Figura 1.

Figura 2.

Figura 3.

Figura 4.

Figura 5.

Clinical case

A 63-year-old female patient, hypertensive, dyslipidemic, with no known history of cardiovascular disease, was admitted to another institution due to an ischemic stroke with hemorrhagic transformation in the right cerebral hemisphere. A cranial CT angiography showed a severe obstruction in the right internal carotid artery (RICA), for which she was referred to our center for carotid angiography. Imaging showed an obstruction >80% of the RICA, without significant angiographic lesions of the left internal carotid artery (Figure 1), so a choice was made for scheduled endovascular treatment.

After using a 7-Fr introducer to achieve right radial access, a 260-cm 0.035” hydrophilic wire was introduced into the external carotid artery through a Simmons 1 catheter. That was then exchanged for a 7-Fr multipurpose guidewire catheter, which was then positioned in the right common carotid artery. A cerebral protection filter was advanced distally to the obstruction site and a 7 × 40-mm closed-cell carotid stent was subsequently implanted at the lesion site, with angiographic control and a successful outcome (Figure 2).

In the 48 hours following the procedure, the patient experienced headaches, vomiting, and postural instability, leading to hospitalization due to suspicion of a new neurovascular event. A cranial CT scan showed no evidence of new ischemic and/or hemorrhagic foci, and a new carotid angiography identified an image compatible with a carotid intrastent thrombus (Figure 3) with persistent blood flow.

Anticoagulation with unfractionated heparin (UFH) was chosen, with aPTT monitoring for seven days, followed by a control angiography showing partial improvement of carotid flow, but persistent thrombosis (Figure 4). A choice was made to perform a new stent-in-stent intervention, using the same technique and materials as in the first angioplasty. This new procedure yielded a successful outcome (Figure 5).

Discussion

The causes of this potentially catastrophic complication are usually subdivided into local and systemic causes. Systemic causes include inadequate antiplatelet therapy and a hypercoagulable state. Local causes include vascular dissection, severe plaque protrusion, early stent restenosis, stent underexpansion, and other technical problems such as stent kinking or twisting, long stenotic lesions, increased stent length, use of a second overlapping stent as rescue, and type of carotid stent.

Therapeutic options include thrombolysis, mechanical thrombectomy, thromboaspiration, combination with pharmacological therapy, surgery, and stent-in-stent angioplasty.

A systematic review of published ACST cases over the past two decades showed that clopidogrel resistance, defined as continued activity of platelet P2Y12 receptors even under adequate therapy, together with nonadherence to DAPT, remain one of the main causes of ACST. One of our diagnostic hypotheses was clopidogrel resistance, but it was not confirmed by laboratory tests, since aggregometry studies are not available in our center. In extrapolation with coronary disease, several studies have attempted to demonstrate the use of resistance-guided dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) (GRAVITAS – TRIGGER-PCI – ANTARTIC), without any net clinical benefit. Despite demonstrated lower antiplatelet resistance with prasugrel or ticagrelor due to reduced enzymatic polymorphisms, there is a clear contraindication in our patient with stroke4, 5.

This potentially serious complication can also be a result of local causes, among which we can mention vascular dissection, severe plaque protrusion, early stent restenosis, stent expansion, residual carotid kinking, stent twisting or coiling, long stenotic lesions, increased stent length, use of a second overlapping stent as rescue, and type of carotid stent. The control angiography performed in the patient after stent implantation shows residual kinking in the internal carotid artery (ICA), which could have caused hemodynamic alterations secondary to different changes in flow direction, thus precipitating ACST (Figure 2).

A hypercoagulable state is uncommon, but it has been described in postprocedural ACST and can occur within the first hours up to several days after the procedure. Regarding the choice between direct oral anticoagulants (DOACs) and coumarins, there is still a lack of solid and specific evidence in randomized clinical trials for ACST, so many decisions are based on observational studies, extrapolations from other clinical situations (atrial fibrillation, deep vein thrombosis [DVT]), and clinical experience. Since inherent or acquired thrombotic disorders (malignant or hematologic disease) could not be ruled out as one of the possible causes of this complication, we decided to consult with the Department of Hematology and, given the suspicion, we initiated acenocoumarol and not direct oral anticoagulants (DOACs), in association with DAPT (ASA–clopidogrel), continuing with outpatient follow-up and hematological studies. In any case, the decision must be individualized considering the patient’s bleeding profile, comorbidities, likelihood of adherence, and monitoring.

The assessment of bleeding risk in patients receiving triple antithrombotic therapy and its duration (oral anticoagulant plus DAPT) is critical, since this type of treatment is associated with a high risk of bleeding, especially gastrointestinal and cerebral bleeding. There are several clinical tools for bleeding risk assessment; we used the HAS-BLED scale (for anticoagulated patients with AF) and PRECISE-DAPT (useful for assessing the duration of antiplatelet therapy), with the limitation that they were not specifically designed for patients on triple antithrombotic therapy. There are also additional clinical factors associated with greater bleeding risk such as age >75, low body weight, anemia or hematologic disease, history of previous major bleeding, GI ulcers or concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs), poor internal normalized ratio (INR) control when on coumarins, and polypharmacy. Finally, we must mention the duration of triple antithrombotic therapy and the different strategies to mitigate bleeding risk, such as reducing the duration of triple therapy, discontinuing ASA as early as possible and continuing with an anticoagulant plus a P2Y12 inhibitor (such as clopidogrel), using low-dose DOACs when appropriate, and adding proton pump inhibitors for gastric protection. In summary, the indication, duration, and follow-up of triple therapy in patients undergoing carotid angioplasty complicated with ACST are not completely clear, and indications must be extrapolated from its use in other types of vascular disease (coronary and peripheral limb); however, its use should be as short as possible and prolonged only in justified cases.

The patient was discharged on triple antithrombotic therapy, evolving favorably, with subsequent medical and imaging follow-up after treatment. There were no new complications related to the endovascular procedure.

The management and outcomes of acute–subacute carotid stent thrombosis (ACST) after successful rescue remain largely unknown. No data have been published on the experience with the ideal strategy for revascularization after ACST, and no randomized trial has ever addressed the treatment of acute ischemic stroke caused by ACST.

Regardless of the treatment approach, ACST can lead to severe neurological consequences and death.

1. Moulakakis KG, Mylonas SN, Lazaris A, et al. Acute Carotid Stent Thrombosis: A Comprehensive Review. Vascular and Endovascular Surgery. 2016;50(7):511-521. doi:10.1177/1538574416665986.

2. Zhang J-B, Fan X-Q, Chen J, Liu P, Ye Z-D. Acute carotid stent thrombosis: A case report and literature review. World J Clin Cases [Internet]. 2022;10(26):9310–7. Available from: http://dx.doi.org/10.12998/wjcc.v10.i26.9310.

3. Coelho AP, Lobo M, Nogueira C, Gouveia R, Campos J, Augusto R, et al. Overview of evidence on risk factors and early management of acute carotid stent thrombosis during the last two decades. J Vasc Surg [Internet]. 2019;69(3):952–64. Disponible en: http://dx.doi.org/10.1016/j.jvs.2018.09.053

4. Price MJ, Angiolillo DJ, Teirstein PS, Lillie E, Manoukian SV, Berger PB, et al. Reactividad plaquetaria y resultados cardiovasculares después de una intervención coronaria percutánea: un análisis dependiente del tiempo del ensayo Gauging Responsiveness With a VerifyNow P2Y12 Assay: Impact on thrombosis and Safety, (GRAVITAS). Circulación [Internet]. 2011; 124(10):1132–7. Disponible en: http://dx.doi.org/10.1161/circulationaha.111.029165

5. Trenk , Stone GW, Gawaz M, Kastrati A, Angiolillo DJ, Müller U, et al. Un ensayo aleatorizado de prasugrel frente a clopidogrel en pacientes con alta reactividad plaquetaria en clopidogrel después de una intervención coronaria percutánea electiva con implante de stents liberadores de fármacos: resultados del estudio TRIGGER-PCI (Testing Platelet Reactivity In Patients Someto Elective Stent Placement on Clopidogrel to Guide Alternative Therapy With Prasugrel). J Am Coll Cardiol

Para descargar el PDF del artículo
Subacute carotid stent thrombosis

Haga click aquí