Abstract
Left atrial appendage occlusion is an alternative therapy to oral anticoagulation for patients with non-valvular atrial fibrillation. Despite design refinements, device-related thrombus (DRT) remains a clinical concern, even with the latest WATCHMAN FLX Pro device (Boston Scientific, Marlborough, MA, USA). We report a case of surgical removal of the WATCHMAN FLX Pro device due to DRT. Despite appropriate antithrombotic therapy, a 77-year-old patient developed DRT leading to cardioembolic cerebral infarction. The thrombus was initially small and nonmobile but rapidly progressed over 45 days to a large, pedunculated, highly mobile thrombus with minimum attachment to the device, necessitating urgent surgical intervention. Subsequent hematologic evaluation revealed previously unrecognized essential thrombocythemia as the underlying prothrombotic condition. This case demonstrates that DRT can occur in patients with unrecognized prothrombotic conditions. Preprocedural thrombophilia screening should be considered in patients with suggestive clinical or laboratory findings, such as unexplained thrombocytosis, along with careful post implantation monitoring.
Learning objectives
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Preprocedural evaluation for underlying prothrombotic disorders, including essential thrombocythemia, should be considered in patients with suggestive clinical or laboratory findings, such as ischemic stroke despite adequate anticoagulation or unexplained thrombocytosis.
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Careful post-procedural monitoring is essential, as initially low-risk device-related thrombus may progress rapidly to high-risk forms requiring surgical intervention.
Keywords: Device-related thrombosis, Essential thrombocythemia, Left atrial appendage occlusion, WATCHMAN
Introduction
Left atrial appendage occlusion (LAAO) has emerged as an alternative to oral anticoagulation (OAC) in patients with non-valvular atrial fibrillation (AF) [1]. However, LAAO devices have the potential to elicit device-related thrombus (DRT) on the left atrial surface during endothelialization. The incidence of DRT has been reported at approximately 2–5% in both the WATCHMAN and WATCHMAN FLX (Boston Scientific, Marlborough, MA, USA) eras and is associated with increased risk of cardiovascular mortality and thromboembolic events [2], [3]. With progressive refinements of the WATCHMAN platform, device design has evolved to improve procedural safety and thromboresistance. The WATCHMAN FLX Pro, which incorporates a fluoropolymer coating on the fabric membrane to enhance thromboresistance, was introduced into clinical practice in Japan in May 2024, and no cerebral embolic events have been reported in postapproval studies to date.
Herein, we report, to the best of our knowledge, the first case of acute-phase DRT following implantation of WATCHMAN FLX Pro device, resulting in multiple cerebral infarctions.
Case report
A 77-year-old man with a history of persistent AF (CHADS2 score 3; CHA2DS2-VASc score 5) had experienced a cardioembolic stroke 12 years earlier, after which apixaban 10 mg/day was initiated. Two months before presentation, he developed a second cerebral infarction. Magnetic resonance imaging (MRI) findings at that time, together with the presence of persistent AF, led the clinical team to consider a possible cardioembolic mechanism. Based on hypertension, chronic kidney disease, prior stroke, and age ≥ 65 years, his HAS-BLED score was 4, indicating high bleeding risk with OAC. Given the occurrence of recurrent cerebral infarction despite anticoagulation along with the elevated bleeding risk, he was referred for WATCHMAN FLX Pro device implantation. Baseline blood testing showed the following: white blood cell count, 10,180/μL; red blood cell count, 358 × 104/μL; platelet count, 57.4 × 104/μL; serum creatinine, 2.2 mg/dL; estimated glomerular filtration rate, 21.5 mL/min/1.73 m2; and plasma B-type natriuretic peptide, 102 pg/mL. Laboratory testing for thrombophilia revealed no significant abnormalities, including protein C activity, protein S activity, antithrombin activity, von Willebrand factor, lupus anticoagulant, anticardiolipin antibodies, and antinuclear antibodies. Genetic testing for essential thrombocythemia (e.g. JAK2, CALR, or MPL mutations) was not performed prior to the procedure because a myeloproliferative disorder was not suspected at that time. Baseline transesophageal echocardiography (TEE) measurements of left atrial appendage (LAA) diameters revealed no exclusion criteria for device implantation. Preprocedural TEE showed that the LAA had a chicken-wing morphology; the maximum LAA ostial width was measured at 23.5 mm at 0°, and a 27-mm WATCHMAN FLX Pro device was implanted. The first attempt resulted in contact with the lateral wall and an incomplete deployment. The device was therefore recaptured and subsequently implanted successfully on the second deployment with 10–30% compression. The anchoring and sealing criteria were confirmed with imaging, an adequate tug test, and Doppler, which showed no peridevice leak. Following release, the location was again verified using TEE, which showed no complications. The total procedural time was 66 min. Intraprocedural anticoagulation was achieved with intravenous unfractionated heparin, maintaining an activated clotting time of 300–350 s. Protamine was not administered at the end of the procedure. The following day, the patient reported right-hand clumsiness and was diagnosed with multiple cerebral infarctions using MRI. The TEE revealed a DRT with a maximum diameter of 2.9 mm attached to the WATCHMAN device (Fig. 1). After the cerebral infarction, antithrombotic therapy was changed from apixaban to warfarin with concomitant aspirin. Considering the small size and nonmobile morphology of the thrombus, along with the patient's elevated bleeding risk, aspirin was discontinued, and he was discharged on warfarin monotherapy. Warfarin was adjusted to a target international normalized ratio (INR) of 2.0–3.0, which was consistently maintained from hospital discharge through the 45-day follow-up without subtherapeutic values. Intravenous unfractionated heparin was administered concomitantly until the INR reached the therapeutic range. However, at the 45-day follow-up TEE, the DRT had progressed to a pedunculated and highly mobile thrombus with a maximum diameter of 11 mm, attached to the device by a small pedicle (Fig. 2). The patient underwent urgent surgical removal of the WATCHMAN device and simultaneous LAA ligation (Fig. 3A). The retrieved device showed good endothelialization without apparent macroscopic evidence of mechanical or surface injury. Macroscopically, white tissue was adherent to the WATCHMAN device (Fig. 3B, C). Histological findings showed that this tissue comprised fibrin-rich, red thrombi with abundant platelets around artificial fibers (Fig. 3D). Gram staining showed no evidence of bacterial aggregation. CD61 immunostaining demonstrated abundant platelet deposition within the thrombus surrounding the artificial fibers. Because thrombus formation progressed despite adequate anticoagulation, further hematologic evaluation was performed. The platelet count exceeded 45.0 × 104/μL, and the JAK2V617F mutation was identified, leading to referral to hematology and a diagnosis of essential thrombocythemia (ET). Cytoreductive therapy and aspirin had not been initiated preprocedurally because ET was not suspected. After surgical left atrial appendage removal and ligation, antithrombotic therapy was resumed with edoxaban 15 mg/day plus aspirin 100 mg/day. Following confirmation of ET, hydroxyurea 500 mg/day was initiated.
Fig. 1.
Device-related thrombosis (DRT) appearance on transesophageal echocardiography (TEE) after cerebral infarction onset. TEE images at (A) 87° and (B) 126° after cerebral infarction onset show a DRT (arrows) with a maximum diameter of 2.9 mm attached to the WATCHMAN FLX Pro.
LA, left atrium.
Fig. 2.
Device-related thrombosis (DRT) appearance on transesophageal echocardiography (TEE) at the 45-day follow-up. On TEE images at (A) 0° and (B) 180° at the 45-day follow-up, DRT (arrows) worsened to a pedunculated thrombus with a maximum diameter of 11 mm.
LA, left atrium.
Fig. 3.
(A) Implanted WATCHMAN with a large mobile thrombus (arrows). (B, C) The extracted WATCHMAN device and the pathological appearance of the thrombus adhering to the device are shown. Macroscopically, white-toned tissue was observed adhering to the surface of the WATCHMAN device fabric. The pathological examination revealed it was primarily composed of red blood cells and fibrin, consistent with fresh thrombus. Gram staining showed no evidence of bacterial aggregates. (D) High-power histologic view of the boxed area in the panel. Histologic findings show fibrin, red thrombi, and platelet thrombi around artificial fibers (hematoxylin and eosin stain). Immunostaining against CD61 showing abundant platelets in thrombi around artificial fibers (inset).
Discussion
This report describes DRT formation after the implantation of WATCHMAN FLX Pro device that resulted in cerebral infarction. The WATCHMAN FLX Pro incorporates a new fluoropolymer coating, polyvinylidene fluoride-co-hexafluoropropylene, on the fabric membrane to enhance thromboresistance and promote rapid tissue ingrowth across the device surface. These features of the new coating have been demonstrated in preclinical animal experiments [4]. In postapproval studies, transient surface changes resembling DRT have been observed; these are thought to reflect a healing phase with endothelialization, and were not associated with clinical thromboembolic events. In contrast, the present case developed clinically significant DRT causing cerebral infarction. Histology showed platelet-rich thrombi, suggesting a possible association with ET as previously reported [5], although the pathological findings alone cannot establish causality.
Risk factors for DRT include AF rhythm at the time of procedure, female sex, older age, non-paroxysmal AF, increased CHA2DS2-VASc score, prior stroke or transient ischemic attack, and deep device implantation [2], [6]. The risk factors for this case included persistent AF and two cerebrovascular accidents. However, there were no issues with the device implantation site and no peri-device leak was observed. This patient had a history of acute ischemic stroke despite receiving OAC and was subsequently diagnosed with ET. The treatment plan for patients with ET is often based on thrombotic and bleeding risk scales [7]. Our patient was considered to have high risk of thrombosis because he was aged >60 years and had a history of stroke, along with JAK2V617F mutation. The treatment of high-risk diseases should include low-dose aspirin and hydroxyurea. It has been reported that the risk of embolism increases when ET and AF coexist [8]. However, the role of LAAO in patients with concomitant ET and AF remains unclear. When implanting an LAAO device, combining anticoagulant therapy with aspirin should be considered.
Recently, criteria have been proposed to classify DRT into high- or low-risk grades based on cardiac computed tomography or TEE images [6], [9]. Patients with high-risk DRT have a significantly higher incidence of stroke, systemic embolism, and cardiovascular death than those with low-risk or no DRT [10]. Moreover, the optimal antithrombotic regimen and duration after the diagnosis of DRT remain uncertain. This case presented as a low-risk DRT on TEE after cerebral infarction onset but progressed to a high-risk DRT at the 45-day follow-up, characterized by large size, pedunculated morphology, high mobility, and minimum attachment to the device. Urgent surgical removal of the WATCHMAN device with simultaneous LAA ligation was performed because the thrombus had grown rapidly over 45 days and posed a significant embolic risk unlikely to be controlled with continued anticoagulation alone. For patients with a history of acute ischemic stroke despite receiving OAC, preoperative evaluation of thrombogenic factors is essential; even low-risk DRT requires careful monitoring because it can progress rapidly. In this case, the platelet count was within the normal range before cerebral infarction 12 years earlier but subsequently became markedly elevated, exceeding 50 × 104/μL, and remained elevated during LAAO; however, it was not recognized as a potential indicator of underlying myeloproliferative disorder. MRI findings and persistent AF led to presumed cardioembolic stroke diagnosis and ET was not recognized before the procedure. Consequently, cytoreductive or antiplatelet therapy was not initiated, potentially delaying optimal thrombosis risk management. This case underscores that even when standard thrombophilia and autoimmune tests are normal, myeloproliferative disorders such as ET may remain undetected. Preprocedural thrombocytosis should prompt hematological evaluation, particularly in patients who experience recurrent thromboembolic events despite OAC, because ET may contribute to DRT formation and influence procedural outcomes.
Conclusion
To the best of our knowledge, this is the first reported case of surgical removal of the WATCHMAN FLX Pro due to DRT. Despite design improvements to reduce the thrombus risk, this case demonstrates that DRT can still occur in patients with undiagnosed thrombotic predispositions. Preoperative screening for thrombotic disorders may be crucial, especially in patients with recurrent stroke despite receiving anticoagulation therapy. Continuous monitoring and early surgical intervention may be necessary when DRT progresses or fails to respond to anticoagulation therapy.
Informed consent
The authors confirm that written consent for the submission and publication of this case report, including image(s) and associated text, has been obtained from the patient in accordance with COPE guidance.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
Akinori Wakamiya received honoraria for lectures from Biosense Webster, Medtronic, and Biotronik outside of the submitted work. Masatoshi Koga received honoraria from AstraZeneca, Bayer Yakuhin, Daiichi-Sankyo, Pfizer, and Otsuka Pharmaceutical and research grants from Daiichi Sankyo and Boston Scientific Japan. Kengo Kusano: Speaker honoria from Daiichi Sankyo and Medtronic Japan; and research grants from Medtronic Japan, Abbott Medical Japan, Boston Scientific Japan, GE Precision Healthcare LLC, Johnson & Johnson, and JSR.
Acknowledgments
We would like to thank Editage (www.editage.com) for English language editing.
Data availability
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.