d-dimer assay precludes further testing in patients with a low or moderate pretest probability of DVT was determined. Clinical diagnosis of deep venous thrombosis (DVT) can be inaccurate. Thus, objective testing is usually considered mandatory in patients with suspected DVT. Whether a negative finding on a quantitative latex d-dimer assay precludes further testing in patients with a low or moderate pretest probability of DVT was determined. MethodsFive hundred fifty-six consecutive outpatients with suspected first DVT seen at 3 Canadian hospitals were enrolled in the prospective study. Before d-dimer testing, patients were classified as having low, moderate, or high pretest probability of DVT. Those with low or moderate pretest probability and a negative d-dimer result did not receive further testing or anticoagulant treatment. All other patients underwent serial compression ultrasonography. Patients who did not receive a diagnosis of DVT were followed up for symptomatic venous thromboembolism. Five hundred fifty-six consecutive outpatients with suspected first DVT seen at 3 Canadian hospitals were enrolled in the prospective study. Before d-dimer testing, patients were classified as having low, moderate, or high pretest probability of DVT. Those with low or moderate pretest probability and a negative d-dimer result did not receive further testing or anticoagulant treatment. All other patients underwent serial compression ultrasonography. Patients who did not receive a diagnosis of DVT were followed up for symptomatic venous thromboembolism. FindingsFifty-one percent of the patients had low or moderate pretest probability and a negative d-dimer test. One of these patients subsequently received a diagnosis of DVT. Overall, the negative likelihood ratio of the d-dimer test was 0.03. Fifty-one percent of the patients had low or moderate pretest probability and a negative d-dimer test. One of these patients subsequently received a diagnosis of DVT. Overall, the negative likelihood ratio of the d-dimer test was 0.03. ConclusionsA negative finding on a quantitative latex d-dimer assay precludes additional evaluation in patients with a low or moderate pretest probability of DVT. Patients with an abnormal finding on d-dimer testing can be managed safely with serial compression ultrasonography. A negative finding on a quantitative latex d-dimer assay precludes additional evaluation in patients with a low or moderate pretest probability of DVT. Patients with an abnormal finding on d-dimer testing can be managed safely with serial compression ultrasonography.

A diagnostic strategy involving a quantitative latex D-dimer assay reliably excludes deep venous thrombosis.

Because clinical diagnosis is inaccurate, objective testing is usually considered necessary when patients present with suspected deep venous thrombosis (DVT). To determine whether a negative result on a quantitative latex D dimer assay eliminates the need for further investigation in patients with a low or moderate pretest probability of DVT. Prospective cohort study. Three tertiary care hospitals in Canada. 556 consecutive outpatients with suspected first DVT. Patients were categorized as having a low, moderate, or high pretest probability of DVT and then underwent D-dimer testing. Patients with low or moderate pretest probability and a negative D-dimer result had no further diagnostic testing and received no anticoagulant therapy. Serial compression ultrasonography was performed in all other patients. Patients who did not receive a diagnosis of DVT were followed for symptomatic venous thromboembolism. Objectively confirmed symptomatic venous thromboembolic events during 3 months of follow-up. 283 patients (51%) had low or moderate pretest probability and a negative D-dimer result. One of these patients had DVT during follow-up (negative likelihood ratio, 0.05 [CI, 0.01 to 0.23]). The negative likelihood ratio of the d -dimer test in all patients was 0.03 (CI, 0.01 to 0.16). A negative result on a quantitative latex d -dimer assay safely eliminates the need for further testing in patients with low or moderate pretest probability of DVT.

Single-detector helical computed tomography as the primary diagnostic test in suspected pulmonary embolism: a multicenter clinical management study of 510 patients.

Helical computed tomography (CT) is a readily available tool for diagnosing pulmonary embolism (PE); however, its role in the management of patients with clinically suspected PE has not been fully established. To determine the effectiveness and safety of using helical CT of the pulmonary arteries as the primary diagnostic test in patients with suspected PE. Multicenter, prospective clinical outcome study. Two academic hospitals and one large teaching hospital in the Netherlands. 510 consecutive inpatients and outpatients with clinically suspected PE followed for 3 months. Patients underwent helical CT of the pulmonary arteries within 24 hours after presenting with signs and symptoms of PE. If CT results were normal or inconclusive, compression ultrasonography was performed on the same day as CT and repeated on days 4 and 7 if findings on the first compression ultrasonography were normal. When CT or compression ultrasonography results were positive for thromboembolism, anticoagulation was started. Anticoagulation was not started when results of CT were negative for PE or indicated an alternative diagnosis that explained the clinical signs and symptoms, or when results on serial compression ultrasonography were normal. Patients received instructions to report any symptoms or signs of PE or deep venous thrombosis (DVT) during the 3-month follow-up period. The authors performed compression ultrasonography or phlebography for suspected DVT and pulmonary angiography for suspected PE. Computed tomography identified PE in 124 of 510 patients (24.3%) and an alternative diagnosis in 130 patients (25.5%); CT scans were normal in 248 patients (48.6%). The CT scan could not be interpreted in 8 patients (1.6%) and was not obtained in 2. Compression ultrasonography revealed DVT in 2 patients at the first examination; findings on repeated compression ultrasonography at days 4 and 7 were normal. Mortality in the patients with normal helical CT scans was 4.1% (10 of 246 patients). No patients in this group died of fatal PE, 1 patient developed nonfatal PE, and venous thromboembolism occurred in 0.4% of these patients (95% CI, 0% to 2.2%). In the patients with alternative diagnoses, 1 patient had DVT on objective testing during follow-up. Mortality in this group was 21.5% (28 of 130 patients); in 1 of these patients, PE could not be confidently ruled out as a contributing cause of death. Venous thromboembolism occurred in 1.5% of these patients (CI, 0.2% to 5.6%). In patients with suspected PE, helical CT can be used safely as the primary diagnostic test to rule out PE. Serial compression ultrasonography has limited additional value.

Pulmonary embolism diagnosis in hospitalized and intensive care unit patients.

The diagnosis of acute pulmonary embolism (PE) remains difficult, and diagnostic strategies must consider the unique challenges of hospitalized and critically ill patients. Diagnostic algorithms that are effective and safe for outpatients may not be effective and safe for inpatients or patients in intensive care units. For example, serial compression ultrasonography (US) of the lower extremities may allow physicians to avoid pulmonary angiography for stable inpatients or outpatients, but this strategy is not validated for patients who require intensive care for serious underlying cardiopulmonary disease. Helical computed tomography (CT) is particularly suited for the evaluation of suspected PE for inpatients with serious cardiopulmonary disease. However, the safety of withholding treatment when a helical CT pulmonary angiogram is negative remains to be demonstrated. Lung perfusion and ventilation scans combined with an assessment of pretest probability remain important objective tests for the evaluation of many hospitalized patients.

Long-term clinical course of proximal deep venous thrombosis and detection of recurrent thrombosis.

Symptomatic proximal deep vein thrombosis of lower extremities carries a high risk for recurrent venous thromboembolism that persists for many years. This risk is dependent on readily identifiable risk factors, being low after a trauma or a surgical intervention and higher in all the other patient categories. Moreover, postthrombotic sequelae will develop in one of every three patients, this risk being strongly related to the development of ipsilateral thrombosis. Although the optimal duration of anticoagulation in patients who experience an episode of proximal vein thrombosis is unknown, it seems reasonable to administer a short-term course of coumarin drugs to patients with thrombosis associated with transient risk factors, whereas a longer course (6 to 12 months) should be considered in patients with idiopathic thrombosis and in those with permanent risk factors. Indefinite anticoagulant therapy is a clinical judgement in the individual patient. The management of patients who develop clinical manifestations suggestive of recurrent ipsilateral venous thrombosis still represents a challenge for clinicians. Recent data suggest that these patients can be safely managed with the use of serial compression ultrasonography.

Diagnostic Accuracy of Compression Ultrasonography for the Detection of Asymptomatic Deep Venous Thrombosis in Medical Patients

We assessed the accuracy of venous compression ultrasonography (CUS) for the detection of asymptomatic deep vein thrombosis in 122 consecutive patients, with a mean age of 69 years, who were hospitalised in an internal medicine unit. All included patients had CUS within 48 h of admission. Twelve out of 17 patients with a positive CUS underwent phlebography, as the others withdrew their consent, whereas the remaining 105 patients with a negative serial CUS testing were clinically followed-up at 3 months. We found that CUS had a sensitivity and a specificity of respectively 1 (95% CI, 0.73 to 1) and 1 (95% CI, 0.96 to 1) for the detection of asymptomatic deep vein thrombosis. Kappa-coefficients for intra-observer and inter-observer agreements were respectively 0.88 and 0.56. We concluded that venous compression ultrasonography, performed as described, fulfils requirements of a screening test that could be available for prophylactic clinical trials or epidemiological researches.

Exclusion and diagnosis of pulmonary embolism by a rapid ELISA D-dimer test and noninvasive imaging techniques within the context of a clinical model.

A negative rapid ELISA D-dimer test alone in out-patients with a low to moderate clinical probability (CP) on pulmonary embolism (PE) is predicted to safely exclude pulmonary embolism. The combination of a negative rapid ELISA D-dimer test and a low to moderate CP on PE followed by compression ultrasonography (CUS) for the detection of deep vein thrombosis (DVT) is safe and cost-effective as it reduces the need for noninvasive imaging techniques to about 50% to 60% of outpatients with suspected PE. A high probability ventilation-perfusion (VP) scan or a positive spiral CT consistent with PE and the detection of DVT by CUS are currently considered to be clear indications for anticoagulant treatment. Subsequent pulmonary angiography (PA) is the gold standard diagnostic strategy to exclude or diagnose PE in suspected outpatients with a negative CUS, a positive rapid ELISA D-dimer test, and a nondiagnostic VP scan or negative spiral CT to prevent overtreatment with anticoagulants. However, the willingness of clinicians and the availability of resources to perform PA is restricted, a fact that has provided an impetus for clinical investigators to search for alternative noninvasive strategies to exclude or detect venous thromboembolism (VTE). Serial CUS testing for the detection of DVT in patients with a low to moderate CP on PE and a nondiagnostic VP scan or negative spiral CT is predicted to be safe and will reduce the need for PA to less than 10% or even less than 5%. This noninvasive serial CUS strategy restricts the need for invasive PA to a minor group of patients (< 5%) with the combination of a low CP on PE and high probability VP scan or the combination of a nondiagnostic VP scan or negative spiral CT and a high CP on PE. Prospective evaluations are warranted to implement and to validate the advantages and the disadvantages of the various combinations of noninvasive strategies and to compare serial CUS testing versus PA in randomized clinical management studies of outpatients with suspected pulmonary embolism.

Assessment of deep vein thrombosis or pulmonary embolism by the combined use of clinical model and noninvasive diagnostic tests.

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are relatively common diseases and are amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with use of the noninvasive imaging tests, but limitations exist. The standard first choice of investigation in patients with suspected DVT is compression ultrasonography (CUS). As with all tests, there is a potential for false-positive and false-negative results. The latter are especially an issue for calf vein thrombi, and this in part has led to the concept of serial CUS testing of the proximal venous system and not imaging of the calf. The premise of the repeat (serial) CUS test is that only thrombi that extend to the proximal system are clinically relevant, and these thrombi will be detected during subsequent testing. However, despite the safety of the serial CUS testing concept, it is inconvenient and expensive. The standard first choice of investigation in patients with suspected PE, the ventilation-perfusion (V/Q) lung scan is nondiagnostic in most cases. In the past few years, the diagnostic process has improved because of the validation of clinical models that accurately categorize patients as having low (5%), moderate (20% to 30%), or high probability (>60%) for venous thromboembolic disease. Among the improvements this provides is the elimination of serial CUS testing if the ultrasound results are normal and the clinical probability is low in patients with suspected DVT. In patients with suspected PE in whom further testing is necessary, determination of clinical probability allows selection of invasive (angiography) or noninvasive testing (serial ultrasound) in patients with non-high-probability V/Q scans. The fibrin degradation product D-dimer has had a high negative predictive value; negative results with enzyme-linked immunosorbent assay (ELISA) tests effectively rule out DVT or PE. In addition, a negative result with less-sentive D-dimer testing and a low clinical probability excludes DVT or PE.

Evaluation of a New Rapid Quantitative D-dimer Assay in Patients with Clinically Suspected Deep Vein Thrombosis

The sensitivity and specificity for deep vein thrombosis (DVT) of a new rapid, quantitative and precise (total imprecision < 10%) D-dimer assay suitable for individual measurements (VIDAS D-DIMER, bio-Mérieux, France) were evaluated in a consecutive series of 103 in- and out-patients submitted to serial compression ultrasonography (C-US) for the clinical suspicion of DVT (n = 66) or of DVT recurrence (n = 37) and symptoms lasting from 1 to 15 days. DVT was found in 22 patients at baseline testing and no patient with an initially negative C-US developed vein incompressibility at follow up. The time elapsed from the onset of symptoms was negatively associated with D-dimer levels both in patients with and in those without DVT. In the entire series of patients, the sensitivity of a positive D-dimer test ( > or = 1.0 microgram/ml) for the presence of DVT was 96% (21/22 patients, 95% confidence interval 75-100%) with a specificity of 75% (64-84%), a negative predictive value of 98% (90-100%), a positive predictive value of 51% (35-67%), and an overall accuracy of 80% (70-87%). A normal D-dimer value (0.22 microgram/ml) was observed in one patient with DVT and symptoms lasting from 15 days. The approach of withholding C-US testing in patients with symptoms lasting from less than 11 days and D-dimer levels below the cut-off value was compared to serial C-US testing alone in a cost-effectiveness analysis subdividing the 66 patients with a first episode according to their clinical pretest probability of DVT. Thrombosis was detected in 6.7% of the patients in the low probability group (n = 15), 16.7% of the patients in the moderate probability group (n = 24), 51.9% of the patients in the high probability group (n = 27) and 8.1% of patients with suspected DVT recurrence. Calculated cost-savings for each DVT diagnosed ranged from 5% in the high pretest probability group to 55% in the low pretest probability group and to 77% in patients with suspected DVT recurrence. The safety of avoiding C-US testing in symptomatic patients with a negative D-dimer test should be evaluated in clinical management studies.