Biomedical subjects
Publications and source records attributed to P S Wells.
The electrocardiogram is shown to be of limited diagnostic value for determining pulmonary embolism in a prospective cohort study of unselected patients with suspected pulmonary embolism.
A patient with chronic thromboembolic pulmonary hypertension and heparin-induced thrombocytopenia successfully underwent pulmonary thromboendarterectomy with circulatory arrest, using recombinant hirudin as an alternative anticoagulant to heparin. Techniques for administration as well as monitoring of this drug's effects are discussed.
The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.
PURPOSE: The Günther Tulip filter is a permanent filter that has a hook to permit retrieval. The authors report their preliminary clinical evaluation of the filter with regard to feasibility and safety of retrieval. MATERIALS AND METHODS: Nine men and six women who ranged in age from 17 to 79 years (mean, 51 years) underwent treatment with use of the Günther Tulip filter. Patients judged to require caval interruption for < 14 days were selected to receive the filter and retrieval was planned for all patients. Indications for filter placement were: recent pulmonary embolism (PE) or proximal deep vein thrombosis (DVT) with a contraindication to anticoagulation (11 patients), massive PE treated with thrombolytic therapy (one patient), PE with heparin-induced thrombocytopenia (one patient), and prophylaxis after major trauma (two patients). Patients were followed for inferior vena cava (IVC) thrombosis, bleeding, and recurrent DVT or PE. RESULTS: In all nine patients in whom it was attempted, the filter was successfully snared and retrieved via a jugular approach. The mean implantation period was 8.6 days (range, 5-13 days). Retrieval required 2.2-13 minutes (mean 5.3 minutes) of fluoroscopy. No caval injuries occurred as a result of retrieval. All retrieved filters had strands of organized thrombus on the filter struts. The patients were followed for 52-285 days (mean, 115 days) after retrieval. One patient developed a recurrent DVT 230 days after retrieval. No other patients developed a recurrent DVT and no patients developed IVC thrombosis, bleeding, or PE. Six filters were not retrieved: five because of an ongoing contraindication to anticoagulation and one because the patient died of causes unrelated to the filter. CONCLUSION: This preliminary study confirms the feasibility and safety of retrieval of the Günther Tulip filter up to 13 days after implantation.
BACKGROUND: Acute normovolemic hemodilution and preoperative autologous donation have been shown to be effective techniques for decreasing the exposure of patients to allogeneic blood during cardiac surgery. They have not, however, been compared to each other, because of perceived difficulties in blinding in such a clinical study. The feasibility of blinding was tested in a pilot trial. STUDY DESIGN AND METHODS: Ten patients were randomly assigned to undergo preoperative autologous blood donation or acute normovolemic hemodilution during cardiac surgery. Patients were blinded during this process by shielding of the arm and by insertion of an intravenous line in each patient. Every attempt was made to blind the clinical staff during and after surgery. The effectiveness of this blinding was determined by using a questionnaire. RESULTS: In the 10 cases, six patients, four surgeons, and one anesthetist answered, "I do not know," with respect to whether preoperative autologous blood donation had occurred. The remaining people interviewed believed the blinding was unsuccessful. However, correct answers were given by 75 percent of the patients (95% CI, 19-99%), 83 percent of the surgeons (95% CI, 36-99.6%), and 66 percent of the anesthetists (95% CI, 29.9-92.5%). The frequency of correct answers did not differ significantly from the 50 percent expected by chance, but the CIs are wide. CONCLUSIONS: Blinding of patients and all members of the surgical team during both the preoperative donation process and acute normovolemic hemodilution in the operating theater was successful most of the time, as the frequency of correct answers did not differ significantly from the 50 percent expected by chance. However, more accurate estimates of the success of blinding require a study with a larger sample. It is possible that, with a larger series, the physician's ability to determine patient assignment would be significantly better than that by chance alone.
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.
The effect of plasmapheresis on the anticoagulant properties of the low molecular weight heparins has never been studied. We had the opportunity to study this effect in a woman who was receiving dalteparin for the treatment of a pulmonary embolus and required plasmapheresis. Over the course of 8 days, five courses of plasmapheresis were performed. Anti-Xa activity was measured pre- and post-dalteparin administration both during and between the first three courses of plasmapheresis. Comparing the rate of change between pairs of anti-Xa activity, the absorption rate was found to have decreased by over 50%. The decay rate, as compared with a historical control, was found to have increased by over 480%. These results suggest that the level of anticoagulation of dalteparin, as monitored through an anti-Xa assay, is reduced by plasmapheresis.
D-dimer, a breakdown product of cross-linked fibrin has been extensively evaluated as a diagnostic test for acute venous thromboembolism. Rapid, highly sensitive D-dimer assays are now available that are suitable for testing in the emergency setting. Preliminary studies suggest that when using a highly sensitive D-dimer assay, a negative test result may,be sufficient to exclude the diagnosis of venous thromboembolism without need for further testing. Less sensitive, but more specific D-dimer assays are also available. The negative predictive value of these latter assays is insufficient to exclude venous thromboembolism on the basis of a negative test result alone. However, their utility is increased by identifying patient populations at low risk for venous thromboembolism using consideration of clinical probability or radiographic testing. Further, large multicenter management studies are required to confirm the safety of relying on a negative D-dimer result to exclude the diagnosis of venous thromboembolism.
Deep-vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the noninvasive imaging procedure ultrasonography, but limitations exist. 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 testing of the proximal venous system and not imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate, or high probability. Among the improvements this provides is the elimination of serial testing if the ultrasonogram is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic testing strategies that are more safe, effective, and convenient for patients.
Pulmonary embolism (PE) is a common and lethal yet treatable condition. Several authors have reported on the diagnostic value of combinations of arterial blood gas (ABG) and other clinical data (i. e., prediction rules), and have claimed that these combinations can be safely used to exclude PE. The purpose of this investigation was to evaluate the diagnostic value of ABG measurement and to attempt to validate the ABG prediction rules published by these various authors for the assessment of patients with suspected PE. Two hundred ninety-three consecutive patients referred for imaging to investigate suspected PE were approached to participate in the investigation. ABG and other clinical data were obtained from consenting and eligible patients before an outcome classification (PE versus non-PE) was performed. None of the ABG data or prediction rules had sufficient negative predictive value, specificity, or likelihood ratios to be useful in the management of patients with suspected PE. We conclude that ABG data alone or in combination with other clinical data are not useful in the assessment of suspected PE.
BACKGROUND: Pulmonary embolism is a common complication of deep vein thrombosis. It has been established that low molecular weight heparin may be used to treat deep vein thrombosis or pulmonary embolism and randomized studies have established that outpatient management of deep vein thrombosis with low molecular weight heparin is at least as effective as in-hospital management with unfractionated heparin. METHODS: This was a prospective cohort study of eligible patients with pulmonary embolism managed as outpatients using dalteparin (200 U/kg s/c daily) for a minimum of five days and warfarin for 3 months. Outpatients included those managed exclusively out of hospital and those managed initially for 1-3 days as inpatients who then completed therapy out of hospital. Reasons for admission included hemodynamic instability; hypoxia requiring oxygen therapy; admission for another medical reason; severe pain requiring parenteral analgesia or high risk of major bleeding. Patients were followed for three months for clinically apparent recurrent venous thromboembolism and bleeding. RESULTS: Between three teaching hospitals, a total of 158 patients with pulmonary embolism were identified. Fifty patients were managed as inpatients and 108 as outpatients. Of the outpatients, 27 were managed for an average of 2.5 days as inpatients and then completed dalteparin therapy as outpatients. The remaining 81 patients were managed exclusively as outpatients with dalteparin. For all outpatients the overall symptomatic recurrence rate of venous thromboembolism was 5.6% (6/108) with only 1.9% (2/108) major bleeds. There were a total of four deaths with none due to pulmonary embolism or major bleed. CONCLUSIONS: This prospective study suggests that outpatient management of pulmonary embolism is feasible and safe for the majority of patients.
We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores < or =4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
Lattice-fluid models describe molecular ensembles in terms of the number of lattice sites occupied by molecular species (r-mers) and the interactions between neighboring molecules. The lattice-fluid model proposed by Sanchez and Lacombe (Macromolecules, 1978;11:1145-1156) was used to model specific retention volume data for a series of n-alkane solutes with n-alkane, polystyrene, and poly(dimethylsiloxane) stationary liquid phases. Theoretical equations were derived for the specific retention volume and also for the temperature dependence and limiting (high temperature) values for the specific retention volume. The model was used to predict retention volumes within 10% for the n-alkanes phases; 22% for polystyrene; and from 20 to 70% for PDMS using no adjustable parameters. The temperature derivative (enthalpy) could be calculated within 5% for all of the solutes in nine stationary liquid phases. The limiting value for the specific retention volume at high temperature (entropy controlled state) could be calculated within 10% for all of the systems. The limiting data also provided a new chromatographic method to measure the size parameter, r, for any chromatographic solute using characteristic and size parameters for the stationary phase only. The calculated size parameters of the solutes were consistent, i.e. independent of the stationary phase and agreed within experimental error with the size parameters previously reported from saturated vapor pressure, latent heat of vaporization or density data.
BACKGROUND: Although D-dimer assays have high negative predictive values for the diagnosis of deep venous thrombosis, their accuracy in patients with cancer is uncertain. OBJECTIVE: To compare the clinical utility of a whole-blood D-dimer assay for the diagnosis of deep venous thrombosis in patients with and those without cancer. DESIGN: Retrospective analysis of three prospective studies. SETTING: Two tertiary care hospitals. PATIENTS: 1068 consecutive outpatients with suspected deep venous thrombosis. MEASUREMENTS: All patients underwent D-dimer testing and assessment with a priori diagnostic strategies that incorporated impedance plethysmography, compression ultrasonography, or contrast venography. Patients in whom deep venous thrombosis was not diagnosed initially were followed for 3 months for the development of thrombosis. Results of D-dimer testing were assessed according to the final diagnosis based on objective testing and clinical follow-up. Cancer status was identified at presentation. RESULTS: The prevalence of deep venous thrombosis was 48.8% in 121 patients with cancer and 14.6% in 947 patients without cancer. Although the sensitivity of the D-dimer assay was similar in patients with and those without cancer (86.4% [95% CI, 75.0% to 94.0%] and 82.6% [CI, 75.2% to 88.5%], respectively), the specificity was significantly lower in patients with cancer (48.4% [CI, 35.5% to 61.4%] and 82.2% [CI, 79.4% to 84.8%]), as was the negative predictive value (78.9% [CI, 62.7% to 90.4%] and 96.5% [CI, 94.9% to 97.8%]). In contrast, the likelihood ratios of a negative test result (0.28 [CI, 0.14 to 0.56] and 0.21 [CI, 0.15 to 0.31]) did not differ significantly. CONCLUSIONS: A negative D-dimer test result in patients with cancer does not reliably exclude deep venous thrombosis because the negative predictive value of the test is significantly lower in these patients than in patients without cancer.
CONTEXT: The management of patients presenting to hospital emergency departments with suspected deep vein thrombosis (DVT) is problematic because urgent diagnostic imaging capability is sometimes unavailable. Experienced physicians using clinical skills alone can classify patients with suspected DVT into low-, moderate-, and high-probability categories. OBJECTIVES: To determine the accuracy of an explicit clinical model for the diagnosis of DVT when applied by emergency department physicians and to assess the safety and feasibility of a management strategy based on the clinical pretest probability for patients presenting to the emergency department with suspected DVT outside of regular hospital staff work hours. METHODS: A prospective cohort study was performed in the emergency departments of 2 tertiary care institutions involving 344 patients with suspected DVT. Patient conditions were evaluated by an emergency department physician who determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. Patients for whom DVT was considered a low pretest probability were discharged from the emergency department and returned the following day for venous compression ultrasound imaging of the affected leg. Patients for whom DVT was considered a moderate pre-test probability received a single, weight-adjusted dose of subcutaneous unfractionated heparin sodium (between 12 500 and 20 000 U), were discharged from the emergency department, and returned the next morning to undergo ultrasonography. Patients for whom DVT was considered a high pretest probability were admitted to the hospital, administered intravenous unfractionated heparin, and ultrasonography was arranged within 24 hours. Patients with positive ultrasonographic findings were diagnosed with DVT, except for those with low pretest probability for whom confirmatory venography was performed. Patients with DVT excluded in the initial evaluation period did not receive anticoagulant therapy. All patients were followed up for 90 days to monitor development of thromboembolic or bleeding complications. RESULTS: Twenty-four (49.0% [95% confidence interval (CI), 34.5%-63.6%]) of 49 patients in the high-probability category, 15 (14.3% [95% CI, 8.3%-22.4%]) of 105 in the moderate-, and 6 (3.2% [95% CI, 1.2%-6.7%]) of 190 in the low-probability category were confirmed to have DVT. Overall, 45 (13.1%) of 344 patients were confirmed to have DVT. No patient developed pulmonary embolism or major bleeding complications within 48 hours of initial evaluation in the emergency department. Of the 301 patients who had DVT excluded during the initial evaluation period, only 2 (0.7% [95% CI, 0.1%-2.3%]) developed venous thromboembolic complications (calf vein thromboses in both) in the 3-month follow-up period. CONCLUSIONS: Using an explicit clinical model, emergency department physicians can accurately classify patients with suspected DVT into high-, moderate-, and low-probability groups. A management plan based on probability for DVT that avoids the need for urgent diagnostic imaging is safe and feasible in the emergency department setting.
Deep vein thrombosis is a relatively common disease, amenable to therapy but with a potentially fatal outcome if untreated. The diagnosis can be made in most patients with the non-invasive imaging procedure ultrasonography, but limitations exist. 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 testing of the proximal venous system rather than imaging the calf. The premise of the repeat (serial) test is that only thrombi that extend to the proximal system are clinically relevant and such thrombi will be detected on the repeat test. However, despite the safety of the serial-testing concept, it is inconvenient and expensive. In the last few years, the diagnostic process has been improved by the validation of a clinical model that accurately categorizes patients as having low, moderate or high probability of deep vein thrombosis. Among the improvements this provides is the elimination of serial testing if the ultrasound is normal and the clinical probability low. The fibrin degradation product D-dimer has been demonstrated to have a high negative predictive value and has also proven useful in diagnostic algorithms. The combination of the D-dimer with clinical model assessment will enable diagnostic-testing strategies that are more safe, effective and convenient for patients.
The purpose of this study was to evaluate whether the determination of pretest probability using a simple clinical model and the SimpliRED D-dimer could be used to improve the management of hospitalized patients with suspected deep-vein thrombosis. Consecutive hospitalized patients with suspected deep-vein thrombosis, had their pretest probability determined using a clinical model and had a SimpliRED D-dimer assay. Patients at low pretest probability underwent a single ultrasound test. A negative ultrasound excluded the diagnosis of deep-vein thrombosis whereas a positive ultrasound was confirmed by venography. Patients at moderate pretest probability with a positive ultrasound were treated for deep-vein thrombosis whereas patients with an initial negative ultrasound underwent a single follow-up ultrasound one week later. Patients at high pretest probability with a positive ultrasound were treated whereas those with negative ultrasound underwent venography. All patients were followed for three months for the development of venous thromboembolic complications. Overall, 28% (42/150), and 10% (5/50), 21% (14/71) and 76% (22/29) of the low, moderate and high pretest probability patients. respectively, had deep vein thrombosis. Two of 111 (1.8%; 95% CI = 0.02% to 6.4%) patients considered to have deep vein thrombosis excluded had events during three-month follow-up. Overall 13 of 150 (8.7%) required venography and serial testing was limited to 58 of 150 (38.7%) patients. The negative predictive value of the SimpliRED D-dimer in patients with low pretest probability was 96.2%, which is not statistically different from the negative predictive value of a negative ultrasound result in low pretest probability patients (97.8%). Management of hospitalized patients with suspected deep-vein thrombosis based on clinical probability and ultrasound of the proximal deep veins is safe and feasible.
Upper extremity deep vein thrombosis (DVT) is now recognized as a major cause of morbidity and mortality. There is little information regarding the most effective treatment of this condition. We report a prospective cohort study of the use of low molecular weight heparin (LMWH) in the outpatient management of upper extremity DVT. Forty-six patients were managed as outpatients for objectively documented upper extremity DVT with dalteparin (200 aXa u/kg), for a minimum of five days. Warfarin was usually initiated on the first day with a target INR of 2.0-3.0. Most patients had an underlying malignancy or a history of a central line. All patients were followed for 12 weeks from diagnosis. Only one patient had a major bleed. No patients developed pulmonary emboli. One patient had a recurrence of DVT during the treatment with LMWH with extension of the existing thrombus. Seven patients died, all due to their underlying disease. This study supports the safety and effectiveness of dalteparin in the treatment of upper extremity DVT. Given that these patients were treated as outpatients, there is a potential for huge cost savings.