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1: Arch Intern Med  2002 Apr 8;162(7):747-56

Plasma D-dimers in the diagnosis of venous thromboembolism.

Kelly J, Rudd A, Lewis RR, Hunt BJ.

SpR in Elderly Care/GIM, Elderly Care Dept, c/o Alexandra Ward, North Wing, Ninth Floor, St Thomas' Hospital, Lambeth Palace Road, Lambeth, London SE1 7EH, England. jameskelly@northbrookfm.fsnet.co.uk

Clinical suspicion for venous thromboembolism (VTE) mandates objective testing to confirm or exclude the diagnosis. However, current imaging modalities are imperfect because of a small but important risk of complications with invasive techniques or limited sensitivity with noninvasive ones. A diagnostic tool for VTE is needed that is noninvasive and highly accurate, allowing immediate treatment decisions to be made in most cases. Plasma D-dimers (D-ds), specific cross-linked fibrin derivatives, partially fulfill these criteria in that they are sensitive markers for thrombosis but lack specificity. They therefore cannot be used to make a positive diagnosis of VTE; however, they generally have high negative predictive value and are useful as an exclusionary test, a potentially important role given that VTE is eventually ruled out in most patients investigated. Clinical management studies are clarifying the role of D-ds in the diagnostic paradigm of VTE: negative ultrasound and D-d findings obviate the need for serial imaging in suspected deep vein thrombosis, and anticoagulant therapy can be safely withheld in patients with non-high clinical suspicion for pulmonary embolism and non-high probability ventilation perfusion scan if D-d test results are negative. More recently, the combination of a negative SimpliRED (AGEN Biomedical Ltd, Brisbane, Australia) D-d result and low clinical suspicion derived using a formal scoring system has been shown to exclude deep vein thrombosis and pulmonary embolism and to obviate the need for imaging. Several different D-d assays are now available, and clinicians should be aware of the performance characteristics of the test used before incorporation into diagnostic algorithms as these will differ between assays, and the results of clinical management studies cannot necessarily be safely extrapolated to assays other than those specifically evaluated. If alternative assays are to be substituted, these should consistently have been shown to possess equivalent or greater sensitivity.

Publication Types:

Review

2: Postgrad Med  2002 Mar;111(3):27-8, 33-4, 39-40 passim [Texto completo]

Early intervention in massive pulmonary embolism. A guide to diagnosis and triage for the critical first hour.

Gossage JR.

Department of Medicine, Medical College of Georgia School of Medicine, Section of Pulmonary and Critical Care Medicine, BBR-5513, 1120 15th St, Augusta, GA 30912-3135, USA. jgossage@mail.mcg.edu

The diagnosis of massive pulmonary embolism should be considered expeditiously in all patients with unexplained hypotension, syncope, cardiac arrest, or hypoxemic respiratory failure. The presence of right ventricular overload on physical examination or electrocardiogram is an especially important clue. Depending on local expertise and the patient's stability, V/Q scanning, CT angiography, echocardiography, and right heart catheterization can be useful in establishing a diagnosis of pulmonary embolism. Supportive treatment includes oxygen, vasoactive medicines, and sometimes fluids. Although heparin is important in nearly all patients, 70% to 80% of patients also require an IVC filter, thrombolysis, or embolectomy.

Publication Types:

Review

3: Clin Radiol  2001 Oct;56(10):838-42

Clinical validity of a normal pulmonary angiogram in patients with suspected pulmonary embolism--a critical review.

van Beek EJ, Brouwerst EM, Song B, Stein PD, Oudkerk M.

Section of Academic Radiology, Royal Hallamshire Hospital, Sheffield, UK. e.vanbeek@sheffield.ac.uk

AIM: To determine the validity of a normal pulmonary angiogram in the exclusion of pulmonary embolism (PE), based on the safety of withholding anticoagulant therapy in patients with a normal pulmonary angiogram. MATERIALS AND METHODS: A review of English reports published between 1965 and April 1999 was carried out. Eligible articles described prospective studies in patients with suspected PE and a normal pulmonary angiogram, who remained untreated and were followed-up for a minimum of 3 months. Articles were evaluated by two authors, using pre-defined criteria for strength of design. End points consisted of fatal and non-fatal recurrent thromboembolic events. A sensitivity analysis was performed, by removing one study at a time from the overall results and by comparing pre- and post-1990 publications. RESULTS: Among 1050 patients in eight articles included in the analysis, recurrent thromboembolic events were described in 18 patients (1.7% 95% CI: 1.0-2.7%). These were fatal in three patients (0.3% 95% CI: 0.02-0.7%). The recurrence rate of PE decreased from 2.9% (95% CI: 1.4-6.8%) before 1990 to 1.1% (95% CI: 0.5-2.2%) after 1990. CONCLUSION: It would appear that the ability to exclude PE by angiography has improved over the years, as indicated by recurrence rate of PE. The low recurrence rate of PE supports the validity of a normal pulmonary angiogram for the exclusion of PE.

Publication Types:

Review

4: Chest  2002 Mar;121(3):877-905

Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism.

Wood KE.

Department of Medicine, University of Wisconsin Hospitals & Clinics, Madison, WI 53792, USA. kew@medicine.wisc.edu

Major pulmonary embolism (PE) results whenever the combination of embolism size and underlying cardiopulmonary status interact to produce hemodynamic instability. Physical findings and standard data crudely estimate the severity of the embolic event in patients without prior cardiopulmonary disease (CPD) but are unreliable indicators in patients with prior CPD. In either case, the presence of shock defines a threefold to sevenfold increase in mortality, with a majority of deaths occurring within 1 h of presentation. A rapid integration of historical information and physical findings with readily available laboratory data and a structured physiologic approach to diagnosis and resuscitation are necessary for optimal therapeutics in this "golden hour." Echocardiography is ideal because it is transportable, and is capable of differentiating shock states and recognizing the characteristic features of PE. Spiral CT scanning is evolving to replace angiography as a confirmatory study in this population. Thrombolytic therapy is acknowledged as the treatment of choice, with embolectomy reserved for those in whom thrombolysis is contraindicated.

Publication Types:

Review

5: Mayo Clin Proc  2002 Feb;77(2):130-8

Outcomes after withholding anticoagulation from patients with suspected acute pulmonary embolism and negative computed tomographic findings: a cohort study.

Swensen SJ, Sheedy PF 2nd, Ryu JH, Pickett DD, Schleck CD, Ilstrup DM, Heit JA.

Department of Radiology, Mayo Clinic, Rochester, Minn 55905, USA.

OBJECTIVE: To determine the outcome of withholding anticoagulation from patients with suspected acute pulmonary embolism in whom computed tomographic (CT) findings are interpreted as negative for pulmonary embolism. PATIENTS AND METHODS: This retrospective cohort study included 1512 consecutive patients referred from August 7, 1997, to November 30, 1998, for CT because of clinically suspected acute pulmonary embolism. All patients were examined by electron beam CT, and scanning was performed in a cephalocaudad direction from the top of the aortic arch to the base of the heart with 3-mm collimation, 2-mm table incrementation, and an exposure time of 0.2 second (130 peak kV, 620 mA, and standard reconstruction algorithm). Contrast material was infused at a rate of 3 to 4 mL/s through an antecubital vein with an automated injector. Findings on CT were interpreted as either positive or negative. The main outcome measures were deep venous thrombosis, pulmonary embolism, and vital status within 3 months after the CT scan and the cause of death based on medical record review, mailed patient questionnaires, and telephone interviews. RESULTS: In 1010 patients (67%) CT scans were interpreted as negative for acute pulmonary embolism. Seventeen patients were excluded because they received anticoagulation. Of the remaining 993 patients, deep venous thrombosis or pulmonary embolism developed in 8; 118 patients died, 3 of pulmonary embolism. Nineteen patients were known to be alive, but additional clinical information could not be obtained. The 3-month cumulative incidence of overall deep venous thrombosis or pulmonary embolism was 0.5% (95% confidence interval, 0.1%-1.0%) and of fatal pulmonary embolism, 0.3% (95% confidence interval, 0.0%-0.7%). CONCLUSIONS: The incidence of (1) overall deep venous thrombosis or pulmonary embolism or (2) fatal pulmonary embolism among patients with suspected acute pulmonary embolism, negative CT results, and no other evidence of venous thromboembolism is low. Withholding anticoagulation in these patients appears to be safe.

6: Hosp Med  2001 Dec;62(12):757-64

Treating venous thromboembolism: enoxaparin.

Perry DJ.

Haemophilia Centre and Haemostasis Unit, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF.

This article reviews the developments that have occurred in the treatment of venous thromboembolism during the last decade, with emphasis on the establishment of low molecular weight heparin as a therapeutic agent of proven efficacy and examines the evidence that supports the movement from inpatient to outpatient hospital management of venous thromboembolism.

Publication Types:

Review

7: N Engl J Med  2001 Nov 15;345(20):1465-72

Chronic thromboembolic pulmonary hypertension.

Fedullo PF, Auger WR, Kerr KM, Rubin LJ.

Department of Medicine, University of California, San Diego, Medical Center, La Jolla 92037-1300, USA.

Publication Types:

Review

8: Anesthesiol Clin North America  2001 Dec;19(4):673-703

Monitoring for suspected pulmonary embolism.

Capan LM, Miller SM.

Department of Anesthesiology, New York University School of Medicine, Bellevue Hospital Center, New York, New York, USA. lcapan@anes.med.nyu.edu

It is fortunate that serious embolic phenomena are uncommon because, with the exception of neurosurgery in the sitting position and cardiac surgery, thoracic echocardiography and the precordial Doppler device, the most sensitive indicators of embolism, are seldom used. Vigilance is required of the anesthesiologist to recognize the rapid fall in end-tidal PCO2, the usual first indicator of a clinically significant PE. Any sudden deterioration in the patient's vital signs should include embolism in the differential diagnosis, particularly during procedures that carry a high risk of the complication.

Publication Types:

Review

9: Emerg Med Clin North Am  2001 Nov;19(4):995-1011

Emergency department management of pulmonary embolism.

Edlow JA.

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. jedlow@caregroup.harvard.edu

There are several points that bear repetition. First, consider the diagnosis of PE in all patients presenting with chest pain, dyspnea, syncope, oxygen desaturation, or unexplained hypotension. Evaluate these patients in a rational manner. At any individual hospital, develop algorithms with consultants so that when one is faced with a patient with a PE, the flow of both diagnostics and therapeutics flows smoothly and rapidly. Consider the concept of risk stratification, and remember that not all patients with PE are created equal. In particular, be on the same page with all consultants regarding the use of right heart echocardiography, both for its potential diagnostic capabilities and for its ability to identify patients who could be at greater risk for bad outcomes.

Publication Types:

Review

10: Emerg Med Clin North Am  2001 Nov;19(4):975-94

Newer diagnostic modalities for pulmonary embolism. Pulmonary angiography using CT and MR imaging compared with conventional angiography.

Bloomgarden DC, Rosen MP.

Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

CTPA is a highly sensitive and excellent primary method for evaluating patients with symptoms of PE. Ongoing studies will demonstrate the good clinical outcome of patients with negative CTPA results. The ability to visualize the lung parenchyma in addition to the pulmonary vasculature, and the smaller number of nondiagnostic scans, make CT more cost effective than V/Q scans, and CT therefore should be used as a first-line evaluation. MR imaging is a continually developing modality with more imaging options that could make it an invaluable or adjunctive test in the near future.

Publication Types:

Review

11: Emerg Med Clin North Am  2001 Nov;19(4):957-73

Ventilation/perfusion scintigraphy.

Kumar AM, Parker JA.

Department of Emergency Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.

V/Q imaging is often very useful in evaluating patients in whom a PE is suspected. A normal scan result can be used to exclude embolism and a high likelihood ratio scan can be used to make the diagnosis of PE. Most patients with PE do not have high likelihood ratio scans; therefore, it is important to pursue this diagnosis in patients with intermediate likelihood ratio scans and in the appropriate clinical setting for patients with the low likelihood ratio scans. In patients with parenchymal chest x-ray abnormalities who are likely to fall into the intermediate category, it can be more appropriate to use CT angiography instead of V/Q scintigraphy. This strategy probably increases the fraction of scans with high diagnostic utility.

Publication Types:

Review

12: Emerg Med Clin North Am  2001 Nov;19(4):943-55

Nonspecific tests for pulmonary embolism.

Weiner SG, Burstein JL.

Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Many tests have been proposed as useful in the diagnostic evaluation of suspected PE, but nonspecific tests for PE can only add to the level of suspicion one has for the diagnosis. As Anderson indicates, "virtually all clinical and laboratory findings neither diagnose nor exclude the diagnosis of PE. They merely serve to heighten suspicion of the diagnosis and prompt the clinician to pursue additional diagnostic studies." D-dimer measurement is promising as a test to exclude PE in young healthy out-patients, and further study and improvements in technology, can clarify the usefulness of the different methods of performing this assay. For now, diagnostic algorithms for PE should continue to incorporate multiple tests and decision points, but the standard remains specialized imaging techniques.

Publication Types:

Review

13: Emerg Med Clin North Am  2001 Nov;19(4):925-42

Clinical manifestation of pulmonary embolism.

Lee LC, Shah K.

Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. lilly.lee@worldnet.att.net

Results of prospective studies have shown that physicians' estimate of clinical likelihoods of PE have predictive value. The ability of clinicians to assess the factors that determine the probability of disease based on clinical manifestations such as history and signs and symptoms at presentation, and to make bedside estimates of that probability, has not been systematically studied. Data suggest that that this would be a fruitful area of future investigation. Susec et al noted that there has been a total of three studies (including their own) which have examined the clinical features such as risk factors, signs, and symptoms associated with PE in ambulatory outpatients. Hence, the data collected thus far might not be generalizable to the ED patient population. As with other illnesses, the ED patients usually present later and more atypically. The prevalence of PE could be lower among this population compared with hospitalized patients, causing a lower positive predictive value, derivable from the clinical features and risk factors at presentation. Finally, the ED patient population is usually healthier and younger than the hospitalized patients, and it is well recognized that PE can be clinically silent in young patients and that 28% have no associated risk factors. Based on their finding, the authors argue that clinical pathways to risk stratify patients in an ambulatory setting could be less useful than anticipated. The validity of these findings needs further investigation, however.

Publication Types:

Review

14: Mayo Clin Proc  2001 Nov;76(11):1102-10

Incidence of venous thromboembolism in hospitalized patients vs community residents.

Heit JA, Melton LJ 3rd, Lohse CM, Petterson TM, Silverstein MD, Mohr DN, O'Fallon WM.

Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

OBJECTIVE: To estimate the incidence rates of deep venous thrombosis (DVT) and pulmonary embolism (PE) in hospitalized patients and to compare these with incidence rates in community residents. PATIENTS AND METHODS: We performed a retrospective review of the complete medical records from a population-based inception cohort of patients who resided in Olmsted County, Minnesota, and had an incident DVT or PE from 1980 through 1990. RESULTS: From 1980 through 1990, 911 Olmsted County residents experienced their first lifetime event of definite, probable, or possible venous thromboembolism. Of these residents, 253 had been hospitalized for some reason other than a diagnosis of DVT or PE (in-hospital cases), and 658 were not hospitalized at onset of venous thromboembolism (community residents). The average annual age- and sex-adjusted incidence of in-hospital venous thromboembolism was 960.5 (95% confidence interval, 795.1-1125.9) per 10,000 person-years and was more than 100 times greater than the incidence among community residents at 7.1 (95% confidence interval, 6.5-7.6) per 10,000 person-years. The incidence of venous thromboembolism rose markedly with increasing age for both groups, with PE accounting for most of the age-related increase among in-hospital cases. Incidence rates in the 2 groups changed little over time despite a reduction in the average length of hospital stay between 1980 and 1990. CONCLUSIONS: Venous thromboembolism is a major national health problem, especially among elderly hospitalized patients. This finding emphasizes the need for accurate identification of hospitalized patients at risk for venous thromboembolism and a better understanding of the mechanisms involved so that safe and effective prophylaxis can be implemented.

15: Crit Care Med  2001 Nov;29(11):2211-9

Thrombolysis during cardiopulmonary resuscitation in fulminant pulmonary embolism: a review.

Bailen MR, Cuadra JA, Aguayo De Hoyos E.

Intensive Care Unit, Critical Care and Emergencies Department, Hospital de Poniente, El Ejido, Almeria, Spain. MRB1604@teleline.es

OBJECTIVE: To review current knowledge on thrombolysis in patients with fulminant pulmonary embolism (FPE) who need cardiopulmonary resuscitation (CPR). DATA SOURCES: The bibliography for the study was compiled through a search of different databases between 1966 and 2000. References cited in the articles selected were also reviewed. STUDY SELECTION: The selection criteria included all reports published on thrombolysis, pulmonary embolism, and CPR, from case reports and case series to controlled studies. DATA SYNTHESIS: Very few studies evaluated thrombolysis in cases of FPE that required CPR and most of these were clinical case reports and case series with a low level of scientific evidence. There has been no clinical trial to address this issue. CONCLUSIONS: FPE can frequently produce cardiac arrest, which has an extremely high mortality despite application of the usual CPR measures. The administration of thrombolytic therapy during CPR could help to reduce the mortality, although it has classically been contraindicated. There are no published clinical trials or other high-grade studies that evaluated the efficacy and safety of this approach. From the few existing studies, it can be inferred that thrombolysis may be efficacious and safe for patients with FPE who need CPR. However, a clinical trial is required to provide evidence of value for sound clinical decision-making.

Publication Types:

Review

16: Curr Opin Pulm Med  2001 Sep;7(5):354-9

Prognosis in pulmonary embolism.

Douketis JD.

Department of Medicine, St. Joseph's Hospital, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada. jdouket@mcmaster.ca

Acute pulmonary embolism has a wide prognostic spectrum, ranging from sudden death within minutes of a thromboembolic episode to a benign treatable condition associated with a stable clinical course and no long-term sequelae. In patients who survive an initial thromboembolic episode and receive antithrombotic therapy, the clinical course can be complicated by recurrent nonfatal venous thromboembolism, fatal pulmonary embolism, the postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension. Identifying which patients are at increased risk of experiencing these sequelae is important in decision making relating to the aggressiveness of initial antithrombotic therapy, the duration of antithrombotic therapy, and the frequency of clinical surveillance. In addition, this information may be helpful to clinicians in discussing disease prognosis with patients. The objectives of this review are to provide reasonable estimates of the risks of recurrent nonfatal venous thromboembolism, fatal pulmonary embolism, the postthrombotic syndrome, and chronic thromboembolic pulmonary hypertension in patients with treated pulmonary embolism, and to identify risk factors for these sequelae.

Publication Types:

Review

17: Curr Opin Pulm Med  2001 Sep;7(5):349-53

New methods for estimating pretest probability in the diagnosis of pulmonary embolism.

Ghali WA, Cornuz J, Perrier A.

Department of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.

The clinical assessment of the probability of pulmonary embolism is a key step in proposed diagnostic strategies for pulmonary embolism, because the interpretation of noninvasive test results is conditional on the pretest probability derived from the presence or absence of clinical factors. The past year has brought important progress in the general area of clinical prediction of pulmonary embolism with the publication of two new simple clinical prediction rules. Each of the prediction rules includes a total of seven clinical variables that, when combined, allow for the categorization of patients into categories of low, intermediate, or high pretest probability of pulmonary embolism. Although these clinical prediction rules are perhaps only slightly better than the estimates of experienced clinicians, they provide an explicit method for estimating the probability of PE as an adjunct to diagnostic testing. Further validation work is now needed to assess how well these new prediction rules perform in settings other than the derivation sites.

Publication Types:

Review

18: BMJ  2001 Sep 15;323(7313):601-2 [Texto completo]

Seasonal variations in hospital admission for deep vein thrombosis and pulmonary embolism: analysis of discharge data.

Boulay F, Berthier F, Schoukroun G, Raybaut C, Gendreike Y, Blaive B.

Department of Public Health and Medical Information, Nice Teaching Hospital, BP 1179, 06003 Nice, Cedex 1, France.

19: Eur Heart J 2000 Aug;21(16):1301-36 [Texto completo en formato PDF]

Guidelines on diagnosis and management of acute pulmonary embolism.

Task Force on Pulmonary Embolism, European Society of Cardiology. Publication Types: Consensus Development Conference Guideline Practice Guideline Review

20: Ann Intern Med  2000 Feb 1;132(3):227-32

Sensitivity and specificity of helical computed tomography in the diagnosis of pulmonary embolism: a systematic review.

Rathbun SW, Raskob GE, Whitsett TL.

Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.

PURPOSE: To determine the sensitivity and specificity of helical computed tomography (CT) for the diagnosis of pulmonary embolism and to determine the safety of withholding anticoagulant therapy in patients who have clinically suspected pulmonary embolism and negative results on helical CT. DATA SOURCES: The MEDLINE database was searched for all reports published from 1986 to October 1999 that evaluated the use of helical CT for the diagnosis of pulmonary embolism. Bibliographies of the retrieved articles were cross-checked to identify additional studies. STUDY SELECTION: All prospective English-language studies were selected. Retrospective studies, review articles, and case reports were excluded, and 5 of the 20 identified articles were excluded. The scientific validity of the remaining 15 articles was assessed. DATA EXTRACTION: Two of the authors used a priori, pre-defined criteria to independently assess each study. A third author resolved disagreements by adjudication. The pre-defined criteria were inclusion of a consecutive series of all patients with suspected pulmonary embolism, inclusion of patients with and those without pulmonary embolism, a broad spectrum of patient characteristics, performance of helical CT and pulmonary angiography (or an appropriate reference test) in all patients, and independent interpretation of the CT scan and pulmonary angiogram (or reference test). Specific data on sensitivity and specificity and the associated 95% Cis were recorded when available. DATA SYNTHESIS: No study met all of the predefined criteria for adequately evaluating sensitivity and specificity. The reported sensitivity of helical CT ranged from 53% to 100%, and specificity ranged from 81% to 100%. In no prospective study was anticoagulant therapy withheld without further testing for venous thromboembolism in consecutive patients with suspected pulmonary embolism. One prospective study reported the outcome of selected patients with negative results on helical CT who did not receive anticoagulant therapy. CONCLUSIONS: Use of helical CT in the diagnosis of pulmonary embolism has not been adequately evaluated. The safety of withholding anticoagulant treatment in patients with negative results on helical CT is uncertain. Definitive large, prospective studies should be done to evaluate the sensitivity, specificity, and safety of helical CT for diagnosis of suspected pulmonary embolism.

Publication Types:

Meta-Analysis