Idiopathic deep venous thrombosis. Is a search for malignant disease justified?
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Biomedical subjects
Publications and source records attributed to A W Lensing.
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Compression ultrasonography is regarded as the non-invasive gold-standard to detect deep vein thrombosis (DVT) in patients presenting with symptoms. However, its use as a screening method in symptom-free postoperative patients at high risk of developing DVT remains controversial. In 100 consecutive patients who had undergone craniotomy, we compared the results of bilateral compression ultrasonic measurements of the results of bilateral compression ultrasonic measurements of the entire legs with the outcomes of contrast venography. Proximal DVT was detected in 13 patients, 5 of whom also had an abnormal ultrasonic result (sensitivity 38%, 95% CI 8-69%). Only 5 of the 9 patients with an abnormal ultrasound result for the proximal veins had proximal DVT (positive predictive value, 56%, 18-94%). Calf sonograms were evaluable in 71 of the 91 patients with bilaterally normal ultrasound results for the proximal veins. Of the 16 patients with calf DVT, ultrasound was abnormal in 8 (sensitivity 50%, 25-75%). Overall, ultrasound detected 13 of the 26 patients with proximal or isolated calf DVT (sensitivity 50%, 29-71%). The positive predictive value for the whole leg examination was 41% (24-60%). Most thrombi missed by ultrasound were non-occlusive and smaller than 5 cm. We conclude that compression ultrasound is not useful for screening for DVT in symptom-free postoperative high-risk patients.
BACKGROUND: The effectiveness of graduated compression stockings in prophylaxis of postoperative venous thromboembolism is unclear to many physicians. Surveys show there is considerable variability in their use and their perceived effectiveness. We undertook to establish, by a systematic overview of the literature, the effectiveness of graduated compression stockings in the prophylactic setting of postoperative venous thromboembolism. METHODS: Studies published between 1966 and June 1992 were identified through the MEDLINE database, with a search in all languages, through reviews of Current Contents, and including references cited in identified articles. Articles were selected for initial analysis if they assessed the use of graduated compression stockings for the prophylaxis of venous thromboembolism, and if the stocking group was compared with an untreated or unconfounded control group. Criteria were established a priori, to select only studies with sound methods. On the basis of these criteria, 12 studies were identified for the combined analysis. Each eligible study was independently analyzed for the risk of development of deep venous thrombosis in the control and stocking groups, and this was expressed as an odds ratio. Odds ratios were combined across studies by means of the Mantel-Haenszel chi 2 procedure. The data were analyzed separately for orthopedic surgery because of its high risk for venous thromboembolism. RESULTS: Eleven of the 12 studies were in moderate-risk surgery (abdominal, gynecologic, and neurosurgery); the summary odds ratio was 0.28, which translates into a risk reduction of 68% (95% confidence interval, 53% to 73%), which is statistically significant (P < .0001). In the one study in orthopedic surgery that was eligible for inclusion, the odds ratio was 0.50 (95% confidence interval, 0.19 to 1.29; P = .17). CONCLUSIONS: The use of graduated compression stockings for prophylaxis of venous thromboembolism after moderate-risk surgery results in a significant risk reduction. It is unknown whether the use of graduated compression stockings in combination with other forms of prophylaxis results in further risk reduction. The efficacy of graduated compression stockings in orthopedic surgery has been assessed by only one study that used sound methods, hence no definitive conclusions can be made in these high-risk patients.
LMWHs are an important new class of antithrombotic agents. They differ from UFH in having relatively more anti-Xa activity, greater bioavailability at low doses, longer half-life, and more predictable anticoagulant response when administered in fixed doses. These properties allow LMWHs to be administered QD or at most BID and without laboratory monitoring. The incidence of heparin-induced thrombocytopenia also appears to be lower with an LMWH than with heparin. Given their favorable pharmacological profile, it was of interest to critically appraise clinical trials of thromboprophylaxis and treatment with these new agents. In orthopedic trials, it was noted that LMWH provided safe and effective thromboprophylaxis for patients undergoing major orthopedic surgery of the lower limb. In those having hip arthroplasty, LMWH was as effective as low-intensity warfarin therapy, but its use was associated with more wound hematomas. In those having total knee arthroplasty, LMWH was more effective than warfarin and did not increase bleeding. However, the prevalence of DVTs complicating this procedure as well as acute hip fracture remains unacceptably high, and additional studies of LMWH in combination with other prophylactic methods, such as external pneumatic compression, are needed. Only one adequately designed trial found less bleeding resulted from LMWH prophylaxis administered at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH appeared to be as effective as UFH and had the advantages of less frequent injections and fewer injection site hematomas. In general surgical patients, there was a lower risk of thromboembolism but a trend toward an increase in bleeding events. Subjects with strokes and spinal cord injuries benefited from fewer thrombotic events, and the latter had fewer bleeding complications. Other potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis, and preservation of graft patency, are presently under study. Perhaps the most impressive benefits of LMWH will be realized when it is used for the treatment of venous thromboembolism. The meta-analysis presented in this review showed a trend toward greater efficacy with LMWH and fewer major bleeding events in comparison with adjusted-dose intravenous UFH. Also, during the months following the thrombotic event, there was significantly less mortality in patients receiving LMWH. A further advantage was the subcutaneous route of administration and lack of requirement for laboratory monitoring. Additional treatment trials are presently in progress and may establish LMWH as the treatment of choice for patients with thromboembolic disorders.
BACKGROUND: Two different diagnostic strategies are used to perform compression (real-time) ultrasound for the diagnosis of clinically suspected deep-vein thrombosis. One is to examine the entire proximal venous system from common femoral to distal popliteal vein; the other is a limited examination of only the common femoral and the entire popliteal vein. The latter strategy, which is less time-consuming and requires less expensive equipment, is based on a strong impression from prospective studies using limited compression ultrasound that proximal vein thrombi always involve the common femoral or popliteal vein. This impression, which is supported by the demonstrated safety at long-term follow-up of not treating patients whose limited compression ultrasound is normal at presentation and then repeated within the next week, has not been tested in a formal study. Therefore, we reviewed a large series of venograms performed in consecutive patients with clinically suspected venous thrombosis to determine the distribution of venous thrombosis in symptomatic patients. METHODS: Venograms were performed using 150 mL of radiographic contrast material. Before the study, a panel of experts agreed on the standardized criteria for the assessment of venograms. Venograms were adjudicated blindly for the presence of deep vein thrombosis and to determine the distribution of proximal vein thrombosis and isolated calf-vein thrombosis, the size of proximal thrombi, and whether they were occlusive or nonocclusive. Subsequently, the duration of symptoms was related to the venographic findings. RESULTS: Five hundred sixty-two venograms from consecutive patients with a first episode of clinically suspected deep vein thrombosis were adjudicated. Of these, 20 (3.6%) were inadequate for interpretation. In the remaining 542, venous thrombosis was demonstrated in 189 instances (prevalence, 35%; 95% confidence interval, 31% to 39%) and were located in the proximal veins in 166 (88%; 95% confidence interval, 82% to 92%) venograms. Isolated calf-vein thrombosis was present in the remaining 23 (12%; 95% confidence interval, 8% to 18%) venograms. Proximal with concurrent calf thrombosis was detected in 164 (99%) of the 166 patients. Proximal thrombi involved only the popliteal vein in 16 (10%); the popliteal and superficial femoral veins in 70 (42%); and the popliteal, superficial, and common femoral vein in eight (5%); whereas thrombi involving the entire proximal deep venous system were detected in 58 (35%) venograms. Isolated thrombosis of the superficial femoral, common femoral, and iliac vein was not observed. Proximal venous thrombi were occlusive in 146 (88%) patients. No relation between the duration of symptoms and the extent or the occlusiveness of venous thrombi could be demonstrated. CONCLUSIONS: Most symptomatic patients have extensive occlusive proximal vein thrombosis at the time of presentation. Thrombi isolated to the superficial femoral or iliac vein were not observed in this large sample of consecutive patients. Our data support the use of the relatively simple, inexpensive, and rapid compression ultrasound method that limits the examination of the proximal veins to the common femoral and popliteal veins.
BACKGROUND: Impedance plethysmography performed serially over a one-week period has been shown to be an effective diagnostic strategy for patients with clinically suspected acute deep-vein thrombosis. Compression ultrasonography has a high sensitivity and specificity for the detection of proximal-vein thrombosis. The clinical value of repeated ultrasonography in the management of symptomatic deep-vein thrombosis is unknown. METHODS: We conducted a randomized trial in 985 consecutive outpatients with clinically suspected deep-vein thrombosis to compare the diagnostic value of serial impedance plethysmography (494 patients) and serial compression ultrasonography (491 patients). We compared the positive predictive values of both tests for the diagnosis of venous thrombosis, using contrast venography as a reference. The frequencies of venous thromboembolism during a six-month follow-up period were also compared in patients with repeatedly normal results in order to evaluate the safety of withholding anticoagulant therapy from such patients. RESULTS: The positive predictive value of an abnormal ultrasonogram was 94 percent (95 percent confidence interval, 87 to 98 percent), whereas the predictive value of impedance plethysmography was 83 percent (95 percent confidence interval, 75 to 90 percent) (P = 0.02). In patients with repeatedly normal results, the incidence of venous thromboembolism during the six-month follow-up period was 1.5 percent (95 percent confidence interval, 0.5 to 3.3 percent) for serial compression ultrasonography, as compared with 2.5 percent (95 percent confidence interval, 1.2 to 4.6 percent) for serial impedance plethysmography. CONCLUSIONS: In making the diagnosis of deep-vein thrombosis in symptomatic outpatients, serial compression ultrasonography is preferable to impedance plethysmography, in view of its superior performance in detecting venous thrombosis.
In a prospective study, we compared real-time B-mode ultrasonography, using the simple criteria of common femoral and popliteal vein compressibility (Compression US), and Doppler ultrasound, using a standardized technique (Doppler US), with contrast venography in 158 consecutive outpatients symptomatic for deep-vein thrombosis of the lower limbs (DVT). For proximal vein thrombosis, the sensitivities documented for Compression US and Doppler US were 100% (95% CI: 90% to 100%) and 89% (95% CI: 76% to 96%), respectively. This difference is not statistically significant (p = 0.056). For all thrombi (including isolated calf-vein thrombosis), however, the sensitivity of Compression US was significantly higher than that of Doppler US (95% and 76%, respectively; p < 0.04). Compression US was normal in all patients with normal venogram (specificity, 100%; 95% CI: 95% to 100%), while Doppler US was abnormal in two patients with normal venogram (specificity, 98%; 95% CI: 92% to 100%). The specificities of the two tests did not differ significantly. The results of our comparison suggest that Compression US is superior to Doppler US in the detection of DVT in symptomatic outpatients.
OBJECTIVE: To determine the reasons why 125I-fibrinogen leg scanning, a screening test which was reported to be very sensitive for the detection of post-operative thrombosis, has shown poor sensitivity in contemporary studies. STUDY IDENTIFICATION: English-language reports were identified through a Medline computer search (1965-1991), Current Contents, and an extensive manual search of the bibliographies in identified articles. STUDY SELECTION: Studies in orthopaedic or general surgical patients were reviewed that compared 125I-fibrinogen leg scanning with venography in all patients (accuracy studies) or in patients in whom 125I-fibrinogen leg scanning became positive (positive predictive value studies). DATA EXTRACTION: A systematic appraisal of study design and specific descriptive information concerning the selection of patients. RESULTS OF DATA SYNTHESIS: Six of the 15 studies which compared 125I-fibrinogen leg scanning with venography were level 1 studies (potential for bias minimized) and nine were classified as level 2 studies (potential for bias not minimized). In orthopaedic surgical patients, the pooled sensitivity of leg scanning for isolated calf vein thrombosis, for all venous thrombosis, and the pooled specificity were 55%, 45%, and 92% for the level 1 studies, respectively. These indices were 88%, 82%, and 79%, respectively for the level 2 studies (P < 0.001). Only two (level 2) studies were found that evaluated the accuracy of leg scanning for venous thrombosis in general surgical patients. CONCLUSION: We conclude that leg scanning is an insensitive method for the screening of post-operative venous thrombosis in orthopaedic patients. Our findings call into question the validity of the many studies (including meta-analyses) evaluating prophylactic agents for venous thrombosis which used leg scanning as the only test for the assessment of efficacy.
OBJECTIVE: To re-evaluate the accuracy of impedance plethysmography (IPG) for the detection of proximal deep-vein thrombosis (DVT). PATIENTS: A total of 384 of 390 consecutive outpatients referred with their first episode of clinically suspected deep-vein thrombosis. SETTING: University-based tertiary care medical center associated with a cancer clinic. DESIGN: A retrospective analysis of a cohort of patients whose data were recorded and stored prospectively on a computerized data base over a 22-month period. MEASUREMENTS: Patients were evaluated by a physician and underwent IPG testing. Patients with abnormal IPG tests and those with normal IPG results in whom there was a high clinical suspicion of DVT or in whom follow-up IPG testing was not feasible were referred for venography. Venography and IPG results were interpreted by a panel of independent observers. Two models of the IPG instrument were used (Codman 200 and Electrodiagnostic Instruments 800). RESULTS: Venography (or compression ultrasound) was done in 57 patients with an abnormal IPG test and in 85 patients with normal IPG results. Impedance plethysmography was abnormal in only 37 of 56 patients with confirmed proximal-vein thrombosis (sensitivity, 66%; 95% Cl, 52% to 78%). Of the 57 patients with an abnormal IPG result, 37 had DVT (positive predictive value, 65%). The sensitivity for the detection of proximal DVT did not differ between the IPG 200 and 800 instruments (sensitivity, 63% and 71%, respectively; P > 0.2). Of the 19 proximal-vein thrombi not detected by IPG, 12 (63%) were occlusive and 11 (58%) involved at least the popliteal and superficial femoral veins. CONCLUSIONS: At our center, IPG has a far lower sensitivity for proximal-vein thrombosis than has been previously reported for symptomatic outpatients. The reason for this low sensitivity is unclear. Our findings indicate that centers using IPG as the initial diagnostic test for suspected DVT should be aware of this potential problem and should consider re-evaluating the sensitivity of their IPG machines by performing venography in a cohort of their patients with normal test results.
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OBJECTIVE: To evaluate the ability of color Doppler ultrasound to detect proximal deep venous thrombosis (DVT) in asymptomatic high-risk patients who subsequently underwent contrast venography. DESIGN: Prospective cohort study using blinded observers, with contrast venography as the comparison standard. SETTING: Seven medical centers (university and community hospitals) participating in a clinical trial of low-molecular-weight heparin for prevention of DVT. PATIENTS: A total of 385 consecutive patients undergoing elective unilateral hip or knee replacement. MEASUREMENTS: Ten days after surgery or before hospital discharge (whichever occurred first), patients had bilateral color Doppler ultrasound examinations of the proximal veins of the lower extremities. Subsequently, a contrast venogram of the operated leg was obtained. RESULTS: Color Doppler ultrasound studies and venograms were both evaluable in 319 of the 385 patients. Deep venous thrombosis was identified by contrast venography in 80 patients (prevalence, 25%; 95% CI, 20% to 30%) and involved the proximal veins in 21 patients (prevalence, 7%; CI, 4% to 10%). For proximal DVT, color Doppler ultrasound showed poor sensitivity (38%; CI, 18% to 62%), moderately good specificity (92%; CI, 89% to 95%), and a poor positive predictive value for this population (26%). CONCLUSION: Color Doppler ultrasound examinations are insensitive to proximal DVT in asymptomatic high-risk patients and should not be substituted for venography for identifying proximal DVT in such patients.
BACKGROUND: In contrast to the established relation between overt cancer and subsequent venous thromboembolism, it is unclear whether symptomatic deep-vein thrombosis is associated with a risk of subsequent overt malignant disease. METHODS: Two hundred sixty consecutive patients with symptomatic, venographically proved deep-vein thrombosis were enrolled in a study, of whom 250 were followed during a two-year period. Among those assessed during follow-up, the incidence of subsequently detected cancer in the 105 patients with secondary venous thrombosis (i.e., thrombosis associated with a well-recognized risk factor other than cancer) was compared with the incidence of cancer in the 145 patients with idiopathic venous thrombosis. RESULTS: Routine examination at the time of diagnosis of the venous thrombosis revealed cancer in 5 of the 153 enrolled patients with idiopathic venous thrombosis (3.3 percent) and in none of the 107 enrolled patients with secondary venous thrombosis. During follow-up, overt cancer developed in 2 of the 105 patients with secondary venous thrombosis (1.9 percent) and in 11 of the 145 patients with idiopathic venous thrombosis (7.6 percent; odds ratio, 2.3; 95 percent confidence interval, 1.0 to 5.2; P = 0.043). Of the 145 patients with idiopathic venous thrombosis, 35 had confirmed recurrent thromboembolism. Overt cancer subsequently developed in 6 of the 35 (17.1 percent). The incidence of cancer in the patients with recurrent idiopathic venous thrombosis was higher than that in the patients with secondary venous thrombosis (P = 0.008; odds ratio, 9.8; 95 percent confidence interval, 1.8 to 52.2) or in the patients with idiopathic venous thrombosis that did not recur (P = 0.024; odds ratio, 4.3; 95 percent confidence interval, 1.2 to 15.3). CONCLUSIONS: There is a statistically significant and clinically important association between idiopathic venous thrombosis and the subsequent development of clinically overt cancer, especially among patients in whom venous thromboembolism recurs during follow-up.
OBJECTIVE: To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans. DESIGN: A randomized trial. STUDY POPULATION: Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism. INTERVENTION: Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme. MEASUREMENTS: Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic. RESULTS: Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P less than 0.01), whereas intra-observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09). CONCLUSION: Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism.
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We studied the usefulness of the determination of plasma D-dimer levels (using an ELISA) in combination with non-invasive testing with impedance plethysmography (IPG) or real-time ultrasonography (US) for the diagnosis of deep-vein thrombosis (DVT), in outpatients with clinically suspected DVT. This combined approach was compared to serial non-invasive testing alone in these patients. The sensitivity of a positive D-dimer test (greater than 300 micrograms/l) for the presence of DVT was 100% (70/70 patients; 95% C.I.: 95-100%), whereas the specificity was 29% (69/239 patients; 95% C.I.: 23-34%). The proportion of patients in which a definitive decision about the presence or absence of DVT could be made on the day of referral, was calculated for both approaches. When applying the combined approach, in 42% of all referred patients the diagnosis of DVT could either be established or refuted on entry, as opposed to only 19% of patients using serial non-invasive testing alone. Also, the costs per DVT diagnosed were calculated for the two diagnostic approaches. For the diagnosis of DVT the costs using serial IPG were comparable to the costs using the combination of IPG and the D-dimer test. The same conclusion holds for the comparison of serial US with the combination of US and D-dimer testing. We conclude that for the diagnosis of DVT in symptomatic outpatients the combination of non-invasive testing with the D-dimer test might be preferred over serial non-invasive testing alone, although the safety of such an approach remains to be established in future management studies.
In view of the potential of low-molecular-weight heparins (LMWH) to simplify initial therapy and allow outpatient treatment of proximal deep-vein thrombosis, we undertook a randomised comparison of fixed-dose subcutaneous LMWH with adjusted-dose intravenous standard heparin in the initial treatment of this disorder. Our main objectives were to compare the efficacy of these regimens for 6 months of follow-up and to assess the risk of clinically important bleeding. Of 170 consecutive symptomatic patients with venographically proven proximal deep-venous thrombosis, 85 received standard heparin (to achieve an activated partial thromboplastin time of 1.5 to 2.0 times the pretreatment value) and 85 LMWH (adjusted only for body weight) for 10 days. Oral coumarin was started on day 7 and continued for at least 3 months. The frequency of recurrent venous thromboembolism diagnosed objectively did not differ significantly between the standard-heparin and LMWH groups (12 [14%] vs 6 [7%]; difference 7% [95% confidence interval -3% to 15%]; p = 0.13). Clinically important bleeding was infrequent in both groups (3.5% for standard heparin vs 1.1% for LMWH; p greater than 0.2). We conclude that fixed-dose subcutaneous LMWH is at least as effective and safe as intravenous adjusted-dose heparin in the initial treatment of symptomatic proximal-vein thrombosis. Since there is no need for laboratory monitoring with the LMWH regimen, patients with venous thrombosis can be treated at home.
To determine whether the Rabinov-Paulin or the long-leg venography technique should be preferred in the diagnostic management of patients with clinically suspected deep-vein thrombosis, two independent experienced radiologists blindly assessed two different series of venograms of consecutive outpatients with clinically suspected deep-vein thrombosis. Venograms were obtained from two outpatient clinics of primary referral centres. In one centre the venograms were performed according to the technique of Rabinov and Paulin with the use of 100 ml of radiographic material and spot films of the calf, popliteal and more proximal veins. In the other centre, long-leg films were obtained after the administration of 150 ml of contrast material. The percentage venograms adjudicated as inadequate by at least one radiologist and inter-observer disagreement for both series were used as the main study outcome measures. Prior to the study, both radiologists agreed on the standardized criteria for a normal, abnormal and inadequate test result using a separate set of films. An inadequacy rate of 20% was found for the Rabinov-Paulin venography series (n = 123), whereas only 2% of the 126 long-leg films were inadequate for interpretation (p less than 0.001). The inter-observer diagreement for inadequacy, presence or absence of deep-vein thrombosis was 21% for the Rabinov and Paulin venograms and 4% for the long-leg films (kappa, 0.65 and 0.92; 95% confidence intervals: 0.53 to 0.77 and 0.84 to 0.99, respectively; p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)
In the diagnostic management of patients with clinically suspected recurrent deep-vein thrombosis (DVT), there are potential limitations to all available diagnostic techniques. Since venous abnormalities may persist for some time after an acute thrombosis, the usefulness of compression ultrasonography (US) for the detection of recurrent DVT may be jeopardized. We determined the rate of normalization of an abnormal compression US test of the popliteal and the common femoral veins in patients after a first episode of proximal DVT. In a cohort of 60 consecutive patients, the test result was normalized in only 29, 44, 54, and 60% of patients at 3, 6, 9, and 12 months, respectively. The investigation shows that for the detection of recurrent DVT of the leg, real-time compression US (using the single criterion of compression of the common femoral and popliteal vein) is of limited value. Future studies need to be performed, using more subtle interpretation of the compression US result, by quantifying the extent of residual thrombus, which may increase the usefulness of this test in patients with recurrent symptoms.