Accepted Manuscript Atypical Aortic Thrombus: Should Non-Operative Management Be First Line? Ryan Turley, MD Joshua Unger, MD Mitchell Cox, MD Jeffrey Lawson, MD Richard McCann, MD Cynthia Shortell, MD PII:

S0890-5096(14)00217-9

DOI:

10.1016/j.avsg.2014.03.028

Reference:

AVSG 1997

To appear in:

Annals of Vascular Surgery

Received Date: 19 February 2014 Accepted Date: 12 March 2014

Please cite this article as: Turley R, Unger J, Cox M, Lawson J, McCann R, Shortell C, Atypical Aortic Thrombus: Should Non-Operative Management Be First Line?, Annals of Vascular Surgery (2014), doi: 10.1016/j.avsg.2014.03.028. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT

Atypical Aortic Thrombus: Should Non-Operative Management Be First Line? Ryan S. Turley MD, Joshua Unger MD, Mitchell W. Cox MD, Jeffrey Lawson MD,

AC C

EP

TE D

M AN U

SC

RI PT

Richard L. McCann MD, Cynthia K. Shortell MD

ACCEPTED MANUSCRIPT

Abstract: OBJECTIVE: Aortic thrombus in the absence of atherosclerotic plaque or aneurysm is rare, and

RI PT

its optimal management remains unclear. Although atypical aortic thrombus (AAT) has been historically managed operatively, successful non-operative strategies have been recently reported. Here, we report our experience in treating patients with AAT that has evolved from a primarily operative approach to a first-line, non-operative strategy. METHODS: Records of

SC

patients treated for AAT between 2008 and 2011 at our institution were reviewed. RESULTS: Ten female and three male patients with ages ranging from 27 to 69 were identified. Seven were

M AN U

treated operatively and six non-operatively. Initial presentation was variable and included limb thromboembolic events (n=6), visceral ischemia (n=5), and stroke (n=1). Associated risk factors included hypercoagulability (76%; n=10,) and hyperlipidemia (38%, n=5). In the non-operative group, complete thrombus resolution was obtained via anticoagulation (n=5) or systemic

TE D

thrombolysis (n=1). Complete thrombus extraction was achieved in all operative patients, There were 11 significant complications in 5 of the 7 patients (71%) in the operative group; including intraoperative lower extremity embolism, pericardial effusion, stroke, and one death. There was

EP

one complication in the patients treated non-operatively. The median hospital length of stay was 9 days (range 3-49) for those treated non-operatively and 30 days (range 4-115) for those

AC C

undergoing operative thrombectomy. CONCLUSIONS Although AAT has traditionally been treated operatively, non-operative management of AAT with anticoagulation or thrombolysis is feasible in selected patients and may lessen morbidity and length of hospitalization in those patients for whom it is appropriate.

ACCEPTED MANUSCRIPT

INTRODUCTION:

RI PT

Acute thrombosis of the aorta is usually a catastrophic clinical event which may result in acute lower extremity ischemia, renal artery thrombosis, or bowel infarction.

In most cases,

aortic thrombosis is due to underlying atherosclerotic disease with superimposed acute thrombus,

reconstruction or extra-anatomic bypass.

SC

and treatment is necessarily directed at the underlying atherosclerotic occlusion with direct aortic Less commonly, thrombosis of the aorta may be

M AN U

caused by an acute embolic event, most often from a cardiac source. A large embolus may lodge at the level of the aortic bifurcation, almost always producing acute bilateral lower extremity ischemia. Treatment in such cases is directed at extraction of the thrombus in the immediate term, and subsequent long-term anticoagulation to prevent recurrence.

A much less common

clinical scenario is the development of de novo aortic thrombus in the absence of underlying

TE D

atherosclerotic disease, aortic aneurysm, or a cardiac embolic source. These lesions are usually

EP

not occlusive lesions, but rather mural or pedunculated. (1, 2)

In contrast to the venous system, primary thrombosis of a normal artery is a distinctly

AC C

unusual problem, and the aorta is uniquely resistant to such events, possibly due to its large diameter and high flow. However, in a very small subset of patients presenting with visceral or lower extremity ischemic events, the etiology is the presence of primary aortic thrombus. There may be diverse underlying etiologies, but the common denominator is believed to be a hypercoaguable state. There is no consensus nomenclature for the de-novo aortic thrombus; prior studies have utilized terms such as Mural Aortic Thrombus (MAT) or Aortic Mural Thrombus (AMT), which do not differentiate between thrombus caused by cardiac source,

ACCEPTED MANUSCRIPT

atherosclerotic disease, or unusual etiology. Here, we introduce the terminology of Atypical Aortic Thrombus (AAT) to both characterize the thrombus location and specify that the lesion

RI PT

develops in the absence of underlying aortic pathology or embolic events.

The optimal treatment for patients with AAT is not yet well defined, but alternatives

SC

include thrombectomy and/or embolectomy, open aortic replacement, endovascular exclusion, catheter directed or systemic thrombolysis, and anticoagulation. Traditionally, an aggressive

M AN U

surgical approach has been advocated to obviate potential acute ischemia and prevent any subsequent embolic events. (1, 2) Surgical removal of thrombus from the thoracic, paravisceral, and infrarenal aorta, however, confers significant morbidity in patients who are already critically ill. While patients with visceral or renal artery occlusion may require immediate transaortic thrombectomy, systemic anticoagulation or thrombolysis may be reasonable options for patients

TE D

in whom symptoms are not life or limb threatening. The purpose of this study is to examine our institutional experience with AAT and review the available literature regarding non-operative

AC C

METHODS:

EP

and operative treatment strategies.

With Institutional Review Board approval, we used surgeon case logs to identify 421 patients presenting to Duke University Medical Center with any aortic thrombus between 2008 and 2011. We defined patients as having atypical aortic thrombus (AAT) if the etiology of their thrombus did not include embolus from a cardiac source, aortic atherosclerosis, or aortic aneurysm. To identify the subset of these patients with AAT, all Cross-sectional imaging was reviewed by two vascular surgeons to exclude patients with evidence of significant underlying

ACCEPTED MANUSCRIPT

atherosclerotic disease or aneurysmal disease. All patients included in this study underwent a transthoracic or transesophageal echo to rule out a cardiac source. Using these inclusion and exclusion criteria, 13 of the original 421 (3%) were found to have AAT and were used for this

RI PT

study. Medical records for these patients were then reviewed for presenting symptoms and risk factors for thrombosis such as documented hypercoaguable states, smoking history, inflammatory state, or steroid use.

Length of stay, morbidity, mortality, and perioperative

M AN U

versus operative treatment of the aortic thrombus itself.

SC

outcomes were also reviewed and comparison was made between patients having non-operative

For the purposes of this study, operative cases were considered to be those that involved an attempt to extract an intra-aortic thrombus, whether via direct aortotomy or with a balloon embolectomy catheter. For example, if a patient required lower extremity thromboembolectomy

TE D

or bowel resection but the primary aortic thrombus was treated with anticoagulation, they were classified as receiving non-operative treatment because the focus of the study is the optimal

AC C

RESULTS:

EP

treatment of the aortic thrombus.

Thirteen patients, 10 women and 3 men, with a median age of 47 (range 27 to 69) were identified with AAT as summarized in Table 1. Six patients were managed non-operatively and seven were managed operatively. Comparison of outcomes between non-operative and operative management is summarized in Table 2. The median age of patients in the non-operative group

ACCEPTED MANUSCRIPT

was 40.5 years as compared to 50 years in the operative group. The median length of stay was lower in the non-operative group (9 days) compared to 30 days in the operative group. The length of ICU stay was also lower (1.5 days) in patients managed non-operatively group

RI PT

compared to 7 days for those in the operative group. Complications were less frequent in the non-operative group with one complication (17% of patients) of a below the knee amputation after a failed femoral exploration for embolectomy in Patient #6. In contrast, there were 11

SC

complications in the operative group with complications occurring in five out of seven patients

M AN U

(71%).

Eight patients (62%) had a defined or identifiable hypercoagulable state (including current smoking) and five patients (38%) had hyperlipidemia. Hypercoagulable states included JAK2 mutation, disseminated intravascular coagulopathy (DIC) associated with miscarriage, and

to the development of AAT.

TE D

associated malignancy. Three patients (#5, # 10, and #11) were diagnosed with malignancy prior Patient #10 had a history of carotid body paraganglioma which

was untreated (patient choice) prior to her presentation with AAT. Patient #11 presented after

EP

craniotomy for glioblastoma while being treated with bevacizumab (Avastin, Genentech/Roche,

AC C

San Francisco) which is reported to be a risk factor for arterial thrombosis.(3) Computed tomography angiogram (CTA) images of his AAT are shown in Figure 1A and 1B. Patient #8 was diagnosed with malignancy after treatment for AAT revealed intra-aortic sarcoma on the final pathology report. Figure 1C and 1D show the CTA appearance of intra-aortic sarcoma in Patient #8.

ACCEPTED MANUSCRIPT

Location of AAT at presentation was the aortic arch (4 patients, 30%), descending thoracic aorta (2 patient, 15%), suprarenal abdominal aorta (4 patients, 30%), and infrarenal abdominal aorta (3 patients, 25%).

Clinical presentations included lower extremity

8%).

RI PT

thromboembolic events (6 patients, 46%), visceral ischemia (5 patients, 38%), and stroke (1, The AAT in patient #2 was found during imaging acquired for complications from

bariatric surgery.

She was asymptomatic from her AAT.

Of the six patients with lower

SC

extremity embolic events, three presented with critical limb ischemia. The remaining three patients with lower limb thromboembolic events included two patients with blue toe syndrome Of the three patients with visceral ischemia,

M AN U

and one patient with sub-acute limb ischemia.

patients #1 and #9 presented with signs and symptoms of bowel ischemia and peritonitis. The remaining patients with visceral ischemia had less acute presentations with flank pain from renal and/or splenic infarcts. Patient # 13 was referred after suffering an embolic stroke from her arch

TE D

AAT. Surgery was delayed 7 days in this case based on recommendations from the neurology service.

EP

In the non-operative group, complete thrombus resolution was achieved with

AC C

anticoagulation (5 patients, 83%) or thrombolysis (1 patient, 17%). Patient #1 was a 27 year old female who was transferred to our institution after resection of the majority of her small bowel at outside hospital due to superior mesenteric artery (SMA) embolism. She had a hypercoagulable state due to DIC following intrauterine demise in the 2nd trimester. At transfer she had AAT located in the visceral segment of the abdominal aorta at the level of the SMA. After nine days of intravenous therapeutic heparin (goal partial thromboplastin time [PTT] 60 to 90 seconds), repeat CTA showed complete resolution of AAT. Patient #2 was a 52 year old female who

ACCEPTED MANUSCRIPT

underwent a revision of her Roux-en-Y gastrojejunostomy that was complicated by an anastomotic leak.

She had an asymptomatic descending thoracic AAT found on imaging

acquired during workup for a pleural effusion. She was treated with anticoagulation, and her Patient #3 was a 61 year old male who

RI PT

AAT completely resolved on subsequent imaging.

presented with flank pain and was found to have splenic and renal infarcts and a suprarenal AAT, which was successfully treated with anticoagulation. His hypercoaguable workup was Patient #4 was a 42 year male without any significant

SC

significant for a JAK2 mutation.

medical history who presented with right flank pain and CTA demonstrating two small right

M AN U

renal infarcts and the finding of AAT in the aortic arch and infrarenal aorta. The patient underwent systemic thrombolysis using tissue plasminogen activator (tPA, Actevase, Genentech/Roche, San Francisco) at a rate of 25 mg given over 2 hours followed by a rate of 5 mg/hr for 22 hours. This dosing regimen was estimated as there is no data for dosing of systemic

TE D

thrombolytics for aortic thrombus, though one group (4) used alteplase 0.625mg/kg body weight given every 24 hours for 3 days as dose and another group (5) used alteplase 20 mg over 5 minutes followed by 100 mg over 100 minutes as dose. Repeat CTA following thrombolysis

EP

showed complete resolution of AAT. Although his hematologic testing did not demonstrate a specific hypercoaguable state, he was presumed to have a hypercoaguable phenotype and he was

AC C

treated with warfarin for a year followed by conversion to long term antiplatelet therapy. Patient #5 was a 36 year old female with a known brain tumor who presented with flank pain cause by bilateral renal infarcts. Her suprarenal AAT was treated with anticoagulation alone and resolved on subsequent imaging. Patient #6 presented with critical limb ischemia of right lower extremity resulting from a thromboembolus from a descending thoracic AAT. She underwent an urgent femoral artery thrombectomy, which was technically successful but did not achieve limb

ACCEPTED MANUSCRIPT

salvage. She eventually required a below the knee amputation. Her AAT was treated only with

RI PT

anticoagulation with complete resolution on subsequent imaging.

For all patients with AAT treated with either anticoagulation or thrombolytic therapy as summarized above, there were no additional embolic complications once treatment was initiated.

SC

However, Patient #6 required an amputation as described previously. Therefore, there was one

M AN U

complication in the non-operative group for an overall complication rate of 17%.

The clinical presentation in the six patients with AAT who were treated operatively also varied, including visceral ischemia (1 patient, 14%), lower extremity thromboembolism (5 patients, 72%), and stroke (1 patient, 14%). Operative approaches to aortic thrombus extraction

TE D

varied. Two patients (28%) underwent femoral cut-down and balloon thrombectomy. One of these patients refused a laparotomy for infrarenal AAT. Two patients (28%) had laparotomy for aortotomy and thrombectomy, one of whom required a bowel resection. One patient (14%) had

EP

a thoracoabdominal aortic exposure with thrombectomy. Another patient (14%) had bilateral thoracosternotomy, circulatory arrest, and resection and graft of distal aortic arch. The remaining

AC C

patient had a sternotomy, deep circulatory arrest, and aortic arch thrombectomy. Pathology from the retrieved specimens was benign except for patient #8 who was found to have intra-aortic sarcoma. In all cases, complete thrombus removal was achieved.

In the operative group there were 11 complications occurring in five out of seven patients (71%). Patient #7 developed pleural and pericardial effusion requiring pericardial window after

ACCEPTED MANUSCRIPT

thoracoabdominal exposure for direct aortotomy.

Patient #8 experienced an intraoperative

embolism during aortic arch cross clamp that resulted in return to the operating room for bilateral femoral thrombectomy and lower extremity four-compartment fasciotomies. She also had a

RI PT

postoperative stroke, urinary tract infection, and renal failure requiring temporary hemodialysis. Patient #9 died after a prolonged postoperative course following laparotomy and small bowel resection for suprarenal abdominal AAT which caused SMA thrombosis.

Patient # 10 suffered

M AN U

SC

cardiopulmonary arrest post-operatively but recovered without long term sequalae.

DISCUSSION:

The natural history and appropriate management of acute aortic occlusion is well described in the literature; this potentially catastrophic event confers in-hospital mortality between 20-50%. (6-8) Non-occlusive aortic thrombosis is less morbid, usually presenting with

TE D

embolic events to end organs such as the kidneys, intestine, or lower extremity. With regard to arterial thromboembolic events in general, the origin of thrombus was historically characterized

EP

as predominantly cardiac (80-90%), in situ thrombosis due to underlying aneurysm (5-10%), or unknown or “cryptogenic” (10-15%). (9-12) Of the “cryptogenic” group, modern imaging has The

AC C

shown that the etiology is predominantly atherosclerosis causing arterial thrombosis.

minority of the “cryptogenic” group is due to de novo arterial thrombosis, which we have termed Atypical Aortic Thrombus. Primary development of a thrombus within a normal thoracic or abdominal aorta is a distinctly rare occurrence, and there is no consensus around optimal management. Clearly acute ischemia of the viscera or the lower extremities due to embolus from any source must be addressed surgically via either embolectomy or bowel resection, however, the appropriate approach to the underlying aortic thrombus has not yet been determined.

ACCEPTED MANUSCRIPT

Williams et. al.(1) and Gagliardi et. al.(2) described their respective experiences with transaortic

RI PT

aortic thrombus resulting in distal embolism, and both authors recommended

thrombus extraction since catheter embolectomy alone was associated with a high rate of recurrent embolism,. However, these early series included diverse etiologies and were heavily weighted toward atherosclerotic causes with little consideration of hypercoagulable states Endovascular approaches to AAT have been

SC

beyond heparin-induced thrombocytopenia (HIT).

reported in small cases reports, (4, 13) but their widespread application may be limited due to the

M AN U

high embolic risk of AAT and lack of adequately sized embolic protection devices for the aorta. Nonetheless, endovascular repairs may provide a less-invasive treatment option for stable, shortsegment thrombi located far from major branch vessels.

In recent years, there has been

increasing awareness of a variety of genetic or acquired hypercoaguable states that are associated

TE D

with the development of primary aortic thrombus in the absence of any underlying atherosclerotic disease or recent aortic instrumentation. (5, 14) Additionally AAT has been associated with underlying malignancy (15), steroid use (16), and inflammatory bowel disease. Recently, Hahn et al. (18) and Bowdish et al. (19) reported success with systemic

EP

(17)

anticoagulation alone for patients with AAT. As with our study, the later series report minimal

AC C

complications associated with systemic anticoagulation for AAT. Aortic thrombus associated with atherosclerosis may also respond to systemic anticoagulation as success was reported in several case series. (4, 20-22) Additionally, thrombolytic therapy to treat aortic thrombus was reported in case reports and series (23-25), giving additional support for non-operative treatment of AAT. Previous case series have described either operative or non-operative management of

ACCEPTED MANUSCRIPT

the aortic lesion in AAT but none have compared the outcomes of operative versus non-operative

RI PT

management as we have done in this study.

The demographics of the patients in our series is similar to the more recent case series, with a preponderance of females (77%) and a mean age of 47 years, while aortic thrombosis due

SC

to atherosclerotic disease occurs primarily in older male smokers. Eight of thirteen patients in our study had a defined or identifiable hypercoaguable state. Therefore, we recommend a

M AN U

hypercoaguable workup for all AAT patients including measurement of anti-thrombin III levels, protein C/S activity, Factor V leiden and prothrombin 20120a mutations, anti-phospholipid antibodies, and homocysteine. If this biochemical workup is negative, a malignancy evaluation including serum makers, endoscopy, and clinically appropriate imaging should be considered as four of thirteen patients in our series harbored a malignancy.

TE D

These findings suggest that AAT is a usually manifestation of hypercoaguable state, and therefore that all patients should be treated initially with systemic anticoagulation even in the

EP

absence of an identified biochemical abnormality. Supporting this recommendation are several case reports of recurrent embolic events in patients with AAT who were not anticoagulated or

AC C

noncompliant after initial operative or non-operative treatment of the aortic thrombus. (13, 14, 24) Once anticoagulation has been initiated, the decision to operate can be separated into two components: the decision to treat embolic sequelae of AAT such as ischemic end organs (i.e. bowel or extremity) and the decision to operate on the thrombus itself. The decision to intervene surgically on the ischemic end organ, often a relatively limited procedure, is based on standard vascular surgical treatment algorithms. In contrast, our study suggests that the aortic thrombus should be managed with anticoagulation or thrombolysis and that surgical intervention on the

ACCEPTED MANUSCRIPT

thrombus itself be reserved for situations in which this approach is unsuccessful given the high rate of success for medical therapy and the high rate of complications for operative therapy. Ultimately, the decision between operative and non-operative treatment can be difficult; in our

RI PT

own series Patient #5 (Figure 1E and 1F), with a mildly pedunculated AAT, was treated with operative thoracoabdominal aortic thrombus extraction as an initial therapy and might have had an improved outcome if systemic anticoagulation was used instead.

SC

If non-operative therapy is to be pursued, the immediate options are catheter directed thrombolysis, systemic thrombolysis, or systemic anticoagulation with intravenous heparin or

M AN U

subcutaneous enoxaparin. Recent reports of success with catheter directed thrombolysis report a high incidence of distal embolization and therefore recommend systemic thrombolysis, which is not associated with this complication. (10) Unfortunately, thrombolysis will only be applicable to a very small subset of patients: those presenting with an acute embolic event requiring short-

TE D

term clearance of the thrombus who have not had and will not require other surgical procedures and have no other contraindications to lysis. If the aortic thrombus does not resolve with anticoagulation or thrombolysis, malignancy should be considered as one patient had intra-aortic

EP

sarcoma. Although anticoagulation or thrombolysis was not attempted for this patient, we presume that neither approach would have resulted in thrombus resolution given the underlying

AC C

aortic malignancy. While primary aortic malignancy is very rare, sarcoma is the most common. It has been associated with elevated erythrocyte sedimentation rate (ESR) and suggested diagnostic modalities are magnetic resonance imaging (MRI) to characterize the aortic lesion and bone scan to rule out metastasis. (26, 27) Prognosis is overall poor with mean survival 12-14 months despite surgical resection. (28). Furthermore, our data would suggest that AAT may be a harbinger of occult malignancy leading to a hypercoaguable state which could potentiate de novo

ACCEPTED MANUSCRIPT

aortic thrombosis. The reasons for this are speculative but may be related to cancer-related endothelial damage, cytokine activation, tumor/endothelial cell apoptosis, and/or increased tissue factor activity. (29)

The optimal duration of anticoagulation for AAT is ill-defined. Our

RI PT

practice is to continue anticoagulation indefinitely unless the underlying etiology is identified and effectively treated.

For the rare patient who presents with asymptomatic AAT, we would avoid operative

SC

management given its morbidity reported here and elsewhere. Thus, our strategy would be similar to the symptomatic patient, where we would evaluate for a hypercoaguable disorder, If there were no resolution in

M AN U

initiate systemic anticoagulation, and reimage in 48-72 hours.

clot burden, we would consider thrombolysis and reserve surgery for refractory patients at high risk of embolization.

There are a few limitations inherent in this study. First, it is a retrospective review with

TE D

likely significant selection bias, as patients with more acute presentation or more extensive thrombus may have preferentially undergone a more aggressive surgical approach. As patients were selected from surgeon case logs, asymptomatic patients AAT would less likely be included.

EP

Nonetheless, this series did include patients with incidentally discovered AAT that resolved with

AC C

systemic anticoagulation, thereby supporting a first-line, non-operative treatment strategy for asymptomatic patients.

In the operative group there were three cases of AAT involving either

the aortic arch or descending thoracic aorta compared to just one patient in the non-operative group.

Furthermore, precise reasoning for pursuing one treatment option over another varied

among the seven surgeons in this series and was generally difficult to decipher retrospectively. Finally, the patients in our series were identified by surgeon case log and we may have missed patients who presented to our institution who never were seen in surgical consultation.

ACCEPTED MANUSCRIPT

Despite these limitations, our data suggests that systemic anticoagulation or systemic

RI PT

thrombolysis as the initial treatment for AAT is feasible and may confer reduced morbidity and mortality compared to surgical extraction or exclusion. In cases with acute lower extremity or visceral ischemia, thrombectomy or revascularization in the affected vascular territories is mandatory. However, the aortic source does not necessarily need to be addressed at the time of

SC

the original procedure. Workup should include evaluation of a source for hypercoaguable state

M AN U

including occult malignancy. CONCLUSION:

Atypical aortic thrombus is a distinct clinical entity occurring most often in middle-aged female patients with a known or occult hypercoaguable state and without significant underlying aortic pathology.

Even if serologic studies are negative, patients should be presumed to have

TE D

hypercoaguable phenotype and treated accordingly with long term anticoagulation. While prior studies have advocated aggressive operative intervention, we demonstrate that non-operative

EP

management of AAT using systemic anticoagulation or thrombolysis is feasible and may be associated with fewer complications and a shorter hospital stay.

Larger studies are needed to

AC C

confirm the safety and superiority of a first-line, non-operative strategy for treating AAT.

RI PT

ACCEPTED MANUSCRIPT

B

C

D

TE D

M AN U

SC

A

E

F

Figure 1. Cross sectional imaging of patients with Atypical Aortic Thrombus. A and B show a

EP

near occlusive lesion in the infrarenal aorta in Patient #11, a 62 year old male who had hypercoagulable state secondary to bevacizumab (Avastin) treatment for glioblastoma

AC C

multiforme. C and D show a more heterogeneous lesion in the aortic arch in Patient #8, a 48 year old female who was treated with bilateral thoracosternotomy and removal of lesion. E and F show a lesion in the suprarenal aorta in Patient #7, a 47 year old female who was treated with thoracoabdominal approach and aortotomy.

ACCEPTED MANUSCRIPT

References

RI PT

1. Williams GM, Harrington D, Burdick J, White RI. Mural thrombus of the aorta: an important, frequently neglected cause of large peripheral emboli. Ann Surg. [Case Reports]. 1981 Dec;194(6):737-44. 2. Gagliardi JM, Batt M, Khodja RH, Le bas P. Mural thrombus of the aorta. Ann Vasc Surg. 1988 Jul;2(3):201-4. 3. Scappaticci FA, Skillings JR, Holden SN, Gerber HP, Miller K, Kabbinavar F, et al. Arterial thromboembolic events in patients with metastatic carcinoma treated with chemotherapy and bevacizumab. J Natl Cancer Inst. [Meta-Analysis

AC C

EP

TE D

M AN U

SC

Research Support, Non-U.S. Gov't]. 2007 Aug 15;99(16):1232-9. 4. Tsilimparis N, Hanack U, Pisimisis G, Yousefi S, Wintzer C, Ruckert RI. Thrombus in the non-aneurysmal, non-atherosclerotic descending thoracic aorta--an unusual source of arterial embolism. Eur J Vasc Endovasc Surg. 2011 Apr;41(4):450-7. 5. Onwuanyi A, Sachdeva R, Hamirani K, Islam M, Parris R. Multiple aortic thrombi associated with protein C and S deficiency. Mayo Clin Proc. [Case Reports]. 2001 Mar;76(3):319-22. 6. McCullough JL, Jr., Mackey WC, O'Donnell TF, Jr., Millan VG, Deterling RA, Jr., Callow AD. Infrarenal aortic occlusion: a reassessment of surgical indications. Am J Surg. 1983 Aug;146(2):178-82. 7. Dossa CD, Shepard AD, Reddy DJ, Jones CM, Elliott JP, Smith RF, et al. Acute aortic occlusion. A 40-year experience. Arch Surg. 1994 Jun;129(6):603-7; discussion 7-8. 8. Babu SC, Shah PM, Nitahara J. Acute aortic occlusion--factors that influence outcome. J Vasc Surg. 1995 Apr;21(4):567-72; discussion 73-5. 9. Lord JW, Jr., Rossi G, Daliana M, Drago JR, Schwartz AM. Unsuspected abdominal aortic aneurysms as the cause of peripheral arterial occlusive disease. Ann Surg. 1973 Jun;177(6):767-71. 10. Elliott JP, Jr., Hageman JH, Szilagyi E, Ramakrishnan V, Bravo JJ, Smith RF. Arterial embolization: problems of source, multiplicity, recurrence, and delayed treatment. Surgery. [Case Reports]. 1980 Dec;88(6):833-45. 11. Abbott WM, Maloney RD, McCabe CC, Lee CE, Wirthlin LS. Arterial embolism: a 44 year perspective. Am J Surg. [Comparative Study]. 1982 Apr;143(4):460-4. 12. Machleder HI, Takiff H, Lois JF, Holburt E. Aortic mural thrombus: an occult source of arterial thromboembolism. J Vasc Surg. [Case Reports]. 1986 Nov;4(5):473-8. 13. Martens T, Van Herzeele I, Jacobs B, De Ryck F, Randon C, Vermassen F. Treatment of symptomatic mobile aortic thrombus. Acta Chir Belg. [Case Reports Review]. 2010 May-Jun;110(3):361-4. 14. Beldi G, Bissat A, Eugster T, Gurke L, Stierli P, Huber AR. Mural thrombus of the aorta in association with homozygous plasminogen activator inhibitor type 1 (PAI-1)-675(4G) and heterozygous GP Ia 807C/T genotypes. J Vasc Surg. [Case Reports]. 2002 Sep;36(3):632-4. 15. Rafiq MU, Jajja MM, Qadri SS, Robinson GJ, Cale AR. An unusual presentation of pedunculated thrombus in the distal arch of the aorta after splenectomy for B-cell lymphoma. J Vasc Surg. [Case Reports]. 2008 Dec;48(6):1603-4.

ACCEPTED MANUSCRIPT

16. Lozano P, Gomez FT, Julia J, E MR, Garcia F. Recurrent embolism caused by floating thrombus in the thoracic aorta. Ann Vasc Surg. [Case Reports

M AN U

SC

RI PT

Review]. 1998 Nov;12(6):609-11. 17. Perler BA, Kadir S, Williams GM. Aortic mural thrombus in young women: premature arteriosclerosis or separate clinical entity? Surgery. [Case Reports]. 1991 Nov;110(5):912-6. 18. Hahn TL, Dalsing MC, Sawchuk AP, Cikrit DF, Lalka SG. Primary aortic mural thrombus: presentation and treatment. Ann Vasc Surg. [Case Reports]. 1999 Jan;13(1):52-9. 19. Bowdish ME, Weaver FA, Liebman HA, Rowe VL, Hood DB. Anticoagulation is an effective treatment for aortic mural thrombi. J Vasc Surg. 2002 Oct;36(4):713-9. 20. Lau LS, Blanchard DG, Hye RJ. Diagnosis and management of patients with peripheral macroemboli from thoracic aortic pathology. Ann Vasc Surg. [Case Reports]. 1997 Jul;11(4):348-53. 21. Reber PU, Patel AG, Stauffer E, Muller MF, Do DD, Kniemeyer HW. Mural aortic thrombi: An important cause of peripheral embolization. J Vasc Surg. 1999 Dec;30(6):1084-9. 22. Choukroun EM, Labrousse LM, Madonna FP, Deville C. Mobile thrombus of the thoracic aorta: diagnosis and treatment in 9 cases. Ann Vasc Surg. [Evaluation Studies Review]. 2002 Nov;16(6):714-22. 23. Kruger T, Liske B, Ziemer S, Lindemann S, Ziemer G. Thrombolysis to treat thrombi of the aortic arch. Clin Appl Thromb Hemost. [Case Reports]. 2011 Aug;17(4):340-5. 24. Hausmann D, Gulba D, Bargheer K, Niedermeyer J, Comess KA, Daniel WG. Successful thrombolysis of an aortic-arch thrombus in a patient after mesenteric embolism. N Engl J Med. [Case Reports

TE D

Letter]. 1992 Aug 13;327(7):500-1. 25. Dougherty MJ, Calligaro KD, Rua I, Delaurentis DA. Idiopathic pedunculated mural thrombus of the nonaneurysmal infrarenal aorta presenting with popliteal embolization: two cases treated with thrombolytic therapy. J Vasc Surg. [Case Reports]. 2000 Aug;32(2):383-7. 26. Thalheimer A, Fein M, Geissinger E, Franke S. Intimal angiosarcoma of the aorta: report of a case and review of the literature. J Vasc Surg. [Case Reports

AC C

EP

Review]. 2004 Sep;40(3):548-53. 27. Seelig MH, Klingler PJ, Oldenburg WA, Blackshear JL. Angiosarcoma of the aorta: report of a case and review of the literature. J Vasc Surg. [Case Reports]. 1998 Oct;28(4):732-7. 28. Nicotera SP, Simosa HF, Campbell DR. Postoperative outcomes in intimal aortic angiosarcoma: a case report and review of the literature. J Vasc Surg. [Case Reports Review]. 2009 Jul;50(1):186-9. 29. Haddad TC, Greeno EW. Chemotherapy-induced thrombosis. Thromb Res. [Review]. 2006;118(5):555-68.

ACCEPTED MANUSCRIPT Patient

Treatment

Age

Sex

Presentation

Location

Hypercoaguable

Smoker

Disorder

Days to

Severity of

Surgery

Syptoms§

Complications

Path

CT followup

LOS (days)

(days)

2

anticoag*

anticoag

27

52

F

F

visceral

infrarenal

ischemia

abd

Aysmptomatic

descending

pregnancy / DIC

Yes

Severe

None

9

15 / 3

Mild

None

5

11 / 0

Moderate

None

28

3/0

Moderate

None

1

5/3

No

Moderate

None

41

7/0

Yes

Severe

Below the Knee

67

49/9

94

7‡ / 2‡

RI PT

1

No

thoracic

tPA

61

42

M

M

visceral

suprarenal

ischemia

abd

visceral

arch

JAK2 Mutation

No

ischemia

OR –

39

47

F

F

F

thoracoabd 8

OR –

48

F

thoracostern

OR –

52

F

OR – groin explore

abd

lower ext

descending

embolism

thoracic

lower ext

suprarenal

embolism

abd

lower ext

malignancy

arch

malignancy

visceral

Amputation No

1

Moderate

55

F

Yes

Admitted

Moderate

electively

lower ext

infrarenal abd

lower ext

sarcoma

39 / 28

embolism, stroke, ARF, UTI

arch

embolism

pericardial and pleural effusions

No

1

Severe

ischemia

laparotomy

10

suprarenal

embolism

bilateral

9

visceral ischemia

TE D

7

anticoag

36

EP

6

anticoag

AC C

5

No

SC

4

anticoag*

M AN U

3

ARF, SBO,

20

115 / 37

14

4/0

EC fistula, death

malignancy

Yes

20

Mild

None

persistent thrombus

ACCEPTED MANUSCRIPT OR –

62

M

laparotomy 12

OR –

37

F

groin

lower ext

suprarenal

embolism

abd

lower ext

infrarenal

embolism

malignancy

No

1

Moderate

None

8/4

Yes

5

Severe

Right BKA

40/7

Yes

7

Cardiopulmonary

30/10

abd

exploration 13

OR

43

F

Stroke

arch

RI PT

11

Moderate

Arrest

AC C

EP

TE D

M AN U

SC

Table 1. Summary of patient profiles, presentation with Atypical Aortic Thrombus, and outcomes. Patients 1 through 4 were treated non-operatively and patients 5 through 10 were treated operatively. For all operative patients, pathology was benign unless otherwise specified. Values for length of stay (LOS) are listed first as overall length in days followed by number of ICU days. * denotes patients who were treated with anticoagulation for the aortic lesion but also had procedure done at an outside hospital prior to treatment at our institution. † denotes a complication that occurred at an outside hospital associated with an intervention not on the aorta. ‡ denotes that additional days of hospitalization at outside hospital are unknown, but should be added to the overall LOS. §Mild severity infers no to minimal symptoms, Moderate severity means patient was hospitalized for that symptom, and severe denotes symptoms which required surgical intervention.

Operative

Number of patients

6

7

Median age (Range)

40.5 (27-61) years

50 (37-69) years

Median LOS (Range)

9 (3-49) days

30 (4-115) days

LOS (ICU)

1.5 (days)

7 (days)

Complications

1

11

% patients with complications

17

71

SC

Non-operative

RI PT

ACCEPTED MANUSCRIPT

AC C

EP

TE D

M AN U

Table 2. Summary of outcomes between operative and non-operative treatment of atypical aortic thrombus. LOS is length of stay both for overall hospitalization and for ICU.