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Acute Ischemia due to Superficial Femoral Artery Thrombosis: Results of In Situ Fibrinolysis
Clinical Research Acute Ischemia due to Superficial Femoral Artery Thrombosis: Results of In Situ Fibrinolysis Matthieu Arsicot,1 Nellie Della Schiava,1 Tarek Boudjelit,1 Olivier Rouviere,2 Patrick Feugier,1 Patrick Lermusiaux,1 and Antoine Millon,1 Lyon, France
Background: The management of acute ischemia due to the thrombosis superficial femoral artery (SFA) stents is complex. In situ arterial fibrinolysis, still not evaluated in this indication, would allow, by lifting the ischemia and uncovering its cause, to avoid thrombectomy, endovascular recanalization, or arterial bypass. The purpose of the study was to evaluate the effectiveness, the complications, and the assisted secondary patency of in situ fibrinolysis for thrombosis of SFA stents. Methods: We conducted a retrospective monocentric study with prospective collection of the data. Between October 2011 and December 2014, 86 in situ fibrinolysis procedures were carried out for acute lower limb ischemia. Twelve procedures were carried out for acute ischemia due to the thrombosis of SFA stents. Clinical success was defined by the lifting of acute ischemia. The causes of thromboses, the complications related to the fibrinolysis, and the secondary assisted patency were analyzed. Results: The mean age of the patients was 66.3 (55e90) years. The average length of the stents was 119.3 (18e270) mm. In 10 patients, the thrombosis extended in the full length of the artery. The average time between the implantation of the stent and the initiation of the fibrinolysis was 180 (11e369) days. The average time between the beginning of the symptoms and fibrinolysis was 5 (0e12) days. The average duration of treatment was 46 (24e72) hr. Clinical success was obtained in all the patients. Diagnosed isolated or associated lesions were a progression of the atheromatous disease upstream or downstream of the stent in 6 cases, and an isolated intrastent restenosis in 3 cases. In 2 cases, no obvious cause was found. One or more additional endovascular procedures were carried out in 9 cases at the end of the fibrinolysis, and consisted of a transluminal intrastent angioplasty with an active balloon in 5 cases, an additional stenting in 3 cases, and the stenting of upstream or downstream arteries in 5 cases. Secondary assisted patency was 100% at 5 months. No major hemorrhagic complication was observed. Two false aneurysms at the site of femoral puncture were observed. Conclusion: Our results suggest that ischemia due to the thrombosis of SFA stents can be dealt with first intention in situ fibrinolysis which allows the endovascular treatment of the causal lesion, thus avoiding thrombectomy or bypass.
Presented at the 30th Annual Meeting of the French Society for Vascular Surgery, Montpellier, France, June 26e29, 2015. 1 Service de chirurgie vasculaire, Etablissement Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 2 Service de Radiologie, Etablissement Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Place d’Arsonval Lyon, France; E-mail: matthieu.arsicot@gmail. com Ann Vasc Surg 2016; -: 1–8 http://dx.doi.org/10.1016/j.avsg.2015.10.029 Ó 2016 Elsevier Inc. All rights reserved. Manuscript received: July 3, 2015; manuscript accepted: October 11, 2015; published online: ---.
Correspondence to: Matthieu Arsicot, Service de chirurgie vasculaire, Etablissement Edouard Herriot, Hospices Civils de Lyon,
1
2 Arsicot et al.
Annals of Vascular Surgery
INTRODUCTION
Table I. Characteristics of patients
Endovascular surgery is the first surgical treatment for peripheral arterial occlusive disease (PAOD) but the number of stents thromboses is increasing (more than 50% of intrastent stenoses at 1 year).1,2 The seriousness of the acute ischemia of the lower extremities (up to 42.5% and 15% of mortality and amputation at 1 year, respectively) led to the development of many pharmacological and mechanical therapeutic techniques.3 Since the year 1990, fibrinolysis belongs to the therapeutic armamentarium of acute ischemia. It proved its effectiveness in terms of limb salvage and mortality.4 The management of acute ischemia due to the thrombosis of stents implanted in the superficial femoral artery (SFA) is complex. In situ arterial fibrinolysis which has not been evaluated in this indication would allow, by lifting the ischemia and by uncovering its cause, to avoid thrombectomy, endovascular recanalization, or arterial bypass.5 The purpose of the study was to evaluate the effectiveness, the complications, and the assisted secondary patency of in situ fibrinolysis of thrombosed SFA stents.
Characteristics of patients (n ¼ 12)
MATERIALS AND METHODS
Antiplatelet treatment, acetylsalicylic acid and/or clopidogrel; Cl, creatinine clearance calculated according to the MDRD formula; MDRD, modification of the diet in renal disease; SAT, supraaortic trunks.
This was a monocentric, retrospective therapeutic study with prospective data collection. Between October 2011 and December 2014, 86 in situ fibrinolysis procedures were carried out for acute ischemia of the lower extremities. Twelve procedures were carried out for acute ischemia due to the thrombosis of stents implanted in the SFA. Asymptomatic patients and those presenting a recurrent claudication were not included in this study. We included in this study patients <80 years of age who presented with a stage I to IIa acute ischemia according to the classification of Rutherford,6e8 and an arterial thrombosis of less than 6 weeks. Patients with contraindication to arterial fibrinolysis were excluded from the study.9 Clinical success was defined by the lifting of acute ischemia. The causes of thromboses, the complications related to the fibrinolysis, and the assisted secondary patency were analyzed. A total of 12 patients (Table I) with an average age of 66 (55e90) years were included in the study, representing 12 in situ intrastent femoral fibrinolysis procedures. Eight patients had a femoral stent implanted for severe claudication, and 4 for rest pain. In situ fibrinolysis was performed with urokinase (ACTOSOLV; Eumedica, Brussels, Belgium).10 The active product was delivered with a dose of 2500 UI/kg/hr (maximum 2 MUI/12 hr) using a
Age (years, mean ± standard deviation) Gender (men:women) Smoking Diabetes Hypertension Dyslipidemia Length of stenting (mm) <150 150 mm Renal insufficiency (Cl, mL/min/1.73 m2) No renal insufficiency Mild insufficiency (Cl 90) Moderate insufficiency (30 < Cl 60) Severe insufficiency (15 < Cl 30) End-stage insufficiency (Cl 15) PAOD, Rutherford stage Class 0 Class 1, 2, and 3 Class 4 Class 5 and 6 SAT occlusive disease Coronary disease Antiplatelet treatment
66 ± 10.7 11:1 11 9 5 9 5 7 5 4 3 0 0 0 8 4 0 2 9 12
multiperforated 5F probe positioned within the thrombus. The probe was installed in the interventional radiology suite under local anesthesia with xylocaine, 5 mg/mL (lidocaine hydrochloride; AstraZeneca, Rueil-Malmaison, France), through a retrograde ultrasound-guided puncture of the contralateral common femoral artery. The puncture was always retrograde, allowing a simple puncture and a single arterial access. A failure of femoral puncture led to a delay in the initiation of fibrinolysis to limit the risk of hematoma at the site of puncture. Moreover, contralateral puncture allowed fixing the extra-arterial material to the skin in line with the exit of the 5F sheath left in place without risk of plication of the catheter. Crossover was carried out with a RIM probe (Cook, Charenton-lePont, France) and over a 0.03500 Terumo hydrophilic guidewire (Terumo, Guyancourt, France). The guidewire was pushed downstream through the thrombus as an effectiveness test and to make it accessible to lysis. A bolus of 100,000 UI of urokinase was then delivered in situ in the interventional radiology suite. Fibrinolysis was carried out and supervised in the ward of the unit of vascular surgery of our center. Clinical monitoring (neurological
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status, site of arterial puncture, hemodynamic constants, and any sign in favor of bleeding) was obtained every 2 hr from a dedicated nurse. Biological monitoring was carried out every 8 hr through serum fibrinogen, activated partial thromboplastin time (ATP), prothrombin time, hemoglobin level, platelet count, and serum creatinine. Posology was adapted according to the protocol of the unit, having for objective a drop in the serum concentration of fibrinogen, but never below 1 g/ L. The treatment also associated unfractioned heparin by continuous intravenous infusion at a dose of 200 IU/kg/24 hr as long as the intra-arterial material was in place. The patient was kept in supine position during all the treatment. Fibrinolysis was maintained for a maximum duration of 72 hr. The effectiveness of the treatment was evaluated by a daily arteriography during which the multiperforated probe was advanced as the thrombus dissolved. The effectiveness of fibrinolysis was defined as the recovery of an anterograde arterial flow in the totality of the femoral axis in continuity with upstream and downstream arteries. At the end of the procedure, one or more complementary endovascular procedures were carried out on the diagnosed arterial lesions (Fig. 1). Short and midterm patency was evaluated by duplex examination of the lower extremities. Statistical Analysis Statistical analysis was performed with Excel 2011 version 14.4.4 (Copyright Microsoft Corporation, Redmond, WA).
RESULTS Twelve patients were included and received 12 intrastent fibrinolysis procedures in the SFAs. Table II summarizes the management of the patients. Eight patients had an SFA stenting for severe intermittent claudication and 4 for critical ischemia with rest pain. Postprocedural angiograms did not show residual stenosis. The average time between initial stenting and intrastent thrombosis was 180 (11e369) days. The average time between the beginning of the symptoms and the initiation of in situ fibrinolysis was 5 (0e12) days. Eight of the12 patients presented a thrombosis extending to the whole native arterial axis. The mean duration of treatment was 46 (24e72) hr. The average total dose of urokinase was 5,700,000 (3.000.000e 9.000.000) IU, that is, 133.333 (125.000e150.000) IU/hr. The average duration of hospital stay was 9 (3e17) days. Intrastent patency was immediately
Patients’s management 3
reestablished in the 12 cases. There was no correlation between the length of the stenting and the effectiveness of fibrinolysis (7 patients had a stenting >150 mm, 5 had a stenting <150 mm, and all responded to fibrinolysis). Isolated or associated diagnosed lesions were an evolution of the PAOD upstream or downstream of the stent in 6 cases and an isolated intrastent restenosis in 3 cases. Three patients presented a fracture of stent (2 grade 3 and 1 grade 2).11 In 2 cases, no obvious cause was found. At the end of the fibrinolysis, one or more additional endovascular procedures were carried out in 9 cases and consisted of a transluminal intrastent angioplasty with an active balloon in 5 cases, an additional stenting in 3 cases, and upstream or downstream stenting in 5 cases. The immediate primary patency was 12/12 patients. The secondary assisted patency at 1 and 5 months (10e442 days) was 12/12 patients. The secondary assisted patency at 10 months (66e759 days) was 11/12 patients. One patient presented a recurrent ischemia 10 days after the fibrinolysis. No cause had been found at the time of the first fibrinolysis, without an additional treatment. A second procedure of fibrinolysis was carried out uncovering an intrastent stenosis treated by iterative stenting. This patient did not present a recurrence after a follow-up of 5 months. A second patient presented a recurrent SFA thrombosis 46 days after fibrinolysis and stenting of an upstream SFA stenosis. No other lesion could explain the early rethrombosis, and an above-knee femoropopliteal prosthetic bypass was performed, which was patent at 12 months. No major hemorrhagic complication was observed. Two false aneurysms at the femoral puncture sites were observed. The first was dealt with a compression dressing kept on for 48 hr; the exclusion of the false aneurism was confirmed by duplex examination. The second was treated surgically through an oblique short femoral incision. One patient presented ischemic neuralgias as sequels. Remotely (>8 month) 2 patients presented a recurrent intermittent claudication due to femoral intrastent stenosis. A new intrastent angioplasty with an active balloon allowed the disappearance of the painful symptomatology in 2 cases. No major amputation was observed in this series. At the biological level, fibrinolysis led to an average drop in the fibrinogen level of 2.55 (0.5 to 5.9) g/L with a mean lowest average fibrinogen level of 1.53 (1e2.5) g/L. During fibrinolysis, mean hemoglobin level drop was 0.94 (0.8 to 5.4) g/dL, and the mean reduction in the platelet count was 48,916 (13,000 to 137,000). The average APT of the patients was 38 sec
4 Arsicot et al.
Annals of Vascular Surgery
Fig. 1. Arteriography of the same patient at different times of the treatment: (A) before fibrinolysis, (B) after in situ intrastent fibrinolysis, and (C) after angioplasty of diagnosed lesions.
(27e55) versus 59 sec (23e140) before the procedure. All the patients were discharged with a 3-month dual antiplatelet regimen. Only 1 patient received an anticoagulant treatment because no causal lesion had been uncovered except a pathological downstream arterial bed.
DISCUSSION According to the results of our study, intrastent fibrinolysis is an effective and safe treatment of femoral intrastent thromboses. Our results suggest that Class I and IIa acute ischemia due to SFA stent thrombosis can be managed with in situ fibrinolysis as first-line treatment allowing the endovascular treatment of the causal lesion and thus avoiding thrombectomy or bypass. Since the improvement of endovascular techniques fibrinolysis can be delivered in contact with the thrombus for any peripheral arterial site. The management of patient presenting with acute limb ischemia uses different techniques. In situ arterial fibrinolysis offers a minimally invasive therapeutic solution. It makes it possible to reduce the need for a general anesthesia or an operating room without increasing the risk of amputation or mortality.3,4 Conventional Fogarty embolectomy is associated with many complications (intimal dissection, diffuse intimal hyperplasia, distal embolization) and often requires an associated procedure.12 Percutaneous thromboaspiration associated or not with fibrinolysis increases the blood losses and the risk of distal embolism due to the mobilization of the thrombus.13 To this must be added the higher risk of hematoma at the site of puncture induced by the larger size of the introducers used. The recanalization during the acute phase is at high risk of distal embolism but direct stenting would make it possible to limit this risk.14
Our study confirms that, in the cases of acute ischemia due to SFA stent thrombosis, fibrinolytic treatment allows to decrease the need for conventional surgery and the incidence of amputations by restoring the patency of the thrombosed artery.5,15 In our study, no patient required amputation. Only one patient needed conventional surgery for bypass. This patient had the treatment of an SFA stenosis upstream of the precedent stenting at the end of fibrinolysis. Because no other lesion explained early rethrombosis, an above-knee prosthetic femoropopliteal bypass was performed. One patient presented a recurrent ischemia 10 days after fibrinolysis which required a new fibrinolysis. The latter revealed an intrastent stenosis that was not diagnosed initially, which was treated by stenting iterative. This confirms that the long-term patency depends on finding the lesions at the origin of thrombosis and the systematic treatment of these lesions.4,5 The literature reports additional procedures after thrombolysis in 89% of the patients.15 The patients of our study in which a lesion was diagnosed were treated during the same hospitalization. Only 1 patient who responded to fibrinolysis and in whom no lesion was found was prescribed an anticoagulant treatment after fibrinolysis. To our knowledge, this study is the only one in the literature analyzing specifically the effectiveness and the durability of the medico-surgical treatment of SFA stents thromboses. Many teams use fibrinolysis for the treatment of chronic atheromatous lesions with a predominating thrombus. The analysis of the target lesion makes it possible to differentiate the atheromatous lesions with predominating thrombus from those with predominating plaque.16 The low echogenicity of the lesion is in favor of thrombus. The feeling of an easy crossing of the lesion by a flexible hydrophilic guidewire is also in favor of thrombus. In this study, the indication of fibrinolysis was planned mainly on the grounds of
Results of Diagnosed fibrinolysis lesions
Success
2
A
18
5-mm chrome cobalt Palmaz Blue Cordis
230
20-mm intrastent SFA
2
3
C
210
8-mm nitinol Everflex EV3
244
3
2
C
180
6-mm nitinol Lifestent Bard
11
4
2
C
270
6-mm nitinol Lifestent Bard
20
Success 280-mm intrastent SFA and above-knee popliteal artery Success 120-mm intrastent SFA and above-knee popliteal artery 280-mm Success Intrastent SFA
5
2
A
24
5-mm chrome cobalt Palmaz Blue Cordis
160
6
2
C
210
7
2
A
40
6-mm steel Valeo Bard and 7-mm Zilver PTX Cook 6-mm nitinol Lifestent Bard
95
13
Success 30-mm intrastent Hunter SFA Success 260-mm intrastent SFA Success 440-mm SFA and above-knee popliteal artery
Length of follow-up (days)
Type 3 fracture Intrastent stenting 6 100 mm of stent and Lifestent BARD downstream stenosis Intrastent and Upstream stenting upstream 6 40 mm stenosis Lifestent Bard and intrastent TLA 5 20 mm Lutonix Bard Intrastent Intrastent TLA stenosis 6 20 mm Lutonix Bard
Patent
431
Patent
759
Patent
277
Intrastent and downstream stenosis
Downstream stenting 5 60 mm Lifestent Bard
652
Intrastent stenosis
Intrastent TLA 5 40 mm Lutonix Bard
Patent after TLA with active balloon for intrastent restenosis Patent
546
Type 2 stent fracture
Intrastent stenting 7 40 mm Omnilink Abott Proximal SFA stenting 6 40 mm Lifestent Bard
Patent
349
Upstream stenosis
Treatment of diagnosed lesions
141 Above-knee femoropopliteal bypass at D46
(Continued)
Patients’s management 5
1
Patency at the end of follow-up
2016
Duration of patency before occlusion Length of (days) thrombosis
-, -
Type of stents (commercial name)
No.
Length of stenting (mm)
-,
Type of Rutherford’s lesion Patient stage (TASC II)
Vol.
Table II. Management of the patients
Duration of patency before occlusion Length of (days) thrombosis
Type of Rutherford’s lesion Patient stage (TASC II)
Length of stenting (mm)
Type of stents (commercial name)
8
2
C
200
5-mm nitinol Lifestent Bard
9
2
D
320
369 6-mm nitinol Everflex EV3 and 6-mm steel Omnilink Abbott
10
3
A
130
344
11
3
D
250
7-mm nitinol Lifestent Bard 6-mm nitinol Lifestent Bard
12
3
A
130
7-mm nitinol Lifestent Bard
361
18
302
Results of Diagnosed fibrinolysis lesions
Treatment of diagnosed lesions
Patency at the end of follow-up
Patent
Length of follow-up (days)
Success 168-mm intrastent SFA and above-knee popliteal artery Success 115-mm proximal SFA
No lesion diagnosed
d
Intrastent and upstream stenosis
147-mm intrastent SFA 230-mm intrastent SFA
Success
No lesion diagnosed
231 es External iliac stenting Patent apr after TLA with 7 30 mm Lifestent active balloon Bard and intrastent for intrastent TLA 5 150 mm restenosis Lutonix Bard d Patent 152
Success
130-mm intrastent SFA
Success
Patent Type 3 stent Common femoral fracture and stenting 8 29 mm upstream and Omnilink Abbott downstream and SFA + abovestenosis knee popliteal 5 80 mm Everflex EV3, intrastent SFA TLA 5 150 mm Lutonix Bard Patent Intrastent Intrastent stenting stenosis 7 30 mm Zilver PTX Cook
66
147
139
Annals of Vascular Surgery
ATL, angioplastie transluminale; mm, millimetre; SFA, superficial femoral artery; PTX, paclitaxel; D, day.
6 Arsicot et al.
Table II. Continued
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the time of appearance of the symptoms (on average 5 days) and the absence of sensory motor deficit. A maximum threshold length of thrombosis accessible to fibrinolysis was not found in the literature. Only the clinical tolerance should restrict the use of fibrinolysis. The study comprised 7 femoral stentings with a length >150 cm and 5 with a length <150 mm. In analogy with native arteries or bypasses, there was thus no correlation between the effectiveness of fibrinolysis and the length of the initial stenting. First-line endovascular management often brings the advantage of not degrading the clinical status of the patient in the event of intrastent thrombosis because the patient recovers his initial vascular status. This advantage appears limited in the event of thromboses extended to the whole native arterial axis. Indeed, in this study, 8 of the 12 patients presented a thrombosis extending to the whole native arterial bed. One can then suppose that clinical degradation was due to the loss of the collaterality. During the period of inclusion, we could not compare the 12 included patients with the patients presenting an asymptomatic thrombosis of an SFA stent. In this study, we included only the patients presenting an acute ischemia. Recurrent claudication or asymptomatic occlusions are managed with a rehabilitation program and a close monitoring. In this study, we observed an isolated stent fracture in 3 patients. The SFA is subjected to different external forces: compression, torsion, and elongation. Among the recognized risk factors, there was a long and multiple stenting (210 and 250 mm) in 2 patients. The third patient presented a single chrome cobalt short stenting (18 mm). This fracture of stent was the only pathology explaining the SFA thrombosis, confirming that stent fracture may induce restenosis or thrombosis.17,18 Each of them had an intrastent stenting. However, the duration of patency demonstrates that the additional stenting does not affect long-term secondary assisted patency: 431, 349, and 147 days, respectively. The complications of fibrinolysis are the main arguments of the literature for its nonuse.19 The rates of major complications (puncture hematoma, superinfection of an hematoma, false aneurysm, catheter infection, hematuria, and red cell transfusion) oscillate between 2% and 16%.15 In our study, 2 false aneurysms at the femoral puncture site were observed. The first was treated by compression dressing, and the second was operated. We also observed one failed puncture of the femoral artery delaying the initiation of fibrinolysis by 8 days to limit the risk of local hemorrhagic complication. In our center, a system of arterial closing is used in all the
Patients’s management 7
patients treated by in situ fibrinolysis. The use of this closing system enabled us to decrease the risk of false aneurysm at the puncture site. The amounts of urokinase used in our protocol are among the high values used in the various studies (between 50,000 and 250,000 UI).20 However, the rate of hemorrhagic complications in our series is not higher than in the literature and we did not observe embolic complications. In the same way the duration of the fibrinolytic treatment did not exceed 3 days in our center.21 The patients who did not answer to a 3-day fibrinolysis present a chronic thrombus resistant to fibrinolysis. The continuation of thrombolysis beyond the third day represents a serious hemorrhagic risk.
CONCLUSION Intrastent fibrinolysis is an effective and safe treatment of femoral intrastent thromboses. Our results suggest that in situ fibrinolysis can be the first-line treatment for Class I and IIa acute ischemia due to the thrombosis of SFA stents and allows the endovascular treatment of causal lesions, thus avoiding thrombectomy or bypass. The fibrinolysis procedure must be realized in a center familiar with its management and we recommend the use of a system of percutaneous arterial closing limiting the hemorrhagic complications at the end of the procedure.
REFERENCES 1. Gary T, Rief P, Stojakovic T, et al. Parameters of the lipid profile and association with the development of reobstruction after stent implantation in the SFA in PAD-patients. Atheroscler Suppl 2010;11:17e108. 2. Cvirn G, Hoerl G, Schlagenhauf A, et al. Stent implantation in the superficial femoral artery: short thrombelastometryderived coagulation times identify patients with late instent restenosis. Thromb Res 2012;130:485e90. 3. Branco BC, Montero-Baker MF, Mills JL. The pros and cons of endovascular and open surgical treatments for patients with acute limb ischemia. J Cardiovasc Surg 2015;56:1e2. 4. Kuoppala M, Akeson J, Acosta S. Outcome after thrombolysis for occluded endoprosthesis, bypasses and native arteries in patients with lower limb ischemia. Thromb Res 2014;134: 23e8. 5. Working Party on Thrombolysis in the Management of Limb Ischemia. Thrombolysis in the management of lower limb peripheral arterial occlusionda consensus document. Am J Cardiol 1998;81:207e18. 6. Blaisdell FW. The pathophysiology of skeletal muscle ischemia and the reperfusion syndrome: a review. Cardiovasc Surg 2002;10:620e30. 7. Rutherford RB, Baker JD, Ernst C, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 1997;26:517e38.
8 Arsicot et al.
8. Piriou V, Closon M, Feugier P. Prise en charge en urgence d’un patient en ischemie aigu€e des membres inferieurs. EMC; M edecine d’urgence, 25-190-A-20. 9. NIH Consensus Development Conference summary: thrombolytic therapy in thrombosis. J Tenn Med Assoc 1980;73:751e5. 10. Ouriel K, Kandarpa K. Safety of thrombolytic therapy with urokinase or recombinant tissue plasminogen activator for peripheral arterial occlusion: a comprehensive compilation of published work. J Endovasc Ther 2004;11:436e46. 11. Nakazawa G, Finn AV, Vorpahl M, et al. Incidence and predictors of drug-eluting stent fracture in human coronary artery. J Am Coll Cardiol 2009;54:1924e31. 12. Ouriel K, Shortell CK, DeWeese JA, et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994;19:1021e30. 13. Wagner HJ, Starck EE. Acute embolic occlusions of the infrainguinal arteries: percutaneous aspiration embolectomy in 102 patients. Radiology 1992;182:403e7. 14. Kim C, Jeon W, shin T. Stent assisted recanalisation of acute occlusive arteries in patients with acute limb ischaemia. Eur J Vasc Endovasc Surg 2010;39:89e96.
Annals of Vascular Surgery
15. Byrne RM, Taha AG, Avgerinos E, et al. Contemporary outcomes of endovascular interventions for acute limb ischemia. J Vasc Surg 2014;59:988e95. 16. Zhan F, Zhang H, Luo X, et al. Catheter-directed thrombolysis-assisted angioplasty for chronic lower limb ischemia. Ann Vasc Surg 2014;28:590e5. 17. Schneinert D, Scheinert S, Sax J, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol 2005;45:312e5. 18. Adlakha S, Sheikh M, Wu J, et al. Stent fracture in the coronary and peripheral arteries. J Interv Cardiol 2010;23: 411e9. 19. Breukink SO, Vrouenraets BC, Davies GA, et al. Thrombolysis as initial treatment of peripheral native artery and bypass graft occlusion in a general community hospital. Ann Vasc Surg 2004;18:314e20. 20. Ebben HP, Nederhoed JH, Lely RJ, et al. Low-dose thrombolysis for thromboembolic lower extremity arterial occlusion is effective without major hemorrhagic complications. Eur J Vasc Endovasc Surg 2014;48:551e8. 21. Kashyap VK, Gilani R, Bena JF, et al. Endovascular therapy for acute limb ischemia. J Vasc Surg 2011;53:340e6.
Background: The management of acute ischemia due to the thrombosis superficial femoral artery (SFA) stents is complex. In situ arterial fibrinolysis, still not evaluated in this indication, would allow, by lifting the ischemia and uncovering its cause, to avoid thrombectomy, endovascular recanalization, or arterial bypass. The purpose of the study was to evaluate the effectiveness, the complications, and the assisted secondary patency of in situ fibrinolysis for thrombosis of SFA stents. Methods: We conducted a retrospective monocentric study with prospective collection of the data. Between October 2011 and December 2014, 86 in situ fibrinolysis procedures were carried out for acute lower limb ischemia. Twelve procedures were carried out for acute ischemia due to the thrombosis of SFA stents. Clinical success was defined by the lifting of acute ischemia. The causes of thromboses, the complications related to the fibrinolysis, and the secondary assisted patency were analyzed. Results: The mean age of the patients was 66.3 (55e90) years. The average length of the stents was 119.3 (18e270) mm. In 10 patients, the thrombosis extended in the full length of the artery. The average time between the implantation of the stent and the initiation of the fibrinolysis was 180 (11e369) days. The average time between the beginning of the symptoms and fibrinolysis was 5 (0e12) days. The average duration of treatment was 46 (24e72) hr. Clinical success was obtained in all the patients. Diagnosed isolated or associated lesions were a progression of the atheromatous disease upstream or downstream of the stent in 6 cases, and an isolated intrastent restenosis in 3 cases. In 2 cases, no obvious cause was found. One or more additional endovascular procedures were carried out in 9 cases at the end of the fibrinolysis, and consisted of a transluminal intrastent angioplasty with an active balloon in 5 cases, an additional stenting in 3 cases, and the stenting of upstream or downstream arteries in 5 cases. Secondary assisted patency was 100% at 5 months. No major hemorrhagic complication was observed. Two false aneurysms at the site of femoral puncture were observed. Conclusion: Our results suggest that ischemia due to the thrombosis of SFA stents can be dealt with first intention in situ fibrinolysis which allows the endovascular treatment of the causal lesion, thus avoiding thrombectomy or bypass.
Presented at the 30th Annual Meeting of the French Society for Vascular Surgery, Montpellier, France, June 26e29, 2015. 1 Service de chirurgie vasculaire, Etablissement Edouard Herriot, Hospices Civils de Lyon, Lyon, France. 2 Service de Radiologie, Etablissement Edouard Herriot, Hospices Civils de Lyon, Lyon, France.
Place d’Arsonval Lyon, France; E-mail: matthieu.arsicot@gmail. com Ann Vasc Surg 2016; -: 1–8 http://dx.doi.org/10.1016/j.avsg.2015.10.029 Ó 2016 Elsevier Inc. All rights reserved. Manuscript received: July 3, 2015; manuscript accepted: October 11, 2015; published online: ---.
Correspondence to: Matthieu Arsicot, Service de chirurgie vasculaire, Etablissement Edouard Herriot, Hospices Civils de Lyon,
1
2 Arsicot et al.
Annals of Vascular Surgery
INTRODUCTION
Table I. Characteristics of patients
Endovascular surgery is the first surgical treatment for peripheral arterial occlusive disease (PAOD) but the number of stents thromboses is increasing (more than 50% of intrastent stenoses at 1 year).1,2 The seriousness of the acute ischemia of the lower extremities (up to 42.5% and 15% of mortality and amputation at 1 year, respectively) led to the development of many pharmacological and mechanical therapeutic techniques.3 Since the year 1990, fibrinolysis belongs to the therapeutic armamentarium of acute ischemia. It proved its effectiveness in terms of limb salvage and mortality.4 The management of acute ischemia due to the thrombosis of stents implanted in the superficial femoral artery (SFA) is complex. In situ arterial fibrinolysis which has not been evaluated in this indication would allow, by lifting the ischemia and by uncovering its cause, to avoid thrombectomy, endovascular recanalization, or arterial bypass.5 The purpose of the study was to evaluate the effectiveness, the complications, and the assisted secondary patency of in situ fibrinolysis of thrombosed SFA stents.
Characteristics of patients (n ¼ 12)
MATERIALS AND METHODS
Antiplatelet treatment, acetylsalicylic acid and/or clopidogrel; Cl, creatinine clearance calculated according to the MDRD formula; MDRD, modification of the diet in renal disease; SAT, supraaortic trunks.
This was a monocentric, retrospective therapeutic study with prospective data collection. Between October 2011 and December 2014, 86 in situ fibrinolysis procedures were carried out for acute ischemia of the lower extremities. Twelve procedures were carried out for acute ischemia due to the thrombosis of stents implanted in the SFA. Asymptomatic patients and those presenting a recurrent claudication were not included in this study. We included in this study patients <80 years of age who presented with a stage I to IIa acute ischemia according to the classification of Rutherford,6e8 and an arterial thrombosis of less than 6 weeks. Patients with contraindication to arterial fibrinolysis were excluded from the study.9 Clinical success was defined by the lifting of acute ischemia. The causes of thromboses, the complications related to the fibrinolysis, and the assisted secondary patency were analyzed. A total of 12 patients (Table I) with an average age of 66 (55e90) years were included in the study, representing 12 in situ intrastent femoral fibrinolysis procedures. Eight patients had a femoral stent implanted for severe claudication, and 4 for rest pain. In situ fibrinolysis was performed with urokinase (ACTOSOLV; Eumedica, Brussels, Belgium).10 The active product was delivered with a dose of 2500 UI/kg/hr (maximum 2 MUI/12 hr) using a
Age (years, mean ± standard deviation) Gender (men:women) Smoking Diabetes Hypertension Dyslipidemia Length of stenting (mm) <150 150 mm Renal insufficiency (Cl, mL/min/1.73 m2) No renal insufficiency Mild insufficiency (Cl 90) Moderate insufficiency (30 < Cl 60) Severe insufficiency (15 < Cl 30) End-stage insufficiency (Cl 15) PAOD, Rutherford stage Class 0 Class 1, 2, and 3 Class 4 Class 5 and 6 SAT occlusive disease Coronary disease Antiplatelet treatment
66 ± 10.7 11:1 11 9 5 9 5 7 5 4 3 0 0 0 8 4 0 2 9 12
multiperforated 5F probe positioned within the thrombus. The probe was installed in the interventional radiology suite under local anesthesia with xylocaine, 5 mg/mL (lidocaine hydrochloride; AstraZeneca, Rueil-Malmaison, France), through a retrograde ultrasound-guided puncture of the contralateral common femoral artery. The puncture was always retrograde, allowing a simple puncture and a single arterial access. A failure of femoral puncture led to a delay in the initiation of fibrinolysis to limit the risk of hematoma at the site of puncture. Moreover, contralateral puncture allowed fixing the extra-arterial material to the skin in line with the exit of the 5F sheath left in place without risk of plication of the catheter. Crossover was carried out with a RIM probe (Cook, Charenton-lePont, France) and over a 0.03500 Terumo hydrophilic guidewire (Terumo, Guyancourt, France). The guidewire was pushed downstream through the thrombus as an effectiveness test and to make it accessible to lysis. A bolus of 100,000 UI of urokinase was then delivered in situ in the interventional radiology suite. Fibrinolysis was carried out and supervised in the ward of the unit of vascular surgery of our center. Clinical monitoring (neurological
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No.
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2016
status, site of arterial puncture, hemodynamic constants, and any sign in favor of bleeding) was obtained every 2 hr from a dedicated nurse. Biological monitoring was carried out every 8 hr through serum fibrinogen, activated partial thromboplastin time (ATP), prothrombin time, hemoglobin level, platelet count, and serum creatinine. Posology was adapted according to the protocol of the unit, having for objective a drop in the serum concentration of fibrinogen, but never below 1 g/ L. The treatment also associated unfractioned heparin by continuous intravenous infusion at a dose of 200 IU/kg/24 hr as long as the intra-arterial material was in place. The patient was kept in supine position during all the treatment. Fibrinolysis was maintained for a maximum duration of 72 hr. The effectiveness of the treatment was evaluated by a daily arteriography during which the multiperforated probe was advanced as the thrombus dissolved. The effectiveness of fibrinolysis was defined as the recovery of an anterograde arterial flow in the totality of the femoral axis in continuity with upstream and downstream arteries. At the end of the procedure, one or more complementary endovascular procedures were carried out on the diagnosed arterial lesions (Fig. 1). Short and midterm patency was evaluated by duplex examination of the lower extremities. Statistical Analysis Statistical analysis was performed with Excel 2011 version 14.4.4 (Copyright Microsoft Corporation, Redmond, WA).
RESULTS Twelve patients were included and received 12 intrastent fibrinolysis procedures in the SFAs. Table II summarizes the management of the patients. Eight patients had an SFA stenting for severe intermittent claudication and 4 for critical ischemia with rest pain. Postprocedural angiograms did not show residual stenosis. The average time between initial stenting and intrastent thrombosis was 180 (11e369) days. The average time between the beginning of the symptoms and the initiation of in situ fibrinolysis was 5 (0e12) days. Eight of the12 patients presented a thrombosis extending to the whole native arterial axis. The mean duration of treatment was 46 (24e72) hr. The average total dose of urokinase was 5,700,000 (3.000.000e 9.000.000) IU, that is, 133.333 (125.000e150.000) IU/hr. The average duration of hospital stay was 9 (3e17) days. Intrastent patency was immediately
Patients’s management 3
reestablished in the 12 cases. There was no correlation between the length of the stenting and the effectiveness of fibrinolysis (7 patients had a stenting >150 mm, 5 had a stenting <150 mm, and all responded to fibrinolysis). Isolated or associated diagnosed lesions were an evolution of the PAOD upstream or downstream of the stent in 6 cases and an isolated intrastent restenosis in 3 cases. Three patients presented a fracture of stent (2 grade 3 and 1 grade 2).11 In 2 cases, no obvious cause was found. At the end of the fibrinolysis, one or more additional endovascular procedures were carried out in 9 cases and consisted of a transluminal intrastent angioplasty with an active balloon in 5 cases, an additional stenting in 3 cases, and upstream or downstream stenting in 5 cases. The immediate primary patency was 12/12 patients. The secondary assisted patency at 1 and 5 months (10e442 days) was 12/12 patients. The secondary assisted patency at 10 months (66e759 days) was 11/12 patients. One patient presented a recurrent ischemia 10 days after the fibrinolysis. No cause had been found at the time of the first fibrinolysis, without an additional treatment. A second procedure of fibrinolysis was carried out uncovering an intrastent stenosis treated by iterative stenting. This patient did not present a recurrence after a follow-up of 5 months. A second patient presented a recurrent SFA thrombosis 46 days after fibrinolysis and stenting of an upstream SFA stenosis. No other lesion could explain the early rethrombosis, and an above-knee femoropopliteal prosthetic bypass was performed, which was patent at 12 months. No major hemorrhagic complication was observed. Two false aneurysms at the femoral puncture sites were observed. The first was dealt with a compression dressing kept on for 48 hr; the exclusion of the false aneurism was confirmed by duplex examination. The second was treated surgically through an oblique short femoral incision. One patient presented ischemic neuralgias as sequels. Remotely (>8 month) 2 patients presented a recurrent intermittent claudication due to femoral intrastent stenosis. A new intrastent angioplasty with an active balloon allowed the disappearance of the painful symptomatology in 2 cases. No major amputation was observed in this series. At the biological level, fibrinolysis led to an average drop in the fibrinogen level of 2.55 (0.5 to 5.9) g/L with a mean lowest average fibrinogen level of 1.53 (1e2.5) g/L. During fibrinolysis, mean hemoglobin level drop was 0.94 (0.8 to 5.4) g/dL, and the mean reduction in the platelet count was 48,916 (13,000 to 137,000). The average APT of the patients was 38 sec
4 Arsicot et al.
Annals of Vascular Surgery
Fig. 1. Arteriography of the same patient at different times of the treatment: (A) before fibrinolysis, (B) after in situ intrastent fibrinolysis, and (C) after angioplasty of diagnosed lesions.
(27e55) versus 59 sec (23e140) before the procedure. All the patients were discharged with a 3-month dual antiplatelet regimen. Only 1 patient received an anticoagulant treatment because no causal lesion had been uncovered except a pathological downstream arterial bed.
DISCUSSION According to the results of our study, intrastent fibrinolysis is an effective and safe treatment of femoral intrastent thromboses. Our results suggest that Class I and IIa acute ischemia due to SFA stent thrombosis can be managed with in situ fibrinolysis as first-line treatment allowing the endovascular treatment of the causal lesion and thus avoiding thrombectomy or bypass. Since the improvement of endovascular techniques fibrinolysis can be delivered in contact with the thrombus for any peripheral arterial site. The management of patient presenting with acute limb ischemia uses different techniques. In situ arterial fibrinolysis offers a minimally invasive therapeutic solution. It makes it possible to reduce the need for a general anesthesia or an operating room without increasing the risk of amputation or mortality.3,4 Conventional Fogarty embolectomy is associated with many complications (intimal dissection, diffuse intimal hyperplasia, distal embolization) and often requires an associated procedure.12 Percutaneous thromboaspiration associated or not with fibrinolysis increases the blood losses and the risk of distal embolism due to the mobilization of the thrombus.13 To this must be added the higher risk of hematoma at the site of puncture induced by the larger size of the introducers used. The recanalization during the acute phase is at high risk of distal embolism but direct stenting would make it possible to limit this risk.14
Our study confirms that, in the cases of acute ischemia due to SFA stent thrombosis, fibrinolytic treatment allows to decrease the need for conventional surgery and the incidence of amputations by restoring the patency of the thrombosed artery.5,15 In our study, no patient required amputation. Only one patient needed conventional surgery for bypass. This patient had the treatment of an SFA stenosis upstream of the precedent stenting at the end of fibrinolysis. Because no other lesion explained early rethrombosis, an above-knee prosthetic femoropopliteal bypass was performed. One patient presented a recurrent ischemia 10 days after fibrinolysis which required a new fibrinolysis. The latter revealed an intrastent stenosis that was not diagnosed initially, which was treated by stenting iterative. This confirms that the long-term patency depends on finding the lesions at the origin of thrombosis and the systematic treatment of these lesions.4,5 The literature reports additional procedures after thrombolysis in 89% of the patients.15 The patients of our study in which a lesion was diagnosed were treated during the same hospitalization. Only 1 patient who responded to fibrinolysis and in whom no lesion was found was prescribed an anticoagulant treatment after fibrinolysis. To our knowledge, this study is the only one in the literature analyzing specifically the effectiveness and the durability of the medico-surgical treatment of SFA stents thromboses. Many teams use fibrinolysis for the treatment of chronic atheromatous lesions with a predominating thrombus. The analysis of the target lesion makes it possible to differentiate the atheromatous lesions with predominating thrombus from those with predominating plaque.16 The low echogenicity of the lesion is in favor of thrombus. The feeling of an easy crossing of the lesion by a flexible hydrophilic guidewire is also in favor of thrombus. In this study, the indication of fibrinolysis was planned mainly on the grounds of
Results of Diagnosed fibrinolysis lesions
Success
2
A
18
5-mm chrome cobalt Palmaz Blue Cordis
230
20-mm intrastent SFA
2
3
C
210
8-mm nitinol Everflex EV3
244
3
2
C
180
6-mm nitinol Lifestent Bard
11
4
2
C
270
6-mm nitinol Lifestent Bard
20
Success 280-mm intrastent SFA and above-knee popliteal artery Success 120-mm intrastent SFA and above-knee popliteal artery 280-mm Success Intrastent SFA
5
2
A
24
5-mm chrome cobalt Palmaz Blue Cordis
160
6
2
C
210
7
2
A
40
6-mm steel Valeo Bard and 7-mm Zilver PTX Cook 6-mm nitinol Lifestent Bard
95
13
Success 30-mm intrastent Hunter SFA Success 260-mm intrastent SFA Success 440-mm SFA and above-knee popliteal artery
Length of follow-up (days)
Type 3 fracture Intrastent stenting 6 100 mm of stent and Lifestent BARD downstream stenosis Intrastent and Upstream stenting upstream 6 40 mm stenosis Lifestent Bard and intrastent TLA 5 20 mm Lutonix Bard Intrastent Intrastent TLA stenosis 6 20 mm Lutonix Bard
Patent
431
Patent
759
Patent
277
Intrastent and downstream stenosis
Downstream stenting 5 60 mm Lifestent Bard
652
Intrastent stenosis
Intrastent TLA 5 40 mm Lutonix Bard
Patent after TLA with active balloon for intrastent restenosis Patent
546
Type 2 stent fracture
Intrastent stenting 7 40 mm Omnilink Abott Proximal SFA stenting 6 40 mm Lifestent Bard
Patent
349
Upstream stenosis
Treatment of diagnosed lesions
141 Above-knee femoropopliteal bypass at D46
(Continued)
Patients’s management 5
1
Patency at the end of follow-up
2016
Duration of patency before occlusion Length of (days) thrombosis
-, -
Type of stents (commercial name)
No.
Length of stenting (mm)
-,
Type of Rutherford’s lesion Patient stage (TASC II)
Vol.
Table II. Management of the patients
Duration of patency before occlusion Length of (days) thrombosis
Type of Rutherford’s lesion Patient stage (TASC II)
Length of stenting (mm)
Type of stents (commercial name)
8
2
C
200
5-mm nitinol Lifestent Bard
9
2
D
320
369 6-mm nitinol Everflex EV3 and 6-mm steel Omnilink Abbott
10
3
A
130
344
11
3
D
250
7-mm nitinol Lifestent Bard 6-mm nitinol Lifestent Bard
12
3
A
130
7-mm nitinol Lifestent Bard
361
18
302
Results of Diagnosed fibrinolysis lesions
Treatment of diagnosed lesions
Patency at the end of follow-up
Patent
Length of follow-up (days)
Success 168-mm intrastent SFA and above-knee popliteal artery Success 115-mm proximal SFA
No lesion diagnosed
d
Intrastent and upstream stenosis
147-mm intrastent SFA 230-mm intrastent SFA
Success
No lesion diagnosed
231 es External iliac stenting Patent apr after TLA with 7 30 mm Lifestent active balloon Bard and intrastent for intrastent TLA 5 150 mm restenosis Lutonix Bard d Patent 152
Success
130-mm intrastent SFA
Success
Patent Type 3 stent Common femoral fracture and stenting 8 29 mm upstream and Omnilink Abbott downstream and SFA + abovestenosis knee popliteal 5 80 mm Everflex EV3, intrastent SFA TLA 5 150 mm Lutonix Bard Patent Intrastent Intrastent stenting stenosis 7 30 mm Zilver PTX Cook
66
147
139
Annals of Vascular Surgery
ATL, angioplastie transluminale; mm, millimetre; SFA, superficial femoral artery; PTX, paclitaxel; D, day.
6 Arsicot et al.
Table II. Continued
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the time of appearance of the symptoms (on average 5 days) and the absence of sensory motor deficit. A maximum threshold length of thrombosis accessible to fibrinolysis was not found in the literature. Only the clinical tolerance should restrict the use of fibrinolysis. The study comprised 7 femoral stentings with a length >150 cm and 5 with a length <150 mm. In analogy with native arteries or bypasses, there was thus no correlation between the effectiveness of fibrinolysis and the length of the initial stenting. First-line endovascular management often brings the advantage of not degrading the clinical status of the patient in the event of intrastent thrombosis because the patient recovers his initial vascular status. This advantage appears limited in the event of thromboses extended to the whole native arterial axis. Indeed, in this study, 8 of the 12 patients presented a thrombosis extending to the whole native arterial bed. One can then suppose that clinical degradation was due to the loss of the collaterality. During the period of inclusion, we could not compare the 12 included patients with the patients presenting an asymptomatic thrombosis of an SFA stent. In this study, we included only the patients presenting an acute ischemia. Recurrent claudication or asymptomatic occlusions are managed with a rehabilitation program and a close monitoring. In this study, we observed an isolated stent fracture in 3 patients. The SFA is subjected to different external forces: compression, torsion, and elongation. Among the recognized risk factors, there was a long and multiple stenting (210 and 250 mm) in 2 patients. The third patient presented a single chrome cobalt short stenting (18 mm). This fracture of stent was the only pathology explaining the SFA thrombosis, confirming that stent fracture may induce restenosis or thrombosis.17,18 Each of them had an intrastent stenting. However, the duration of patency demonstrates that the additional stenting does not affect long-term secondary assisted patency: 431, 349, and 147 days, respectively. The complications of fibrinolysis are the main arguments of the literature for its nonuse.19 The rates of major complications (puncture hematoma, superinfection of an hematoma, false aneurysm, catheter infection, hematuria, and red cell transfusion) oscillate between 2% and 16%.15 In our study, 2 false aneurysms at the femoral puncture site were observed. The first was treated by compression dressing, and the second was operated. We also observed one failed puncture of the femoral artery delaying the initiation of fibrinolysis by 8 days to limit the risk of local hemorrhagic complication. In our center, a system of arterial closing is used in all the
Patients’s management 7
patients treated by in situ fibrinolysis. The use of this closing system enabled us to decrease the risk of false aneurysm at the puncture site. The amounts of urokinase used in our protocol are among the high values used in the various studies (between 50,000 and 250,000 UI).20 However, the rate of hemorrhagic complications in our series is not higher than in the literature and we did not observe embolic complications. In the same way the duration of the fibrinolytic treatment did not exceed 3 days in our center.21 The patients who did not answer to a 3-day fibrinolysis present a chronic thrombus resistant to fibrinolysis. The continuation of thrombolysis beyond the third day represents a serious hemorrhagic risk.
CONCLUSION Intrastent fibrinolysis is an effective and safe treatment of femoral intrastent thromboses. Our results suggest that in situ fibrinolysis can be the first-line treatment for Class I and IIa acute ischemia due to the thrombosis of SFA stents and allows the endovascular treatment of causal lesions, thus avoiding thrombectomy or bypass. The fibrinolysis procedure must be realized in a center familiar with its management and we recommend the use of a system of percutaneous arterial closing limiting the hemorrhagic complications at the end of the procedure.
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8. Piriou V, Closon M, Feugier P. Prise en charge en urgence d’un patient en ischemie aigu€e des membres inferieurs. EMC; M edecine d’urgence, 25-190-A-20. 9. NIH Consensus Development Conference summary: thrombolytic therapy in thrombosis. J Tenn Med Assoc 1980;73:751e5. 10. Ouriel K, Kandarpa K. Safety of thrombolytic therapy with urokinase or recombinant tissue plasminogen activator for peripheral arterial occlusion: a comprehensive compilation of published work. J Endovasc Ther 2004;11:436e46. 11. Nakazawa G, Finn AV, Vorpahl M, et al. Incidence and predictors of drug-eluting stent fracture in human coronary artery. J Am Coll Cardiol 2009;54:1924e31. 12. Ouriel K, Shortell CK, DeWeese JA, et al. A comparison of thrombolytic therapy with operative revascularization in the initial treatment of acute peripheral arterial ischemia. J Vasc Surg 1994;19:1021e30. 13. Wagner HJ, Starck EE. Acute embolic occlusions of the infrainguinal arteries: percutaneous aspiration embolectomy in 102 patients. Radiology 1992;182:403e7. 14. Kim C, Jeon W, shin T. Stent assisted recanalisation of acute occlusive arteries in patients with acute limb ischaemia. Eur J Vasc Endovasc Surg 2010;39:89e96.
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15. Byrne RM, Taha AG, Avgerinos E, et al. Contemporary outcomes of endovascular interventions for acute limb ischemia. J Vasc Surg 2014;59:988e95. 16. Zhan F, Zhang H, Luo X, et al. Catheter-directed thrombolysis-assisted angioplasty for chronic lower limb ischemia. Ann Vasc Surg 2014;28:590e5. 17. Schneinert D, Scheinert S, Sax J, et al. Prevalence and clinical impact of stent fractures after femoropopliteal stenting. J Am Coll Cardiol 2005;45:312e5. 18. Adlakha S, Sheikh M, Wu J, et al. Stent fracture in the coronary and peripheral arteries. J Interv Cardiol 2010;23: 411e9. 19. Breukink SO, Vrouenraets BC, Davies GA, et al. Thrombolysis as initial treatment of peripheral native artery and bypass graft occlusion in a general community hospital. Ann Vasc Surg 2004;18:314e20. 20. Ebben HP, Nederhoed JH, Lely RJ, et al. Low-dose thrombolysis for thromboembolic lower extremity arterial occlusion is effective without major hemorrhagic complications. Eur J Vasc Endovasc Surg 2014;48:551e8. 21. Kashyap VK, Gilani R, Bena JF, et al. Endovascular therapy for acute limb ischemia. J Vasc Surg 2011;53:340e6.