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Background The rate of recurrent venous thromboembolism (VTE) in patients with a first unprovoked VTE who had a negative qualitative D-dimer test one month after stopping anticoagulant therapy was higher than expected in the D-dimer Optimal Duration Study (DODS). Objectives To determine whether quantitative D-dimer levels using a low threshold, age- and sex-specific thresholds, or repeated measurements, would improve identification of patients at low risk of recurrent VTE. Materials and methods D-dimer levels were quantified in banked samples from 307 patients in DODS who had a negative qualitative D-dimer test while on, and 1 month after stopping, anticoagulant therapy and the rates of recurrent VTE were determined in patients with D-dimer levels below various predefined thresholds. Results The rate (per patient year) of recurrent VTE was: 5.9% with D-dimer levels < 250 μg/l at one month; 5.2% with D-dimer levels between 250 and 499 μg/l at one month; 5.0% with D-dimer levels less than predefined age- and sex-specific thresholds at one month; and 6.3% when D-dimer levels were < 500 μg/l at both one and 7 months after stopping anticoagulant therapy. These rates are similar to the overall event rate of 6.3% in patients who stopped treatment. Conclusions Among unprovoked VTE patients who had a negative qualitative D-dimer test during and after anticoagulant therapy, low D-dimer thresholds, age and sex-adjusted thresholds or repeated measurements, did not identify subgroups with a very low rate of recurrence. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article focuses on the guidelines on the diagnosis and management of acute pulmonary embolism. It mentions that evaluation of clinical pre-test probability (CPTP) is the point of entry in the diagnosis of pulmonary embolism. Topics include risk factors for pulmonary embolism, test results that confirm or exclude pulmonary embolism, and duration of anticoagulant therapy for venous thromboembolism.

Background: Elevated total homocysteine levels are associated with a higher risk for venous thromboembolism. Whether decreasing homocysteine levels with vitamin therapy reduces the risk for venous thromboembolism is not known.Objective: To determine whether decreasing homocysteine levels alters the risk for symptomatic venous thromboembolism.Design: Secondary analysis of data from the randomized, placebo-controlled Heart Outcomes Prevention Evaluation 2 (HOPE-2) trial.Setting: 145 clinical centers in 13 countries.Participants: 5522 persons 55 years of age or older with known cardiovascular disease or diabetes mellitus and at least 1 other risk factor for vascular disease.Intervention: A daily supplement of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) or matching placebo for 5 years.Measurement: Prospectively diagnosed and confirmed symptomatic deep venous thrombosis or pulmonary embolism.Results: The geometric mean homocysteine level decreased by 2.2 micromol/L in the vitamin therapy group and increased by 0.80 micromol/L in the placebo group. Venous thromboembolism occurred in 88 participants during a mean follow-up of 5 years. The incidence rate of venous thromboembolism was the same in the vitamin therapy group and the placebo group (0.35 per 100 person-years; hazard ratio, 1.01 [95% CI, 0.66 to 1.53]). Vitamin therapy did not reduce the risk for deep venous thrombosis (hazard ratio, 1.04 [CI, 0.63 to 1.72]), pulmonary embolism (hazard ratio, 1.14 [CI, 0.57 to 2.28]), or unprovoked venous thromboembolism (hazard ratio, 1.21 [CI, 0.66 to 2.23]).Limitations: The proportion of patients with a previous episode of venous thromboembolism at enrollment was not known, and venous thromboembolism events were not centrally adjudicated.Conclusion: Decreasing homocysteine levels with folic acid and vitamins B6 and B12 did not reduce the risk for symptomatic venous thromboembolism. [ABSTRACT FROM AUTHOR]

Background: It may be safe to omit additional diagnostic testing in selected patients with suspected pulmonary embolism (PE) who have a negative D-dimer test, but this approach has never been evaluated in a randomized, controlled trial.Objective: To determine if additional diagnostic testing can be safely withheld in patients with suspected PE who have negative erythrocyte agglutination D-dimer test results.Design: Randomized comparisons in 2 subgroups of a prospective multicenter study.Setting: 7 university hospitals.Patients: 1126 outpatients or inpatients with suspected PE; of these, 456 patients with negative erythrocyte agglutination D-dimer test results were randomly assigned to the intervention groups. Patients were classified into 2 clinical probability groups: those with a low clinical probability of PE (low-probability group) and those with a moderate or high clinical probability of PE, a nondiagnostic ventilation-perfusion lung scan, and no evidence of proximal deep venous thrombosis on bilateral ultrasonography (moderate- or high-probability group).Interventions: The experimental intervention for both probability groups was no further diagnostic testing for PE. The control intervention for the low-probability group was a ventilation-perfusion lung scan followed by ultrasonography of the proximal deep veins of the legs on the same day. If the lung scan was nondiagnostic, ultrasonography of the legs was repeated 7 and 14 days later. The control intervention for the moderate- or high-probability group was ultrasonography of the proximal deep veins of the legs after 7 and 14 days. In the control and experimental groups, anticoagulation was withheld or withdrawn if PE was not diagnosed.Measurements: Symptomatic venous thromboembolism (VTE) during 6 months of follow-up.Results: Prevalence of VTE was 15.2% in the 1126 enrolled patients. In the low-probability group, VTE occurred during follow-up in 0 of 182 patients who had no additional diagnostic testing and in 1 of 185 patients who had additional testing (difference, -0.5 percentage point [95% CI, -3.0 to 1.6 percentage points]). In the moderate- or high-probability group, VTE occurred during follow-up in 1 of 41 patients who had no additional diagnostic testing and in 0 of 41 patients who had additional testing (difference, 2.4 percentage points [CI, -6.4 to 12.6 percentage points]).Limitations: The authors could not enroll 2000 patients as originally planned; 3 randomly assigned patients did not receive the allocated intervention, and 7 received inadequate follow-up. Personnel who performed follow-up evaluations were not blinded to the results of diagnostic testing at enrollment or to allocation group assignments.Conclusion: In patients with a low probability of PE who have negative D-dimer results, additional diagnostic testing can be withheld without increasing the frequency of VTE during follow-up. Low clinical probability and negative D-dimer results occur in 50% of outpatients and in 20% of inpatients with suspected PE. [ABSTRACT FROM AUTHOR]

Discusses the management of patients with hereditary hypercoagulable disorders. Clinical manifestations of hereditary hypercoagulable disorders; Duration of anticoagulation following a first episode of venous thromboembolism; Relationship between venous thromboembolism and pregnancy.

Background: This article addresses the treatment of VTE disease.Methods: We generated strong (Grade 1) and weak (Grade 2) recommendations based on high-quality (Grade A), moderate-quality (Grade B), and low-quality (Grade C) evidence.Results: For acute DVT or pulmonary embolism (PE), we recommend initial parenteral anticoagulant therapy (Grade 1B) or anticoagulation with rivaroxaban. We suggest low-molecular-weight heparin (LMWH) or fondaparinux over IV unfractionated heparin (Grade 2C) or subcutaneous unfractionated heparin (Grade 2B). We suggest thrombolytic therapy for PE with hypotension (Grade 2C). For proximal DVT or PE, we recommend treatment of 3 months over shorter periods (Grade 1B). For a first proximal DVT or PE that is provoked by surgery or by a nonsurgical transient risk factor, we recommend 3 months of therapy (Grade 1B; Grade 2B if provoked by a nonsurgical risk factor and low or moderate bleeding risk); that is unprovoked, we suggest extended therapy if bleeding risk is low or moderate (Grade 2B) and recommend 3 months of therapy if bleeding risk is high (Grade 1B); and that is associated with active cancer, we recommend extended therapy (Grade 1B; Grade 2B if high bleeding risk) and suggest LMWH over vitamin K antagonists (Grade 2B). We suggest vitamin K antagonists or LMWH over dabigatran or rivaroxaban (Grade 2B). We suggest compression stockings to prevent the postthrombotic syndrome (Grade 2B). For extensive superficial vein thrombosis, we suggest prophylactic-dose fondaparinux or LMWH over no anticoagulation (Grade 2B), and suggest fondaparinux over LMWH (Grade 2C).Conclusion: Strong recommendations apply to most patients, whereas weak recommendations are sensitive to differences among patients, including their preferences. [ABSTRACT FROM AUTHOR]

The article presents the findings of a study which investigates whether the anticoagulant effect of enoxaparin goes away when the last dose is given before surgery is safety. The researchers stopped warfarin four or five days before surgery and replaced it with twice-daily injection of enoxaparin three days before the surgical procedure. The researchers found out that at least some anticoagulant activity was found in the flood of 99 percent of the patients.

The article presents a study that compares the safety of D-dimer based management strategy with routine repeated ultrasonography in patients with suspected deep venous thrombosis (DVT). Patients with suspected first episode of DVT and negative results on proximal vein ultrasonography in 4 university hospitals in Hamilton, Ontario were observed for 6 months. The study concludes that the safety of a D-dimer based management strategy has no difference from the routine repeated ultrasonography.

Venous thromboembolism (VTE) prophylaxis is indicated while in the hospital after major surgery. There is evidence that the prevalence of asymptomatic deep-vein thrombosis, detected by routine venography after major orthopedic surgery, is lower at hospital discharge in patients who have received 10 days rather than 5 days of prophylaxis. This observation supports the current American College of Chest Physicians (ACCP) recommendation for a minimum of 7 to 10 days of prophylaxis after hip and knee replacement, even if patients are discharged from the hospital within 7 days of surgery. As risk of VTE persists for up to 3 months after surgery, patients at high risk for postoperative VTE may benefit from extended prophylaxis (eg, an additional 3 weeks after the first 7 to 10 days). Extended prophylaxis with low-molecular-weight heparin (LMWH) reduces the frequency of postdischarge VTE by approximately two thirds after hip replacement; however, the resultant absolute reduction in the frequency of fatal pulmonary embolism is small (ie, estimated at 1 per 2,500 patients). Indirect evidence suggests that, compared with LMWH, efficacy of extended prophylaxis after hip replacement is greater with fondaparinux, similar with warfarin, and less with aspirin. Extended prophylaxis is expected to be of less benefit after knee than after hip replacement. In keeping with current ACCP recommendations, at a minimum, extended prophylaxis should be used after major orthopedic surgery in patients who have additional risk factors for VTE (eg, previous VTE, cancer). If anticoagulant drug therapy is stopped after 7 to 10 days, an additional month of prophylaxis with aspirin should be considered. [ABSTRACT FROM AUTHOR]

BACKGROUND: It is unknown whether the true risk of recurrent venous thromboembolism (VTE) is increased in patients with proximal deep vein thrombosis who are treated with continuous intravenous heparin and fail to reach a therapeutic activated partial thromboplastin time (APTT) within 24 to 48 hours of initiation of treatment. METHODS: To compare the risk of recurrent VTE in patients with early subtherapeutic APTT results and those with APTT results above the lower limit of the therapeutic range, we performed a formal review of the literature. We examined all available studies that provided information on the relation between the risk of recurrent VTE and the APTT response to heparin when initiated as a bolus followed by a continuous intravenous infusion of at least 30 000 U/24 h. RESULTS: Five studies were included in the final analysis. The overall recurrence rate was 6.3% in patients whose APTT results were subtherapeutic for the first 24 to 48 hours and 7% in patients whose APTT results were above the lower limit of the therapeutic range, providing a pooled odds ratio of 0.89 with a 95% confidence interval of 0.2 to 4.0. CONCLUSIONS: In patients with VTE who are treated with a bolus of heparin followed by a continuous intravenous infusion of at least 30 000 U/24 h, no convincing evidence shows that the risk of recurrent VTE is critically dependent on achieving a therapeutic APTT result at 24 to 48 hours. [ABSTRACT FROM AUTHOR]

Background Although venous thromboembolism ( VTE) is an important cause of postoperative morbidity and mortality, there is still no consensus on the optimal strategy for VTE prevention after major surgery. The objective of this review was to determine the benefits and risks of thromboprophylaxis with both compression and anticoagulation, compared with either modality alone. Methods A systematic review of MEDLINE, CENTRAL and Embase databases was performed to identify eligible randomized trials. The literature search and data extraction were carried out independently by two reviewers. Outcomes of interest were deep vein thrombosis ( DVT), pulmonary embolism, bleeding, limb injury and mortality. Results Twenty-five studies were eligible for inclusion. Adding compression to anticoagulation decreased the risk of DVT by 49 per cent (risk ratio ( RR) 0·51, 95 per cent confidence interval 0·36 to 0·73). The corresponding funnel plot suggested publication bias and, overall, the evidence for this comparison was judged to be of low quality. Adding anticoagulation to compression decreased the risk of DVT by 44 per cent ( RR 0·56, 0·45 to 0·69) while increasing the risk of bleeding ( RR 1·74, 1·29 to 2·34). There was no suggestion of publication bias and the evidence for this comparison was judged to be of moderate quality. Conclusion Combined compression and anticoagulation is more effective at preventing postoperative DVT than either modality alone. However, adding anticoagulation to compression increases the risk of bleeding, and the evidence that adding compression to anticoagulation reduces VTE risk is of low quality. [ABSTRACT FROM AUTHOR]

The article summarizes a research study which analyzed individual patient data to determine the accuracy of the Wells rule combined with D-dimer testing for excluding deep vein thrombosis in different patient subgroups. An overview of the selection criteria for studies is presented. The link between increasing scores on the Wells rule and higher probability of deep vein thrombosis is discussed. It mentions the variation in the prevalence of deep vein thrombosis in a number of studies reviewed.

Background: D-Dimer testing is sensitive but not specific for diagnosing deep venous thrombosis (DVT). Changing the use of testing and the threshold level for a positive test result on the basis of risk for DVT might improve the tradeoff between sensitivity and specificity and reduce the need for testing. Objective: To determine whether using a selective D-dimer testing strategy based on clinical pretest probability (C-PTP) for DVT is safe and reduces diagnostic testing compared with using a single D-dimer threshold for all patients. Design: Randomized, multicenter, controlled trial. Patients were allocated using a central automated system. Ultrasonographers and study adjudicators but not other study personnel were blinded to trial allocation. (ClinicalTrials.gov: NCT00157677) Setting: 5 Canadian hospitals. Patients: Consecutive symptomatic patients with a first episode of suspected DVT. Intervention: Selective testing (n = 860), defined as D-dimer testing for outpatients with low or moderate C-PTP (DVT excluded at D-dimer levels <1.0 µg/mL [low C-PTP] or <0.5 µg/mL [moderate C-PTP]) and venous ultrasonography without D-dimer testing for outpatients with high C-PTP and inpatients, or uniform testing (n = 863), defined as D-dimer testing for all participants (DVT excluded at D-dimer levels <0.5 µg/mL). Measurements: The proportion of patients not diagnosed with DVT during initial testing who had symptomatic venous thromboembolism during 3-month follow-up and the proportion of patients undergoing D-dimer testing and ultrasonography. Results: The incidence of symptomatic venous thromboembolism at 3 months was 0.5% in both study groups (difference, 0.0 percentage point [95% CI, -0.8 to 0.8 percentage points]). Selective testing reduced the proportion of patients who required D-dimer testing by 21.8 percentage points (CI, 19.1 to 24.8 percentage points). It reduced the proportion who required ultrasonography by 7.6 percentage points (CI, 2.9 to 12.2 percentage points) overall and by 21.0 percentage points (CI, 14.2 to 27.6 percentage points) in outpatients with low C-PTP. Limitation: Results may not be generalizable to all D-dimer assays or patients with previous DVT, study personnel were not blinded, and the trial was stopped prematurely. Conclusion: A selective D-dimer testing strategy seems as safe as and more efficient than having everyone undergo D-dimer testing when diagnosing a first episode of suspected DVT. Primary Funding Source: Heart and Stroke Foundation of Ontario. [ABSTRACT FROM AUTHOR]

Background: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain.Objective: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy.Design: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment.Setting: 14 anticoagulant therapy clinics in Canada, the United States, and Italy.Patients: Nonbleeding patients with INR values of 4.5 to 10.0.Intervention: Oral vitamin K, 1.25 mg (355 patients randomly assigned; 347 analyzed), or matching placebo (369 patients randomly assigned; 365 analyzed).Measurements: Bleeding events (primary outcome), thromboembolism, and death (secondary outcomes).Results: 56 patients (15.8%) in the vitamin K group and 60 patients (16.3%) in the placebo group had at least 1 bleeding complication (absolute difference, -0.5 percentage point [95% CI, -6.1 to 5.1 percentage points]); major bleeding events occurred in 9 patients (2.5%) in the vitamin K group and 4 patients (1.1%) in the placebo group (absolute difference, 1.5 percentage points [CI, -0.8 to 3.7 percentage points]). Thromboembolism occurred in 4 patients (1.1%) in the vitamin K group and 3 patients (0.8%) in the placebo group (absolute difference, 0.3 percentage point [CI, -1.4 to 2.0 percentage points]). Other adverse effects were not assessed. The day after treatment, the INR had decreased by a mean of 1.4 in the placebo group and 2.8 in the vitamin K group (P < 0.001).Limitation: Patients who were actively bleeding were not included, and warfarin dosing after enrollment was not mandated or followed.Conclusion: Low-dose oral vitamin K did not reduce bleeding in warfarin recipients with INRs of 4.5 to 10.0.Funding: Canadian Institutes of Health Research and Italian Ministry of Universities and Research. [ABSTRACT FROM AUTHOR]

Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varied considerably between studies, accounting in part for the variation in the rates of bleeding reported. Since the last review, there have been several meta-analyses published on the rates of major bleeding in trials of anticoagulants for atrial fibrillation and ischemic heart disease. The major determinants of oral anticoagulant-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that low-intensity oral anticoagulant therapy (targeted INR of 2.5; range, 2.0 to 3.0) is associated with a lower risk of bleeding than therapy targeted at a higher intensity. Lower-intensity regimens (INR < 2.0) are associated with an even smaller increase in major bleeding. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. The risk of bleeding associated with IV heparin in patients with acute venous thromboembolism is < 3% in recent trials. There is some evidence to suggest that this bleeding risk increases with the heparin dosage and age (> 70 years). LMW heparin is not associated with increased major bleeding compared with standard heparin in acute venous thromboembolism. Standard heparin and LMW heparin are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract. Wells PS, Hirsh J, Anderson DR, Lensing AWA, Foster G, Kearon C, Weitz J, D'Ovidio R, Cogo A, Prandoni P, Girolami A, Ginsberg JS (Ottawa Civic Hospital, Ottawa, Hamilton Civic Hospitals Research Centre, Henderson General Hospital, and McMaster University, Hamilton, Ontario, and Victoria General Hospital, Nova Scotia, Canada; Instituto di Semeioti Medica, Padua, Italy; and Academic Medical Centre, Amsterdam, the Netherlands). A simple clinical model for the diagnosis of deep-vein thrombosis combined with impedance plethysmography: potential for an improvement in the diagnostic process. J Intern Med 1998; 243: 15–23. ObjectivesWe 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. DesignAn open, nonrandomized, multicentre trial. SettingThree centres, two in Canada, and one in Italy. SubjectsAmbulatory patients with suspected deep-vein thrombosis. InterventionsAll 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. ResultsImpedance 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. ConclusionsThe 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. [ABSTRACT FROM AUTHOR]

Background: Patients with suspected pulmonary embolism often have nondiagnostic lung scans and may present in circumstances where lung scanning is unavailable. Levels of D-dimer, a fibrin-specific product, are increased in patients with acute thrombosis; this may simplify the diagnosis of pulmonary embolism.Objective: To determine the sensitivity and specificity of a whole-blood D-dimer assay in patients with suspected pulmonary embolism and in subgroups of patients with low pretest probability of pulmonary embolism or nondiagnostic lung scans.Design: Prospective cohort.Setting: Four tertiary care hospitals.Patients: 1177 consecutive patients with suspected pulmonary embolism.Measurements: All patients underwent an assessment of pretest probability by use of a standardized clinical model, a D-dimer assay, ventilation-perfusion lung scanning, and bilateral compression ultrasonography. Patients in whom pulmonary embolism was not initially diagnosed were followed for 3 months. Accordingly, patients were categorized as positive or negative for pulmonary embolism.Results: Of the 1177 patients, 197 (17%) were classified as positive for pulmonary embolism. Overall, the D-dimer assay showed a sensitivity of 84.8% and a specificity of 68.4%. In 703 patients (3.4%) with a low pretest probability of pulmonary embolism, the likelihood ratio associated with a negative D-dimer test result was 0.27, resulting in a posterior probability of 1.0% (95% CI, 0.3% to 2.2%). In 698 patients with nondiagnostic lung scans (previous probability, 7.4%), the likelihood ratio associated with a negative D-dimer test result was 0.36, resulting in a posterior probability of 2.8% (CI, 1.4% to 4.8%).Conclusions: A normal D-dimer test result is useful in excluding pulmonary embolism in patients with a low pretest probability of pulmonary embolism or a nondiagnostic lung scan. [ABSTRACT FROM AUTHOR]

Background: The low specificity of ventilation-perfusion lung scanning complicates the management of patients with suspected pulmonary embolism.Objective: To determine the safety of a clinical model for patients with suspected pulmonary embolism.Design: Prospective cohort study.Setting: Five tertiary care hospitals.Patients: 1239 inpatients and outpatients with suspected pulmonary embolism.Interventions: A clinical model categorized pretest probability of pulmonary embolism as low, moderate, or high, and ventilation-perfusion scanning and bilateral deep venous ultrasonography were done. Testing by serial ultrasonography, venography, or angiography depended on pretest probability and lung scans.Measurements: Patients were considered positive for pulmonary embolism if they had an abnormal pulmonary angiogram, abnormal ultrasonogram or venogram, high-probability ventilation-perfusion scan plus moderate or high pretest probability, or venous thromboembolic event during the 3-month follow-up. All other patients were considered negative for pulmonary embolism. Rates of pulmonary embolism during follow-up in patients who had a normal lung scan and those with a non-high-probability scan and normal serial ultrasonogram were compared.Results: Pretest probability was low in 734 patients (3.4% with pulmonary embolism), moderate in 403 (27.8% with pulmonary embolism), and high in 102 (78.4% with pulmonary embolism). Three of the 665 patients (0.5% [95% CI, 0.1% to 1.3%]) with low or moderate pretest probability and a non-high-probability scan who were considered negative for pulmonary embolism had pulmonary embolism or deep venous thrombosis during 90-day follow-up; this rate did not differ from that in patients with a normal scan (0.6% [CI, 0.1% to 1.8%]; P > 0.2).Conclusion: Management of patients with suspected pulmonary embolism on the basis of pretest probability and results of ventilation-perfusion scanning is safe. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Post-thrombotic syndrome (PTS) occurs in 20-50% of patients following proximal deep vein thrombosis (DVT), despite anticoagulation treatment. The International Society on Thrombosis and Haemostasis recommends using the Villalta scale to standardize the diagnosis of PTS and to quantify its severity. However, many investigators use the Venous Clinical Severity Score (VCSS) to assess PTS. Different to the Villalta score, the VCSS was developed as a measure for chronic venous disease and not PTS specifically. The aim of the study was to determine which of Villalta and VCSS best captures clinically important PTS and PTS severity by analyzing the relationship of each to QoL scores in the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial study population. A secondary analysis of the ATTRACT randomized controlled clinical trial was conducted. 621 ATTRACT patients with symptomatic proximal DVT are included in this analysis. Correlations of the Villalta and VCSS scores with QoL scores (Short-Form Health Survey-36 physical component score/mental component score [SF-36 PCS/MCS]; the Venous Insufficiency Epidemiological and Economic Study-QoL/Symptoms [VEINES-QoL/Sym] questionnaire) were examined at study visits. The correlation of the random intercept (mean scores) and random slope (rate of change of the scores) between the Villalta, VCSS and the VEINES-QoL/Sym scores was assessed using a multivariate longitudinal model. The mean age at enrolment was 51 years of age, 78% were white, 62% were male, the mean BMI was 32 kg/m2, 57% had iliofemoral DVT, 19% had a previous ipsilateral DVT and 93% were taking one or more anticoagulation therapies prior to randomization. The median (range) correlation coefficients across all follow-up visits for the Villalta scale and VEINES-QOL and the Villalta scale and VEINES-Sym were -0.73 (0.51, -0.73) and -0.75 (-0.50, -0.76), respectively. The median (range) correlation coefficients for the Villalta scale and the SF-36 PCS or the SF-36 MCS across all follow-up visits were -0.51 (-0.35, -0.54) and -0.31 (-0.21, -0.38), respectively. In all correlation analyses between the Villalta scale and QoL measures, correlations at baseline were the weakest, and then increased until 6 months, after which the correlation coefficients remained relatively constant. The median correlation coefficient (range) across all follow-up visits for VCSS and VEINES-QOL and for VCSS and VEINES-Sym were -0.39 (-0.37, -0.39) and -0.41 (-0.36, -0.41), respectively. The median correlation (range) between VCSS and SF-36 PCS and for VCSS and MCS were -0.32 (-0.31, -0.32) and -0.12 (-0.12, -0.14), respectively. The magnitude of the correlations remained relatively constant from 6 months to 24 months follow-up visits. The Villalta scale had a strong negative correlation with VEINES-QoL and VEINES-Sym, a moderate negative correlation with SF-36 PCS, and a weak negative correlation with SF-36 MCS. Conversely, the VCSS had a weak negative correlation with VEINES-QoL, VEINES-Sym and SF-36 PCS, and a very weak negative correlation with SF-36 MCS. Adjustment for age, sex, ethnicity, race, extent of DVT and previous ipsilateral DVT did not change our findings. Each pair of disease severity scales and QoL scales were analyzed as a multivariate outcome in a multivariate longitudinal model. A random intercept (mean scores) and random slope (rate of change of the scores) were present in all these multivariate longitudinal models. The impact of covariates (i.e. age, sex and BMI) was also examined. The Villalta score and VCSS score have a positive correlation between their random intercept and random slope. This suggests that patients with a higher average Villalta score also tend to have a higher average VCSS score (correlation is 0.74 and 0.69 if adjusted). Those that have a higher rate of change in Villalta score over time tend to have a higher rate of change in VCSS (correlation is 0.72 and 0.84 if adjusted). The impact from covariate adjustment by age, sex and BMI was minor. For all measures, the Villalta scale has a substantially higher correlation with QOL than the VCSS. Our findings support the use of the Villalta scale to assess PTS in preference to VCSS, as it better captures the impact of PTS on patient reported QoL, a key consideration in patients with chronic PTS. [ABSTRACT FROM AUTHOR]

Evaluates patients with suspected pulmonary embolism (PE) with an absence of risk factors for venous thromboembolism (VTE) and symptoms of deep vein thrombosis (DVT) and its implications for PE diagnosis. Prevalence of abnormal ultrasound results based on the presence of signs and symptoms of DVT and risk factors for VTE; Limited number of patients with neither risk factors nor symptoms of DVT that are positive for PE.

Background: Objective testing for DVT is crucial because clinical assessment alone is unreliable and the consequences of misdiagnosis are serious. This guideline focuses on the identification of optimal strategies for the diagnosis of DVT in ambulatory adults.Methods: The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.Results: We suggest that clinical assessment of pretest probability of DVT, rather than performing the same tests in all patients, should guide the diagnostic process for a first lower extremity DVT (Grade 2B). In patients with a low pretest probability of first lower extremity DVT, we recommend initial testing with D-dimer or ultrasound (US) of the proximal veins over no diagnostic testing (Grade 1B), venography (Grade 1B), or whole-leg US (Grade 2B). In patients with moderate pretest probability, we recommend initial testing with a highly sensitive D-dimer, proximal compression US, or whole-leg US rather than no testing (Grade 1B) or venography (Grade 1B). In patients with a high pretest probability, we recommend proximal compression or whole-leg US over no testing (Grade 1B) or venography (Grade 1B).Conclusions: Favored strategies for diagnosis of first DVT combine use of pretest probability assessment, D-dimer, and US. There is lower-quality evidence available to guide diagnosis of recurrent DVT, upper extremity DVT, and DVT during pregnancy. [ABSTRACT FROM AUTHOR]

This chapter about hemorrhagic complications of anticoagulant treatment is part of the seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines. Bleeding is the major complication of anticoagulant therapy. The criteria for defining the severity of bleeding varies considerably between studies, accounting in part for the variation in the rates of bleeding reported. The major determinants of vitamin K antagonist-induced bleeding are the intensity of the anticoagulant effect, underlying patient characteristics, and the length of therapy. There is good evidence that vitamin K antagonist therapy, targeted international normalized ratio (INR) of 2.5 (range, 2.0 to 3.0), is associated with a lower risk of bleeding than therapy targeted at an INR > 3.0. The risk of bleeding associated with IV unfractionated heparin (UFH) in patients with acute venous thromboembolism (VTE) is < 3% in recent trials. This bleeding risk may increase with increasing heparin dosages and age (> 70 years). Low molecular weight heparin (LMWH) is associated with less major bleeding compared with UFH in acute VTE. UFH and LMWH are not associated with an increase in major bleeding in ischemic coronary syndromes, but are associated with an increase in major bleeding in ischemic stroke. Information on bleeding associated with the newer generation of antithrombotic agents has begun to emerge. In terms of treatment decision making for anticoagulant therapy, bleeding risk cannot be considered alone, ie, the potential decrease in thromboembolism must be balanced against the potential increased bleeding risk. [ABSTRACT FROM AUTHOR]