Large mural thrombus in the distal arch of the aorta without atherosclerotic disease

Abstract

Aortic mural thrombus (AMT) is an uncommon cause of arterial thromboembolism. It is very rare in patients without significant cardiovascular risk factors. Many aetiologies can cause AMT, but there are no clear guidelines for the evaluation and treatment. We present the case of a 43-year-old woman without arteriosclerotic disease who was admitted to the hospital with peripheral embolisation from the mural thrombus in the distal arch of the aorta. Therapy with systemic anticoagulation resulted in complete resolution without necessitating any surgical or endovascular interventions. There were no reported recurrence or complications of the intra-aortic thrombus within 1-year surveillance imaging study.

Background

Aortic mural thrombus (AMT) formation on a non-atherosclerotic wall is a very uncommon but important cause of arterial thromboembolism. Although a specific aetiology cannot be identified in most cases of AMT, it is often associated with hypercoagulable states such as primary polycythemia vera, antiphospholipid syndrome, malignancy, primary endothelial disorders, hyperhomocysteinemia, heparin-induced thrombocytopenia (HIT) and complication of the intra-aortic balloon pump (IABP).^{1 2} For clinicians, the management of AMT can be particularly challenging as the data on the systematic guidelines are limited.

Case presentation

A 43-year-old woman with a previous medical history of gastro-oesophageal reflux disease presented with sudden-onset, sharp right lower quadrant (RLQ) abdominal pain that began 3 days ago. During interview, she had no other gastrointestinal, cardiac, pulmonary or neurological symptoms. On presentation, she was normotensive, afebrile at 98.6 °F, a heart rate of 85 bpm, respiratory rate of 16 bpm and oxygen saturation of 98% on ambient air. The patient was overweight with a body mass index of 26.2 kg/m² and weight of 85 kg (188 pounds). On physical examination, cardiovascular, pulmonary, musculoskeletal and integument systems were unremarkable. On the abdominal examination, there was tenderness present on light palpation in the RLQ and bowel sounds were present. A lower extremity examination revealed decreased sensation over her left great toe. She had no focal neurological deficits. On social history, the patient denied smoking cigarettes, excessive alcohol use or intravenous drug use. Her family history was negative for malignancy or coagulopathy. The patient denied a history of recurrent first-trimester miscarriages, systemic lupus erythematosus or use of oral contraceptives.

Investigations

Initially, complete blood count showed leucocytosis of 21.4×10⁹/L. Comprehensive metabolic panel revealed normal electrolytes, kidney and liver functions. Other laboratory studies revealed erythrocyte sedimentation rate of 8 mm/hour, C reactive protein of 4.4 mg/L, haemoglobin A1c of 6.0%, thyroid-stimulating hormone of 1.48 mIU/L, total cholesterol of 187 mg/dL, triglycerides of 186 mg/dL, high-density lipoprotein of 43 mg/dL and low-density lipoprotein of 107 mg/dL. Haematologic and rheumatologic workup including Factor V Leiden, protein C and S, coagulation studies, lupus anticoagulant, cardiolipin and antithrombin were all unremarkable. Infectious workup including blood culture, urinalysis, HIV antigen/antibody test, hepatitis panel and syphilis enzyme immunoassay (EIA) screen were negative as well.

Chest CT was negative for pulmonary embolism or any infectious processes. CT of abdomen and pelvis with contrast revealed a large wedge-shaped hypoenhancing area of the right kidney and a small wedge-shaped hypoenhancing area in the lateral aspect of the spleen (left kidney) (figure 1). CT scan of head without contrast showed no acute intracranial haemorrhage, midline shift or mass effect. An ECG showed a normal sinus rhythm without any evidence of active ischaemia. A transthoracic echocardiogram showed a structurally normal heart with ejection fraction of 55%–60% and no evidence of valvular disease or vegetations. However, a transoesophageal echocardiogram (TEE) revealed a highly mobile, elongated 1.9×0.9 cm mural thrombus with multiple satellite extensions adherent to the distal arch of the aorta (figure 2, video 1). The agitated saline study revealed no evidence of patent foramen ovale (PFO), atrial septal defect or other intracardiac shunts. The left lower extremity arterial Doppler showed mild pedal digital occlusive disease. The renal arterial Doppler study was negative for renal artery stenosis and renal vein thrombosis bilaterally.

Figure 1.

CT abdomen and pelvis, coronal view, showing wedge-shaped hypo-enhancing area in the inferior pole of the right kidney (blue arrow), and in the lateral aspect of the spleen (red arrow).

Figure 2.

The TEE showing a highly mobile, elongated 1.9×0.9 cm mural thrombus with multiple satellite extensions adherent to distal arch of the aorta. TTE, transthoracic echocardiogram.

Video 1.

Download video file ^{(540.5KB, mp4)}

DOI: 10.1136/bcr-2021-243493.video01

Given the increased long-term risk of thromboembolism, she was deemed by a multidisciplinary team consisting of Internal Medicine, Haematology, Cardiology and Cardiothoracic surgery services a good candidate for systemic anticoagulation (SAC) therapy. Thus, treatment with subcutaneous (SC) enoxaparin 80 mg/mL two times a day was initiated based on her weight. Given her 10-year atherosclerotic cardiovascular disease risk was less than 5%, there was no indication for starting high-intensity statin therapy. Although the ability of SAC to dissolve the clot completely was thought to be unlikely, it was expected to contract the clot, thus reducing the risk of future embolisation. Given patient had minimal atherosclerotic risk factors, we hypothesised that the aortic thrombus would resolve spontaneously. Thus, CT angiogram of the thorax was performed, which showed no evidence of aortitis, thoracic aortic aneurysm, dissection or thrombus (figure 3). CT scan of head without contrast was also repeated at day 5 to exclude an eventual embolism not clinically manifested caused during the thrombus resolution, which was unremarkable. A repeat TEE with 5 days of SAC treatment did not reveal any evidence of residual thrombus and showed complete resolution (figure 4, video 2).

Figure 3.

CT angiogram of the thorax, sagittal view, showed no evidence of aortitis, thoracic aortic aneurysm, dissection or thrombus.

Figure 4.

A repeat TEE with 5 days of SAC therapy showing the complete resolution of thrombus. TEE, transthoracic echocardiogram; SAC, systemic anticoagulation.

Video 2.

Download video file ^{(920.6KB, mp4)}

DOI: 10.1136/bcr-2021-243493.video02

Differential diagnosis

The differential diagnosis for the aetiology of AMT in our patient includes malignancy, arrhythmia, paradoxical shunt and hypercoagulable states. Extensive laboratory workup for infectious and hypercoagulable states including HIV, hepatitis panel and syphilis EIA screen, myeloperoxidase antibody, serine protease 3 antibody, antinuclear antibody (ANA), fluorescent ANA, antineutrophil cytoplasmic antibody immunofluorescence assay, peripheral blood smear, Factor V Leiden, protein C and S, coagulation studies, lupus anticoagulant, cardiolipin and antithrombin III were all negative. Family history was unremarkable, which had essentially ruled out rare familial causes of AMT such as hyperhomocysteinemia or primary endothelial disorder. The patient did not have any previous procedures such as the IABP and there were no laboratory findings consistent with the diagnosis of HIT. This ultimately ruled out other iatrogenic causes. Cardiac monitoring in the hospital stay did not reveal any significant arrhythmias such as atrial fibrillation or flutter. TEE essentially ruled out PFO or intracardiac shunts. Social history revealed no recent steroid or contraceptive use, trauma, cigarette smoking or drug abuse. Malignancy was also high in our differential diagnosis. Thus, we encouraged outpatient age-related cancer screening with mammograms and papanicolaou test (PAP smears).

Treatment

During a total of 7-day hospital stay, treatment with SAC with SC enoxaparin 80 mg/mL two times a day was administered. After a multidisciplinary team meeting, it was decided to switch to direct oral anticoagulants (DOACs) therapy with rivaroxaban 20 mg/day.

Outcome and follow-up

The patient was counselled to follow-up with a cardiologist for subsequent surveillance imaging with TEE within the next 12 months to evaluate for recurrence. A repeated TEE within a year was performed and it did not show any recurrence or further complications. Additionally, an event monitor test showed multiple episodes of sinus tachycardia associated with unspecific symptoms, but no other arrhythmias noted. We also counselled the patient on following up with a haematologist for further evaluation of the transient aortic thrombus and management with anticoagulation. Primary care physician follow-up was recommended to undergo age-appropriate screening for malignancy. Breast cancer screening with bilateral mammography and cervical cancer screening with PAP smear was unremarkable during follow-up visits.

Discussion

Arterial thromboembolism can be a challenging diagnosis due to its uncommon presentation. Patients often present with end-organ ischaemia and injury due to embolisation, which includes cerebrovascular accident, mesenteric ischaemia and acute limb ischaemia.³ Most emboli or arterial thrombi have cardiac origins such as atrial fibrillation, valvular pathologies and complications of myocardial infarction.⁴ AMT is a rare source of origin for an arterial embolus. An AMT is seldom seen in a healthy aorta without significant atherosclerotic changes.⁵ It is often associated with pathologies such as aortic aneurysms and aortic dissection. The aetiologies associated with AMT are wide ranging, which includes arrhythmia, malignancy, obesity, hypercoagulable states, paradoxical shunt such as PFO and coagulopathy.^1–3 Our case is unique in that there were no identifiable attributable risk factors for atherosclerosis, while most of the reported cases show an association with multiple risk factors (table 1).

Table 1.

Presents four similar cases found in the literature and compares risk factors, diagnostic modalities, treatment strategies and outcomes associated with AMT

Cases	Age, gender	Risk factors	Diagnostic modality	Medical vs surgical therapy	Outcomes
Our patient	43, F	No identifiable risk factor, unknown aetiology	TEE	Enoxaparin then rivaroxaban	No recurrence within a year with close follow-up with a cardiologist and a haematologist
Khine et al3	65, F	Hypercoagulable state, age, hypertension, dyslipidaemia	CT angiogram/MRI	Intravenous heparin bridged with warfarin for 3 months	No recurrence with close follow-up
Onwuanyi et al10	48, F	Protein C and S deficiency, peripheral arterial disease	TEE	Warfarin lifetime therapy	No recurrence and close follow-up with a haematologist
Maloberti et al11	40, M	Hypertension and dyslipidaemia	CT angiogram/TEE	Low molecular weight heparin	No recurrence
Habib et al6	46, F	Age and smoking history	TEE	Intravenous heparin infusion then thoracic aortic endograft	No recurrence reported smoking cessation but lost to follow-up

It uncovers that most cases of AMT published in previous literature were associated with atherosclerotic disease, which was different from our case.

AMT, aortic mural thrombus; TEE, transthoracic echocardiogram.

A TEE is very sensitive in the early detection of AMT and correlates well with the operative findings.⁶ A TEE can also display mobility of the thrombus in real time, which is very helpful as a mobile thrombus increases the risk of embolism. Less invasive methods include CT and MRI, which are less sensitive than a TEE. An aortography is invasive and carries the risk of dislodging the thrombus. One of the drawbacks of TEE is that it cannot detect the underlying vascular endothelial injury predisposing to thrombus formation. On review of the literature, most of the cases that report a ‘normal-appearing aorta’ have used TEE to reach that conclusion. Thus, overlooked risk factors predisposing to AMT formation can include cigarette smoking, which can lead to endothelial injury and atheroma formation. A tissue biopsy of the aortic wall would be needed for a definite diagnosis of a normal aorta. In the absence of these risk factors, the formation of AMT is unlikely¹

AMT and resulting peripheral embolisation can have grim outcomes due to the potential ischaemia and infarction of major organ systems. At present, there are no standardised guidelines for the diagnosis and treatment of an aortic thrombus.⁷ Anticoagulation with warfarin and heparin is usually used in haemodynamically stable patients while monitoring them for thrombus resolution.¹ On the other hand, surgical methods are preferred more in patients who are haemodynamically unstable.¹ Interestingly, further plans for invasive interventions such as covered stenting were discussed as an alternative option for our patient.⁸ However, given the patient did not have atherosclerotic disease, no aortic aneurysm, no recurrent embolism, no occurrence of embolism under heparin or persistent thrombus, we had decided against it.

Literature review showed an increased rate of recurrence and complications associated with anticoagulation therapy. A meta-analysis compared 200 patients where 112 patients received anticoagulation and 88 underwent aortic surgery as primary treatment for AMT. The study demonstrated that an increased recurrence of 26.4% in the group treated with anticoagulation while only 5.7% was observed in the group of patients treated by surgery (p<0.001).⁹ Also, the study showed an increase in the recurrence of peripheral arterial embolisation, an increase in the rate of major limb amputation and a higher rate of complications in the group treated with SAC, although the mortality rate remained the same in both groups. Collectively, our case is distinctive in that the intra-aortic thrombus was formed without significant atherosclerotic changes, the aetiology remains unknown, and there was a spontaneous resolution of the mural thrombus with anticoagulation alone with no incidence of recurrent thrombosis or distal embolisation within a year.

Clinicians need to be aware of the imaging modalities for the diagnosis of AMT. Although it can be challenging to diagnose and treat such an entity, it is worthwhile for clinicians to assiduously scan the arch of the aorta as these findings of thrombus formation can be easily missed particularly when trying to work up a cardiac cause of emboli. However, TEE remains the cornerstone of diagnosis while there are no standard guidelines for the management. Currently, there are no existing guidelines regarding the need for repeating investigation and the frequency that it needs to be done. However, it can be hypothesised that patients with increased risk of atherosclerosis or history of recurrent or persistent thrombus should be screened more frequently when compared with patients without such high-risk factors. Anticoagulation remains the standard of care with frequent monitoring for resolution. Combined treatment of medical with surgical interventions or endograft is now gaining popularity. Further studies are required to develop a standard in the line of treatment and for the management of complex cases.

Patient’s perspective.

I am only 43 years old; I do not know why this had happened to me. I have to work on myself and start taking care of my body. My family is very worried about me. I want to be there for my children. I will do my best.

Learning points.

• Although cardiovascular risk factors are highly associated with aortic mural thrombus (AMT) formation, other aetiologies such as malignancy, intracardiac shunts, arrhythmias and coagulopathy should be in the differential diagnosis.

• Data on guidelines for the diagnosis and treatment of an AMT are very limited, so clinical judgement is very important.

• Anticoagulation therapy is used for haemodynamically stable patients while surgical therapy is reserved for patients with haemodynamic compromise.

• Transoesophageal echocardiogram is considered the keystone in identifying ascending aorta and arch abnormalities such as a thrombus.

Ethics statements

Patient consent for publication

Obtained.