Analysis of Rescue Strategies for Acute Thrombosis in Moyamoya Patients during STA-MCA Bypass Surgery and the Literature Review

doi:10.21203/rs.3.rs-3874877/v1

Background and objectives: Moyamoya disease is most improtantly treated with superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery, and the intraoperative patency of the reconstructive vessels is critical to the efficacy of the procedure. This study aimed to evaluate the efficacy of intra-arterially infused tirofiban for the treatment of acute thrombosis during STA-MCA bypass surgery and countermeasures for acute thrombosis.

Methods: We retrospectively reviewed the clinical and imaging data, surgical procedure, and follow-up outcomes of eight patients who developed acute thrombosis during the surgical procedure. We implemented the different thrombolytic methods to evaluate the optimal thrombosis management during the bypass surgery. After three months, we assessed neurological functions using the modified Rankin Scale (mRS) and conducted a literature review using PubMed.

Results: Eight patients (four male patients and four female patients) developed acute thrombosis during the bypass surgery. Of the eight patients, two underwent re-anastomosis after thrombus removal, three received local injections of tirofiban into the anastomosis or the branches of the superficial temporal artery, and three underwent superselective intra-arterial tirofiban infusion using a microcatheter. Thrombosis were resolved, and arteries were recanalized in all patients. The mRS score was 0 in all patients. No major ischemic or hemorrhagic complications occurred.

Conclusion: Our treatment methods were efficacious in the management of acute thrombosis. Intra-arterial tirofiban administration seems to be a simple and effective treatment option for acute thrombosis during STA-MCA bypass surgery.

Moyamoya disease

Bypass

Acute thrombosis

Tirofiban

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disorder with an unknown etiology. MMD is characterized by progressive stenosis at the terminal ends of the internal carotid arteries and abnormalities in the basal brain vessels^[1]. Surgical revascularization is the standard treatment for MMD^{[2, 3]}. Previous studies reported that direct bypass is more efficacious than surgical revascularization. Greater angiographic collateralization, superiority in restoring cerebrovascular reserve capacity (CVRC), increased symptomatic improvement, and longer stroke-free survival are the primary benefits^{[4, 5]}. However, acute thrombosis is a unique event in MMD^[6]. Similar to intracranial arterial thrombosis, an anastomotic thrombus, if not promptly resolved, may result in direct vascular reconstruction failure. Thrombus expansion could provoke occlusion of the recipient artery, triggering related ischemic complications such as stroke or neurological functional impairment. The success of bypass surgery depends on the degree of anastomotic patency^[7]. We implemented three distinctive approaches for patients with MMD who developed acute thrombosis during STA-MCA procedures. These encompassed re-anastomosis post-thrombus extraction, tirofiban injections through the anastomosis or the branches of the STA, and superselective intra-arterial tirofiban infusion using microcatheter.

Patients

We included eight patients who developed acute thrombosis during the STA-MCA bypass surgery between October 2020 and December 2023. Of the eight patients, two underwent re-anastomosis after thrombus removal, three received local tirofiban injection into the anastomosis or the branches of the STA, and three underwent superselective intra-arterial tirofiban infusion using microcatheter. All patients provided consent for the publication of their images. The Institutional Review Board of our hospital approved this study. The requirement for written informed consent was waived due to the retrospective nature of the study. Patients with an underlying disease associated with Moyamoya syndrome are included within the broader spectrum of "MMD" under the same treatment strategies, specifically referred to as patients with sporadic MMD^[8].

Assessment of acute thrombosis

The STA-MCA bypass surgery was performed by an experienced neurosurgeon. The donor artery was selected among the parietal and frontal branches. The anastomosis was performed end-to-side, secured with approximately 8–12 stitches of 10 − 0 prolene thread. Before securing the final two stitches, we ensured that no thrombosis and no sutures penetrated the wall of the vessel on the opposite side. The patency was verified post-bypass through ICG^{[9, 10]}. When occlusion occurred at the anastomotic site, we conducted an initial assessment outside the vessel to detect any thrombus formation. This involved assessing for muscle tension in the temporal region, examining the folding of the STA, and using local massages or gentle artery wall compression with micro-forceps alongside local papaverine injections. Despite these measures, patients with persistent occlusion were suspected to have developed an anastomotic thrombus, which was subsequently confirmed through suture removal or DSA imaging.

Countermeasures in acute thrombosis

The initial approach involves the direct extraction of thrombosis. Initially, the incision of the donor artery opens the anastomosis, allowing the thrombosis to be retrieved. After complete thrombosis removal, refining the rough tissue from the opening of the recipient artery and the temporal superficial artery creates a pristine surface. After that, a complete re-anastomosis was performed from start to finish.

After the removal of 1–2 stitches at the anastomosis site, the second approach involves injecting tirofiban into partially opened anastomoses and the STA branch, followed by thorough irrigation and subsequent reanastomosis.

The third approach stems from our previous experience. In our previous studies, we employed the second method for addressing anastomotic thrombosis, achieving successful thrombus removal. However, considering the potential risk of damaging the vascular endothelium by removing certain anastomotic sutures, we endeavored to preserve these sutures. Selective catheter angiography was performed through the femoral artery-stained STA with tirofiban introduced using a 5F catheter sheath. We proceeded with selective catheterization of the STA and administered approximately 2–4 mL of tirofiban using a 5F single-curved catheter. Following a waiting period of about 1 min, we reassessed the patency of the anastomosis using DSA and ICG.

A simple illustration of the three methods is shown in Fig. 1. All three methods involved a reassessment of anastomotic patency post-thrombus removal using ICG. We used tirofiban hydrochloride sodium Injection, available in a 100 mL formulation comprising 5 mg of tirofiban hydrochloride and 0.9 g of sodium chloride. Approximately 2–4 mL of the injection was administered per instance.

Clinical Characteristics

Table 1 shows the clinical characteristics of the eight patients. We included four male patients and four female patients in our series, aged 23–66 years. The initial symptoms in our patients included hemorrhagic stroke (n = 5) and ischemic stroke (n = 3).

Table 1 Patients clinical characteristics
Case no.	Sex/Age	Symptoms	Operated side	Bypass	Anastomosis patency	Method	mRs	3-6 months patency
1	Male/40	Hemorrhagic stroke	Left	STA-MCA	Yes	3	0	Yes
2	Female/66	Ischemic stroke	Right	STA-MCA	Yes	1	0	Yes
3	Female/23	Hemorrhagic stroke	Left	STA-MCA	Yes	2	0	Yes
4	Female/50	Hemorrhagic stroke	Right	STA-MCA	Yes	3	0	Yes
5	Male/59	Ischemic stroke	Left	STA-MCA	Yes	3	0	No
6	Female/36	Hemorrhagic stroke	Left	STA-MCA	Yes	2	0	No
7	Male/47	Hemorrhagic stroke	Right	STA-MCA	Yes	1	0	Yes
8	Male/60	Ischemic stroke	Right	STA-MCA	Yes	2	/	/

Method1:re-anastomosis after thrombus removal

Method2:local injection of tirofiban into the anastomosis or the branches of the STA

Method3:superselective intra-arterial tirofiban infusion via a microcatheter

Procedure and outcome of three cases of salvage occluded bypasses

Post-completion of the anastomosis during surgery, ICG revealed occlusion at the anastomotic site (Fig. 2A). Additionally, the Flow 800 device was utilized to assess the patency and hemodynamic parameters, confirming the anastomotic occlusion (Fig. 2B). We carefully removed approximately two stitches from the anastomotic site, revealing an internal thrombus (Fig. 2C). We incised the donor artery and carefully managed the internal thrombus using forceps, among other tools (Fig. 2D). After trimming the rough tissue at the opening of the recipient artery and STA and administering heparin, we re-performed the anastomosis. Subsequently, ICG distinctly demonstrated the restored patency of the anastomotic site (Fig. 2E). Employing Flow 800 for evaluating hemodynamic parameters at the anastomosis unveiled unhindered flow (Fig. 2F) ¹¹.

Following the completion of the anastomosis during surgery, ICG revealed occlusion at the anastomotic site (Fig. 3A).Infrared thermography were performed to acess anastomosis patency(Fig. 3B). Subsequently, we partially removed sutures from the anastomosis, confirmed the presence of a thrombus, and administered tirofiban using a syringe into the anastomosis (Fig. 3C). Subsequently, we temporarily occluded the proximal STA to direct the solution of tirofiban injected through its branches toward the anastomosis. We administered tirofiban to branches of the STA (Fig. 3D). We re-anastomosed the opened section and found that the anastomotic site was patent after ICG evaluation (Fig. 3E). Employing infrared thermography for evaluating anastomosis patency(Fig. 3F).

Due to the history of arterial aneurysms before the bypass, a re-evaluation using DSA during the procedure was necessary. Hence, we decided to perform the bypass surgery in the hybrid operating room. DSA was promptly utilized to ascertain the patency of the anastomosis after the bypass procedure. After selective catheterization of the STA, the anastomotic patency was verified. The yellow arrow on the DSA images revealed contrast medium stasis at the anastomosis, raising suspicion of a thrombus at the anastomosis (Fig. 4A). Subsequently, we injected approximately 2 mL of tirofiban using the catheter directed at the anastomosis site. Approximately 1 min later, we confirmed the patency of the anastomosis using DSA. The images displayed restored patency at the anastomosis (Fig. 4B). For further validation of the anastomotic patency, we employed ICG, which revealed patent anastomosis (Fig. 4C). Simultaneously, hemodynamic parameters at the anastomosis¹⁵ were evaluated using Flow 800, which revealed unobstructed flow (Fig. 4D).

Of the eight patients, two underwent re-anastomosis after thrombus removal, three received tirofiban injection through the anastomosis or STA branches, and three underwent superselective intra-arterial tirofiban infusion via a microcatheter. Thromboses were resolved, and arteries were recanalized in all patients. No hemorrhagic complications related to intra-arterial tirofiban infusion occurred.

Literature Review

Table 2 shows recent treatments for acute thrombosis encountered during STA-MCA procedures. However, researchers have seldom explored the application of tirofiban in STA-MCA bypass surgery. Our study was the first to administer tirofiban for acute thrombosis during STA-MCA procedures.

Table 2

Strategies for managing acute thrombosis during STA-MCA bypass surgery
Series (ref. no.)	Countermeasure in acute thrombosis
Kimura T et al., 2018^[13]	1.re-anastomosis after thrombus removal
Takeshi Mikami et al., 2019^[5]	1.local massage, local administration of papaverine hydrochloride and intravenous administration of heparin
	2.the local tight binding should be untied and resutured.
Winkler EA et al., 2021^[9]	local in situ fibrinolysis with r-TPA
Jin Woo Bae et al., 2021^[10]	heparin solution, re-anastomosis.
Buchanan IA, et al., 2021^[11]	abciximab
Takahashi JC et al., 2022^[12]	1.Systemic heparinization.、Nasogastric administration of aspirin.
	2.re-anastomosis after thrombus removal
Current research	1.re-anastomosis after thrombus removal
	2.local injection of tirofiban into the anastomosis or the branches of the STA
	3.superselective intra-arterial tirofiban infusion via a microcatheter

Surgical revascularization is the standard treatment for MMD ^{[2, 3]}. Establishment and maintenance of bypass patency are essential for the procedure to be successful and for patient morbidity and mortality to be reduced^[13]. Acute thrombus formation is a complication of direct revascularization surgery^[6]. We compared three distinct thrombus removal methods.

The initial approach involved re-anastomosis after thrombus removal. This method offers a clear view of thrombus color and location during surgery. Using forceps for extraction is more direct and efficient. Furthermore, the anastomosis was re-opened immediately in the case of non-thrombotic closures, such as those caused by suture-related constriction. Anastomotic sutures were partially dissected In the second method, and tirofiban was injected directly into the temporal artery branch and intra-anastomotic space after comprehensive lavage. This approach reduces surgical duration and, compared to direct thrombectomy, results in a lesser degree of injury.

As demonstrated in the literature review, most patients choose to have the suture removed at the anastomotic site.^{[6, 12, 14, 16]} Kimura T employed direct surgical embolectomy to rescue 12 patients who developed acute thrombi. Of the 12 patients, 11 had intraoperative reperfusion^[12]. Undoubtedly, the outcomes following suture removal at the anastomotic site have been exceptionally positive. However, the first and second approaches necessitate re-opening and re-anastomosing, which presents a challenge to the skills and experience of the surgeon and may expose the patients to the risk of recurrence of thrombosis due to similar endothelial damage or other pathological triggers. The third approach did not disrupt the sutures at the anastomosis. Therefore, compared to the first and second methods, it avoids potential vascular endothelial damage and demonstrates the efficacy of tirofiban in eliminating acute thrombosis. Moreover, this approach minimizes the procedural complexities at the anastomotic site and avoids vascular spasms after repeated manipulations and vessel narrowing following multiple sutures. However, vigilance is necessary for intraoperative and postoperative bleeding complications. In patients subjected to this method, we did not observe bleeding complications associated with tirofiban.

Our drug selection is primarily determined by the mechanisms underlying thrombus formation^[17]. The recruitment and activation of circulating platelets and the formation of an initial platelet plug (which is frequently observed intraoperatively in white) occur in response to initial tissue injury ^{[15, 17, 18]}.Tirofiban is a non-peptide platelet GP IIb/IIIa receptor antagonist, which prevents the aggregation of platelets at atherosclerotic sites by inhibiting the binding of fibrinogen to platelets.^[19] Hyun-Seung Kang et al. used microcatheter-guided selective intra-arterial tirofiban infusion to manage thrombi or emboli occurring during aneurysm procedures. Among 25 patients with aneurysms, 24 achieved successful revascularization without any associated bleeding complications^[20].

Rt-PA, a thrombolytic agent, degrades fibrin, thereby exerting its thrombolytic effect ^[21], hence its limited efficacy on white thrombosis. Due to the highly destructive nature of intracerebral hemorrhage (ICH) as a complication of rt-PA therapy^[22], we refrained from selecting rt-PA. Takeshi Mikami, Jin Woo Bae, Takahashi JC, et al. have employed heparin intraoperatively to manage acute thrombosis.^6,14,16 Additionally, we conducted studies involving the administration of heparin through anastomosis in patients. However, as the thrombus was unresolved, we refrained from using heparin in subsequent studies.

Due to the potential risk of intracranial bleeding associated with other medications, the suboptimal effects post-administration of heparin, and the recognized safety and efficacy of tirofiban when applied intracranially, we opted for tirofiban to manage acute thrombosis during STA-MCA procedures.

Limitations

The small number of patients who have undergone treatment with this technique and the rarity of other studies may lead to an insufficient evaluation of the effectiveness, limitations, and safety of this technique. Higher case series are essential to evaluate this technique further.

Our method of treatment was efficacious in acute thrombosis management. Intra-arterial administration of tirofiban seems to be a simple and effective treatment option for acute thrombosis during the STA-MCA bypass surgery.

Funding

This research was funded by grants from the Ningbo Science and Technology Innovation 2025 Major Project (2022Z134), Ningbo Health Branding Subject Fund (PPXK2018-04),and Ningbo Top Medical and Health Research Program (2022020304) to XG, Zhejiang Traditional Chinese Medicine Scientific Research Fund Project (2021ZA129), Medical Scientific Research Foundation of Zhejiang Province (2024KY1513)to JL, Zhejiang Traditional Medicine and Technology Program (2020ZB216), and Medical Scientific Research Foundation of Zhejiang Province (2020ky820) to WL.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Author Contributions

Conceptualization, X.G. and B.X.; methodology, J.W., T.Q. and X.L.; software, J.Y. and X.W.;

validation, J.L. and H.X.; formal analysis, Z.D.,X.W.; investigation, H.X. and W.L.; writing—original draft preparation,H.X. and H.N.; writing—review and editing, C.Z. and J.W.; supervision, X.G. and B.X.; project administration, X.G. and J.L.; funding acquisition, W.L. and J.L.All authors reviewed the manuscript and agreed to the published version of the manuscript.

Ethics approval

We declare that this study has been approved by The First Affiliated Hospital of Ningbo University (no. 187RS -01) and was performed in accordance with the ethical standards of the 1964 Declaration of Helsinki and its later amendments. This study is a retrospective study and has been submitted to the Ethics Committee for approval without informed consent.The consents to participate and publish are not applicable

Data availability statement

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

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No competing interests reported.

Analysis of Rescue Strategies for Acute Thrombosis in Moyamoya Patients during STA-MCA Bypass Surgery and the Literature Review

Status:

Version 1

Abstract

Figures

Introduction

Methods

Patients

Assessment of acute thrombosis

Countermeasures in acute thrombosis

Results

Clinical Characteristics

Procedure and outcome of three cases of salvage occluded bypasses

Literature Review

Discussion

Limitations

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1