| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Vascular and Interventional Radiology |
1 From the Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215. Received May 9, 2000; revision requested June 18; revision received August 8; accepted August 30. Address correspondence to R.G.S. (e-mail: rsheiman@caregroup.harvard.edu).
 |
ABSTRACT |
|---|
 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
MATERIALS AND METHODS: Fifty-four iatrogenic femoral pseudoaneurysms were treated with US-guided thrombin injection. Forty-five were classified as simple (single lobe) and nine, as complex (at least two lobes and a single neck to the native vessel). Pseudoaneurysm volume, classification, thrombin dose, anticoagulation therapy status, and sheath size were compared between failed and successful cases. Seven- to 10-day follow-up US and a minimum 4-month clinical follow-up were also performed to evaluate success.
RESULTS: Fifty of 54 pseudoaneurysms were successfully treated with topical thrombin without complication and included all 45 simple and five of nine complex pseudoaneurysms. US follow-up in all 50 successful cases and clinical follow-up in 37 of these revealed no recurrence. Only a complex pseudoaneurysm classification was significantly associated with failure (P < .01). Among the complex pseudoaneurysms, successful cases involved two injections and a total thrombin dose of at least 1,500 units. In failed cases, pseudoaneurysms were treated with a single injection of 1,000 units, initially thrombosed, and recurred.
CONCLUSION: Simple iatrogenic femoral pseudoaneurysms, regardless of size or concomitant anticoagulation therapy, can be treated with a single injection of up to 1,000 units of topical thrombin and require no follow-up. Complex pseudoaneurysms will likely require a second injection (total thrombin dose of at least 1,500 units) and short-term clinical and US follow-up to ensure successful treatment.
Index terms: Aneurysm, femoral, 92.732 • Arteries, thrombosis, 92.1269 • Catheters and catheterization, complications, 92.44, 92.732 • Ultrasound (US), Doppler studies, 92.12983, 92.12984 • Ultrasound (US), guidance, 92.12986
|
INTRODUCTION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
At our institution and at others (6,7), patients who have undergone successful pseudoaneurysm obliteration with direct injection of topical thrombin routinely undergo follow-up duplex and color Doppler US to ensure persistent pseudoaneurysm obliteration and to exclude recurrence. The purpose of this study was to assess the clinical success of US-guided thrombin injection for the treatment of iatrogenic femoral pseudoaneurysms and to identify criteria that may predispose to treatment failure.
|
MATERIALS AND METHODS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
A total of 54 pseudoaneurysms met the criteria for thrombin repair and were treated with an injection as first-line therapy within 24 hours of initial diagnosis. All treated pseudoaneurysms resulted from cardiac catheterization. Forty-five pseudoaneurysms were diagnosed and treated within 48 hours of catheterization; two, within 72 hours of catheterization; and seven, at longer than 1 week after catheterization.
Thrombin injection was therefore performed in all 54 patients (29 women, 25 men; mean age, 69 years; age range, 47–85 years), as has been previously described (5). Briefly, US identification of all pseudoaneurysms was carried out with a US machine (ATL Ultramark 9 or ATL 3000; Advanced Technology Laboratories, Bothell, Wash) with duplex and color Doppler capabilities by using a 4–7-MHz linear transducer. For each pseudoaneurysm, total volume was calculated, based on the assumption of an elliptical shape (length x width x height x 0.52), as well as identification of the pseudoaneurysm vessel of origin, the neck, and the neck insertion into the pseudoaneurysm. Neck insertion was identified solely for planning the site for thrombin injection. We did not document neck size because this has been previously shown (5) to have no effect on the success or morbidity of the use of topical thrombin to treat iatrogenic femoral pseudoaneurysms. However, the sheath size used during catheterization was recorded in each case.
In addition, pseudoaneurysms were classified as simple (n = 45) if they consisted of a single contained compartment directly communicating with the femoral artery or as complex if they were multilobulated (n = 9). A multilobulated pseudoaneurysm was formally defined as one that had two or more lobes separated from each other by a patent tract of a diameter less than the minimum dimension of the smallest lobe. All complex multilobulated pseudoaneurysms were bilobed and had only one of the two lobes joined to their vessel of origin.
After informed consent was obtained from each patient, clinical assessment of ipsilateral lower extremity pulses was performed, as well as Doppler US examination of the posterior tibial and dorsalis pedis arteries. For all simple pseudoaneurysms, a 22-gauge spinal needle was then inserted freehand under sterile conditions by one of two attending radiologists (R.G.S., D.P.B.) into the periphery of the pseudoaneurysm with US guidance and as far from the neck as possible. A dose of 1,000 units of topical thrombin (Thrombin-JMI; Jones Medical Industries, St Louis, Mo) was injected under real-time US guidance. The rate of injection was determined with direct gray-scale visualization of clot formation and was maintained until thrombus filled the entire pseudoaneurysm lumen.
Duplex and color Doppler examination was then repeated after 10 minutes to ensure persistent pseudoaneurysm thrombosis. For all simple pseudoaneurysms, the injection time was 5–10 seconds. No injection was continued until the pseudoaneurysm neck was also thrombosed, as we have found that this will always spontaneously thrombose within 10 minutes after pseudoaneurysm lumen obliteration.
For the nine complex pseudoaneurysms, the lobe most distal to and not directly communicating with the underlying native femoral vessel was first injected; this injection resulted in immediate and complete thrombosis of this lobe. Doppler US was repeated in 10 minutes to assess for thrombus development in the connecting lobe joined via the pseudoaneurysm neck to the femoral artery.
We chose to initially inject the distal lobe, since we did not know the blood flow pattern within a complex pseudoaneurysm and believed it safer to begin with the lobe farthest from the native vessel. In addition, if clot development did not occur due to sufficient alteration of flow in the proximal lobe, the hemodynamics would now mimic those of a simple pseudoaneurysm, and a second injection could be performed. If complete obliteration of both lobes was documented at the 10-minute follow-up US, the procedure was terminated, and the patient was scheduled for follow-up duplex and color Doppler US. If patency of the remaining lobe persisted, a second separate injection was immediately performed directly into this lobe until complete thrombosis occurred. This required no more than an additional 1,000 units of thrombin, with thrombosis also occurring within 10 seconds in all cases. All patients underwent immediate clinical and Doppler US reevaluation of lower extremity pulses to evaluate for possible distal emboli or thrombosis.
We required that all patients be restricted to nonstrenuous activity (eg, avoiding heavy lifting, excessive walking, or any routine exercise) for 24 hours and imposed 1 hour of bed rest immediately following the procedure. Seven- to 10-day follow-up US was performed to assess for persistent pseudoaneurysm obliteration. If there was clinical suspicion of recurrence, repeat US was performed sooner. Pseudoaneurysm repair was deemed successful if complete obliteration occurred at the time of initial injection with no alteration in clinical or Doppler examination findings of distal pulses and if complete thrombosis persisted at follow-up US.
In addition, clinical follow-up of patients who underwent successful pseudoaneurysm treatment was performed at a minimum of 4 months after treatment. This follow-up was carried out with clinical evaluation by the patient’s referring physician or with phone contact by the radiologist responsible for the procedure. Patients were questioned concerning the sensation of inguinal fullness, discomfort, or pain that limited their activity and about the development of or change in extent of peripheral claudication.
Finally, all 54 patients were evaluated with respect to pseudoaneurysm volume, pseudoaneurysm architectural classification (simple vs complex), thrombin dose, concomitant anticoagulation therapy (in addition to the heparin received by all patients during cardiac catheterization as is routine in our invasive cardiology laboratory), and sheath size to identify criteria that may predispose to failure of pseudoaneurysm obliteration with administration of thrombin. Factors were evaluated by using the Fisher exact test or the Mann-Whitney rank sum test to compare pseudoaneurysm volumes, with a P value of less than .05 considered to indicate a statistically significant difference.
|
RESULTS |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
US follow-up was performed within 7–10 days of injection in all 50 patients who were successfully treated, and findings confirmed persistent thrombosis. In addition, findings from clinical follow-up of a minimum of 4 months (mean, 6.5 months) were available in 33 of 45 successfully treated simple pseudoaneurysms and in all five of the successfully treated complex pseudoaneurysms. In all 38 of these pseudoaneurysms, there was no evidence of a recurrent inguinal mass, discomfort, or symptoms to suggest complications from thrombin injection (change in distal pulses, worsening of or new onset of claudication or rest pain).
Data used to compare the failed and successfully treated femoral pseudoaneurysms with respect to architectural classification, total volume, anticoagulation therapy at the time of thrombin injection, amount of thrombin injected, and sheath size are shown in the Table. Only a complex pseudoaneurysm architecture was significantly associated with failure (P < .01). Failure to achieve permanent pseudoaneurysm obliteration with topical thrombin administration occurred in four patients, all with complex (bilobed) pseudoaneurysms. Though anticoagulation therapy was not significantly associated with failure to achieve pseudoaneurysm thrombosis, development of a complex, bilobed pseudoaneurysm was significantly associated with anticoagulation (P < .02). Sheath size and time from catheterization to diagnosis were similar for both simple and complex pseudoaneurysms.
|
|
|
|
|
DISCUSSION |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
To our knowledge, we present findings from the longest follow-up in the largest number of patients undergoing thrombin injection for femoral artery pseudoaneurysm repair. Although Liau et al (4) found no evidence of recurrence at clinical examination or at US up to 28 months after successful treatment, the total number of patients in their series was only five. Kang et al (3) found no recurrence in 18 of 22 of their successful cases; however, this was based on follow-up US findings obtained only 1–4 days after topical thrombin injection. In a more recent study, Paulson et al (7) successfully treated 25 of 26 femoral artery pseudoaneurysms with thrombin, with success being based on persistent thrombosis at 24-hour follow-up US.
In our series, all 45 patients in whom a simple pseudoaneurysm was successfully thrombosed underwent initial 7–10-day follow-up US that revealed no evidence of early recurrence. In addition, 33 of these 45 patients also underwent clinical follow-up for a minimum of 4 months, which revealed no evidence of late recurrence. Our results indicate that once thrombosis of a simple pseudoaneurysm is achieved, US and clinical follow-up are not necessary to ensure continued obliteration and to exclude recurrence, despite patient mobility after 1 hour and the presence of anticoagulation therapy.
All nine patients with a complex bilobed pseudoaneurysm were receiving heparin therapy during and after thrombin injection, and all had an elevated partial thromboplastin time. Hence, our data do not allow comment on the response of a complex pseudoaneurysm to thrombin in the absence of concomitant anticoagulation. However, it is clear that in this scenario, both lobes need to be injected to achieve success. The thrombus formed during direct thrombin injection has a supraphysiologic concentration of thrombin bound to fibrin. Fibrin-bound thrombin cannot be inactivated by heparin and also activates factor XI. Once activated, factor XI contributes to both the generation of additional thrombin and the activation of a fibrinolysis inhibitor, thereby protecting the clot from fibrinolysis (11).
In the five cases of successful treatment of a complex pseudoaneurysm, separate injections were performed and likely evoked the previously mentioned scenario in each lobe. This can also explain the high success rate for the treatment of simple pseudoaneurysms. In the four unsuccessfully treated complex pseudoaneurysms, injection and thrombosis of the more peripheral lobe was performed initially, with clot development in the lobe that was joined directly to the native vessel via the pseudoaneurysm neck. The thrombus within this proximal lobe likely resulted more from intrinsic thrombin with the addition of some injected thrombin, was more susceptible to inhibition by heparin, and, overall, had a relatively lower concentration of fibrin-bound thrombin.
In addition, the proximal lobe is in direct contact with damaged vessel endothelium, which expresses thrombomodulin, which complexes with thrombin to activate protein C. Activated protein C is known to activate an anticoagulation pathway (12) and reduce the relative size and number of fibrin fibers within maturing thrombus (13). These reasons may help explain why the clot, which developed within the proximal lobe of the unsuccessfully treated bilobed pseudoaneurysms, underwent spontaneous thrombolysis within 48 hours, leading to pseudoaneurysm recurrence. In the five cases in which treatment of a bilobed pseudoaneurysm with topical thrombin was successful, there was failure to develop occlusive clot in the proximal, initially uninjected lobe, and a second direct thrombin injection was performed. Hence, in these successful cases, both lobes received an exorbitant load of extrinsic thrombin, which theoretically overrode the effects of heparin and the patient’s activated anticoagulation and fibrinolysis pathway.
Other than the amount of thrombin injected, there were no factors that could be discerned between the five successfully treated and four unsuccessfully treated complex pseudoaneurysms. Even when the size of both lobes of each complex pseudoaneurysm was reviewed separately, the volumes of the proximal lobes in the unsuccessful and successful cases were similar.
Although the hemodynamics of a bilobed pseudoaneurysm are complex, the blood flow to and, hence, flow from the lobe joining the native vessel must be equal to its volume plus the volume of the more distant lobe. In addition, at some point, the proximal lobe must receive flow from the distal lobe while emptying into the native vessel. For these reasons, our current recommendation on the management of bilobed iatrogenic femoral pseudoaneurysms is to initially inject the lobe of the pseudoaneurysm farthest removed from and not in direct contact with the native femoral artery, thereby causing thrombosis. We believe this theoretically minimizes the possibility of thrombin or thrombus entrance into the native vessel. If thrombosis of the remainder of the pseudoaneurysm rapidly occurs before a second injection is possible, no additional injection is performed. However, because this scenario has been associated with recurrence in our experience, prolonged bed rest of at least 6 hours and follow-up US at 48 hours (or sooner if clinically warranted) is recommended. If at follow-up, recanalization of the proximal lobe is documented, a second thrombin injection of up to 1,000 units is performed. Bed rest is also prescribed for at least 6 hours, and these patients undergo US follow-up at 48 hours to exclude recurrence. We have adopted this approach regardless of whether the patient is receiving concomitant anticoagulation therapy.
As mentioned, in our study, all nine patients with complex pseudoaneurysms were receiving heparin therapy. Until now, we have not treated a patient with a complex pseudoaneurysm who was not receiving anticoagulation therapy. Though not the focus of this study, our data indicate that anticoagulation therapy is significantly associated with the development of a complex rather than a simple pseudoaneurysm. Sixteen of 45 patients with a simple pseudoaneurysm were receiving anticoagulation therapy compared with all nine patients with complex pseudoaneurysms. Hence, our approach to an iatrogenic complex bilobed femoral pseudoaneurysm in a patient receiving heparin therapy and the difficulty in successfully treating it appears to be more relevant.
In none of our complex pseudoaneurysms did we first inject the lobe directly joined to the native vessel via the pseudoaneurysm neck. Hence, we cannot exclude the possibility that direct injection into this lobe could cause thrombosis, eliminate flow in the more distal lobe, and lead to total spontaneous thrombosis of the entire pseudoaneurysm. Still, we believe that it is safest first to address that portion of the pseudoaneurysm farthest from and not in direct communication with the native vessel and then to perform a second thrombin injection if required.
The use of bovine-derived thrombin poses a potential risk of an allergic response and hemorrhage in patients with a known allergy to bovine-derived products or previous exposure to topical thrombin (14–16). The hemorrhagic complications appear to be related to antibodies developed against bovine coagulation factors that cross-react with human clotting factors and require a prior remote exposure. To our knowledge, there has been no complication substantiated in the literature that can be attributed to an allergic response when bovine-derived thrombin has been used to treat pseudoaneurysms. In addition, there is no contraindication to a second injection within 48 hours in patients with a complex pseudoaneurysm who have a recanalized proximal lobe. However, our policy is to avoid the use of topical thrombin if there is a question of an allergy to bovine-derived products or when there has been exposure (topical or intravascular) to these products in the distant past.
In conclusion, topical thrombin injection should be considered the main therapy for simple iatrogenic femoral pseudoaneurysms that meet size criteria because it is highly effective, easy to perform, fast acting, and without apparent associated morbidity. Pseudoaneurysms containing only a single lobe can be treated with just a single US-guided injection of up to 1,000 units of topical thrombin. Once thrombosis is achieved and documented at US, no additional imaging follow-up is required, regardless of pseudoaneurysm size or concomitant anticoagulation therapy. In cases in which a bilobed pseudoaneurysm is present, injection and thrombosis of the lobe not directly joined with the native femoral artery can be performed first. This should be immediately followed by a second injection into the lobe communicating with the femoral artery if still patent. More conservative management—including longer bed rest, closer observation, and 48-hour follow-up US—is then warranted in these cases to ensure complete and persistent pseudoaneurysm thrombosis.
|
FOOTNOTES |
|---|
|
REFERENCES |
|---|
|
TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
This article has been cited by other articles:
|
|
 |
|
  G. W. Webber, J. Jang, S. Gustavson, and J. W. Olin Contemporary Management of Postcatheterization Pseudoaneurysms Circulation, May 22, 2007; 115(20): 2666 - 2674. [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Stone, A. F. AbuRahma, S. K. Flaherty, and M. C. Bates Femoral Pseudoaneurysms Vascular and Endovascular Surgery, March 1, 2006; 40(2): 109 - 117. [Abstract] [PDF]
|
|
|
|
 |
|
 A. K. Dasyam, W. D. Middleton, and S. A. Teefey Development of Nonobstructive Intraarterial Thrombi After Injection of Thrombin into Pseudoaneurysms Am. J. Roentgenol., February 1, 2006; 186(2): 401 - 405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Krueger, M. Zaehringer, D. Strohe, H. Stuetzer, J. Boecker, and K. Lackner Postcatheterization Pseudoaneurysm: Results of US-guided Percutaneous Thrombin Injection in 240 Patients Radiology, September 1, 2005; 236(3): 1104 - 1110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Vazquez, M. Reus, A. Pinero, D. Abellan, M. Canteras, M. E. de Rueda, D. Morales, and P. Parrilla Human Thrombin for Treatment of Pseudoaneurysms: Comparison of Bovine and Human Thrombin Sonogram-Guided Injection Am. J. Roentgenol., May 1, 2005; 184(5): 1665 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. G. Sheiman and M. Mastromatteo Iatrogenic Femoral Pseudoaneurysms That Are Unresponsive to Percutaneous Thrombin Injection: Potential Causes Am. J. Roentgenol., November 1, 2003; 181(5): 1301 - 1304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ghersin, T. Karram, D. Gaitini, A. Ofer, S. Nitecki, H. Schwarz, A. Hoffman, and A. Engel Percutaneous Ultrasonographically Guided Thrombin Injection of Iatrogenic Pseudoaneurysms in Unusual Sites J. Ultrasound Med., August 1, 2003; 22(8): 809 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kruger, M. Zahringer, F.-D. Sohngen, A. Gossmann, O. Schulte, C. Feldmann, D. Strohe, and K. Lackner Femoral Pseudoaneurysms: Management with Percutaneous Thrombin Injections--Success Rates and Effects on Systemic Coagulation Radiology, February 1, 2003; 226(2): 452 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Vrachliotis and R. G. Sheiman Treatment of Massive Hemoptysis with Intraarterial Thrombin Injection of a Bronchial Artery Am. J. Roentgenol., July 1, 2002; 179(1): 113 - 114. [Full Text] [PDF]
|
|
|
|
 |
|
 E. R Mohler III, M. E Mitchell, J. P Carpenter, D E. Strandness Jr, M. R Jaff, J. A Beckman, and M. Gerhard-Herman Therapeutic thrombin injection of pseudoaneurysms: a multicenter experience Vascular Medicine, November 1, 2001; 6(4): 241 - 244. [Abstract] [PDF]
|
|
|
|
|
|
A. I. Bloom, R. G. Sheiman, and D. P. Brophy Iatrogenic Femoral Pseudoaneurysms Drs Sheiman and Brophy respond: Radiology, January 1, 2002; 222(1): 292 - 293. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| RADIOLOGY | RADIOGRAPHICS | RSNA JOURNALS ONLINE |
