Free-floating
Deep Venous Thrombosis
A Retrospective Analysis
ROBERT E. BERRY, M.D., JEFFREY E. GEORGE, M.D., and WILLIAM A. SHAVER, M.D.
Duplex scan to diagnose deep venous thrombosis is an established technique. As experience accumulated, patients with free-floating thrombi were identified. A retrospective review of 65 patients was performed to study these thrombi, to evaluate treatment regimens, and to analyze patient outcome. A 26% incidence of pulmonary embolus occurred. However patients who had bilateral free-floating thrombi had a 42.8% incidence of pulmonary embolus. Receiving a 7-day course of heparin therapy with a partial thromboplastin time (PTI) at 1.5 times control was 53.2% of patients; 55.4% of the patients underwent follow-up examination, and the mean time to clot attachment was 9.2 days. Patients should receive anticoagulation for 10 days or until clot attachment. Patients with persistent, bilateral free-floating thrombi, or propagation of thrombus are candidates for potential caval interruption. Serial scans should be performed to monitor the thrombus for attachment or alteration.
HE B-MODE DUPLEX scan is an established technique to diagnose intravenous thrombosis of the extremities. Conceived by Barber et al.' and applied to venous diagnosis of the lower extremities by Talbot,2 many studies have demonstrated the accuracy and usefulness of the examination. The scan provides additional anatomic and functional information about the veins and can define thrombus morphology. The advantages of the study also pose dilemmas. As more patients were examined, the presence of an unattached or freefloating proximal end of the thrombus was noted. To understand the diagnostic and therapeutic implications of this finding, a retrospective review of patients identified with a proximal free-floating thrombus component was performed. The objectives of the study were to obtain information about the thrombus, the influence of treatment on the thrombus, and patient outcome. With this data management recommendations might be made. Presented at the 101st Annual Meeting of the Southern Surgical Association, Hot Springs, Virginia, December 3-6, 1989. Address reprint requests to Robert E. Berry, M.D., Department of Surgical Education, Roanoke Memorial Hospitals, P.O. Box 13367, Roanoke, VA 24033.
From the Department of Surgical Education, Roanoke Memorial Hospitals, Roanoke, Virginia
Methods From May 1986 until August 15 1989, 2527 consecutive patients were scanned for venous thrombosis of the lower extremities. Three-hundred ninety-nine (15.8%) patients were diagnosed with deep vein thrombosis. Seventy-four of the patients with thrombosis (18.5%) had a free-floating thrombus that was defined as an unattached proximal thrombus tail, without quantifying the length of the free segment. The records of nine outpatients were not available and these patients were excluded from the study. Sixty-five (16%) patients were entered into the study. All scans were performed with a Duplex scanner with 4 MHz and 8 MHz moving mirror-fixed transducers integrated with a 5 MHz pulsed Doppler (Biosound Inc., Indianapolis, IN). The scans were performed by two technologists and interpreted by two staff surgeons in the manner previously described.3 Subsequent follow-up patient scans as well as treatment regimens were determined by the individual patient's physician. Previous studies at our institution documented the diagnostic accuracy of our venous duplex scanning.
Results The 65 patients ranged in age from 18 to 99 years, with a mean age of 67 years. The group included 35 (54%) women, with a mean age of 70.4 years, and 30 (46%) men, with a mean age of 63.1 years. Multiple risk factors were noted in 57 (87.7%) patients, which included age over 40 years (94%), malignant neoplasms, cardiac disease, neurologic problems, postoperative status, trauma, and a history of previous deep vein thrombosis (Table 1). The mean length of hospital stay was 21.98 days. Eight patients died. One death was presumed to be due to a pulmonary
719
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720
TABLE 3. Free-floating Thrombus in Right Lower Extremity
TABLE 1. Risk Factors
Conditions
n
%
Malignant neoplasms Postoperative Neurologic Cardiac Trauma Previous DVT Age >40 Other
15 12 10 8 8 3 3 6 57
23.0 18.5 15.4 12.3 12.3 4.6 4.6 9.3 87.7
Multiple
Involvement Site Right
CFV-EI CFV
SFV/CFV SFV POP Total
Site of Involvement The left lower extremity was primarily involved by a free-floating thrombus in 43 (66.2%) patients and diagnosis was made primarily in the right lower extremity in 22 (33.8%) patients. Bilateral involvement occurred in 18 (27.7%) patients, of whom 14 (21.5%) had bilateral freefloating thrombi (Tables 2 and 3).
Pulmonary Emboli Seventeen (26%) patients incurred pulmonary emboli. In fourteen patients the embolus was documented by V/ Q scan, in one patient by autopsy, and in two patients by strong presumptive evidence, which included symptoms, abnormal blood gases, and the disappearance of the freefloating thrombus discovered by duplex scan. In six patients the scan was performed before the occurrence of pulmonary embolus, five of whom were on treatment or had completed treatment before embolization. Six of fourteen (42.9%) patients with bilateral free-floating thrombi spawned pulmonary emboli (Table 4). Thirteen patients with pulmonary emboli had free-floating thrombi proximal to the superficial femoral veins, two in the superficial femoral veins and two in the popliteal veins. In these latter four cases we suspect that the thrombi represented remnants subsequent to embolization. TABLE 2. Free-floating Thrombus in Left Lower Extremity
Vein Site
n
CFV-EI CFV SFV/CFV SFV POP Total
7 12 14 6 4 43 (66.2%)
(2) (6) (3) (1) (1) (13)
3 4 3 1 -11
BIL FF
(PE)
(1) (3)
(1)
2 4 3 1
(1)
(5)
10
(5)
(1) (3)
(PE)
4 2 5 6 5 22 (33.8%)
(1)
BIL
(PE)
( 1 I )
BIL FF
(PE)
1
(-)
1 2 4
(-)
(1)()() (1) (1) (4)
4 2 7
(-) (-) (1) (1)
(-) (1) (1)
PE, pulmonary embolus; BIL, bilateral, BIL FF, bilateral free floating.
embolus. One death was attributed to a complication of heparin therapy. Six deaths were caused by the patients's primary illness.
Involvement Site Left (PE) BIL (PE)
n
Vein Site
PE, pulmonary embolus; BIL, bilateral; BIL FF, bilateral free floating.
Follow-up Examination
Follow-up duplex scans of 36 (55.4%) patients were reviewed to ascertain changes in the thrombi. Free-floating thrombi in 21 patients became attached to the vein wall between the 4th and 18th days, with a mean time of 9.19 ± 3.7 days. Ten patients demonstrated unattached thrombi from 3 to 22 days, with a mean time of 7.6 ± 6.1 days. The proximal portion of the thrombus disappeared in four patients, confirming embolization. The floating thrombus in one patient treated with urokinase lysed in 1 day. Five patients exhibited propagation of the thrombus while on heparin therapy or after treatment was stopped. Treatment
Sixty-two (95.4%) patients were treated with heparin for 9.87 ± 3.7 days. Two patients had bleeding complications requiring transfusions. One patient died of an intracranial hemorrhage. Using a therapeutic partial thromboplastin time (PTT) as two times control, 39 (62.9%) patients were in the therapeutic range within 24 hours, 49 (79%) patients within 72 hours, and 57 (91.9%) patients by the fifth day of therapy. Fourteen (22.5%) patients remained in the therapeutic range for 1 week. Ten of sixteen patients with pulmonary emboli and treated with heparin (62.5%) reached the therapeutic level in 24 hours, and 12 (75%) patients within 72 hours. Using the currently recommended therapeutic PTT as 1.5 times control,7 51 (82.3%) patients reached the therapeutic range in 24 hours and 60 (96.8%) patients within 72 hours. Thirty-three (53.2%) patients remained in the therapeutic range for 7 days. Thirteen of sixteen patients TABLE 4. Bilateral Thrombosis
All Patients
Total PE-documented PE-empirical Total PE
65 15 (23%) 2 (3%) 17 (26%)
Bilateral DX
Bilateral FFI
18 (27.7%) 5 (27.8%) 1 (5.6%) 6 (33.3%)
14 (21.5%) 5 (35.7%) 1 (7.1%)
6 (42.9%)
PE, pulmonary embolus; DX, diagnosis; FFr, free-floating thrombus.
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FREE-FLOATING DEEP VENOUS THROMBOSIS
with pulmonary emboli who received heparin (81.3%) reached the therapeutic level in 24 hours and 100% were in the therapeutic range in 72 hours. Greenfield filters were placed in 16 patients (24.6%), 13 of whom also received heparin. Nine (56.3%) patients received filters because of persistent or propagating floating thrombi while on heparin therapy. Five of these patients developed the pulmonary embolus before anticoagulant therapy. Four patients had contraindications to heparin therapy, although one patient with cerebral metastatic adenocarcinoma subsequently received heparin. Filters were placed in two patients because of bleeding complications of heparin therapy. One patient who received a filter subsequently embolized from a proved thrombus that developed on the previously placed filter.
Residual Thrombi Ten patients had scans that demonstrated thrombosis interpreted as residual thrombi after embolization. One patient died after 8 days of heparin therapy. A second patient clinically sustained a pulmonary embolus, although the V/Q scan was not definitely positive. In both instances the scan documented a loss of the proximal freefloating thrombus. The remaining eight patients all had documented pulmonary emboli. The venous scans confirmed the diagnosis of venous thrombosis and the more distal locations of the thrombi were consistent with embolization of the proximal portions of the thrombi. Recurrences Recurrent events occurred in four patients. Two patients had documented recurrent pulmonary emboli. A third patient was readmitted for a massive pulmonary embolus subsequent to hospitalization for lower extremity trauma and clinical evidence of a pulmonary embolus not confirmed by V/Q scan. A venous scan was not performed at the first hospitalization. The fourth patient had a recurrent free-floating thrombus in the left lower extremity 1 month after therapy for a floating thrombus in the right lower extremity. Discussion The ability to image deep veins of the lower extremities noninvasively by duplex scan is confirmed by several recent studies.34'8"l Although not yet reliable for evaluation of the iliac veins, the distal portion of the external iliac vein sometimes may be visualized. Norris noted in a study of free-floating iliofemoral thrombi that this is a clinical dilemma that is not yet well evaluated.'2 Surely the entity of free-floating thrombus has existed in many cases, previously unrecognized, and was successfully treated. As more information is obtained, will diagnostic and therapeutic maneuvers require change? Repeated scans may
721
permit the determination of the evolving thrombus and its natural history. This study confirms the preponderance of deep vein thrombosis in women, the left lower extremity, the known and multiple risk factors, and the significant bilateral involvement. Unexpected was the incidence of bilateral freefloating thrombi in nearly one fourth of the patients. Of this subgroup, nearly 50% experienced pulmonary emboli. Bilateral free-floating thrombi serve as a marker for increased risk of pulmonary embolus. The incidence of pulmonary emboli in these patients (26%) is less than that noticed by Norris in patients with free-floating iliofemoral thrombi (60%). 12 The difference appears related to the more distal site location of the thrombi in this study. However the study emphasizes that the free-floating thrombus, above the knee but below the inguinal ligament, is also a potential embolus. Duplex scan can diagnose and monitor the progress of intravenous thrombosis and the effectiveness of anticoagulant therapy. Propagation, attachment, resolution, or movement of the thrombus can be observed. Previous observation suggested that free-floating thrombi do not readily attach to the vein wall.8 Data from our follow-up scans indicate that the time of attachment was 9.2 days and that the majority of thrombi were unattached at the fourth day of therapy. After the initial scan, interval scans on the third, sixth, and tenth day, or until thrombus attachment should identify patients at high risk for pulmonary embolus. A propagating or persistent floating thrombus noted in 13 of these patients is a marker for a possible pulmonary embolus. Seven of these patients experienced a pulmonary embolus. The observed loss of the proximal portion of a thrombus can indicate a pulmonary embolus despite the results of other diagnostic studies. Therapy and physician treatment practices vary. 13 Current recommendation for anticoagulation of 7 days or less before long-term oral anticoagulation may not be appropriate,'4 allowing subsequent propagation of thrombi, as was seen in five of the patients in this study, three of whom had pulmonary emboli. Treatment with heparin for a minimum of 10 days or until thrombus attachment with a PTT of at least 1.5 times control appears warranted in these patients. With propagating thrombus or with persistent floating thrombus for 10 days while on therapy, or with bilateral free-floating thrombi, vena caval filter implantation may be required. We conclude (1) duplex scan, in areas accessible to imaging, can identify patients who have deep venous freefloating thrombi and who are at risk for pulmonary emboli; (2) patients with bilateral thrombosis, especially bilateral free-floating thrombi, are at increased risk of embolization; (3) to monitor free-floating thrombi after the initial study, duplex scan should be performed at the third, sixth, and tenth day or until thrombus attachment; (4)
722
BERRY, GEORGE, AND SHAVER
Anticoagulation for 10 days or until thrombus attachment is recommended; (5) patients with propagating, persistent floating or bilateral floating thrombi are potential candidates for caval interruption; and (6) a carefully designed prospective study would help to elucidate questions raised by this review. References 1. Barber FE, Baker DW, Strandness DE, et al. Duplex scanner II for simultaneous imaging of artery tissues and flow. I EEE Publication 74 1974, CH08961 SU, Ultrasonics Symposium Proceedings. 2. Talbot SR. Use of real time imaging in identifying deep venous obstruction. A preliminary report. Bruit 1982; 6:41-42. 3. Sullivan ED, Peter DJ, Cranley JJ. Real time B-mode venous ultrasound. J Vasc Surg 1984; 1:465-471. 4. George JE, Smith MO, Berry RE. Duplex scanning for the detection of deep venous thrombosis of lower extremities in a community hospital. Curr Surg 1987; 44:202-204. 5. Cranley JJ, Higgins RF, Berry RE, et al. Near parity in the final diagnosis of deep venous thrombosis by duplex scan and phlebography. Phlebology 1989; 4:71-74.
DISCUSSION
DR. ROBERT BARNES (Little Rock, Arkansas): Dr. Berry and his colleagues have provided us with a contemporary study of the risk of freefloating venous thrombi of the lower extremities, a subject originally investigated by Norris working in our laboratory at the Medical College of Virginia in Richmond. Although both of those studies were retrospective, the current reporting includes a much larger series of femoropopliteal free-floating venous thrombi detected by duplex scanning, whereas Norris reviewed iliofemoral venous thrombi documented by venography. I have several concerns that may influence the conclusions drawn from this study. First, the authors only report the outcome for 65 patients with freefloating venous thrombi. Without information about the course of the 325 patients with adherent thrombi, I find it difficult to accept a change in therapeutic approach for free-floating thrombi. Second, it is unclear as to when the pulmonary emboli occurred in relation to the initial detection of the venous thrombi by duplex scanning. Unless routine lung scanning is carried out, both at the time of initial diagnosis and later in the course of treatment, I would take issue with the recommendation that heparin therapy be extended until thrombi become adherent to prevent late emboli. Third, the authors analyzed the time necessary to achieve therapeutic anticoagulation, but it was unclear to me whether the timing of later pulmonary emboli correlated with inadequate levels of heparin therapy. Such information would be necessary to appropriately address the role of inferior vena cava filters in these patients. These concerns prompt the following three questions for the authors. First, do you have any data about the incidence of pulmonary emboli in the 325 patients who had duplex scan evidence of adherent or nonfloating thrombi? Second, what fraction of the pulmonary emboli clearly occurred after initiating heparin therapy? And third, of those emboli, how many occurred before therapeutic levels of heparin anticoagulation was achieved? DR. ROBERT MENTZER (Buffalo, New York): I congratulate Dr. Berry and his colleagues on this comprehensive review of their experience using the B-mode duplex scan to diagnose deep-vein thrombosis in 399 patients. It should be noted that these patients were studied within a consecutive 3-year period and this number represents only 20% of the total number of patients evaluated. The authors are to be especially congratulated for bringing to our attention the natural history of the venous thrombus. Dr. Berry's presentation and the manuscript, which I enjoyed reading, provides us with
Ann. Surg.June 1990
6. George JE, Berry RE. Noninvasive detection ofdeep venous thrombosis: a critical evaluation. Am Surg 1990; 56:76-78. 7. Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1989; 95:37S-5 IS. 8. Flanagan LD, Sullivan ED, Cranley JJ. Venous imaging of the extremities using real-time B-mode ultrasound. In Bergan JJ, Yao JST, eds. Surgery of the Veins. Orlando, FL: Grune & Statton, 1985. pp. 89-98. 9. Flinn WR, Sandager GP, Cerullo LU, et al. Duplex venous scanning for the prospective surveillance of perioperative venous thrombosis. Arch Surg 1989; 124:901-905. 10. Persson AV, Jones C, Zide R, et al. Use of the triplex scanner in diagnosis of deep venous thrombosis. Arch Surg 1989; 124:593596. 11. White RH, McGahan JP, Daschbach MM, et al. Diagnosis of deep vein thrombosis using duplex ultrasound. Ann Int Med 1989; 111:297-304. 12. Norris CS, Greenfield U, Herrmann JB. Free-floating iliofemoral thrombus. A risk of pulmonary embolism. Arch Surg 1985; 120: 806-808. 13. Wheeler AP, Jaquiss RDB, Newman JH. Physician practices in the treatment of pulmonary embolism and deep vein thrombosis. Arch Int Med 1988; 148:1321-1325. 14. Gallus A, Jackaman J, Tillett J, et al. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet 1986; ii:1293-1296.
important insights regarding the natural history of the free-floating thrombus and appropriately emphasizes the fundamental issue that must be addressed. That is, what is the optimum duration of intravenous heparin treatment before the initiation of oral coagulation? This issue is an important one because, at many institutions, including my own, there is considerable controversy as to when intravenous heparin should be started, how closely should the partial thromboplastin time be monitored, and how soon should oral anticoagulation be started and intravenous heparin stopped? Much of the confusion surrounding this issue is due to reports that indicate that when intravenous heparin is administered for 7 to 10 days, the frequency of recurrent venous thrombosis is low, i.e., less than 5%. These studies contrast, however, with other reports that support the view that heparin and coumadin should be administered together at the time of diagnosis and that heparin therapy can be discontinued empirically on the fourth or fifth day. Although this controversy undoubtedly will continue, the findings by Dr. Berry and his colleagues allow us to develop a rational approach to the management of patients with free-floating thrombi. I was impressed to learn that among his patients with significant bilateral involvement, one quarter of these patients had bilateral free-floating thrombi and that nearly one half of these patients experienced pulmonary emboli. The use of the duplex scan to monitor thrombus attachment should allow us to develop prospective studies to define the rational basis for discontinuing heparin treatment or proceeding to caval interruption in this patient population. The questions I would like to ask you, Dr. Berry, include: What were the clinical indications for using the B-mode scan in more than 1500 patients who did not have venous thrombosis? Is there a role for thrombolytic therapy, say tPA combined with heparin, in the treatment of patients with free-floating thrombi? And because the duplex scan is limited with respect to its ability to visualize the iliac veins, would you speculate as to whether we should also use impedance plethysmography in a complimentary manner to follow the progression of disease? DR. ROBERT M. MILES (Memphis, Tennessee): This certainly was a thought-provoking presentation and an important contribution to the knowledge of deep venous thrombosis, particularly its free-floating variety. However, as the TV detective Lieutenant Columbo might say, 'I have just one problem with this,' and that is conservative treatment of a freefloating thrombus. Let me present my personal series, but don't get nervous. There are only two patients in my series. This was years ago, before duplex imaging.
Deep Venous Thrombosis
A Retrospective Analysis
ROBERT E. BERRY, M.D., JEFFREY E. GEORGE, M.D., and WILLIAM A. SHAVER, M.D.
Duplex scan to diagnose deep venous thrombosis is an established technique. As experience accumulated, patients with free-floating thrombi were identified. A retrospective review of 65 patients was performed to study these thrombi, to evaluate treatment regimens, and to analyze patient outcome. A 26% incidence of pulmonary embolus occurred. However patients who had bilateral free-floating thrombi had a 42.8% incidence of pulmonary embolus. Receiving a 7-day course of heparin therapy with a partial thromboplastin time (PTI) at 1.5 times control was 53.2% of patients; 55.4% of the patients underwent follow-up examination, and the mean time to clot attachment was 9.2 days. Patients should receive anticoagulation for 10 days or until clot attachment. Patients with persistent, bilateral free-floating thrombi, or propagation of thrombus are candidates for potential caval interruption. Serial scans should be performed to monitor the thrombus for attachment or alteration.
HE B-MODE DUPLEX scan is an established technique to diagnose intravenous thrombosis of the extremities. Conceived by Barber et al.' and applied to venous diagnosis of the lower extremities by Talbot,2 many studies have demonstrated the accuracy and usefulness of the examination. The scan provides additional anatomic and functional information about the veins and can define thrombus morphology. The advantages of the study also pose dilemmas. As more patients were examined, the presence of an unattached or freefloating proximal end of the thrombus was noted. To understand the diagnostic and therapeutic implications of this finding, a retrospective review of patients identified with a proximal free-floating thrombus component was performed. The objectives of the study were to obtain information about the thrombus, the influence of treatment on the thrombus, and patient outcome. With this data management recommendations might be made. Presented at the 101st Annual Meeting of the Southern Surgical Association, Hot Springs, Virginia, December 3-6, 1989. Address reprint requests to Robert E. Berry, M.D., Department of Surgical Education, Roanoke Memorial Hospitals, P.O. Box 13367, Roanoke, VA 24033.
From the Department of Surgical Education, Roanoke Memorial Hospitals, Roanoke, Virginia
Methods From May 1986 until August 15 1989, 2527 consecutive patients were scanned for venous thrombosis of the lower extremities. Three-hundred ninety-nine (15.8%) patients were diagnosed with deep vein thrombosis. Seventy-four of the patients with thrombosis (18.5%) had a free-floating thrombus that was defined as an unattached proximal thrombus tail, without quantifying the length of the free segment. The records of nine outpatients were not available and these patients were excluded from the study. Sixty-five (16%) patients were entered into the study. All scans were performed with a Duplex scanner with 4 MHz and 8 MHz moving mirror-fixed transducers integrated with a 5 MHz pulsed Doppler (Biosound Inc., Indianapolis, IN). The scans were performed by two technologists and interpreted by two staff surgeons in the manner previously described.3 Subsequent follow-up patient scans as well as treatment regimens were determined by the individual patient's physician. Previous studies at our institution documented the diagnostic accuracy of our venous duplex scanning.
Results The 65 patients ranged in age from 18 to 99 years, with a mean age of 67 years. The group included 35 (54%) women, with a mean age of 70.4 years, and 30 (46%) men, with a mean age of 63.1 years. Multiple risk factors were noted in 57 (87.7%) patients, which included age over 40 years (94%), malignant neoplasms, cardiac disease, neurologic problems, postoperative status, trauma, and a history of previous deep vein thrombosis (Table 1). The mean length of hospital stay was 21.98 days. Eight patients died. One death was presumed to be due to a pulmonary
719
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BERRY, GEORGE, AND SHAVER
720
TABLE 3. Free-floating Thrombus in Right Lower Extremity
TABLE 1. Risk Factors
Conditions
n
%
Malignant neoplasms Postoperative Neurologic Cardiac Trauma Previous DVT Age >40 Other
15 12 10 8 8 3 3 6 57
23.0 18.5 15.4 12.3 12.3 4.6 4.6 9.3 87.7
Multiple
Involvement Site Right
CFV-EI CFV
SFV/CFV SFV POP Total
Site of Involvement The left lower extremity was primarily involved by a free-floating thrombus in 43 (66.2%) patients and diagnosis was made primarily in the right lower extremity in 22 (33.8%) patients. Bilateral involvement occurred in 18 (27.7%) patients, of whom 14 (21.5%) had bilateral freefloating thrombi (Tables 2 and 3).
Pulmonary Emboli Seventeen (26%) patients incurred pulmonary emboli. In fourteen patients the embolus was documented by V/ Q scan, in one patient by autopsy, and in two patients by strong presumptive evidence, which included symptoms, abnormal blood gases, and the disappearance of the freefloating thrombus discovered by duplex scan. In six patients the scan was performed before the occurrence of pulmonary embolus, five of whom were on treatment or had completed treatment before embolization. Six of fourteen (42.9%) patients with bilateral free-floating thrombi spawned pulmonary emboli (Table 4). Thirteen patients with pulmonary emboli had free-floating thrombi proximal to the superficial femoral veins, two in the superficial femoral veins and two in the popliteal veins. In these latter four cases we suspect that the thrombi represented remnants subsequent to embolization. TABLE 2. Free-floating Thrombus in Left Lower Extremity
Vein Site
n
CFV-EI CFV SFV/CFV SFV POP Total
7 12 14 6 4 43 (66.2%)
(2) (6) (3) (1) (1) (13)
3 4 3 1 -11
BIL FF
(PE)
(1) (3)
(1)
2 4 3 1
(1)
(5)
10
(5)
(1) (3)
(PE)
4 2 5 6 5 22 (33.8%)
(1)
BIL
(PE)
( 1 I )
BIL FF
(PE)
1
(-)
1 2 4
(-)
(1)()() (1) (1) (4)
4 2 7
(-) (-) (1) (1)
(-) (1) (1)
PE, pulmonary embolus; BIL, bilateral, BIL FF, bilateral free floating.
embolus. One death was attributed to a complication of heparin therapy. Six deaths were caused by the patients's primary illness.
Involvement Site Left (PE) BIL (PE)
n
Vein Site
PE, pulmonary embolus; BIL, bilateral; BIL FF, bilateral free floating.
Follow-up Examination
Follow-up duplex scans of 36 (55.4%) patients were reviewed to ascertain changes in the thrombi. Free-floating thrombi in 21 patients became attached to the vein wall between the 4th and 18th days, with a mean time of 9.19 ± 3.7 days. Ten patients demonstrated unattached thrombi from 3 to 22 days, with a mean time of 7.6 ± 6.1 days. The proximal portion of the thrombus disappeared in four patients, confirming embolization. The floating thrombus in one patient treated with urokinase lysed in 1 day. Five patients exhibited propagation of the thrombus while on heparin therapy or after treatment was stopped. Treatment
Sixty-two (95.4%) patients were treated with heparin for 9.87 ± 3.7 days. Two patients had bleeding complications requiring transfusions. One patient died of an intracranial hemorrhage. Using a therapeutic partial thromboplastin time (PTT) as two times control, 39 (62.9%) patients were in the therapeutic range within 24 hours, 49 (79%) patients within 72 hours, and 57 (91.9%) patients by the fifth day of therapy. Fourteen (22.5%) patients remained in the therapeutic range for 1 week. Ten of sixteen patients with pulmonary emboli and treated with heparin (62.5%) reached the therapeutic level in 24 hours, and 12 (75%) patients within 72 hours. Using the currently recommended therapeutic PTT as 1.5 times control,7 51 (82.3%) patients reached the therapeutic range in 24 hours and 60 (96.8%) patients within 72 hours. Thirty-three (53.2%) patients remained in the therapeutic range for 7 days. Thirteen of sixteen patients TABLE 4. Bilateral Thrombosis
All Patients
Total PE-documented PE-empirical Total PE
65 15 (23%) 2 (3%) 17 (26%)
Bilateral DX
Bilateral FFI
18 (27.7%) 5 (27.8%) 1 (5.6%) 6 (33.3%)
14 (21.5%) 5 (35.7%) 1 (7.1%)
6 (42.9%)
PE, pulmonary embolus; DX, diagnosis; FFr, free-floating thrombus.
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FREE-FLOATING DEEP VENOUS THROMBOSIS
with pulmonary emboli who received heparin (81.3%) reached the therapeutic level in 24 hours and 100% were in the therapeutic range in 72 hours. Greenfield filters were placed in 16 patients (24.6%), 13 of whom also received heparin. Nine (56.3%) patients received filters because of persistent or propagating floating thrombi while on heparin therapy. Five of these patients developed the pulmonary embolus before anticoagulant therapy. Four patients had contraindications to heparin therapy, although one patient with cerebral metastatic adenocarcinoma subsequently received heparin. Filters were placed in two patients because of bleeding complications of heparin therapy. One patient who received a filter subsequently embolized from a proved thrombus that developed on the previously placed filter.
Residual Thrombi Ten patients had scans that demonstrated thrombosis interpreted as residual thrombi after embolization. One patient died after 8 days of heparin therapy. A second patient clinically sustained a pulmonary embolus, although the V/Q scan was not definitely positive. In both instances the scan documented a loss of the proximal freefloating thrombus. The remaining eight patients all had documented pulmonary emboli. The venous scans confirmed the diagnosis of venous thrombosis and the more distal locations of the thrombi were consistent with embolization of the proximal portions of the thrombi. Recurrences Recurrent events occurred in four patients. Two patients had documented recurrent pulmonary emboli. A third patient was readmitted for a massive pulmonary embolus subsequent to hospitalization for lower extremity trauma and clinical evidence of a pulmonary embolus not confirmed by V/Q scan. A venous scan was not performed at the first hospitalization. The fourth patient had a recurrent free-floating thrombus in the left lower extremity 1 month after therapy for a floating thrombus in the right lower extremity. Discussion The ability to image deep veins of the lower extremities noninvasively by duplex scan is confirmed by several recent studies.34'8"l Although not yet reliable for evaluation of the iliac veins, the distal portion of the external iliac vein sometimes may be visualized. Norris noted in a study of free-floating iliofemoral thrombi that this is a clinical dilemma that is not yet well evaluated.'2 Surely the entity of free-floating thrombus has existed in many cases, previously unrecognized, and was successfully treated. As more information is obtained, will diagnostic and therapeutic maneuvers require change? Repeated scans may
721
permit the determination of the evolving thrombus and its natural history. This study confirms the preponderance of deep vein thrombosis in women, the left lower extremity, the known and multiple risk factors, and the significant bilateral involvement. Unexpected was the incidence of bilateral freefloating thrombi in nearly one fourth of the patients. Of this subgroup, nearly 50% experienced pulmonary emboli. Bilateral free-floating thrombi serve as a marker for increased risk of pulmonary embolus. The incidence of pulmonary emboli in these patients (26%) is less than that noticed by Norris in patients with free-floating iliofemoral thrombi (60%). 12 The difference appears related to the more distal site location of the thrombi in this study. However the study emphasizes that the free-floating thrombus, above the knee but below the inguinal ligament, is also a potential embolus. Duplex scan can diagnose and monitor the progress of intravenous thrombosis and the effectiveness of anticoagulant therapy. Propagation, attachment, resolution, or movement of the thrombus can be observed. Previous observation suggested that free-floating thrombi do not readily attach to the vein wall.8 Data from our follow-up scans indicate that the time of attachment was 9.2 days and that the majority of thrombi were unattached at the fourth day of therapy. After the initial scan, interval scans on the third, sixth, and tenth day, or until thrombus attachment should identify patients at high risk for pulmonary embolus. A propagating or persistent floating thrombus noted in 13 of these patients is a marker for a possible pulmonary embolus. Seven of these patients experienced a pulmonary embolus. The observed loss of the proximal portion of a thrombus can indicate a pulmonary embolus despite the results of other diagnostic studies. Therapy and physician treatment practices vary. 13 Current recommendation for anticoagulation of 7 days or less before long-term oral anticoagulation may not be appropriate,'4 allowing subsequent propagation of thrombi, as was seen in five of the patients in this study, three of whom had pulmonary emboli. Treatment with heparin for a minimum of 10 days or until thrombus attachment with a PTT of at least 1.5 times control appears warranted in these patients. With propagating thrombus or with persistent floating thrombus for 10 days while on therapy, or with bilateral free-floating thrombi, vena caval filter implantation may be required. We conclude (1) duplex scan, in areas accessible to imaging, can identify patients who have deep venous freefloating thrombi and who are at risk for pulmonary emboli; (2) patients with bilateral thrombosis, especially bilateral free-floating thrombi, are at increased risk of embolization; (3) to monitor free-floating thrombi after the initial study, duplex scan should be performed at the third, sixth, and tenth day or until thrombus attachment; (4)
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Anticoagulation for 10 days or until thrombus attachment is recommended; (5) patients with propagating, persistent floating or bilateral floating thrombi are potential candidates for caval interruption; and (6) a carefully designed prospective study would help to elucidate questions raised by this review. References 1. Barber FE, Baker DW, Strandness DE, et al. Duplex scanner II for simultaneous imaging of artery tissues and flow. I EEE Publication 74 1974, CH08961 SU, Ultrasonics Symposium Proceedings. 2. Talbot SR. Use of real time imaging in identifying deep venous obstruction. A preliminary report. Bruit 1982; 6:41-42. 3. Sullivan ED, Peter DJ, Cranley JJ. Real time B-mode venous ultrasound. J Vasc Surg 1984; 1:465-471. 4. George JE, Smith MO, Berry RE. Duplex scanning for the detection of deep venous thrombosis of lower extremities in a community hospital. Curr Surg 1987; 44:202-204. 5. Cranley JJ, Higgins RF, Berry RE, et al. Near parity in the final diagnosis of deep venous thrombosis by duplex scan and phlebography. Phlebology 1989; 4:71-74.
DISCUSSION
DR. ROBERT BARNES (Little Rock, Arkansas): Dr. Berry and his colleagues have provided us with a contemporary study of the risk of freefloating venous thrombi of the lower extremities, a subject originally investigated by Norris working in our laboratory at the Medical College of Virginia in Richmond. Although both of those studies were retrospective, the current reporting includes a much larger series of femoropopliteal free-floating venous thrombi detected by duplex scanning, whereas Norris reviewed iliofemoral venous thrombi documented by venography. I have several concerns that may influence the conclusions drawn from this study. First, the authors only report the outcome for 65 patients with freefloating venous thrombi. Without information about the course of the 325 patients with adherent thrombi, I find it difficult to accept a change in therapeutic approach for free-floating thrombi. Second, it is unclear as to when the pulmonary emboli occurred in relation to the initial detection of the venous thrombi by duplex scanning. Unless routine lung scanning is carried out, both at the time of initial diagnosis and later in the course of treatment, I would take issue with the recommendation that heparin therapy be extended until thrombi become adherent to prevent late emboli. Third, the authors analyzed the time necessary to achieve therapeutic anticoagulation, but it was unclear to me whether the timing of later pulmonary emboli correlated with inadequate levels of heparin therapy. Such information would be necessary to appropriately address the role of inferior vena cava filters in these patients. These concerns prompt the following three questions for the authors. First, do you have any data about the incidence of pulmonary emboli in the 325 patients who had duplex scan evidence of adherent or nonfloating thrombi? Second, what fraction of the pulmonary emboli clearly occurred after initiating heparin therapy? And third, of those emboli, how many occurred before therapeutic levels of heparin anticoagulation was achieved? DR. ROBERT MENTZER (Buffalo, New York): I congratulate Dr. Berry and his colleagues on this comprehensive review of their experience using the B-mode duplex scan to diagnose deep-vein thrombosis in 399 patients. It should be noted that these patients were studied within a consecutive 3-year period and this number represents only 20% of the total number of patients evaluated. The authors are to be especially congratulated for bringing to our attention the natural history of the venous thrombus. Dr. Berry's presentation and the manuscript, which I enjoyed reading, provides us with
Ann. Surg.June 1990
6. George JE, Berry RE. Noninvasive detection ofdeep venous thrombosis: a critical evaluation. Am Surg 1990; 56:76-78. 7. Hyers TM, Hull RD, Weg JG. Antithrombotic therapy for venous thromboembolic disease. Chest 1989; 95:37S-5 IS. 8. Flanagan LD, Sullivan ED, Cranley JJ. Venous imaging of the extremities using real-time B-mode ultrasound. In Bergan JJ, Yao JST, eds. Surgery of the Veins. Orlando, FL: Grune & Statton, 1985. pp. 89-98. 9. Flinn WR, Sandager GP, Cerullo LU, et al. Duplex venous scanning for the prospective surveillance of perioperative venous thrombosis. Arch Surg 1989; 124:901-905. 10. Persson AV, Jones C, Zide R, et al. Use of the triplex scanner in diagnosis of deep venous thrombosis. Arch Surg 1989; 124:593596. 11. White RH, McGahan JP, Daschbach MM, et al. Diagnosis of deep vein thrombosis using duplex ultrasound. Ann Int Med 1989; 111:297-304. 12. Norris CS, Greenfield U, Herrmann JB. Free-floating iliofemoral thrombus. A risk of pulmonary embolism. Arch Surg 1985; 120: 806-808. 13. Wheeler AP, Jaquiss RDB, Newman JH. Physician practices in the treatment of pulmonary embolism and deep vein thrombosis. Arch Int Med 1988; 148:1321-1325. 14. Gallus A, Jackaman J, Tillett J, et al. Safety and efficacy of warfarin started early after submassive venous thrombosis or pulmonary embolism. Lancet 1986; ii:1293-1296.
important insights regarding the natural history of the free-floating thrombus and appropriately emphasizes the fundamental issue that must be addressed. That is, what is the optimum duration of intravenous heparin treatment before the initiation of oral coagulation? This issue is an important one because, at many institutions, including my own, there is considerable controversy as to when intravenous heparin should be started, how closely should the partial thromboplastin time be monitored, and how soon should oral anticoagulation be started and intravenous heparin stopped? Much of the confusion surrounding this issue is due to reports that indicate that when intravenous heparin is administered for 7 to 10 days, the frequency of recurrent venous thrombosis is low, i.e., less than 5%. These studies contrast, however, with other reports that support the view that heparin and coumadin should be administered together at the time of diagnosis and that heparin therapy can be discontinued empirically on the fourth or fifth day. Although this controversy undoubtedly will continue, the findings by Dr. Berry and his colleagues allow us to develop a rational approach to the management of patients with free-floating thrombi. I was impressed to learn that among his patients with significant bilateral involvement, one quarter of these patients had bilateral free-floating thrombi and that nearly one half of these patients experienced pulmonary emboli. The use of the duplex scan to monitor thrombus attachment should allow us to develop prospective studies to define the rational basis for discontinuing heparin treatment or proceeding to caval interruption in this patient population. The questions I would like to ask you, Dr. Berry, include: What were the clinical indications for using the B-mode scan in more than 1500 patients who did not have venous thrombosis? Is there a role for thrombolytic therapy, say tPA combined with heparin, in the treatment of patients with free-floating thrombi? And because the duplex scan is limited with respect to its ability to visualize the iliac veins, would you speculate as to whether we should also use impedance plethysmography in a complimentary manner to follow the progression of disease? DR. ROBERT M. MILES (Memphis, Tennessee): This certainly was a thought-provoking presentation and an important contribution to the knowledge of deep venous thrombosis, particularly its free-floating variety. However, as the TV detective Lieutenant Columbo might say, 'I have just one problem with this,' and that is conservative treatment of a freefloating thrombus. Let me present my personal series, but don't get nervous. There are only two patients in my series. This was years ago, before duplex imaging.
