Hyperacute thrombosis of a vertebral artery stent with a single missed dose of a P2Y12 inhibitor and poor stent wall apposition: illustrative case

Abstract

BACKGROUND

Iatrogenic vertebral artery injury during surgery can cause pseudoaneurysm, hemorrhage, thrombosis, ischemia, or death. Strategies to prevent cerebrovascular embolic complications include surgical ligation, endovascular stenting, and/or antiplatelet therapy.

OBSERVATIONS

A 73-year-old female with a known right vertebral artery occlusion underwent a C2–3 laminectomy, complicated by left vertebral artery injury and occlusion with subsequent posterior circulation ischemia. She underwent immediate angioplasty and stenting of the injured artery with undersized drug-eluting stents. Dual antiplatelet therapy of aspirin 81 mg daily and ticagrelor 90 mg twice daily was initiated. On two occasions, more than 6 months after stenting, holding a single ticagrelor dose led to in-stent thrombosis and embolic stroke within hours of the missed dose. Lifelong therapy with ticagrelor was favored over further procedural intervention.

LESSONS

It is recommended to prioritize optimal wall stent apposition with oversized stents in patients without collateral circulation. The risk of thromboembolism due to poorly apposed stents is very high, even in delayed (> 6 months) settings. Stent construct revision or bypass grafting may not be feasible or desirable options. For patients without wall apposition, endothelialization may not occur, necessitating lifelong P2Y12 inhibitor therapy to prevent recurrent thromboembolic events.

https://thejns.org/doi/10.3171/CASE24296

Iatrogenic injury is a rare complication of cervical spinal surgery, and it increases the risk for pseudoaneurysm, hemorrhage, thrombosis, cerebral ischemia, or death.¹ The most commonly injured vessel in cervical spinal surgery is the vertebral artery.² Asymmetry in the arterial diameter between the right and left vertebral arteries, vertebral artery agenesis, flow-limiting stenosis, or prior occlusion of the vertebral artery further increases the risk of iatrogenic complications.^3–6 Postoperative management of vertebral artery injury includes the prevention of cerebrovascular embolic complications.⁷

One approach is surgical ligation of the injured artery. However, ligation is dependent on adequate collateral circulation, and there are cases in which it may be compromised. In the context of compromised or absent collateral circulation, endovascular stenting and antiplatelet therapy are additional strategies to prevent thrombosis from acute vertebral artery injuries. Stents must be accurately sized to induce endothelialization and thereby reduce the long-term risk of in-stent thromboembolism formation.

We present a case of iatrogenic vertebral artery injury requiring stenting, describe the rationale for our approach to a delayed complication, and share practice considerations for acute and long-term management.

Illustrative Case

A 73-year-old female with a prior right vertebral artery occlusion and solitary fibrous tumors of the left neck elected to undergo resection with a left C2–3 laminectomy. The laminectomy was complicated by intraoperative left V3 vertebral artery injury and occlusion. Due to a prior contralateral vertebral artery occlusion, her collateral circulation was compromised. Thus, an aspiration thrombectomy was performed twice, resulting in successful recanalization. Postthrombectomy angiography showed progressive luminal narrowing. Due to a lack of contrast in the vessel itself, the vessel size was estimated by the treating neurointerventionalists to guide stent selection and sizing. Subsequently, two 3-mm × 12-mm drug-eluting XIENCE Skypoint (Abbott) stents were placed in the left V3 segment. However, the actual luminal diameter measured on anteroposterior and lateral views was 3.8–4.1 mm throughout the V3 segment. As a result, the stents were undersized relative to the vessel diameter. After the procedure, dual antiplatelet therapy of aspirin 81 mg daily and ticagrelor 90 mg twice daily was also initiated.

In the follow-up period, the patient made a good neurological recovery with some continued mild balance deficits and intermittent diplopia. Six months after stent placement, she underwent follow-up computed tomography angiography (CTA). CTA demonstrated no residual thrombus at the site of injury, and the left vertebral artery appeared to have a normal course and contour. Subsequently, she was instructed to discontinue the ticagrelor. Within 8 hours of holding a single dose of ticagrelor, she developed homonymous hemianopsia and was diagnosed with a posterior cerebral artery stroke. Magnetic resonance imaging (MRI) confirmed a new embolic left posterior cerebral artery infarct. The presumed etiology was an in-stent thromboembolic event, and ticagrelor was consequently restarted.

Ten months after stenting, digital subtraction angiography (DSA) demonstrated a healed left vertebral artery without evidence of injury. The patient was again instructed to discontinue ticagrelor. After holding a single evening dose of ticagrelor, she awoke the next morning with worsening vision, right-sided weakness, nausea, and vomiting. She was urgently brought to an outside hospital. Upon presentation, her National Institutes of Health Stroke Scale score was 16, and MRI demonstrated an occlusion of the basilar artery and a subocclusive thrombus within the vertebral artery stents (Fig. 1). She was not a candidate for tenecteplase. Upon transport to our center, emergency DSA demonstrated two undersized stents within the left V3 segment with a significant intrastent acute subocclusive thrombus along with spontaneous recanalization of the basilar artery (Fig. 2). Heparin drip and aspirin were continued to prevent distal migration of the subocclusive thrombus within the vertebral artery.

FIG. 1.

Diffusion-weighted MRI showing multiple acute posterior circulation infarcts involving the thalami (A), corpus callosum (B), occipital lobes (C), and cerebellar hemispheres (D), with additional subacute to early chronic bilateral occipital infarcts.

FIG. 2.

DSA, anteroposterior (left) and lateral (right) views, showing a subocclusive thrombus within the left vertebral artery stent (red arrows).

After 5 days, repeat DSA revealed improvement in the intrastent thrombus. There was no contrast opacification of the right posterior communicating artery and a diminutive left posterior communicating artery. The vertebral artery stents appeared malaligned and undersized, without evidence of wall apposition, and there was an endoleak around the entirety of the stent construct (Fig. 3). An attempt was made to cross the stents to revise the stent construct; however, due to the significant endoleak, this was not safely technically feasible. Since the patient had two thromboembolic events more than 6 months after the initial stent placement, both occurring after stopping ticagrelor, the patient was advised to continue dual antiplatelet therapy of aspirin 81 mg daily and ticagrelor 90 mg twice daily indefinitely.

FIG. 3.

Native unsubtracted anteroposterior (left) and lateral (right) angiography views showing misalignment (red arrows) of the two previously deployed XIENCE Skypoint balloon-mounted stents in the left vertebral artery.

Patient Informed Consent

The necessary patient informed consent was obtained in this study.

Discussion

Observations

We present the case of a woman whose vertebral artery stents, placed as a life-saving intervention to reperfuse her posterior cerebral circulation in the setting of an iatrogenic vertebral artery injury, were undersized. Despite the stent placement occurring more than 6 months earlier, she was unable to miss even a single dose of P2Y12 inhibitor therapy without experiencing multiple recurrent thromboembolic events due to poor stent wall apposition.

Adequate preparation for cervical spine surgeries includes an examination of the relevant vasculature, including the anatomical location of the vertebral arteries, as well as noting any anatomical variations on preoperative imaging. When performing surgical procedures near intracranial and extracranial vascular structures critical to cerebral perfusion, there is a risk of iatrogenic injury to these key structures. When iatrogenic vertebral artery injury occurs, prompt vascular imaging is necessary for guiding the appropriate emergency treatment course. In patients whose posterior circulation is dependent on a single vertebral artery, deconstruction of the vessel is not possible.

Reconstruction with stenting is feasible and generally safe. However, special attention must be paid to the vessel size, as an accurately sized stent must be used to fit the occluded vessel. Determining adequate sizing can be challenging, particularly in the setting of recent surgical manipulation, which can induce arterial vasospasm and limit evaluation of the vessel diameter. In this case, acute vascular injury resulted in diminutive opacification. Vasospasm can also be induced through mechanical irritation of the vessel wall during catheter or guidewire manipulation during thrombectomy. Prior to initial stent placement, our patient underwent two attempts at aspiration thrombectomy of the left vertebral artery, which could have induced persistent luminal narrowing. As a result, the vessel diameter and stent sizing estimated intraprocedurally could have been ultimately undersized relative to the true vessel diameter.

It might have been beneficial to perform CTA as a substitute for DSA in preparation for this surgery, as even CTA would allow for vessel size approximation in the event of an iatrogenic vascular injury. Alternatively, oversizing the stents in the setting of vasospasm may have proven helpful. The maximum postdilatation limit of the 3-mm XIENCE Skypoint stent is only 3.75 mm, while that of the 4-mm XIENCE Skypoint stent is 5.75 mm. Therefore, the larger stent might have been a better choice to allow for additional dilation to approximate the vessel wall during postplacement angioplasty. Undersized stents can result in the failure of endothelialization, resultant thromboembolic complications, and secondary neurological injury. The complications from undersized stents have devastating effects on patients’ long-term outcomes, as seen in our patient.

At the time of initial vessel recanalization and stenting, there are additional options to ensure proper vessel wall apposition. Intravascular ultrasound, three-dimensional rotational angiography, or optical coherence tomography can be used to evaluate apposition, expansion, and the presence of edge dissections. Stent deployment can be optimized at this point to ensure that there is no residual endoleak. The results from angiography visualizing stent placement may additionally serve as a guideline for antiplatelet duration.

In the present case, the patient held a dose of ticagrelor 10 months after stent placement, which resulted in a posterior circulation stroke 12 hours later. At 12 hours after ticagrelor discontinuation, the mean inhibition of platelet aggregation is still high (70%).⁸ However, due to undersizing, adequate endothelialization of the stent did not occur. After occlusion of the basilar artery, the nearly absent posterior communicating arteries failed to provide adequate collateral circulation. Overall, without collateral circulation, including convergent vertebral arterial supply, it is likely the patient was unable to tolerate the P2Y12 inhibitor discontinuation due to the persistent prothrombotic stimulus from the unhealed, undersized stent.

Given the thromboembolic complications from undersized, unhealed stents, there were several options for the patient to avoid lifelong dependence on ticagrelor. One option, which was attempted, was transluminal balloon angioplasty and additional stent placement. Endothelialization of new stents required 1) positioning within the lumen of the initial stents and 2) approximation to the endothelium, thereby avoiding endoleak. It was determined that the new stents would not have telescoped within the lumen of the initial stents. After careful evaluation of the risks, additional stent placement was ultimately deemed unsafe.

Another option considered was high-flow bypass around the vertebral artery occlusion using a radial artery graft or a saphenous vein graft. The bypass was specifically discussed with the patient; however, she declined this offer. Given the patient’s dependence on her sole vertebral artery, it would not have been well tolerated. In patients without collateral circulation, conservative measures must be taken to preserve the anatomical structures present. The procedure of choice in our case was a revision of the stent construct to allow for endothelialization. However, despite extensive effort, it was not feasible to reconstruct in our patient. Thus, lifelong ticagrelor was required.

Clinical judgment regarding the duration of ticagrelor can be challenging, given the increased incidence of bleeding events observed with prolonged therapy.⁹ However, to reduce all-cause mortality, the decision for lifelong therapy was favored for our patient. Especially given her strokes after only holding one dose of ticagrelor on two separate occasions more than 6 months from initial stent placement, there was no clinically appropriate time to discontinue.

Iatrogenic injury, undersized stents, and premature antiplatelet medication discontinuation all contributed to the recurrent strokes observed in our case. Furthermore, in the context of prior occlusion of the vertebral artery contralateral to the site of injury, our patient was likely more susceptible to cerebrovascular ischemia than a patient with codominant vertebral arteries and adequate, compensatory posterior collateral circulation, underscoring the importance of continued management to prevent future thromboembolic strokes.

Lessons

Iatrogenic vertebral artery injury increases the risk of cerebrovascular embolic complications. In patients whose posterior circulation is dependent on a single vertebral artery, deconstruction of the vessel with ligation is not possible. Reconstruction with stenting is feasible and generally safe; however, special attention must be paid to the vessel size, particularly in the setting of recent surgical manipulation, which may induce arterial vasospasm and limit the evaluation of the vessel diameter. Undersized stents and inadequate endothelialization in the extracranial vertebral artery can have devastating long-term outcomes, as the risk of thromboembolism is high, even in delayed time frames. Stent construct revision or bypass grafting is not always feasible and thus could necessitate lifelong P2Y12 inhibitor therapy.

Disclosures

Dr. Tonetti reported personal fees from Route 92 Medical, Scientia Vascular, and IRRAS outside the submitted work.

Author Contributions

Conception and design: Tonetti, Fang. Acquisition of data: Tonetti, Fang, Oliveira. Analysis and interpretation of data: Tonetti, Fang, Koneru, Oliveira, Santucci, Patel. Drafting the article: Tonetti, Fang, Oliveira, Santucci, Patel. Critically revising the article: Tonetti, Fang, Koneru, Oliveira, Santucci, Khalife, Shaikh. Reviewed submitted version of manuscript: Tonetti, Fang, Koneru, Santucci. Approved the final version of the manuscript on behalf of all authors: Tonetti. Administrative/technical/material support: Tonetti. Study supervision: Tonetti, Koneru.

Correspondence

Daniel A. Tonetti: Cooper University Health Care, Camden, NJ. tonetti-daniel@cooperhealth.edu.