Diagnostic tests for deep vein thrombosis. Clinical usefulness depends on probability of disease.

We review the general principles that govern the clinical utility of diagnostic tests, particularly with respect to the diagnosis of deep vein thrombosis (DVT). We stress the importance of clinical probability of disease, which strongly influences the positive predictive value (true-positive rate) and negative predictive value (true-negative rate) of all diagnostic tests. In selecting a diagnostic procedure for DVT, the physician must first consider the clinical probability of disease and then the local accuracy of the test employed and its cost-effectiveness. In 75% to 80% of patients suspected to have DVT, clinical management can be based on the results of noninvasive tests, such as ultrasonography or impedance plethysmography (IPG), rather than venography. Ultrasonography has clear advantages over venography with respect to cost and patient comfort, and it defines the anatomic extent of the thrombus. It should be considered the new diagnostic standard for symptomatic DVT. Despite recent reports of lower sensitivity than previously reported, IPG remains an acceptable alternative to ultrasonography for symptomatic DVT in selected patients. Even if the recently reported lower sensitivity proves to be accurate, the probability of adverse clinical outcomes as a result of overlooked disease is still extremely low in patients with a low probability of DVT. The negative predictive value of IPG under these circumstances approaches 99%. Impedance plethysmography is also useful in patients with a high probability of DVT, in whom the positive predictive value may be as high as 97%. When the findings of IPG (or ultrasonography) are at variance with a strong clinical impression, venography should be considered, especially when there is a high clinical probability of disease and a negative noninvasive test result.

The prevalence of risk factors for venous thromboembolism among hospital patients.

BACKGROUND: This study provides an estimate of the prevalence of risk factors for venous thromboembolism among hospital patients. METHODS: The presence of risk factors for venous thromboembolism was determined from a retrospective review of the medical records of 1,000 randomly selected patients in 16 acute care hospitals in central Massachusetts. RESULTS: The most common risk factors for venous thromboembolism were age 40 years (59%) or more, obesity (28%), and major surgery (23%). The average number of risk factors increased with increasing age. One or more risk factors for venous thromboembolism were present in 78% of hospital patients, two or more in 48%, three or more in 19%, four or more in 6%, and five or more in 1%. CONCLUSION: Risk factors for venous thromboembolism are common among hospital patients, suggesting that prophylaxis should be widely employed. The cost-effectiveness and risk benefit of prophylaxis is well established in patients undergoing major surgery. Further studies are needed to confirm the benefit of prophylaxis in patients with nonsurgical risk factors for venous thromboembolism.

A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study.

A community-wide study was conducted in 16 short-stay hospitals in metropolitan Worcester, Mass, to examine the incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism in patients hospitalized between July 1, 1985, and December 31, 1986. The average annual incidence of deep vein thrombosis alone was 48 per 100,000, while the incidence of pulmonary embolism with or without deep vein thrombosis was 23 per 100,000. The incidence rates of deep vein thrombosis and pulmonary embolism increased exponentially with age. The in-hospital case-fatality rate of venous thromboembolism was 12%. Among patients discharged from the hospital, the long-term case-fatality rates were 19%, 25%, and 30% at 1, 2, and 3 years after hospital discharge. Extrapolation of the data from this population-based study suggests that there are approximately 170,000 new cases of clinically recognized venous thromboembolism in patients treated in short-stay hospitals in the United States each year, and 99,000 hospitalizations for recurrent disease. Because of the silent nature of this disease and the low rate of autopsy in the United States, the total incidence, prevalence, and mortality rates of venous thromboembolism remain elusive.

Changing clinical practice. Prospective study of the impact of continuing medical education and quality assurance programs on use of prophylaxis for venous thromboembolism.

OBJECTIVE: To determine the effect of continuing medical education (CME) with and without a quality assurance component (CME+QA) on physician practices in the prevention of venous thromboembolism. METHODS: A communitywide study was performed in 15 short-stay hospitals in central Massachusetts. The study population included 3158 patients in acute-care hospitals with multiple risk factors for venous thromboembolism. Study hospitals were randomly assigned to one of two educational strategies or to a control group that received no intervention. RESULTS: The proportion of patients at high risk for venous thromboembolism who received effective methods of prophylaxis increased significantly from 29% in 1986 to 52% in 1989 (P < .001). This increase was seen in all study groups: control hospitals, 40% to 51% (P < .001); CME hospitals, 21% to 49% (P < .0001); and CME+QA hospitals, 27% to 55% (P < .0001). The increase in prophylaxis use from 1986 to 1989 was significantly greater among patients cared for in hospitals whose physicians participated in a formal CME program (an increase of 28%) than in control hospitals (an increase of 11%) (P < .001). There was no significant difference in the use of prophylaxis in hospitals whose physicians received CME+QA interventions compared with hospitals whose physicians received CME interventions alone (identical increases of 28%). CONCLUSION: A formal CME program significantly increased the frequency with which physicians prescribed prophylaxis for venous thromboembolism. We believe the key factor in our CME interventions that motivated clinicians to change their practices was the provision of hospital-specific data demonstrating a compelling need for improvement. Despite the substantial investment by hospitals in QA, traditional QA intervention appeared to provide no additional benefit. Even after extensive CME/QA interventions, prophylaxis for venous thromboembolism remained underutilized, suggesting the need to develop new approaches to changing clinical practice.

The clinical implications of bilaterally abnormal impedance plethysmography.

Although impedance plethysmography (IPG) is a test of recognized value in the diagnosis of acute proximal deep venous thrombosis (DVT), its meaning in patients with bilaterally abnormal IPGs is unclear. Consequently, we sought to determine the clinical significance of the bilaterally abnormal IPG in hospitalized patients. In a five-month prospective study, 19% (81/425) of all IPGs done at our institution were bilaterally abnormal (55% of all abnormal IPGs). Acute proximal DVT was found in 26% (14/53) of patients with bilaterally abnormal IPGs who underwent further diagnostic testing. Thirty-five percent of the patients with DVT were found to have either bilateral lower extremity DVT or clots in the inferior vena cava. A numerical score, the venous function index (VFI), was computed for the 101 legs for which further definitive diagnostic evaluations for DVT had been completed. The mean VFI of seven for legs with acute proximal DVT was significantly less than the mean VFI of 13 for legs with no DVT. Fifty percent of legs with a VFI less than or equal to five had DVT, whereas only 7% of legs with a VFI greater than 15 had DVT. The bilaterally abnormal IPG is a common clinical occurrence, is frequently associated with acute DVT, and the VFI is helpful in discriminating legs with acute proximal DVT from normal legs in patients with a bilaterally abnormal IPG.

Occult malignant neoplasm in patients with deep venous thrombosis.

An association between venous thrombosis and cancer was first suggested by Armand Trousseau and subsequently confirmed by multiple postmortem studies. In a previous study, patients with pulmonary embolism, as assessed by pulmonary angiography, were at significantly increased risk of occult cancer with a comparison group of patients without pulmonary embolism. This nonconcurrent prospective epidemiologic study extends these findings by demonstrating a significantly increased risk of occult cancer in patients with deep venous thrombosis (DVT) confirmed by impedance plethysmography as compared with those with suspected DVT in whom the diagnosis was ruled out. Differences in the incidence of malignant neoplasms were greatest within the first two years after the diagnosis of DVT, and patients younger than 50 years with venous thrombosis were at particularly increased risk of occult cancer (relative risk, 19.0). These findings indicate that all patients with DVT or pulmonary embolism should have an appropriate diagnostic workup and careful follow-up, particularly with regard to the risk of occult cancer.

Randomized controlled trial of tissue plasminogen activator in proximal deep venous thrombosis.

PURPOSE: To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg. PATIENTS AND METHODS: Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy. RESULTS: Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone. CONCLUSION: (1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.

Diagnostic approaches for deep vein thrombosis.

This article briefly reviews the advantages and limitations of currently available methods for the diagnosis of deep vein thrombosis (DVT). Clinical evaluation alone is inadequate but still useful in assessing the need for further testing. The medical history, especially the detection of risk factors for DVT, is as important as the physical examination. Confirmation by objective diagnostic tests is essential. Venography has been the traditional standard for determining the optimal management of DVT, but has significant limitations which are not widely appreciated. Noninvasive diagnostic methods for DVT are essential for effective management, but the optimal method for a particular hospital depends on the personnel and resources available.

Transvenous interruption of the inferior vena cava.

Transvenous interruption of the inferior vena cava was successful in 45 of 47 consecutive patients treated during a 41/2-year period. Greenfield filters were used in 40, and Mobin-Uddin umbrellas in 5 others. Technical details of the insertion procedure are of particular importance for successful implantation of the Greenfield device. Follow-up data were available for 34 of 36 surviving patients and autopsy findings for 4 of the 11 who had died. Patency of the vena cava was assessed by radionuclide scan, venography, or autopsy. Of 33 patients with Greenfield filters who were evaluated, only one had an occluded filter, for a patency rate of 97%. One of the three patients with a Mobin-Uddin umbrella had caval thrombosis. Severe postoperative venous stasis was seen in one patient with a Greenfield filter and one with a Mobin-Uddin umbrella. Significant distal migration or angulation of Greenfield filters was observed in six patients and is a theoretical cause for recurrent embolization. The 30-day mortality rate for the patients who had transvenous procedures was 13%, but no deaths were attributed to the procedure itself. There were no clinically evident pulmonary emboli during the follow-up period. In the present study we have documented low operative morbidity and mortality rates as well as complete protection from recurrent pulmonary embolism using transvenous interruption of the inferior vena cava. Although the Greenfield filter is somewhat bulkier and more difficult to insert than the Mobin-Uddin umbrella, it has a clear advantage because of its superior long-term patency.

Long-term survival and quality of life following ruptured abdominal aortic aneurysm.

To document both the long-term survival and the quality of life of patients following surgery for ruptured abdominal aortic aneurysm (AAA), the records of 65 patients with ruptured AAA resection were compared with those of 100 who underwent elective AAA resection. The actuarial survival following ruptured aneurysm surgery was 92%, 51%, and 51% at 1, 5, and 10 years, respectively, and did not differ statistically for patients after elective AAA surgery or for an age- and sex-matched sample from the general population. Based on responses to a quality of life survey, there were no discernible differences in life-style, degree of independence, or productivity following either ruptured or elective AAA surgery. Survivors of ruptured AAA have an excellent long-term prognosis and expectation for a good quality of life.

Noninvasive detection of carotid stenosis following endarterectomy.

Noninvasive diagnostic studies (oculoplethysmography, pulsed Doppler arteriography, and phonoangiography) were used to follow the postoperative courses of 172 patients who had 199 carotid endarterectomies. There were 24 restenotic arteries in 21 patients who underwent 29 operations. Fifteen restenotic lesions in 14 patients were detected solely by noninvasive testing. These patients are being observed closely and remain asymptomatic. One has been operated on for progression of disease. Either transient or permanent neurologic deficits developed in nine as the initial indication of recurrent stenosis or occlusion; three of these subsequently have undergone reoperation. Patients with bilateral disease are at increased risk of restenosis. Routine testing of all patients undergoing carotid endarterectomy is recommended 1, 3, and 12 months postoperatively to detect and observe stenosis on both the side operated on and the contralateral side before clinical symptoms develop.

Prediction of the development of sigmoid ischemia on the day of aortic operations. Indirect measurements of intramural pH in the colon.

A deviation in an indirect measurement of intramural pH below the limits of normality (6.86) was used as a diagnostic test for sigmoid ischemia in 25 high-risk patients undergoing abdominal aortic operations. The clinical diagnosis of ischemic colitis was made by the attending physicians in only two of the 25, on the day after operation in one and three months after operation in another. In neither was the ischemic colitis considered to have been a causative factor in their subsequent deaths. In contrast, six patients developed pH evidence of ischemia on the day of operation. All six subsequently developed a transient episode of guaiac-positive diarrhea, four developed physical signs consistent with ischemic colitis, and four died. Of 19 who did not develop pH evidence of ischemia, none developed guaiac-positive diarrhea, none developed any signs of ischemic colitis, and none died. Stepwise logistic regression showed the duration of pH evidence of ischemia on the day of operation to be the best predictor for the symptoms and signs of ischemic colitis and for death after operation.

Suspected deep vein thrombosis. Management by impedance plethysmography.

Controversy exists as to whether patients suspected of having deep vein thrombosis (DVT) can be studied safely without venography, with its attendant expense, inconvenience, and potential risk. We used impedance plethysmography (IPG) in 1,464 consecutive patients suspected of having DVT, with 96% of these patients with normal IPGs, there were no fatal pulmonary emboli (PE). The incidence of nonfatal PE was 1%. In 284 outpatients suspected of having DVT, but discharged without treatment because of normal IPGs, only one patient returned with subsequent symptoms of DVT (0.4%). Noninvasive testing with IPG is a safe and highly cost-effective alternative to venography for routine management of patients suspected of DVT.

Venous thromboembolism. Risk factors and prophylaxis.

Most deaths from pulmonary embolism can be prevented by providing adequate prophylaxis for hospital patients who are at high risk for venous thromboembolism. Physicians, however, must be able to identify high-risk patients (including those with major trauma, hip or knee replacement, or pelvic fractures) and prescribe an appropriate prophylactic agent for each patient according to his or her level of risk. A number of prophylactic methods have been proven effective in the prevention of venous thromboembolism, including low-dose heparin, low-molecular-weight heparin, warfarin, graduated compression stockings, and intermittent pneumatic compression of the legs.

Recommendations for incorporating palliative care education into the acute care hospital setting.

This article presents recommendations for improving the education of physicians about end-of-life care in the acute care hospital setting. The authors, who have a variety of backgrounds and represent several types of institutions, formulated and reached consensus on these recommendations as members of the Acute Care Hospital Working Group, one of eight working groups convened at the National Consensus Conference on Medical Education for Care Near the End of Life in May 1997. A recently published literature review on the status of palliative care education, a summary of recent research on education about end-of-life care, and expert opinion were helpful in developing the recommendations. The authors emphasize that the acute care setting offers many opportunities for education about care at the end of life. Faculty should support learners' appreciation of the importance of end-of-life care, and convey the meaning and privilege of attending to patients and families at this difficult time. Faculty should teach students and residents to provide care that embodies attention to the control of distressing physical, physiologic, and spiritual symptoms, appropriate awareness of patients' differing cultural backgrounds and their impact upon the experience of dying, excellent communication skills, the application of bioethical principles, timely referral and smooth transition to other care settings that meet patient and family goals, and the role of the interdisciplinary team in meeting the diverse needs of dying patients and their families.

Diagnosis of deep vein thrombosis. Review of clinical evaluation and impedance plethysmography.

This article has briefly reviewed the diagnosis of DVT by clinical evaluation and by impedance plethysmography. Clinical evaluation alone cannot be relied on for patient management, but when carefully performed, it remains useful in determining the need for additional testing. The medical history, especially the detection of risk factors for DVT, is as important as the physical examination. In 1,464 patients suspected of DVT, the incidence of this disease by impedance plethysmography was only 11 percent when there were no major risk factors present but increased to 50 percent when three risk factors were present. Impedance plethysmography is a widely used noninvasive test for the diagnosis of DVT. It has a sensitivity and specificity of 94 percent based on correlation with 2,561 venograms. The method is based on quantitation of the venous outflow from the calf after temporary venous occlusion in the thigh. It is particularly helpful in ruling out DVT in patients with suspicious signs or symptoms. Recent improvements in methods, including computer-assisted data analysis, appear likely to further extend its usefulness.

Prophylaxis against venous thromboembolism in surgical patients.

Venous thromboembolic disease is a common, potentially life-threatening, but preventable complication of surgery. Venographic studies have shown a high incidence of deep vein thrombosis in patients who do not receive prophylaxis. The long-term sequelae of deep vein thrombosis in these patients can be disabling, but the exact prevalence of post-thrombotic complications has not been well documented. Fatal pulmonary embolism has been reported in 0.5% to 1% of patients after major abdominal surgery and in 2% to 6% after total hip replacement. Several methods of prophylaxis against venous thromboembolism have demonstrated efficacy, but a surprising number of patients still do not receive prophylaxis. A medical record review in 16 hospitals recently disclosed that only 32% of high-risk patients received prophylaxis, with a range from 9% in a community hospital to 56% in a major teaching hospital. The possible reasons for this comparatively low rate of utilization are discussed. Current issues and future trends in the prophylaxis of venous thromboembolism are briefly summarized.

Assessment of operative risk with electrocardiographic exercise testing in patients with peripheral vascular disease.

Doppler ankle blood pressures were performed inere obtained in 100 consecutive patients with peripheral arterial insufficiency after treadmill exercise. A twelve lead electrocardiogram was monitored during and after exercise. Despite a restricted ability to exercise because of peripheral vascular insufficiency, forty-six patients had ventricular dysrhythmia or ischemia, or both, usually without associated symptoms. Electrocardiographic monitoring during treadmill exercise proved a useful predictor of postoperative complications. Thirty-two vascular operations were performed in patients with no electrocardiographic evidence of ischemia. No patient had a postoperative myocardial infarction or died. Sixteen vascular procedures were performed in patients with ischemic responses on exercise electrocardiography. Six patients had postoperative myocardial infarctions, two of which were fatal. Electrocardiographic monitoring during treadmill exercise for peripheral vascular insufficiency in recommended (1) to assess the severity of coronary artery disease and the likehood of postoperative complications, and (2) as a precautionary measure to identify potentially dangerous dysrhthmias or ischemia during exercise before the development of clinical symptoms.

Applicability and interpretation of electrocardiographic stress testing in patients with peripheral vascular disease.

Electrocardiographically monitored arterial stress testing was performed before surgery in 130 patients with peripheral vascular disease. When limitations of claudication or pain at rest precluded treadmill exercise, arm ergometry was employed. The electrocardiographically monitored arterial stress test proved a cost-effective, easily applicable means of screening for coronary artery disease in this group of patients. Unlike statistical analyses of historical risk factors, the electrocardiographically monitored arterial stress test evaluates the current functional state of the myocardium. We believe that preoperative electrocardiographic exercise testing should be employed more widely and should be considered in any patient facing major surgery in whom coronary artery disease is suspected on the basis of past history or known risk factors. In patients who have an ischemic response to exercise, particularly at less than 75 percent of the maximum predicted heart rate, coronary angiography and possibly coronary revascularization should be considered before elective major surgery is performed.

Noninvasive detection of axillary and subclavian venous thrombosis by impedance plethysmography.

Venous occlusion impedance plethysmography (IPG) is an objective noninvasive test which is widely employed for the detection of deep venous thrombosis (DVT) in the lower extremities. The IPG technique is easily adapted to the evaluation of upper extremity venous thrombosis, as demonstrated in 46 patients with symptoms of axillary and subclavian venous thrombosis (88 limbs) and 26 normal volunteers (52 limbs). Venograms were obtained in 18 patients (22 limbs) and correlated in all cases with the previous IPG interpretation. The test procedure and interpretation criteria for the noninvasive detection of upper extremity deep venous thrombosis are similar to those previously developed for the lower extremities, but with more emphasis on comparison with the contralateral limb. Vascular laboratories performing IPG for lower extremity DVT should be able to employ this test for the detection of upper extremity venous thrombosis as well.