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Deep venou thrombosis and pulmonary embolism are significant causes of morbidity and mortality in the United States estimates range from 120,000 to 150,000 deaths annually. Although usually symptomatic, deep venous thrombosis can be clinically occult in part due to incomplete obstruction or in part related to duplication, triplication, and fenestration anomalies, primarily of the superficial femoral or popliteal vein. Additionally, pulmonary emboli caused by deep venous thrombosis may be clinically silent. Because of therapeutic implications, especially indications for insertion of inferior vena caval filters, comprehensive assessments of both the disease process (i.e., deep venous thrombosis) and the complication (i.e., pulmonary emboli) are

: important. Thus, when a pulmonary embolus is the presenting process, correlative assessment of deep venous thrombosis, : ;eVen in the absence of symptoms or signs in the lower extremity, .

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may be of therapeutic significance. Conversely, when deep yenous thrombosis of the lower extremities involving the pophteal or superficial femoral vein is the presenting process, correlative assessment of the pulmonary circulation, even when no pulmonary symptoms or signs are present, may be of therapeutic significance. Relative to the diagnosis of pulmonary embolism, the roles of assays of D-dimer, ventilation-perfusion lung scans, and segmental occlusion studies of the pulmonary circulation are discussed. Finally, the indications for insertion of inferior vena caval filters above the renal veins are presented and examples

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It is with great pleasure that I accepted the invitation to give the 1 992 Holmes Lecture. I have been gone from Boston for 1 5 years, but have never forgotten my deep association

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with the radiology community in New England and with the New England Roentgen Ray SocIety Grge Winslow Holmes was born December 21 1 876, in Waldo, ME. After his medical training at Tufts Medical School, his internship in medicine at the Boston CIty Hospital and his

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residency in medicine at the assistant skiagrapher at the : under the direction of James Holmes established the first rgram in the United States Hospital in 1 91 5. By 1 91 7,

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Long Island Hospital, he became Massachusetts General Hospital, Dodd, from 191 0 to 1 91 1 Dr. radiology residency training proat the Massachusetts General Dr. Holmes was roentgenologist

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in chief at the Massachusetts General Hospital. In 1931 he became clinical professor of radiology at Harvard Medical School. He was president of the New England Roentgen Ray Society from 1 921 to 1 922 and gave the first Holmes Lecture .

of the New England Roentgen Ray Society in 1 945. Author of two textbooks and more than 60 articles in the radiologic literature, Dr. Holmes was in great demand as a lecturer and teacher. He delivered the Carmen Lecture of the Radiological Society of North America and received its gold medal in 1937. He also gave the Caldwell Lecture of the American Roentgen Ray Society in 1940. He died March 1 8, 1959, in Belfast, ME. I have chosen the topic of deep venous thrombosis and pulmonary embolism, correlative evaluation and therapeutic implications as the subject of my lecture My interest in this area has its roots in my early experience at Boston City Hospital and Boston University Medical Center. In the past 15 years, it has been my good fortune to expand and update

ReceivedApril 14, 1992; accepted after revision June 10, 1992. Presented at the annual meeting of the New England Roentgen Ray Society, Boston, MA, April 1 992. 1 Department of Radiology, Slot 556, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock,

AR 72205.

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1150

my thinking on this topic at the University of Arkansas for Medical Sciences. The true prevalence of deep venous thrombosis is not known. It has been estimated, however, that between 1 20,000 and 1 50,000 people die each year in the United States of acute pulmonary thromboembolism, and that probably between 750,000 and 900,000 patients have significant severe, usually symptomatic, major pulmonary embolism annually in this country [1]. In order to assess the disease process (i.e., deep venous thrombosis) and its complication (i.e. pulmonary embolism), a structured approach is vital. In this regard, it must be recognized that the clinical manifestations are varied, and hence the use of noninvasive and invasive testing also will vary. Furthermore, dual assessment, first of the process causing the clinical signs and symptoms and then of any other component, be it deep venous thrombosis or pulmonary embolism, may be important with respect to therapeutic implications. I use the term correlative evaluation when deep venous thrombosis is assessed in a patient who has no marked signs or symptoms in the leg but does have major signs and symptoms in the chest. Conversely, correlative evaluation of the pulmonary circulation may be indicated, even though the patient has no pulmonary signs or symptoms, when certain deep venous thrombotic processes occur in the lower extremities. ,

Peripheral Significance

Venous Thrombosis: Diagnostic of Location, and Correlative

Evaluation, Lung Scanning

Peripheral venous thrombosis was studied in detail as early as 1 860 by Virchow [2]. He recognized that many factors were involved, including venous and endothelial damage, venous stasis, and hypercoagulability of blood. In most patients in whom deep venous thrombosis develops, the thrombus forms initially in the calf veins [3, 4]. This is true with the average patient, but in a smaller group of patients who undergo hip surgery, deep venous thrombosis tends to develop initially in the iliofemoral system, rather than in the calf [5]. Because of the increased use of catheters that are inserted into the upper extremity for long periods, particularly for chemotherapy or pain relief, deep venous thrombosis in the upper extremity is becoming commonplace. In a recent review, Monreal et al. [6] found that six of 30 patients with upper extremity thrombosis (20 catheter related) had evidence of abnormal perfusion on radionuclide lung scans, although the probability of having pulmonary emboli was high in only four of them. Several others [7-10] have found similar relationships between pulmonary embolism and upper extremity deep venous thrombosis. Figure 1 shows an intravascular sonogram of the right innominate vein in a 65-year-old man with symptomatic pulmonary emboli as determined by a radionuclide lung scan (high probability according to the criteria of Biello et al. [11]). Duplex sonography showed no obvious deep venous thrombosis involving either lower extremity, and bilateral lower extremity phlebograms of the calf veins showed no thrombosis. Intravascular sonography of the

AJR:159,

December

1992

right innominate vein showed a large filling defect (Fig. 1 A). Findings on venography (Fig. 1 B) confirmed the presence of a thrombus. This thrombus might have been overlooked if intravascular sonography had not been used. The patient had had an indwelling catheter inserted by way of the right subclavian vein, and intravascular sonography was used to look for a thrombus (i.e., the source of pulmonary emboli). He had no previous or current signs or symptoms suggesting venous thrombi in the innominate vein. How is this related to pulmonary emboli? The association is so close between venous thrombosis, detachment, and embolization that it is likely that many patients of this type will have pulmonary emboli. If for some reason anticoagulation is contraindicated, then the problem is placement of a filter in the superior vena cava vs the standard position, the infrarenal portion of the inferior vena cava (Figs. 1 C and 1 D). In our search of the literature, we were able to find only one similar situation in which a filter was placed in the superior vena cava [12]. The diagnosis of deep venous thrombosis is clinically difficult. When signs and symptoms first suggest that the patient might have deep venous thrombosis, diagnosis based on clinical findings is wrong approximately half the time. Furthermore, deep venous thrombosis is asymptomatic in many patients. In one study, in which venography of the lower extremities was performed in patients who had no symptoms or signs of deep venous thrombosis, but who had symptomatic pulmonary emboli, the prevalence of deep venous thrombosis was 30% [5]. Deep venous thrombosis can be asymptomatic for the following reasons [1 3]: (1 ) The thrombus may incompletely block the superficial femoral vein or popliteal vein. As flow is not markedly diminished, collateral circulation or stasis with edema below the thrombus does not occur. (2) In many anomalies, duplication (20%), fenestration (8%), or triplication (2%) of the superficial femoral vein or the popliteal vein (5%) occurs [5] (Fig. 2). When that happens, thrombosis of one of the duplicated veins may be asymptomatic because of patency of the parallel duplicated vein, which allows continued venous return without physical findings of obstruction. Figures 3-5 show venous obstruction with and without symptoms. Furthermore, because of the deep collateral circulation, no external manifestation of obstruction occurs. Yet these patients have a high risk of pulmonary thromboembolic disease, particularly if they are not treated [5]. In general, deep venous thrombosis of the calf propagates to the popliteal or superficial femoral venous system in about 20% of patients [1 4]. It is important to recognize the significance of popliteal venous and superficial femoral venous occlusive disease. Fewer than 1 0% of untreated patients with calf thrombosis have embolization of thrombus to the lung, whereas embolization occurs in approximately 50% in untreated patients with superficial femoral or iliac venous thrombosis. Furthermore, the hemodynamic changes in the pulmonary circulation would logically tend to be greater when the venous thrombus originates from a large vein such as the superficial femoral vein or the iliac vein. Just who should be tested for deep venous thrombosis? Obviously, anyone with swelling, pain, and tenderness of the extremity may have venous thrombi in the deep veins of the

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Fig. 1.-Thrombus in innominate vein of a 65year-old man who had an indweliing catheter inserted via right subclavian vein a few months earlier. A, Intravascular sonogram of right innominate vein shows thrombus (arrows). B, Veno9ram of right innominate vein shows thrombus (arrows). This confirms findings seen on intravascular sonogram. C and D, Frontal (C) and lateral (D) radiographs show a titanium Greenfield filter (arrows) in superior vena cava that was inserted percutaneously via right femoral vein.

Fig. 2.-venous anomalies of leg. Venograms show duplication of superficial femoral vein (arrows, A); partial duplication or “splitting” of femoral creating a fenestrated or windowlike appearance between limbs; and partial duplication of popliteal vein (arrows, C). A-C,

vein with two

iimbs

(arrows,

B),

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1152

Fig. 3.-Duplication of right superficial femoral vein with thrombus in patient with no symptoms or signs of venous disease. Venogram was obtained to search for a source of pulmonary emboli. Only one limb (asterisk) of duplicated superficial femoral vein has thrombus. Other limb (arrows) is patent and serves as “internal collateral.”

FERRIS

AJR:159,

Fig. 4.-Duplication of right superficial femoral vein with thrombi in a patient with findings of edema. Venogram shows thrombi (arrows) in both duplicated segments in midthigh area.

lower extremity. Predisposing factors include varicose veins; abdominal surgery; hip surgery; neoplasia; pregnancy; stasis caused by lack of activity; and hypercoagulable states such as polycythemia, dysproteinemia, and abnormal clotting factors (associated with various malignant tumors). At the University of Arkansas, the diagnosis of deep venous thrombosis is generally approached in one of three distinct ways: (1) If the patient has clinical signs and symptoms that suggest deep venous thrombosis, duplex sonography is performed. A study [1 5] that compared venography and duplex sonography of the lower extremities has shown that this is a highly accurate method of detecting deep venous thrombosis from the popliteal vein and cephalad (more than 98% correlation). (2) In those patients in whom deep venous thrombosis is likely, particularly those who are inactive or have had surgery, duplex sonography screening is performed at the bedside. (3) In those patients who do not have signs and symptoms in the leg and in whom pulmonary embolism is unlikely, pulmonary scintigraphy after injection of radionuclide via the dorsal vein of both feet is used as a screening mechanism to detect occult deep venous thrombosis involving the superficial femoral or iliac veins. In a study [5] of 300 venograms of the lower extremities followed by radionuclide venograms, findings on the radionuclide venogram were abnormal in 75% of those patients with deep venous thrombosis

December

1992

Fig. 5.-Duplication of right superficial vein with thrombus in a patient with known pulmonary emboli, but no signs or symptoms in leg. Venogram shows thrombus (arrows) originating at level of asterisk and extending upward to incompletely obstruct superficial femoral vein. A second patent vein of a fenestrated superficial femoral vein (arrowhead) is present. Incomplete obstruction of superficial femoral vein and presence of thrombus in only one fenestrated vein probably accounted for absence of signs and symptoms in leg.

involving the superficial femoral, popliteal, or iliac veins. Hence, radionuclide venography can be used for screening. If findings on the radionuclide venogram are abnormal, then duplex sonography will be performed. If findings on the radionuclide venogram are normal, however, several alternatives are possible. If findings on the ventilation-perfusion lung scan indicate a high or an indeterminate probability of pulmonary emboli, then duplex sonography is still performed. On the other hand, if findings on the ventilation-perfusion lung scan are normal or indicate a low probability of pulmonary emboli and those on the radionuclide venogram are normal, then the duplex scan is not obtained. Our experience shows the diagnostic yield from such studies is negligible. Although duplex sonography of the extremities could be done in these patients, our impression is that the inherent cost, along with a low yield, does not justify its routine use.

Pulmonary Correlation Approaches Circulation,

Thromboembolism: Method of Lung Scanning, with Lower Extremity Venous Disease, to Angiographic Evaluation of the Pulmonary and Interruption of the Inferior Vena Cava

The routine evaluation cludes analysis of blood

of pulmonary gases, chest

thromboembolism inradiography, and yen-

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1992

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THROMBOSIS

tilation-perfusion scanning. As mentioned previously, ventilation-perfusion scanning can be performed by way ofthe dorsal veins of both feet in patients with no signs or findings in the leg, unless duplex sonography already has shown that deep venous thrombosis is present. The criteria of Biello et al. [1 1] are used to determine whether the ventilation-perfusion scans indicate high, indeterminate, or low probability of pulmonary emboli. Unfortunately, patients whose ventilation-perfusion scans indicate an indeterminate probability of pulmonary emboli need further examination (i.e., pulmonary arteriography). My colleagues and I have not been comfortable concluding that lung scans that indicate low probability mean that the patient has no significant pulmonary emboli. On the other hand, this is the approach generally advocated, and thus we use it with the following modifications. If the lower extremities appear normal, either according to results of duplex sonography or radionuclide venography, and the clinical findings and results on ventilation-perfusion scans indicate a low probability for pulmonary embolism, then we are reasonably confident in eliminating pulmonary embolism as a diagnosis. If any of these factors are debatable, then even the patient whose ventilationperfusion scan indicates a low probability of pulmonary embolism should have pulmonary arteriography. In these instances, the ventilation-perfusion scan might appear to be relatively superfluous. Yet the scan is important because the area of abnormality seen on the lung scan is the area that is primarily examined by arteriography. We know from past experience [1 6] that areas of perfectly normal perfusion do not have pulmonary emboli, and hence these areas are not evaluated by angiography. In a study of patients who had pulmonary emboli [5], as shown by pulmonary arteriography, we assessed the prevalence of asymptomatic deep venous thrombosis involving the popliteal or the superficial femoral vein (where the prevalence of embolization is high). In a series of 78 patients who had evidence of pulmonary emboli on pulmonary arteriograms but no findings in the legs, we found by either radionuclide yenography or venography that 24 patients (31 %) had asymptomatic deep venous thrombosis of the superficial femoral or popliteal vein. Conversely, in those patients who have deep venous thrombosis with involvement of the superficial femoral vein or iliac system, the prevalence of asymptomatic pulmonary embolism as judged by a routine baseline ventilation-perfusion scan was significant. In 62 patients with deep venous thrombosis (mostly popliteal or superficial femoral), 24 (39%) had ventilation-perfusion scans that indicated a high or indeterminate probability of pulmonary embolism.

Occlusion

Pulmonary

Although the raphy is insertion

Artenography

standard approach for pulmonary of a catheter into the left or right

arteriogpulmonary

artery and visualization with different projections, we have sometimes modified this approach. In patients with marked arrhythmias, a Berman flow-directed balloon catheter (Arrow, Inc., Reading, PA) can be used. Because of this approach, the ventricular septum usually is not irritated. This may dimin-

AND

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EMBOLISM

1153

ish cardiac disturbances. In some patients, with the assistance of the ventilation-perfusion scan as a guide, areas just proximal to the abnormal segment can be selectively studied by using balloon occlusion angiography. This type of angiography can be performed with flow-directed balloon catheters such as the modified Swan-Ganz catheter (Arrow, Inc.). By altering the diameter of the lumen of the modified Swan-Ganz catheter, a 0.035-in. (0.089-cm) guidewire and a modified Seldinger technique can be used. The catheters are inserted through a sheath. They can be easily directed and partially controlled via either the gas-filled balloon or various tip-deflecting guidewires [1 7, 1 8]. The balloon ofthe modified SwanGanz catheter can be expanded to approximately 1 2 mm, which is sufficient to obturate and study several segments, including the segments that appear abnormal on ventilationperfusion scans. Figure 6 shows balloon occlusion arteriograms of normal and abnormal pulmonary circulation. In this way, not only is less contrast material used, but also the hemodynamic effect, particularly in those patients who have some increase in pulmonary pressure, is considerably less. In a series of 38 patients who had both pulmonary angiography and balloon occlusion arteriography, four cases of pulmonary emboli in 38 patients would have been missed without the balloon occlusion studies [16].

Pulmonary

Emboli

Intervention

Although the standard therapy for pulmonary emboli and deep venous thrombosis is anticoagulant therapy, in some patients, administration of anticoagulants is not safe or is not effective. In those situations, usually an inferior vena caval filter is introduced. In 1 972, Lazar Greenfield introduced the Kimray-Greenfield filter (Boston Scientific Co., Watertown, MA), which now is the standard for comparison. This filter, initially inserted by using a surgical cutdown and a 24-French carrier, has also been introduced percutaneously through the jugular or femoral vein. The patency rate is high, about 95%, and the prevalence of pulmonary thromboembolism is low, 1-3% [1 9]. In the past few years, various percutaneous filters have been introduced; currently, five filters are approved by the Food and Drug Administration: the Simon nitinol filter (Nitinol Medical Technologies Group, Woburn, MA), the titanium Greenfield modified hook filter (Boston Scientific Co.), the Bird’s Nest filter (Cook, Inc., Bloomington, IN), the Vena Tech filter (Braun Vena Tech, Evanston, IL), and the standard Greenfield filter (Boston Scientific Co.). The carriers used vary from 8 to 1 4 French (except the Greenfield 24-French carrier). Again, the route of insertion is the internal or external jugular vein or the femoral vein [20]. The Simon nitinol filter has been modified so that it can be introduced from an arm vein also. In general, the filter location is infrarenal. In some circumstances, however, the filter is inserted above the renal vein [12,21,22]. In young women who expect to become pregnant at some time, it may be advantageous to insert the filter between the renal vein and the right atrium (i.e., the intrahepatic portion of the inferior vena cava). In this way, the filter will not be compressed by an enlarged uterus. Furthermore, the right ovarian vein drains too far cephalad to exclude its

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FERRIS

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Fig. 6.-Balloon occlusion artenography with modified Swan-Ganz catheter to show circulation in pulmonary arteries in left lower lobe. A and B, Arteriograms show excellent detail of normal pulmonary circulation. C and D, Cineangiograms show a small “saddle embolus” (arrows) in posterior and lateral segments.

Fig. 7.-Right ovarian vein syndrome in a young woman who had abdominal pain and fever for several weeks postpartum. A, CT scan after contrast administration shows thrombus in right ovarian vein (white arrows). Caval enhancing wall “rims” thrombus. Black arrow denotes aorta. B, Anteroposterior inferior venacavogram shows a large thrombus (arrows) that has propagated from right ovarian vein into upper inferior vena cava. C, Angiogram shows titanium Greenfield filter placed in hepatic portion of inferior vena cava above renal veins in this young woman who had massive pulmonary emboli. Arrows show filter base. Note filter carrier, which was percutaneously inserted from right internal jugular vein.

circulation by the placement of an infrarenal filter, and the left normally drains into the left renal vein. One can appreciate the fact that the standard infrarenal filter position would not prevent emboli from the left ovarian vein from entering the

pulmonary circulation. The pelvic area is a frequent site of thrombophlebitis and pulmonary embolism in young women [23]; hence, an infrarenal filter may not be particularly useful in this type of patient. Figure 7 illustrates an example of

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suprarenal filter placement. In those patients who have renal vein thrombosis or who already have a filter in place below the level of the renal veins that is ineffective, a filter might be inserted in the intrahepatic segment of the inferior vena cava. In a patient who has had a second major bout of pulmonary emboli, filter insertion is a customary consideration. How to determine just when a pulmonary embolism is the second episode is not always easy. Thus, it is standard practice at my institution to obtain a baseline ventilation-perfusion scan in any patient who has deep venous thrombosis involving the superficial femoral, popliteal, or iliac veins. The reasons for this are obvious. If signs and symptoms develop in the chest after several days of anticoagulant therapy, another scan can be obtained and comparative analysis done. If no obvious change has occurred, or if the embolus has moved from a lobe area to subsegmental areas in the normal anatomic distribution, it is likely that the patient has not had recurrent pulmonary embolism, but that the initial pulmonary embolus is now clinically manifest. Conversely, if the second ventilation-perfusion lung scan shows that different areas are involved, the most likely situation is failure of anticoagulation and recurrent pulmonary emboli, and a filter might be mdi-

cated. Without decision

that baseline ventilation-perfusion

on placement

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PULMONARY

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to assay D-dimer, a breakdown rently being studied intensively. cludes a pulmonary embolus.

18.

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product of fibrin that is curA normal o-dimer level preHowever, because elevated

levels of D-dimers are common after surgery, o-dimer levels are unreliable indicators of pulmonary embolism in postsurgical patients [25].

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REFERENCES 1. Harmon B. Deep vein thrombosis: a perspective on anatomy and venographic analysis. J Thorac Imaging 1989;4:15-19 2. Virchow R; chance F, trans. Cellular pathology. New York: Dewitt, 1860 3. Becker DM, Phiibnck JT, Abbitt PL. Real-time uitrasonography for the diagnosis of iower extremity deep venous thrombosis: the wave of the future? Arch Intern Med 1989;149:1731-1734 4. Browse NL, Lea-Thomas M. Source of non-lethal pulmonary emboii. Lancet 1974;1 :258-259

deep

venous

thrombosis

and

pulmonary

thrombo-

embolism: correlative diagnostic evaiuation. IntAngiol 1983;2:85-98 6. Monreal M, Lafoz E, Ruiz J, Vaiis R, Aiastrue A. Upper-extremity venous thrombosis and pulmonary embolism: a prospective study.

17.

New

EJ. Peripheral

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EMBOLISM

23.

24.

25.

.

deep Chest

1991:99:280-282 Campbell CB, chandler JG, Tegtmeyer J, Bemstein EF. Axiliary, subciavian, and brachiocephaiic vein obstruction. Surgery 1977;82:816-826 Donayre E, White GH, Mehnnger SM, Wilson SE. Pathogenesis determines late morbidity of axiiiosubciavian vein thrombosis. Am J Surg 1986; 152:179-1 84 Horattas MC, Wright DJ, Fenton Aft Evans DM, Oddi MA. Changing concepts of deep venous thrombosis of the upper extremity: report of a series and review of the literature. Surgery 1988;104:561-567 Ryan JR. Abel AM, Abbott WM, et al. Catheter complications in total parenteral nutrition: a prospective study of 200 consecutive patients. N EngI J Med 1974:290:757-761 Biello DR, Mattar AG, McKnight AC. Ventilation-perfusion studies in suspected pulmonary embolism. MR 1979;133:1033-1037 Pals SO, DeOrchis DF, Mirvis SE. Superiorvena caval placement of KimrayGreenfleid filters. Radiology 1987;65:385-386 Liu GC, Ferris EJ, Reifsteck JR. Baker ML. Effect of anatomic variations on deep venous thrombosis of the lower extremity. AJR 1986:146: 845-848 Kakkar W, Fianc C, Howe CT, Clarke MB. Natural history of postoperative deep vein thrombosis. Lancet 1969:2:230-232 Nix ML, Nelson CL, Harmon BH, Ferris EJ, Barnes RW. Duplex venous scanning: image vs Doppler accuracy. J Vasc Tech 1989;13:121 -1 26 Ferns EJ, Smith PL, Lim WN, Whittle JL, Bios CB, Angtuaco T. Radionuciide-guided balloon occlusion pulmonary cineangiography: an adjunct to pulmonary artenography. Am Heart J 1984;108:539-542 Mcintyre KM. Sharma GvAK. Subselective pulmonary arteriography with baiioon-occiusion for the detection of pulmonary embolism. Am J Cardiol 1974;33:154 Bynum U, Wilson JE, Christensen EE, Sorenson C. Radiographic technique for balloon-occlusion pulmonary angiography. Radiology 1979;133: 51 8-520 Ferris EJ, Carver OK, McCowan TC. inferior vena cava fiiters: technical aspects and foliow up. in: Syllabus: a diagnostic categorical course in interientional radiology. North Brook, iL: ASNA Publications, 1991: 169-1 78 McCowan TC, Ferris EJ, Carver DK, Harshf,eld DL Use of external jugular vein as a route for percutaneous inferior vena cavai flits’ placement. Radiology 1990:175:527-530 Stewart JR. Peyton JWR, Crute SL, Greenfield U. Ciinical results of suprarenai placement of the Greenfleid vena cava filter. Surgery 1982;92: 1-4 Brenner DW, Brenner CJ, Scott J, Wehberg K, Granger JP, Schelihammer PF. Suprarenal Greenfield filter placement to prevent pulmonary embolus in patients with vena caval tumor thrombi. J Urol 1992;147:19-23 Godleski JJ. Pathology of deep venous thrombosis and pulmonary embolism: In: Goldhaber SZ, ed. Pulmonary embolism and deep venous thrombosis. Boston: Saunders 1965:11-25 Shah HA, Buckner CB, Purneli CL, Waiker CW. Computed tomography and magnetic resonance imaging in the diagnosis of pulmonary thromboembolic disease. J Thorac Imaging 1989;4:58-61 Bounameaux H, Schneider P. Aeber G, De Moerloose P. Krahenbuhi B. Measurement of plasma d-dimer for diagnosis of deep venous thrombosis. Am J Clin Pathol 1989;91 :82-85

George W. Holmes Lecture. Deep venous thrombosis and pulmonary embolism: correlative evaluation and therapeutic implications.

Deep venous thrombosis and pulmonary embolism are significant causes of morbidity and mortality in the United States; estimates range from 120,000 to ...
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