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Biomedical subjects

C Kearon

Publications and source records attributed to C Kearon.

At least 55 records · Page 3Linked to original sources

Noninvasive diagnosis of deep venous thrombosis. McMaster Diagnostic Imaging Practice Guidelines Initiative.

PURPOSE: To review noninvasive methods for diagnosis of first and recurrent deep venous thrombosis and provide evidence-based recommendations for the diagnosis of deep venous thrombosis in symptomatic, asymptomatic, and pregnant patients. DATA SOURCES: Accuracy (comparison with contrast venography) and management (safety of withholding anticoagulants when results were normal) studies that evaluated tests for diagnosis of deep venous thrombosis were identified from a MEDLINE search, personal files, and bibliographies of reviews and original studies. STUDY SELECTION: Prospective cohort studies (accuracy and management studies) and randomized comparisons (management studies) that satisfied predefined methodologic criteria were included. DATA EXTRACTION: Sensitivity, specificity, and positive and negative predictive values were determined for accuracy studies. Rates of venous thromboembolism during long-term follow-up of patients with normal results were determined for management studies. DATA SYNTHESIS: Data from individual studies were combined under a random-effects model. The accuracy of noninvasive tests was compared, with emphasis on within-study comparisons. Recommendations for diagnosis of deep venous thrombosis were developed by a multidisciplinary group and graded according to the strength of the supporting evidence. Venous ultrasonography is the most accurate noninvasive test for the diagnosis of a first symptomatic proximal deep venous thrombosis. However, neither ultrasonography nor impedance plethysmography is accurate in asymptomatic postoperative patients. Venous ultrasonography is less accurate for symptomatic isolated distal (calf) deep venous thrombosis than for proximal deep venous thrombosis, and the clinical utility of venous ultrasonography of the distal veins is uncertain. Withholding anticoagulant therapy in symptomatic patients with suspected deep venous thrombosis who have normal results on serial venous ultrasonography or impedance plethysmography is safe. Diagnosis of recurrent deep venous thrombosis requires evidence of new thrombus formation, such as a new noncompressible venous segment detected by venous ultrasonography, conversion of a normal result on impedance plethysmography to abnormal, or presence of an intraluminal filling defect on venography. Suspected deep venous thrombosis in pregnant patients can usually be managed with serial venous ultrasonography or impedance plethysmography. In symptomatic patients with a suspected first episode of deep venous thrombosis, clinical assessment and D-dimer testing are complementary to testing with venous ultrasonography and impedance plethysmography. CONCLUSIONS: Patients with suspected deep venous thrombosis can usually be managed with noninvasive testing. However, if the results of this testing are nondiagnostic or are discordant with the clinical assessment, venography should be considered.

Algorithms↗

Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.

CONTEXT: The most serious complication of deep vein thrombosis (DVT) or nonfatal pulmonary embolism (PE) is fatal PE. However, reliable estimates as to the risk of fatal PE in patients with treated DVT or PE are lacking. OBJECTIVE: To provide reliable estimates of the risk of fatal PE and the case-fatality rate of recurrent DVT or PE among patients presenting with symptomatic DVT or PE, during and following 3 months of anticoagulant therapy. DATA SOURCES: A MEDLINE literature search was performed to identify prospective studies in which patients with symptomatic DVT or PE were treated with 5 to 10 days of heparin and 3 months of oral anticoagulants. We searched the years 1966 to September 1997 using the search terms thrombophlebitis, diagnosis, drug therapy, and prognosis. Current Contents and bibliographies were also scanned. DATA EXTRACTION: Of 137 retrieved studies, 25 studies satisfied predetermined methodologic criteria and were included in the analysis. DATA SYNTHESIS: Among patients presenting with DVT, the rate of fatal PE during anticoagulant therapy was 0.4% (95% confidence interval [CI], 0.2%-0.6%); following anticoagulant therapy it was 0.3 per 100 patient-years (95% CI, 0.1-0.8). The case-fatality rate of recurrent DVT or PE during anticoagulant therapy was 8.8% (95% CI, 5.0%-14.1%); following anticoagulant therapy it was 5.1% (95% CI, 1.4%-12.5%). Among patients presenting with PE, the rate of fatal PE during anticoagulant therapy was 1.5% (95% CI, 0.9%-2.2%); following anticoagulant therapy it was 0 per 265 patient-years (95% CI, 0-3.6). The case-fatality rate of recurrent DVT or PE among patients presenting with PE was 26.4% (95% CI, 16.7%-38.1%). CONCLUSION: Among patients with symptomatic PE or DVT who are treated with anticoagulants for 3 months, fatal PE is rare during and following anticoagulant therapy. Patients presenting with PE are more likely to die of recurrent PE or DVT than are patients presenting with DVT.

Anticoagulants↗

A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process.

OBJECTIVES: We recently demonstrated the utility of a clinical model combined with ultrasonography to assist the diagnostic approach in patients with suspected deep-vein thrombosis (DVT). In this study we also sought to demonstrate that the model is useful with impedance plethysmography, a less accurate and less utilized diagnostic test. The original clinical model is slightly cumbersome to use; thus at the completion of the study we attempted to develop a simpler scoring system with a goal of maintaining accuracy. DESIGN: An open, nonrandomized, multicentre trial. SETTING: Three centres, two in Canada, and one in Italy. SUBJECTS: Ambulatory patients with suspected deep-vein thrombosis. INTERVENTIONS: All patients were assessed clinically to determine the probability for deep-vein thrombosis prior to performing impedance plethysmography and venography. We compared the accuracy of impedance plethysmography between the three pretest probability categories of high, moderate and low. All of the above were performed and interpreted by independent observers. When the study was completed, we revised the clinical model by first performing a simple regression analysis then a multiple logistic regression analysis; a scoring system was devised using the latter. RESULTS: Impedance plethysmography is significantly more sensitive and less specific for all DVT in patients with high pretest probability for deep-vein thrombosis (P = 0.001). The post- test probability (positive predictive value) for deep-vein thrombosis with an abnormal impedance plethysmography result was significantly different (P = 0.0001) between the three pretest probability categories. Multiple regression analysis has provided a new model with only nine variables and a simple scoring system. The retrospective application of the revised clinical model, which is simpler to use, suggests it will provide similar results as the original clinical model when combined with impedance plethysmography. The combination of impedance plethysmography and the clinical model suggests patients are likely to have false positive results if they have a low or moderate pretest probability for deep-vein thrombosis and false negative results if the pretest probability is high. The combination of a low pretest probability and a normal impedance plethysmography result may exclude the need for serial testing, and represented more than 50% of our patient population. CONCLUSIONS: The use of the clinical model in conjunction with impedance plethysmography would decrease the number of false positive and negative diagnoses and could markedly decrease the need for serial impedance plethysmography. Combining the clinical model with impedance plethysmography could overcome the fact that impedance plethysmography is clearly less accurate than venous ultrasound imaging. The use of the revised clinical model may increase acceptability and utility, but prospective testing is required before widespread use.

Diagnosis, Differential↗

Thromboprophylaxis in non-surgical patients: who, when and how?

Because of the serious lack of useable, relevant information, most recommendations for prevention of thrombosis in non-surgical patients are extrapolations from much larger clinical trials experienced in surgery. Directly relevant evidence comes predominantly from very small randomized trials, many of them open label and carried out more than 20 years before the introduction of more recent and important changes in clinical care that may have substantially reduced the baseline thrombosis risk. In these early studies, low-dose heparin and low-molecular-weight heparins prevented subclinical deep vein thrombosis in ischaemic stroke, myocardial infarction and among elderly medical inpatients. Although it is likely that these drugs also prevent subclinical deep vein thrombosis after spinal cord injury or other major trauma, and when patients require intensive medical care, the supporting evidence in these circumstances comes mainly from cohort studies and poorly controlled comparisons. In contrast, the heparins have not reduced mortality or demonstrably prevented pulmonary embolism after ischaemic stroke or among elderly medical inpatients in large and well-conducted clinical endpoint trials, from which no clinically important benefit could be demonstrated. From analyses it is suggested that such benefit is probably more difficult to demonstrate for medical than for surgical patients. In the absence of sufficient information that is specific to medical patients, various forms of prophylaxis known to be effective in surgery will continue to be applied in high-risk individuals. After venous thromboembolism, it now appears that the best duration of oral anticoagulant therapy to prevent a recurrence is determined to a greater extent by whether the thrombotic episode was idiopathic or triggered by a clinically recognizable cause, whether it was transient or continuing, and whether the deep vein thrombosis was extensive, limited to the calf veins or was a first or recurrent event.

Aged↗

Perioperative management of long-term anticoagulation.

When the need for surgery arises, temporary interruption of long-term anticoagulation exposes patients to additional thrombotic risk. There is no consensus as to how perioperative anticoagulation should be managed in this setting. Based on an individual assessment of risk factors for arterial or venous thromboembolism and the risk of postoperative bleeding, this review outlines an approach to the perioperative management of anticoagulation that is designed to optimize patient safety and efficient delivery of health care. The duration of interruption of oral anticoagulation is minimized by withholding four daily doses of warfarin before surgery, and by restarting warfarin the same day that surgery is performed. This will usually achieve satisfactory coagulation status intraoperatively (e.g., International Normalized Ratio of 1.5 or less) with a low risk of postoperative bleeding. Supplemental prophylaxis with therapeutic doses of heparin, usually unfractionated heparin, can be reserved for patients with the highest risk of thromboembolism. In the preoperative period, this applies to patients who have had an episode of arterial or venous thromboembolism in the preceding month. In the postoperative period, this approach is generally reserved for patients with an episode of venous thromboembolism in the preceding 3 months, and patients with an episode of arterial embolism in the preceding month who have a low risk of bleeding. Differences in the approach to management of anticoagulation before and after surgery relate to the fact that surgery is an important risk factor for venous, but not arterial, thromboembolism, and that recent surgery greatly increases the risk of anticoagulant-induced bleeding. Subcutaneous unfractionated or low-molecular-weight heparin, in doses recommended to prevent venous thromboembolism in high-risk surgical patients, should be administered to in-patients who have a lesser risk of thromboembolism until oral anticoagulation is reestablished.

Anticoagulants↗

The use of D-dimer testing and impedance plethysmographic examination in patients with clinical indications of deep vein thrombosis.

OBJECTIVE: To prospectively test the hypothesis that a diagnosis of deep vein thrombosis can be excluded in outpatients who present with clinical indications of deep vein thrombosis and whose results of D-dimer testing and impedance plethysmographic examination on the day of presentation are normal. DESIGN: Prospective cohort study. SETTING: Four university-affiliated hospitals. METHODS: Three hundred ninety-eight consecutive patients with clinical indications of deep vein thrombosis were included in the final analysis. All patients underwent an assessment of pretest probability, bedside D-dimer testing, and impedance plethysmographic examination. In most patients, if the results of D-dimer testing and impedance plethysmographic examination were negative for deep vein thrombosis, anticoagulants were withheld and patients were followed up for 3 months. If the results of one or both tests were abnormal, an examination using venous compression ultrasonography or phlebography was performed. RESULTS: In the majority of patients (69%), the results of D-dimer testing and impedance plethysmographic examination were normal. This combination had a negative predictive value of 98.5% (95% confidence interval, 96.3-99.6) for deep vein thrombosis. CONCLUSION: The results of the D-dimer assay and impedance plethysmographic examination on the day of presentation can be used to treat the majority of outpatients who present with clinical indications of deep vein thrombosis without further testing.

Adult↗

Drug trials that have influenced our practice in the treatment of venous thromboembolism.

Heparin and oral anticoagulants have been the mainstay of antithrombotic therapy for the prevention and treatment of venous thromboembolism for over 50 years. Randomized trials have established their efficacy and have been used to refine the optimal dose and duration of therapy for different indications. Low-dose, subcutaneous, standard heparin and low molecular weight heparin (LMWH) provide effective primary prophylaxis, higher doses being indicated for patients who are at highest risk. OA is an alternative in high risk patients, particularly if there are persistent risk factors. Heparin and OA can be started concomitantly when treating patients with acute VTE. At least 4 days of adjusted dose standard heparin, or fixed dose LMWH, should be administered, and heparin should not be stopped until therapeutic OA is established. Acute DVT can be treated as an outpatient with fixed dose LMWH. In general, OA, with an International Normalization Ratio of 2.0-3.0, should be continued for 3 to 6 months. The optimal duration of OA may differ between patients who have VTE associated with a transient or a continuing (including "idiopathic") risk factors; however, this remains to be defined. New antithrombotic agents, such as direct thrombin inhibitors, are in the preliminary stages of evaluation for the prevention and treatment of VTE.

Anticoagulants↗

Accuracy of clinical assessment of deep-vein thrombosis.

The clinical diagnosis of deep-vein thrombosis is generally thought to be unreliable. From experience, we hypothesised that this widely held view might be incorrect. We developed a clinical model and prospectively tested its ability in three tertiary care centres to stratify symptomatic outpatients with suspected deep-vein thrombosis into groups with high, moderate, or low probability groups of deep-vein thrombosis. We evaluated our clinical model in combination with venous ultrasonography to determine the potential for an improved and simplified diagnostic approach in patients with suspected deep-vein thrombosis. All patients were clinically assessed to determine the probability for deep-vein thrombosis before they had ultrasonography and venography. All tests were performed and interpreted by independent observers. In 529 patients, the clinical model predicted prevalence of deep-vein thrombosis in the three categories: 85% in the high pretest probability category, 33% in the moderate, and 5% in the low category. There was no statistical difference in the performance of the model in the three centres. The model demonstrated excellent interobserver reliability (Kappa = 0.85). There were important differences with ultrasonography between the high and low pretest probability groups for both positive predictive values (100% (95% CI, 94-100%) vs (63% [35-85%], respectively). Thus, use of the clinical model combined with ultrasonography would decrease the number of false positive and negative diagnosis if venography were done when the ultrasound result and pretest probability were discordant. The diagnostic process could be simplified by excluding those patients with low pretest probability and normal ultrasound results from serial testing.

Decision Trees↗

A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis.

BACKGROUND: The clinical utility of using a novel whole blood assay for D-dimer (SimpliRED), alone or in combination with impedance plethysmography (IPG), was investigated in a two-center, prospective cohort study of 214 consecutive patients with clinically suspected deep vein thrombosis (DVT). METHODS AND RESULTS: All patients underwent the SimpliRED D-dimer assay, contrast venography, and IPG. According to the results of venography, 43 patients had proximal DVT (popliteal and/or more proximal veins), 10 had isolated calf DVT, and 161 had DVT ruled out. The D-dimer had a sensitivity of 93% for proximal DVT and of 70% for calf DVT, an overall specificity of 77%, and a negative predictive value of 98% for proximal DVT. The sensitivity and specificity of IPG for proximal DVT were 67% and 96%, respectively. When analyzed in combination with the IPG results, it was determined that (1) the combination of a negative D-dimer and a normal IPG had a negative predictive value of 97% for all DVT and of 99% for proximal DVT and occurred in 58% of patients (likelihood ratio, 0.1) and (2) the combination of a positive D-dimer and an abnormal IPG had a positive predictive value of 93% for any DVT and of 90% for proximal DVT and occurred in 14% of patients (likelihood ratio, 42.6). When the D-dimer and IPG results were discordant, it was not possible to exclude or diagnose DVT reliably; discordant results occurred in 28% of patients. CONCLUSIONS: The SimpliRED D-dimer assay, which can be performed and interpreted at the bedside within 5 minutes, has great potential in patients with clinically suspected DVT, especially for ruling out DVT, and is complementary to IPG. The assay should be evaluated in large clinical management studies.

Agglutination Tests↗

Starting prophylaxis for venous thromboembolism postoperatively.

A large proportion of hospitalized patients who are at high risk for venous thromboembolism (VTE) do not receive prophylaxis. Reluctance to use VTE prophylaxis in surgical patients may be due to fear of perioperative bleeding when anticoagulants are given preoperatively. We preformed a literature review to determine (1) whether prophylaxis for VTE is effective when it is started postoperatively and (2) the relative efficacy of preoperatively and postoperatively initiated prophylaxis. Studies were included in the review (1) if they were randomized trials with "blind" assessment of appropriate VTE outcomes, and (2) if prophylaxis was started postoperatively. Randomized, controlled trials establish that pharmacologic and nonpharmacologic methods of prophylaxis that are effective when started preoperatively are also effective when they are started postoperatively, with relative risks for VTE of 0.16 to 0.49. Low rates of VTE in noncontrolled randomized trials that included postoperatively initiated prophylactic regimens support this finding. The relative efficacy of preoperatively and postoperatively initiated VTE prophylaxis could not be determined definitively, as direct comparisons of the same regimens have not been performed. Indirect comparisons suggest that any loss of efficacy resulting from deferring VTE prophylaxis until after surgery is unlikely to be marked. Randomized trials are required to resolve this question. This comparison may be of greatest clinical importance when twice-daily, low-molecular-weight heparin is used to prevent VTE after major orthopedic surgery.

Clinical Trials as Topic↗

Comparison of the accuracy of impedance plethysmography and compression ultrasonography in outpatients with clinically suspected deep vein thrombosis. A two centre paired-design prospective trial.

Impedance plethysmography (IPG) and compression ultrasonography (CUS) have been reported to be highly accurate for the diagnosis of deep vein thrombosis (DVT) in symptomatic patients. In many centres CUS has become the method of choice. However, direct comparisons of the accuracy of IPG to CUS have not been performed. To determine the test of choice we performed a two centre prospective comparison of IPG and CUS, with venography, and determined how the size and distribution of thrombi influenced the accuracy of each test. 495 symptomatic outpatients with suspected DVT had evaluable venograms. The prevalence of DVT was 27% (130/495), 84% (109) of which were proximal. The sensitivity of IPG and CUS for proximal vein thrombosis was 77% and 90% respectively (p = .002). The specificity of IPG was 93% whereas the specificity of CUS was 98% (p = 0.04). There were significant differences in accuracy between the two centres as a consequence of differences in the size and location of thrombi The majority of proximal thrombi not detected by IPG and CUS involved less than 5 cm of the distal half of the popliteal vein and most of these thrombi occurred in one centre. Exclusion of these thrombi from the analysis increases the sensitivity of CUS to 99% (86/87) and IPG to 91% (72/79), for proximal thrombi (P = .019). The positive predictive value of CUS was strongly influenced by the number of abnormal venous segments (three sites were examined); 100% (80/80) if two or three sites were abnormal, but only 68% if a single site was involved. We conclude that: 1) CUS is more accurate than the IPG for the diagnosis of DVT in symptomatic outpatients, and this relationship holds true regardless of the size or location of the DVT, 2) the sensitivities of IPG and CUS are much lower for small proximal DVT, and 3) confirmatory venography is warranted if the abnormality with CUS is limited to one venous segment.

Ambulatory Care↗

Factors influencing the reported sensitivity and specificity of impedance plethysmography for proximal deep vein thrombosis.

A number of recent studies have found a considerably lower sensitivity of the IPG for proximal DVT than originally reported. We reviewed the literature to try and identify reasons for the between study differences in sensitivity and specificity of the IPG for proximal DVT. A number of biases were identified which may have inflated the sensitivity reported by some earlier studies including: repeated IPG testing prior to venography; inclusion of data from patients used to derive the IPG discriminant line in the final calculation of sensitivity; and inclusion of patients with a known abnormal IPG in the study population. In addition, there is emerging evidence that, at least in some centers, the sensitivity of the IPG may have decreased due to a shift in the spectrum of proximal DVTs to smaller clots. Furthermore, rates of conversion during serial follow-up are considerably higher for IPG than for venous ultrasound, suggesting that IPG conversion is often due to extension of small missed proximal DVTs rather than just extension of calf vein clots. As the smaller proximal DVTs which IPG is prone to miss are likely to be clinically less important than more extensive clots, it is unclear whether the recently reported drop in sensitivity of the IPG places patients at increased risk. IPG users need to be aware of its limitations, and we recommend that additional testing is performed in patients with a high clinical suspicion of DVT who have a normal IPG, as the negative predictive value of IPG may be unacceptable in these circumstances.

Humans↗