- Email: [email protected]
Severe Mesenteric Ischemia in a Pregnant Woman with Antiphospholipid Syndrome
Accepted Manuscript Severe mesenteric ischemia in a pregnant woman with antiphospholipid syndrome Andrea Padricelli, Anna Maria Giribono, Doriana Ferrara, Flavia Spalla, Umberto Bracale, Luca del Guercio, Giuseppe Servillo, Carlo Ruotolo, Umberto Marcello Bracale PII:
S0890-5096(17)30173-5
DOI:
10.1016/j.avsg.2017.04.035
Reference:
AVSG 3373
To appear in:
Annals of Vascular Surgery
Received Date: 5 February 2017 Revised Date:
11 April 2017
Accepted Date: 12 April 2017
Please cite this article as: Padricelli A, Giribono AM, Ferrara D, Spalla F, Bracale U, del Guercio L, Servillo G, Ruotolo C, Bracale UM, Severe mesenteric ischemia in a pregnant woman with antiphospholipid syndrome, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2017.04.035. 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 1
Title: Severe mesenteric ischemia in a pregnant woman with
2
antiphospholipid syndrome.
3
Authors: Andrea Padricelli1, Anna Maria Giribono1, Doriana Ferrara1, Flavia Spalla1, Umberto
5
Bracale2, Luca del Guercio1, Giuseppe Servillo3, Carlo Ruotolo4, Umberto Marcello Bracale1
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4
7
Affiliation:
8
1
9
Naples, Naples, Italy
SC
6
10
2
11
Italy
12
3
13
Federico II of Naples, Naples, Italy
14
4
15
Naples, Italy
General Surgery Unit, Department of Public Health, University Federico II of Naples, Naples,
Department of Neurosciences, Reproductive and Odonthostomatological Sciences, University
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Vascular Surgery Unit, Department of Vascular Surgery “A. Cardarelli” Hospital of Naples,
EP
16 17
M AN U
Vascular and Endovascular Surgery Unit, Department of Public Health, University Federico II of
Corresponding author:
19
Umberto Marcello Bracale, MD
20
Vascular and Endovascular Surgery Unit
21
Federico II University of Naples
22
Tel: +390817464732; Fax: +390817463698
23
Mail: [email protected]
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18
24 25
The authors have no conflicts of interest to declare nor financial disclosure.
ACCEPTED MANUSCRIPT 26 27 28
ABSTRACT
29
autoimmune disease with presence of at least one clinical and one laboratory abnormalities as
30
defined by The Sydney criteria. Clinical criteria include vascular thrombosis of venous, artery,
31
small vessel in any organ and recurrent pregnancy pathologies. Mesenteric ischemia is a rare and
32
threatening manifestation of APS.
33
We herein report a case of 34-years old pregnant woman referred to our Emergency Room with
34
thoracic and abdominal acute pain. Her past medical history was remarkable for positivity to
35
antiphospholipid antibodies, deep vein thrombosis of the right lower limb, chronic occlusion of
36
celiac trunk and superior mesenteric artery and recurrent abortions. Imaging revealed acute
37
occlusion of inferior mesenteric artery (IMA). Both a surgical and endovascular thrombectomy
38
were ineffective to obtain durable IMA patency and so the patient underwent antegrade aorto-
39
inferior mesenteric by-pass with saphenous vein and resection of an ischemic ileal loop. The
40
medical treatment at discharge was lifelong oral anticoagulant associated to double antiplatelet
41
therapy.
42
To the best of our knowledge this is the first case reporting a young pregnant woman with APS and
43
mesenteric ischemia submitted to several attempts of revascularization. Aggressive oral
44
anticoagulant and antiplatelet long-term therapy is advised. Moreover, we recommend strict follow-
45
up in those patients in order to early diagnose thrombotic recurrence.
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The antiphospholipid syndrome (APS), either primary or secondary form, is considered an
Key words: Antiphospholipid syndrome, pregnancy, mesenteric ischemia, surgical bypass.
ACCEPTED MANUSCRIPT 59 60 61
INTRODUCTION
62
morbidity (foetal loss, premature birth or recurrent embryonic loss), thrombocytopenia and arterial
63
and/or venous thrombosis, associated with the presence of circulating antiphospholipid (aPL)
64
elevated antibodies, most commonly lupus anticoagulant (LA) and anti-cardiolipin (aCL). Deep
65
vein thrombosis and stroke are major causes of morbidity and mortality, however thrombosis can
66
occur in any arterial and venous vessel [1-4]. The APS is primary in 53% cases and associated with
67
systemic lupus erythematosus or other autoimmune disorders in about 40% [5].
68
The clinical manifestations of aPL antibodies may be very variable, ranging from an asymptomatic
69
form to pregnancy or vascular complications, alone or combined: APS should not be considered a
70
single disease with a predictable outcome. Mesenteric ischemia is a very rare presentation of this
71
disease and is rarely observed; in fact, only few cases of intestinal ischemia are described in
72
literature determining an underestimated real incidence.
73
We herein report a case of severe mesenteric ischemia secondary to APS in a young pregnant
74
woman; following a therapeutic abortion she was treated by open surgery followed by endovascular
75
means.
76
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The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy
CASE REPORT
78
A 34-years old female, smoker, at 20th week of pregnancy referred to our institute in emergency for
79
thoracic and abdominal sudden pain. She was affected by APS with positive to aPL antibodies (both
80
aCL and LA) and chronically assumed warfarin as anti-coagulant therapy. The patient had recurrent
81
pregnancy complications: spontaneous abortion at six weeks and premature stillbirth at 24 and 27
82
weeks with one episode of pre-eclampsia. Her past medical history was remarkable for deep venous
83
thrombosis of the right lower limb and chronic mesenteric ischemia due to occlusion of the celiac
84
trunk and the superior mesenteric artery (SMA), for which the patient had already been submitted
85
one year earlier to an unsuccessful attempt of SMA endovascular revascularization (Fig.1). At the
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ACCEPTED MANUSCRIPT time of admission, the physical examination showed abdominal tenderness associated with mild
87
distension. Duplex scan was highly suspicious for inferior mesenteric artery (IMA) occlusion.
88
After obstetric consultation, in order to proceed with more invasive exams and intervention, the
89
patient underwent therapeutic abortion of the foetus using mifepristone. Computed tomography
90
angiography (CTA) was performed showing the complete occlusion of IMA without evident signs
91
of colic suffering (Fig.2). Through a trans-peritoneal surgical approach, the IMA was exposed and
92
thrombectomy with a 4 Fr Fogarty catheter performed. At the end of the procedure there were both
93
a good inflow and backflow in the artery without clinical signs of intestinal ischemia. After three
94
days from surgery, abdominal pain suddenly reappeared associated with early diarrhoeic
95
canalization; a new CTA showed re-occlusion of the IMA. At this time an endovascular approach
96
was offered avoiding a new general anaesthesia. In the angio-suite, a right radial access was
97
obtained and the IMA selectively catheterized with a 5Fr 125 cm MPA catheter. Endoluminal
98
thrombectomy with Export aspiration catheter (Medtronic, Minneapoli, MN), was performed. On
99
the completion angiogram a residual ostial stenosis was observed, therefore an angioplasty with
100
Amphirion 3.5 mm x 40 mm balloon (Medtronic, Minneapolis, MN) was realized (Fig.3). In
101
addition, a glycoprotein (GP) IIb/IIIa receptor antagonist (Aggrastat, tirofiban; Correvio, Geneva,
102
Switzerland) was administered intra-arterially as initial bolus, followed by a continuous intravenous
103
infusion for 24 hours. The post-operative period was free from both local and systemic
104
complications. The patient was maintained on parenteral nutrition for all the time of the hospital
105
length of stay till discharge, which occurred after two weeks from the last procedure. An
106
anticoagulant oral therapy with warfarin associated with both clopidogrel and acetylsalicylic acid
107
was prescribed.
108
After three weeks, the patient referred again to the emergency room for sudden and acute
109
abdominal pain. An urgent CTA showed a complete occlusion of the IMA along with small bowel
110
ischemia (Fig.4). Through a redo-transperitoneal surgical approach an anterograde aorto-mesenteric
111
bypass graft using a reversed saphenous vein was performed, followed by resection of an ileal loop.
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ACCEPTED MANUSCRIPT The patient was discharged after 15 days from surgery without post-operative complications and
113
symptom-free. A double anti-platelet and anticoagulant therapy, with an INR over 3, was again
114
administered for prevention of restenosis and new thrombotic events. During follow-up the patient
115
did not refer any symptom and a CTA performed 6 months after surgery revealed good patency of
116
the aorto-mesenteric bypass (Fig.5).
117
DISCUSSION
118
The APS, either primary or secondary form, is considered an autoimmune disease associated with
119
vascular thrombosis, recurrent pregnancy pathologies and laboratory evidence for antiphospholipid
120
antibodies. APL antibodies are present in about 1 to 5% of healthy women, while 15% of women
121
with recurrent first trimester losses have detectable APL serum antibodies [6,7]. The catastrophic
122
variant of APS is a rare (<1% of all cases) and often fatal condition, characterized by multiple
123
vascular thrombosis and consequent multi-organ failure developed over a short period of time [6,8].
124
The Sydney criteria for the diagnosis of APS, a revised version of the Sapporo criteria [9,10],
125
require the presence of at least one clinical manifestation and one laboratory abnormality.
126
Laboratory criteria require the positivity of one or more of the antibodies, as lupus anticoagulant
127
(LAC), anticardiolipin (aCL) antibodies (IgG/IgM) or b2-glycoprotein I (b2-GPI) antibodies
128
(IgG/IgM) [6].
129
The clinical criteria include a history of confirmed obstetric complications or thrombotic events [6].
130
The venous system, especially the deep veins of the leg, but also the renal, pulmonary, inferior
131
cava, hepatic and portal veins are frequently affected [11-17]. Arterial occlusions are less frequent
132
than the venous ones and affect most frequently cerebral vessels. Nevertheless, the coronary, renal,
133
retinal or peripheral arteries can also be involved. To our knowledge the gastrointestinal
134
manifestations associated with APS have been rarely documented. Although several case reports
135
have been published, there are no large descriptions of the clinical and immunologic characteristics
136
of these unusual complications [8].
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ACCEPTED MANUSCRIPT The clinical presentation can be variable from symptoms of acute bowel infarction to chronic
138
mesenteric angina, including gastrointestinal bleeding or asymptomatic forms.
139
In our case we have chosen therapeutic option according to clinical condition, angiogram, CT
140
imaging and clinical history of patient. The endovascular approach was chosen for its less
141
invasiveness after a first, recent surgical revascularization failed.
142
Oral anticoagulation with double anti-platelet was introduced at discharge in order to prevent
143
restenosis after both endovascular and surgical treatments with recommendation to maintain INR >
144
3 [18].
145
Also Kojima et al. reported a case of a pregnant young woman with secondary APS complicated by
146
thrombosis of superior mesenteric artery (SMA) associated with signs of mesenteric ischemia [19].
147
Although no revascularization attempt was performed, a large scale intestinal resection was
148
required and the patient was discharged exclusively with antiplatelet therapy and, as in our case,
149
lost the fetus.
150
In several cases of patients affected by APS with no pregnancy and mesenteric ischemia a
151
recanalization with only anticoagulant therapy has been reported [11,20,21].
152
Otherwise Veraldi et al. described a case of a mesenteric ischemia in a young male patient with
153
APS and fibromuscular dysplasia syndrome and occlusion of three visceral arteries: first
154
endovascular approach with PTA and stenting of a SMA was preferred, without a positive outcome
155
for the absence of stump on the aortic side; a laparotomic reimplantation to the aorta of the SMA
156
and IMA was performed and the patient was prescribed life-long anticoagulant therapy. The results
157
were good, with recovery of the mesenteric vascularization and improvement of the symptoms [22].
158
Instead in Salaun et al. experience was reported the case of a young woman with APS and
159
mesenteric ischemia due to stenosis of SMA and celiac trunk occlusion treated successfully with
160
PTA and stenting of the SMA followed by warfarin therapy for life, with improvement of the
161
clinical condition and negativity of post-operatory CT scans [18].
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ACCEPTED MANUSCRIPT Vahl et al. described a report of a young male patient with APS associated to SMA occlusion and
163
peripheral emboli caused by aortic ulcer. Surgical option was considered necessary and through a
164
thoraco-phreno-lumbotomy the ulcer was excised and revascularization of celiac trunk and SMA
165
performed. A good recovery without any complications was observed in post-operative period; also
166
in this case anticoagulant therapy was prescribed at discharging [23].
167
In other cases, described in literature in patient affected by APS with mesenteric ischemia, only
168
intestinal resection was preferred, no surgical or endovascular revascularization of visceral vessel
169
was attempted but a post-operative option of lifetime anticoagulant therapy was always chosen
170
[24,25]
171
Overall, patients with APS can develop arterial stenosis in visceral district, especially in renal
172
vessels and rarely in the mesenteric arteries.
173
A mesenteric ischemia in pregnant young woman with APS is a threatening complication and its
174
incidence is extremely rare. Therefore, it should always be suspected in a young patient with APS
175
and typical symptoms and without vascular risk factors.
176
Endovascular approach may be preferred in some cases for the less invasiveness but it is not always
177
feasible and effective and in some cases surgical option is required. Post-operative life-long time
178
anticoagulant therapy should be always proposed, in our case we preferred to administer double
179
antiplatelet therapy associated to warfarin (INR>3) in order to avoid the high rate of recurrent
180
restenosis, although there is no consensus of the duration and the dosage of this therapy. Also
181
medical therapy with only warfarin is described in literature with good results and revascularization
182
of affected vessels. Furthermore, we believe that a strict post-operative follow-up of these patients
183
with CTA at 2, 6 and 12 mouths is mandatory with the aim to reveal new arising thrombosis of
184
visceral arteries or implanted grafts, bowel ischemic suffering and prevent dangerous and often fatal
185
complications.
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References:
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1.
Stadler K, Mutzenbach JS, Kalss G. et al. Therapeutic challenges after successful thrombectomy in a patient with an antiphospholipid syndrome associated M1-occlusion: A case report. Interv Neuroradiol 2015;21:598-602.
225 226 227
11. Choi BG, Jeon HS, Lee SO et al. Primary antiphospholipid syndrome presenting with abdominal angina and splenic infarction. Rheumatol Int 2002;22:119-21.
228 229 230 231 232 233
12. Lee HJ, Park JW, Chang JC. Mesenteric and portal venous obstruction associated with primary antiphospholipid antibody syndrome. J Gastroenterol Hepatol 1997;12:822-6.
234 235 236 237 238 239
14. Elis M, Eldo A. Thromboembolism in patients with the ‘lupus’ type circulating anticoagulant. Arch Intern Med 1984;144:510-5.
2. Lim W. Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program 2009: 233-9.
RI PT
3. Lim W. Antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2013:675-80. 4. Cervera R, Piette JC, Font J et al. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002;46:1019-27. Bachmeyer C, Barrier A, Frazier A et al. Diffuse large and small bowel necrosis in catastrophic antiphospholipid syndrome. Eur J Gastroenterol Hepatol 2006;18:1011-4.
SC
5.
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6. Brock CO, Brohl AS, Običan SG. Incidence, pathophysiology, and clinical manifestations of antiphospholipid syndrome. Birth Defects Res C Embryo Today 2015;105:201-8. 7. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet 2010;376:1498-509.
9.
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8. Cervera R, Espinosa G, Cordero A et al. Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group. Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS. Semin Arthritis Rheum 2007;36:287-96.
Miyakis S, Lockshin MD, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295306.
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10. Wilson WA, Gharavi AE, Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999;42:1309-11.
13. Hamilton ME. Superior mesenteric artery thrombosis associated with antiphospholipid syndrome. West J Med 1991;155:174-6.
15. Harris EN, Gharavi AE, Hughes GRV. Anti-phospholipid antibodies. Clin Rheum Dis 1985;11:591609.
ACCEPTED MANUSCRIPT 16. Kalunian KC, Peter JB, Middlekauff HR. Clinical significance of a single test for anticardiolipin antibodies in patients with systemic lupus erythematosus. Am J Med 1988;85:602-8.
243 244 245
17. Asherson RA, Khamashta MA, Ordi-Ros J. The primary antiphospholipid syndrome: major clinical and serological feature. Medicine 1989;68:366-74.
246 247 248
18. Salaun E, Bartoli MA, Soler R et al. Severe symptomatic stenosis of visceral and renal arteries leading primary antiphospholipid syndrome diagnosis. Ann Vasc Surg 2014;28:1796.e9-1796.e13.
249 250 251
19. Kojima E, Naito K, Iwai M et al. Antiphospholipid syndrome complicated by thrombosis of the superior mesenteric artery, co-existence of smooth muscle hyperplasia. Intern Med 1997;36:528-31.
252 253 254 255
20. Crome CR, Rajagopalan S, Kuhan G, Fluck N. Antiphospholipid syndrome presenting with acute digital ischaemia, avascular necrosis of the femoral head and superior mesenteric artery thrombus. BMJ Case Rep 2012 Nov 20;2012.
256 257 258 259
21. Rosenthal E, Sangle SR, Taylor P et al. Treatment of mesenteric angina with prolonged anticoagulation in a patient with antiphospholipid (Hughes) syndrome and coeliac artery stenosis. Ann Rheum Dis 2006;65:1398-9.
260 261 262 263
22. Veraldi GF, Zecchinelli MP, Furlan F, Mesenteric revascularization in a young patient with antiphospholipid syndrome and fibromuscular dysplasia: report of a case and review of the literature. Chir Ital 2009;61:659-65.
264 265 266 267
23. Vahl AC, Gans RO, Mackaay AJ, van der Waal C, Rauwerda JA. Superior mesenteric artery occlusion and peripheral emboli caused by an aortic ulcer in a young patient with antiphospholipid syndrome. Surgery 1997;121:588-90.
268 269 270 271 272 273 274
24. Galarza-Maldonado C, Serrano-Alvarado P. Mesenterial thrombosis with the antiphpholipid syndrome. Isr Med Assoc J 2006;8:858.
276 277 278 279 280 281
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25. England RJA, Woodcock B, Zeiderman MR Superior mesenteric artery thrombosis in patient with antiphospholipid syndrome. Superior mesenteric artery thrombosis in a patient with the antiphospholipid syndrome. Eur J Vasc Endovasc Surg 1995;10:372-3.
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Legend
283
Fig.1
285
Digital Subtraction Angiography (DSA) via trans-collateral micro-catheter injection showing SMA
286
occlusion during an endovascular attempt of recanalization.
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287
Fig.2
289
Pre-operative mulpti-planar-reconstruction (MPR) CT-scan. Coronal view demonstrating ostial
290
acute thrombosis of the IMA (white arrow)(A); the sagittal view also highlight chronic occlusion of
291
both the celiac trunk (single asterisk) and the SMA (double asterisk). In both images post-abortion
292
congested uterus is also noted (arrowhead).
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293
Fig.3
295
Intraoperative picture of the IMA transversal arteriotomy with endoluminal thrombus.
296
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Fig.4
298
Fluoroscopy images during endovascular IMA thrombectomy with Export Aspiration catheter. Pre-
299
aspiration (A), ballooning (B) and post-procedural (C) images are presented.
300
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301
Fig.5
302
CT-scan showing ischemic ileal loop with bowel wall thickening and pneumatosis (white arrow)
303
(A). Post-operative 3D Volume rendering CT-scan showing patency of the vein graft on the
304
ascending branch of the IMA (B).
305 306 307
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ACCEPTED MANUSCRIPT
S0890-5096(17)30173-5
DOI:
10.1016/j.avsg.2017.04.035
Reference:
AVSG 3373
To appear in:
Annals of Vascular Surgery
Received Date: 5 February 2017 Revised Date:
11 April 2017
Accepted Date: 12 April 2017
Please cite this article as: Padricelli A, Giribono AM, Ferrara D, Spalla F, Bracale U, del Guercio L, Servillo G, Ruotolo C, Bracale UM, Severe mesenteric ischemia in a pregnant woman with antiphospholipid syndrome, Annals of Vascular Surgery (2017), doi: 10.1016/j.avsg.2017.04.035. 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 1
Title: Severe mesenteric ischemia in a pregnant woman with
2
antiphospholipid syndrome.
3
Authors: Andrea Padricelli1, Anna Maria Giribono1, Doriana Ferrara1, Flavia Spalla1, Umberto
5
Bracale2, Luca del Guercio1, Giuseppe Servillo3, Carlo Ruotolo4, Umberto Marcello Bracale1
RI PT
4
7
Affiliation:
8
1
9
Naples, Naples, Italy
SC
6
10
2
11
Italy
12
3
13
Federico II of Naples, Naples, Italy
14
4
15
Naples, Italy
General Surgery Unit, Department of Public Health, University Federico II of Naples, Naples,
Department of Neurosciences, Reproductive and Odonthostomatological Sciences, University
TE D
Vascular Surgery Unit, Department of Vascular Surgery “A. Cardarelli” Hospital of Naples,
EP
16 17
M AN U
Vascular and Endovascular Surgery Unit, Department of Public Health, University Federico II of
Corresponding author:
19
Umberto Marcello Bracale, MD
20
Vascular and Endovascular Surgery Unit
21
Federico II University of Naples
22
Tel: +390817464732; Fax: +390817463698
23
Mail: [email protected]
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18
24 25
The authors have no conflicts of interest to declare nor financial disclosure.
ACCEPTED MANUSCRIPT 26 27 28
ABSTRACT
29
autoimmune disease with presence of at least one clinical and one laboratory abnormalities as
30
defined by The Sydney criteria. Clinical criteria include vascular thrombosis of venous, artery,
31
small vessel in any organ and recurrent pregnancy pathologies. Mesenteric ischemia is a rare and
32
threatening manifestation of APS.
33
We herein report a case of 34-years old pregnant woman referred to our Emergency Room with
34
thoracic and abdominal acute pain. Her past medical history was remarkable for positivity to
35
antiphospholipid antibodies, deep vein thrombosis of the right lower limb, chronic occlusion of
36
celiac trunk and superior mesenteric artery and recurrent abortions. Imaging revealed acute
37
occlusion of inferior mesenteric artery (IMA). Both a surgical and endovascular thrombectomy
38
were ineffective to obtain durable IMA patency and so the patient underwent antegrade aorto-
39
inferior mesenteric by-pass with saphenous vein and resection of an ischemic ileal loop. The
40
medical treatment at discharge was lifelong oral anticoagulant associated to double antiplatelet
41
therapy.
42
To the best of our knowledge this is the first case reporting a young pregnant woman with APS and
43
mesenteric ischemia submitted to several attempts of revascularization. Aggressive oral
44
anticoagulant and antiplatelet long-term therapy is advised. Moreover, we recommend strict follow-
45
up in those patients in order to early diagnose thrombotic recurrence.
RI PT
SC
M AN U
TE D
EP
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46 47 48 49 50 51 52 53 54 55 56 57 58
The antiphospholipid syndrome (APS), either primary or secondary form, is considered an
Key words: Antiphospholipid syndrome, pregnancy, mesenteric ischemia, surgical bypass.
ACCEPTED MANUSCRIPT 59 60 61
INTRODUCTION
62
morbidity (foetal loss, premature birth or recurrent embryonic loss), thrombocytopenia and arterial
63
and/or venous thrombosis, associated with the presence of circulating antiphospholipid (aPL)
64
elevated antibodies, most commonly lupus anticoagulant (LA) and anti-cardiolipin (aCL). Deep
65
vein thrombosis and stroke are major causes of morbidity and mortality, however thrombosis can
66
occur in any arterial and venous vessel [1-4]. The APS is primary in 53% cases and associated with
67
systemic lupus erythematosus or other autoimmune disorders in about 40% [5].
68
The clinical manifestations of aPL antibodies may be very variable, ranging from an asymptomatic
69
form to pregnancy or vascular complications, alone or combined: APS should not be considered a
70
single disease with a predictable outcome. Mesenteric ischemia is a very rare presentation of this
71
disease and is rarely observed; in fact, only few cases of intestinal ischemia are described in
72
literature determining an underestimated real incidence.
73
We herein report a case of severe mesenteric ischemia secondary to APS in a young pregnant
74
woman; following a therapeutic abortion she was treated by open surgery followed by endovascular
75
means.
76
EP
TE D
M AN U
SC
RI PT
The antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy
CASE REPORT
78
A 34-years old female, smoker, at 20th week of pregnancy referred to our institute in emergency for
79
thoracic and abdominal sudden pain. She was affected by APS with positive to aPL antibodies (both
80
aCL and LA) and chronically assumed warfarin as anti-coagulant therapy. The patient had recurrent
81
pregnancy complications: spontaneous abortion at six weeks and premature stillbirth at 24 and 27
82
weeks with one episode of pre-eclampsia. Her past medical history was remarkable for deep venous
83
thrombosis of the right lower limb and chronic mesenteric ischemia due to occlusion of the celiac
84
trunk and the superior mesenteric artery (SMA), for which the patient had already been submitted
85
one year earlier to an unsuccessful attempt of SMA endovascular revascularization (Fig.1). At the
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77
ACCEPTED MANUSCRIPT time of admission, the physical examination showed abdominal tenderness associated with mild
87
distension. Duplex scan was highly suspicious for inferior mesenteric artery (IMA) occlusion.
88
After obstetric consultation, in order to proceed with more invasive exams and intervention, the
89
patient underwent therapeutic abortion of the foetus using mifepristone. Computed tomography
90
angiography (CTA) was performed showing the complete occlusion of IMA without evident signs
91
of colic suffering (Fig.2). Through a trans-peritoneal surgical approach, the IMA was exposed and
92
thrombectomy with a 4 Fr Fogarty catheter performed. At the end of the procedure there were both
93
a good inflow and backflow in the artery without clinical signs of intestinal ischemia. After three
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days from surgery, abdominal pain suddenly reappeared associated with early diarrhoeic
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canalization; a new CTA showed re-occlusion of the IMA. At this time an endovascular approach
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was offered avoiding a new general anaesthesia. In the angio-suite, a right radial access was
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obtained and the IMA selectively catheterized with a 5Fr 125 cm MPA catheter. Endoluminal
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thrombectomy with Export aspiration catheter (Medtronic, Minneapoli, MN), was performed. On
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the completion angiogram a residual ostial stenosis was observed, therefore an angioplasty with
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Amphirion 3.5 mm x 40 mm balloon (Medtronic, Minneapolis, MN) was realized (Fig.3). In
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addition, a glycoprotein (GP) IIb/IIIa receptor antagonist (Aggrastat, tirofiban; Correvio, Geneva,
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Switzerland) was administered intra-arterially as initial bolus, followed by a continuous intravenous
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infusion for 24 hours. The post-operative period was free from both local and systemic
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complications. The patient was maintained on parenteral nutrition for all the time of the hospital
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length of stay till discharge, which occurred after two weeks from the last procedure. An
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anticoagulant oral therapy with warfarin associated with both clopidogrel and acetylsalicylic acid
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was prescribed.
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After three weeks, the patient referred again to the emergency room for sudden and acute
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abdominal pain. An urgent CTA showed a complete occlusion of the IMA along with small bowel
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ischemia (Fig.4). Through a redo-transperitoneal surgical approach an anterograde aorto-mesenteric
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bypass graft using a reversed saphenous vein was performed, followed by resection of an ileal loop.
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symptom-free. A double anti-platelet and anticoagulant therapy, with an INR over 3, was again
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administered for prevention of restenosis and new thrombotic events. During follow-up the patient
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did not refer any symptom and a CTA performed 6 months after surgery revealed good patency of
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the aorto-mesenteric bypass (Fig.5).
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DISCUSSION
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The APS, either primary or secondary form, is considered an autoimmune disease associated with
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vascular thrombosis, recurrent pregnancy pathologies and laboratory evidence for antiphospholipid
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antibodies. APL antibodies are present in about 1 to 5% of healthy women, while 15% of women
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with recurrent first trimester losses have detectable APL serum antibodies [6,7]. The catastrophic
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variant of APS is a rare (<1% of all cases) and often fatal condition, characterized by multiple
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vascular thrombosis and consequent multi-organ failure developed over a short period of time [6,8].
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The Sydney criteria for the diagnosis of APS, a revised version of the Sapporo criteria [9,10],
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require the presence of at least one clinical manifestation and one laboratory abnormality.
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Laboratory criteria require the positivity of one or more of the antibodies, as lupus anticoagulant
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(LAC), anticardiolipin (aCL) antibodies (IgG/IgM) or b2-glycoprotein I (b2-GPI) antibodies
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(IgG/IgM) [6].
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The clinical criteria include a history of confirmed obstetric complications or thrombotic events [6].
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The venous system, especially the deep veins of the leg, but also the renal, pulmonary, inferior
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cava, hepatic and portal veins are frequently affected [11-17]. Arterial occlusions are less frequent
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than the venous ones and affect most frequently cerebral vessels. Nevertheless, the coronary, renal,
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retinal or peripheral arteries can also be involved. To our knowledge the gastrointestinal
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manifestations associated with APS have been rarely documented. Although several case reports
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have been published, there are no large descriptions of the clinical and immunologic characteristics
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of these unusual complications [8].
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ACCEPTED MANUSCRIPT The clinical presentation can be variable from symptoms of acute bowel infarction to chronic
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mesenteric angina, including gastrointestinal bleeding or asymptomatic forms.
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In our case we have chosen therapeutic option according to clinical condition, angiogram, CT
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imaging and clinical history of patient. The endovascular approach was chosen for its less
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invasiveness after a first, recent surgical revascularization failed.
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Oral anticoagulation with double anti-platelet was introduced at discharge in order to prevent
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restenosis after both endovascular and surgical treatments with recommendation to maintain INR >
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3 [18].
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Also Kojima et al. reported a case of a pregnant young woman with secondary APS complicated by
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thrombosis of superior mesenteric artery (SMA) associated with signs of mesenteric ischemia [19].
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Although no revascularization attempt was performed, a large scale intestinal resection was
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required and the patient was discharged exclusively with antiplatelet therapy and, as in our case,
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lost the fetus.
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In several cases of patients affected by APS with no pregnancy and mesenteric ischemia a
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recanalization with only anticoagulant therapy has been reported [11,20,21].
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Otherwise Veraldi et al. described a case of a mesenteric ischemia in a young male patient with
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APS and fibromuscular dysplasia syndrome and occlusion of three visceral arteries: first
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endovascular approach with PTA and stenting of a SMA was preferred, without a positive outcome
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for the absence of stump on the aortic side; a laparotomic reimplantation to the aorta of the SMA
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and IMA was performed and the patient was prescribed life-long anticoagulant therapy. The results
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were good, with recovery of the mesenteric vascularization and improvement of the symptoms [22].
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Instead in Salaun et al. experience was reported the case of a young woman with APS and
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mesenteric ischemia due to stenosis of SMA and celiac trunk occlusion treated successfully with
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PTA and stenting of the SMA followed by warfarin therapy for life, with improvement of the
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clinical condition and negativity of post-operatory CT scans [18].
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ACCEPTED MANUSCRIPT Vahl et al. described a report of a young male patient with APS associated to SMA occlusion and
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peripheral emboli caused by aortic ulcer. Surgical option was considered necessary and through a
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thoraco-phreno-lumbotomy the ulcer was excised and revascularization of celiac trunk and SMA
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performed. A good recovery without any complications was observed in post-operative period; also
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in this case anticoagulant therapy was prescribed at discharging [23].
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In other cases, described in literature in patient affected by APS with mesenteric ischemia, only
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intestinal resection was preferred, no surgical or endovascular revascularization of visceral vessel
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was attempted but a post-operative option of lifetime anticoagulant therapy was always chosen
170
[24,25]
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Overall, patients with APS can develop arterial stenosis in visceral district, especially in renal
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vessels and rarely in the mesenteric arteries.
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A mesenteric ischemia in pregnant young woman with APS is a threatening complication and its
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incidence is extremely rare. Therefore, it should always be suspected in a young patient with APS
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and typical symptoms and without vascular risk factors.
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Endovascular approach may be preferred in some cases for the less invasiveness but it is not always
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feasible and effective and in some cases surgical option is required. Post-operative life-long time
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anticoagulant therapy should be always proposed, in our case we preferred to administer double
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antiplatelet therapy associated to warfarin (INR>3) in order to avoid the high rate of recurrent
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restenosis, although there is no consensus of the duration and the dosage of this therapy. Also
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medical therapy with only warfarin is described in literature with good results and revascularization
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of affected vessels. Furthermore, we believe that a strict post-operative follow-up of these patients
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with CTA at 2, 6 and 12 mouths is mandatory with the aim to reveal new arising thrombosis of
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visceral arteries or implanted grafts, bowel ischemic suffering and prevent dangerous and often fatal
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complications.
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References:
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1.
Stadler K, Mutzenbach JS, Kalss G. et al. Therapeutic challenges after successful thrombectomy in a patient with an antiphospholipid syndrome associated M1-occlusion: A case report. Interv Neuroradiol 2015;21:598-602.
225 226 227
11. Choi BG, Jeon HS, Lee SO et al. Primary antiphospholipid syndrome presenting with abdominal angina and splenic infarction. Rheumatol Int 2002;22:119-21.
228 229 230 231 232 233
12. Lee HJ, Park JW, Chang JC. Mesenteric and portal venous obstruction associated with primary antiphospholipid antibody syndrome. J Gastroenterol Hepatol 1997;12:822-6.
234 235 236 237 238 239
14. Elis M, Eldo A. Thromboembolism in patients with the ‘lupus’ type circulating anticoagulant. Arch Intern Med 1984;144:510-5.
2. Lim W. Antiphospholipid antibody syndrome. Hematology Am Soc Hematol Educ Program 2009: 233-9.
RI PT
3. Lim W. Antiphospholipid syndrome. Hematology Am Soc Hematol Educ Program 2013:675-80. 4. Cervera R, Piette JC, Font J et al. Antiphospholipid syndrome: Clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 2002;46:1019-27. Bachmeyer C, Barrier A, Frazier A et al. Diffuse large and small bowel necrosis in catastrophic antiphospholipid syndrome. Eur J Gastroenterol Hepatol 2006;18:1011-4.
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5.
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6. Brock CO, Brohl AS, Običan SG. Incidence, pathophysiology, and clinical manifestations of antiphospholipid syndrome. Birth Defects Res C Embryo Today 2015;105:201-8. 7. Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet 2010;376:1498-509.
9.
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8. Cervera R, Espinosa G, Cordero A et al. Catastrophic Antiphospholipid Syndrome (CAPS) Registry Project Group. Intestinal involvement secondary to the antiphospholipid syndrome (APS): clinical and immunologic characteristics of 97 patients: comparison of classic and catastrophic APS. Semin Arthritis Rheum 2007;36:287-96.
Miyakis S, Lockshin MD, Atsumi T et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006;4:295306.
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10. Wilson WA, Gharavi AE, Koike T et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999;42:1309-11.
13. Hamilton ME. Superior mesenteric artery thrombosis associated with antiphospholipid syndrome. West J Med 1991;155:174-6.
15. Harris EN, Gharavi AE, Hughes GRV. Anti-phospholipid antibodies. Clin Rheum Dis 1985;11:591609.
ACCEPTED MANUSCRIPT 16. Kalunian KC, Peter JB, Middlekauff HR. Clinical significance of a single test for anticardiolipin antibodies in patients with systemic lupus erythematosus. Am J Med 1988;85:602-8.
243 244 245
17. Asherson RA, Khamashta MA, Ordi-Ros J. The primary antiphospholipid syndrome: major clinical and serological feature. Medicine 1989;68:366-74.
246 247 248
18. Salaun E, Bartoli MA, Soler R et al. Severe symptomatic stenosis of visceral and renal arteries leading primary antiphospholipid syndrome diagnosis. Ann Vasc Surg 2014;28:1796.e9-1796.e13.
249 250 251
19. Kojima E, Naito K, Iwai M et al. Antiphospholipid syndrome complicated by thrombosis of the superior mesenteric artery, co-existence of smooth muscle hyperplasia. Intern Med 1997;36:528-31.
252 253 254 255
20. Crome CR, Rajagopalan S, Kuhan G, Fluck N. Antiphospholipid syndrome presenting with acute digital ischaemia, avascular necrosis of the femoral head and superior mesenteric artery thrombus. BMJ Case Rep 2012 Nov 20;2012.
256 257 258 259
21. Rosenthal E, Sangle SR, Taylor P et al. Treatment of mesenteric angina with prolonged anticoagulation in a patient with antiphospholipid (Hughes) syndrome and coeliac artery stenosis. Ann Rheum Dis 2006;65:1398-9.
260 261 262 263
22. Veraldi GF, Zecchinelli MP, Furlan F, Mesenteric revascularization in a young patient with antiphospholipid syndrome and fibromuscular dysplasia: report of a case and review of the literature. Chir Ital 2009;61:659-65.
264 265 266 267
23. Vahl AC, Gans RO, Mackaay AJ, van der Waal C, Rauwerda JA. Superior mesenteric artery occlusion and peripheral emboli caused by an aortic ulcer in a young patient with antiphospholipid syndrome. Surgery 1997;121:588-90.
268 269 270 271 272 273 274
24. Galarza-Maldonado C, Serrano-Alvarado P. Mesenterial thrombosis with the antiphpholipid syndrome. Isr Med Assoc J 2006;8:858.
276 277 278 279 280 281
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25. England RJA, Woodcock B, Zeiderman MR Superior mesenteric artery thrombosis in patient with antiphospholipid syndrome. Superior mesenteric artery thrombosis in a patient with the antiphospholipid syndrome. Eur J Vasc Endovasc Surg 1995;10:372-3.
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Fig.1
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Digital Subtraction Angiography (DSA) via trans-collateral micro-catheter injection showing SMA
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occlusion during an endovascular attempt of recanalization.
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Fig.2
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Pre-operative mulpti-planar-reconstruction (MPR) CT-scan. Coronal view demonstrating ostial
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acute thrombosis of the IMA (white arrow)(A); the sagittal view also highlight chronic occlusion of
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both the celiac trunk (single asterisk) and the SMA (double asterisk). In both images post-abortion
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congested uterus is also noted (arrowhead).
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Fig.3
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Intraoperative picture of the IMA transversal arteriotomy with endoluminal thrombus.
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Fig.4
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Fluoroscopy images during endovascular IMA thrombectomy with Export Aspiration catheter. Pre-
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aspiration (A), ballooning (B) and post-procedural (C) images are presented.
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Fig.5
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CT-scan showing ischemic ileal loop with bowel wall thickening and pneumatosis (white arrow)
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(A). Post-operative 3D Volume rendering CT-scan showing patency of the vein graft on the
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ascending branch of the IMA (B).
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