DOI:10.2214/AJR.04.1892
AJR 2006; 186:401-405
© American Roentgen Ray Society
Development of Nonobstructive Intraarterial Thrombi After Injection of Thrombin into Pseudoaneurysms
Anil K. Dasyam1,2,
William D. Middleton1 and
Sharlene A. Teefey1
1 Mallinckrodt Institute of Radiology, Washington University School of Medicine,
510 S Kingshighway Blvd., St. Louis, MO 63110-1076.
2 Present address: Department of Radiology, University of Pittsburgh School of
Medicine, Pittsburgh, PA.
Received December 13, 2004;
accepted after revision January 12, 2005.
Address correspondence to W. D. Middleton.
Abstract
OBJECTIVE. Our objective was to describe the development of
nonobstructive, localized intraarterial thrombi after percutaneous injection
of thrombin into femoral pseudoaneurysms.
CONCLUSION. Partial extension of thrombi into the arterial lumen may
occur after injection of thrombin into small pseudoaneurysms with short necks.
In our experience, this is an asymptomatic and self-limited complication of
the procedure.
Keywords: color Doppler sonography • peripheral vascular disease • pseudoaneurysm • thrombin • vascular imaging
Introduction
The treatment of iatrogenic pseudoaneurysms after catheterization has
progressed from surgery [1] to
sonographically guided compression repair
[2] to the current widely
accepted method of sonographically guided percutaneous injection of thrombin.
Since it was first described by Liau et al.
[3] in 1997, sonographically
guided injection of thrombin has proved to be a safe, rapid, and effective
means of treating iatrogenic femoral artery pseudoaneurysms. Success rates
range from 91% to 100%, and unlike compression repair, injection of thrombin
is effective in patients receiving anticoagulation therapy
[4-10].
Very few complications have been encountered with this technique. The most
worrisome are thrombotic events in the arterial circulation distal to the
pseudoaneurysm. We have recently encountered three patients in whom a
localized, nonocclusive femoral artery thrombus developed because of injection
of thrombin into a pseudoaneurysm.
Materials and Methods
In three patients with a femoral artery pseudoaneurysm who were treated in
our hospital during 11 months with sonographically guided injection of bovine
thrombin (Thrombin-JMI, GenTrac Inc.), a localized, nonocclusive femoral
artery thrombus developed. Like all patients treated with injection of
thrombin, these three patients gave informed consent before the procedure.
Their sonographic images were reviewed retrospectively to identify potential
factors predisposing them to thrombus development. In each patient, the size
of the pseudoaneurysm was measured and the mean diameter was determined. Only
the active-flow lumen was included in these measurements. The length and the
minimum diameter of the neck connecting the pseudoaneurysm to the femoral
artery were also measured. The site of the needle tip at the time of injection
was determined.
Radiology reports were reviewed to determine the details of the thrombin
injection, including the concentration of thrombin, total dose of thrombin,
and needle gauge. Charts were reviewed retrospectively to determine the
associated symptoms and natural history of this complication.
Table 1 includes information
about the patients' clinical presentations.
Results
In all three patients, the thrombin was injected at a concentration of
1,000 units per milliliter using a 25-gauge needle. The needle tip was
positioned in the superficial aspect of the pseudoaneurysm as distant as
possible from the neck. Table 2
shows the size of the pseudoaneurysm lumina and the dimensions of the
pseudoaneurysm necks. In all three patients, the pseudoaneurysms were small
and the necks were short.
Table 2 also shows the total
thrombin dose used and the size of the intraluminal thrombi. None of the
patients had any signs or symptoms of ischemia during follow-up. Patient 1
(Figs. 1A,
1B, and
1C) was followed clinically for
4 days in the hospital without repeated sonography. Patient 2 underwent
repeated sonography 1 month after the injection, and the intraarterial
thrombus had resolved. Patient 3 (Figs.
2A,
2B,
2C, and
2D) underwent repeated
sonography the day after the procedure, and the intraarterial thrombus was
persistent but slightly smaller. Follow-up sonography 3 weeks after the
injection showed complete resolution of the thrombus.
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Fig. 1A —Patient 1, 53-year-old man with ischemic heart disease. P =
pseudoaneurysm, A = common femoral artery. Transverse color Doppler image 3
days after cardiac catheterization shows small pseudoaneurysm anterior to
common femoral artery.
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Fig. 1B —Patient 1, 53-year-old man with ischemic heart disease. P =
pseudoaneurysm, A = common femoral artery. Transverse color Doppler image
after injection of 200 units of thrombin shows no residual flow in lumen of
pseudoaneurysm.
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Fig. 1C —Patient 1, 53-year-old man with ischemic heart disease. P =
pseudoaneurysm, A = common femoral artery. Longitudinal gray-scale image
obtained immediately after injection of thrombin shows nonocclusive thrombus
(arrow) in common femoral artery.
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Fig. 2A —Patient 3, 72-year-old woman, with spindle cell neoplasm of sacrum.
P = pseudoaneurysm, A = common femoral artery. Color Doppler image and pulsed
Doppler waveform 1 day after tumor embolization shows small pseudoaneurysm
arising from common femoral artery. Typical to-and-fro waveform is documented
in pseudoaneurysm neck.
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Fig. 2B —Patient 3, 72-year-old woman, with spindle cell neoplasm of sacrum.
P = pseudoaneurysm, A = common femoral artery. Longitudinal gray-scale image
obtained immediately after injection of 50 units of thrombin shows
nonocclusive thrombus (arrow) in lumen of artery.
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Fig. 2C —Patient 3, 72-year-old woman, with spindle cell neoplasm of sacrum.
P = pseudoaneurysm, A = common femoral artery. Longitudinal gray-scale image
taken 1 day after injection of thrombin shows residual thrombus
(arrow) that has decreased slightly in size.
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Fig. 2D —Patient 3, 72-year-old woman, with spindle cell neoplasm of sacrum.
P = pseudoaneurysm, A = common femoral artery. Longitudinal gray-scale image
obtained 3 weeks after injection of thrombin shows resolution of intraarterial
thrombus and resolution of pseudoaneurysm.
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Discussion
Percutaneous injection of thrombin under sonographic guidance has proven to
be highly effective and safe. In many studies, the complication rate is 0%
[4,
7,
8,
11,
12]. However, several studies
have reported intraarterial embolization as a rare complication
[8,
10,
13,
14].
The postulated causes for the intraarterial extension of a thrombus have
been inadvertent injection directly into the arterial lumen during an attempt
to inject into the neck of the aneurysm
[10], rapid injection of
thrombin [13], the presence of
a large pseudoaneurysm adjacent to a small artery
[14], and injection of a large
volume of thrombin [8]. The
management of this complication varies: simple observation with spontaneous
resolution [8,
13,
15], resolution with IV
heparin therapy [10],
resolution with intraarterial plasminogen activator
[16,
17], or surgical intervention
[14,
18].
In a group of 13 patients, Ferguson et al.
[13] described a single
patient with a 1.8-cm pseudoaneurysm in whom a localized intraarterial
thrombus developed after injection of 800 units (0.8 mL) of thrombin. In this
patient, the intraarterial thrombus lysed spontaneously within 5 min. In
addition to being of relatively small size, the pseudoaneurysm had the
shortest neck that the authors had encountered in their patient population. In
our experience, all three patients with a localized nonocclusive intraarterial
thrombus had small pseudoaneurysms measuring 16 mm or less in maximum
dimension and had short necks of between 1 and 2 mm in length. Given that we
used small quantities of thrombin (50-200 units) and injected under continuous
sonographic guidance, we believe that these types of pseudoaneurysms are
particularly prone to this complication. Like the patient described by
Ferguson et al., none of our patients had clinical symptoms, and in none did
signs or symptoms of distal ischemia develop during clinical follow-up.
The alternative to injection of thrombin in these patients is simple
observation or compression repair. Kresowik et al.
[19] prospectively followed
seven patients with asymptomatic pseudoaneurysms ranging in size from 1.3 to
3.5 cm (mean, 2 cm) and found that all spontaneously thrombosed at 1-4 weeks
(mean, 1.6 weeks). Kent et al.
[20] prospectively followed 16
patients with pseudoaneurysms, and 9 (56%) thrombosed spontaneously at an
average of 22 days (range, 3-34 days). In this group, the chance was greater
that pseudoaneurysms smaller than 1.8 cm would thrombose spontaneously,
whereas patients receiving anticoagulation therapy had a significantly lower
incidence of spontaneous thrombosis. In a group of 82 patients, Toursarkissian
et al. [21] showed that 87% of
pseudoaneurysms smaller than 3 cm spontaneously thrombosed at an average of 23
days (range, 1-123 days).
On the basis of these studies, Piedad and Kronzon
[22] recommended that
pseudoaneurysms smaller than 1.8 cm be followed weekly with clinical
evaluation and Doppler sonography for spontaneous thrombosis. Sheiman and
Brophy [11] advocated
observation of pseudoaneurysms with a maximum diameter of less than 2 cm or a
volume of less than 6 cm3. We agree that this approach is
reasonable in patients who are not receiving anticoagulation therapy. The
major disadvantage of this approach is that patients require frequent clinical
and sonographic follow-up and must reduce their activity
[22]. This can be both
inconvenient and expensive, and therefore many patients and physicians opt for
early treatment rather than prolonged observation.
If small pseudoaneurysms do not thrombose spontaneously, if they fail a
trial of compression, or if the patients are receiving anticoagulation
therapy, injection of thrombin should be considered. In this situation, it is
important to recognize that some of the injected thrombin is likely to escape
into the arterial lumen. Kruger et al.
[4] have shown an increase in
thrombin-antithrombin III complex after the procedure, suggesting that
thrombin leaks into the systemic circulation. Grewe et al.
[7] confirmed that leakage
occurred in 58% of patients in whom sonographic contrast material was injected
into pseudoaneurysms before thrombin was injected. Both studies suggested that
leakage of thrombin into the artery is probably more common than is generally
realized. Arterial thrombosis is probably rare because the thrombin that
enters the femoral artery is diluted relatively rapidly and deactivated by
natural thrombolytic mechanisms.
The kit that we use provides 5,000 units of powder that is reconstituted in
5 mL of saline, resulting in a concentration of 1,000 units per milliliter.
This is the most commonly used concentration among many studies. However, the
use of dilute concentrations of thrombin has also been advocated by several
authors. The advantage of weaker concentrations is that any thrombin that does
leak into the artery is more dilute and more easily deactivated by natural
thrombolytic mechanisms. Using a concentration of 100 units per milliliter,
Reeder et al. [12] and Taylor
et al. [5] obtained success
rates of 100% and 91%, respectively, with a mean total dose of 192 units
(range, 50-450 units) and 300 units (range, 100-600 units), respectively. No
complications were encountered in either of these studies. Olsen et al.
[23] have also been successful
using dilute thrombin (100 units per milliliter) and minimizing the dose. We
also believe that dilute concentrations of thrombin and small total doses can
be effective and should be considered for small pseudoaneurysms.
In conclusion, caution should be exercised in attempting injection of
thrombin into small pseudoaneurysms with short necks. Simple observation, with
or without an attempt at compression repair, should be considered strongly as
the initial approach. If injection of thrombin becomes necessary, the
concentration, volume, and total dose of injected thrombin should be
minimized. The rate of injection should also be minimized. Careful attention
to these details will decrease the chance of embolization. If a localized,
nonobstructive thrombus does develop, intervention usually will not be
necessary. The patient should be monitored clinically, and spontaneous
resolution should be documented with follow-up sonography.
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Abstract
Introduction
