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1

Fregona, Virginia, GIULIA LURAGHI, Behrooz Fereidoonnezhad, et al. "Impact of thrombus composition on virtual thrombectomy procedures using human clot analogues mechanical data." Journal of the Mechanical Behavior of Biomedical Materials 163 (January 2, 2025): 106886. https://doi.org/10.1016/j.jmbbm.2025.106886.

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Endovascular thrombectomy (EVT) aims at restoring blood flow in case of acute ischemic stroke by removing the thrombus occluding a large cerebral artery. During the procedure with stent-retriever, the thrombus is captured within the device, which is then retrieved, subjecting the thrombus to several forces, potentially leading to its fragmentation. In silico studies, along with mechanical characterisation of thrombi, can enhance our understanding of the EVT, helping the development of new devices and interventional strategies. Our group previously validated a numerical approach to study EVT able to account for thrombus fragmentation. In this study, the same methodology was employed to explore the applicability of the chosen failure criterion to EVT simulations and the impact of thrombus composition on the outcome of the in silico procedure. For the first time, human clot analogues experimental data were applied to this methodology. Clot analogues of three different compositions were tested, and a material model incorporating failure was calibrated, followed by a verification analysis. Finally, the calibrated material model was used to perform EVT simulations, combining the three tested thrombus compositions with three different stent retriever models. The experimental tests confirmed a compression-tension asymmetry in the stress-strain curves, showing decreasing stiffness with increasing the red blood cell (RBC) content. Applying the resulting material models to EVT simulations demonstrated: (i) the dependency of the failure criterion on the thrombus mesh size, (ii) a greater tendency for RBC-rich thrombi to fragment, and (iii) increased difficulty in retrieving RBC-poor thrombi compared to RBC-rich thrombi.
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2

Ohara, Tomoyuki, Bijoy K. Menon, Fahad S. Al-Ajlan, et al. "Thrombus Migration and Fragmentation After Intravenous Alteplase Treatment." Stroke 52, no. 1 (2021): 203–12. http://dx.doi.org/10.1161/strokeaha.120.029292.

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Background and Purpose: There is interest in what happens over time to the thrombus after intravenous alteplase. We study the effect of alteplase on thrombus structure and its impact on clinical outcome in patients with acute stroke. Methods: Intravenous alteplase treated stroke patients with intracranial internal carotid artery or middle cerebral artery occlusion identified on baseline computed tomography angiography and with follow-up vascular imaging (computed tomography angiography or first run of angiography before endovascular therapy) were enrolled from INTERRSeCT study (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography). Thrombus movement after intravenous alteplase was classified into complete recanalization, thrombus migration, thrombus fragmentation, and no change. Thrombus migration was diagnosed when occlusion site moved distally and graded according to degrees of thrombus movement (grade 0–3). Thrombus fragmentation was diagnosed when a new distal occlusion in addition to the primary occlusion was identified on follow-up imaging. The association between thrombus movement and clinical outcome was also evaluated. Results: Among 427 patients in this study, thrombus movement was seen in 54% with a median time of 123 minutes from alteplase administration to follow-up imaging, and sub-classified as marked (thrombus migration grade 2–3 + complete recanalization; 27%) and mild to moderate thrombus movement (thrombus fragmentation + thrombus migration grade 0–1; 27%). In patients with proximal M1/internal carotid artery occlusion, marked thrombus movement was associated with a higher rate of good outcome (90-day modified Rankin Scale, 0–2) compared with mild to moderate movement (52% versus 27%; adjusted odds ratio, 5.64 [95% CI, 1.72–20.10]). No difference was seen in outcomes between mild to moderate thrombus movement and no change. In M1 distal/M2 occlusion, marked thrombus movement was associated with improved 90-day good outcome compared with no change (70% versus 56%; adjusted odds ratio, 2.54 [95% CI, 1.21–5.51]). Conclusions: Early thrombus movement is common after intravenous alteplase. Marked thrombus migration leads to good clinical outcomes. Thrombus dynamics over time should be further evaluated in clinical trials of acute reperfusion therapy.
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3

Li, Zongdong, Michael A. Nardi, Yong-Sheng Li, et al. "C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke." Blood 113, no. 24 (2009): 6051–60. http://dx.doi.org/10.1182/blood-2008-07-170571.

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Abstract Anti-platelet integrin GPIIIa49-66 antibody (Ab) induces complement-independent platelet oxidative fragmentation and death by generation of platelet peroxide following NADPH oxidase activation. A C-terminal 385–amino acid fragment of ADAMTS-18 (a disintegrin metalloproteinase with thrombospondin motifs produced in endothelial cells) induces oxidative platelet fragmentation in an identical kinetic fashion as anti–GPIIIa49-66 Ab. Endothelial cell ADAMTS-18 secretion is enhanced by thrombin and activated by thrombin cleavage to fragment platelets. Platelet aggregates produced ex vivo with ADP or collagen and fibrinogen are destroyed by the C-terminal ADAMTS-18 fragment. Anti–ADAMTS-18 Ab shortens the tail vein bleeding time. The C-terminal fragment protects against FeCI3-induced carotid artery thrombosis as well as cerebral infarction in a postischemic stroke model. Thus, a new mechanism is proposed for platelet thrombus clearance, via platelet oxidative fragmentation induced by thrombin cleavage of ADAMTS-18.
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4

Maegerlein, Christian, Sebastian Mönch, Tobias Boeckh-Behrens, et al. "PROTECT: PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy – evaluation of a double embolic protection approach in endovascular stroke treatment." Journal of NeuroInterventional Surgery 10, no. 8 (2017): 751–55. http://dx.doi.org/10.1136/neurintsurg-2017-013558.

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PurposeStent retriever-based mechanical thrombectomy (MT) for emergent large vessel occlusions (ELVO) is often complicated by thrombus fragmentation causing distal embolization and embolization to new vascular territories. Well-established embolic protection approaches include proximal flow arrest and distal aspiration techniques during stent retriever maneuvers. Aiming at the reduction of thrombus fragmentation during MT we evaluated a technical approach combining proximal balloon occlusion together with direct thrombus aspiration during MT: the PROTECT technique.MethodsWe performed a case-control study comparing the PROTECT technique with sole distal aspiration during MT regarding technical and procedural parameters, n=200 patients with ELVO of either the terminus of the internal carotid artery or the proximal middle artery were included.ResultsPROTECT resulted in a shorter procedure time (29 vs 40 min; P=0.002), in a higher rate of successful recanalizations (100% vs 78%; P=0.001) and a higher rate of complete reperfusions (70% vs 39%; P<0.001) compared with sole distal aspiration during MT.ConclusionThe PROTECT technique is a promising new approach to significantly reduce thrombus fragmentation and, hence distal embolization during MT. This safe and efficient technique needs to be validated in larger trials to confirm our results.
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5

Aludin, Schekeb, Philipp Jost Schäfer, Christoph Borzikowsky, et al. "Experimental Evaluation of the Effectiveness of Aspiration-Based Techniques to Treat Different Types of Acute Thromboembolic Occlusions in the Femoropopliteal Vascular System Using an In Vitro Flow Model." CardioVascular and Interventional Radiology 45, no. 2 (2021): 228–35. http://dx.doi.org/10.1007/s00270-021-03024-8.

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Abstract Purpose In this in vitro study, the effectiveness and safety of four aspiration-based techniques for thrombectomy are evaluated for three types of thrombi in a flow model simulating the femoropopliteal segment. Material and Methods Red, white, and mixed thrombi were produced in a standardized manner and used to simulate occlusion of a superficial femoral artery using a pulsatile flow model. Four techniques were compared: aspiration alone, aspiration + stent retriever, exposing thrombus to laser by an excimer laser system and a laser catheter + aspiration, and aspiration + mechanical fragmentation by a separator. Rate of first-pass recanalization, embolic events, and number of embolized fragments > 1 mm were compared. Results Aspiration alone, stent retriever, laser, and separator differed in rates of first-pass recanalization (53.3%; 86.6%; 20%; and 100%) and embolic events (40%; 93.3%; 73.3%; and 60%). Number of embolized fragments was lowest with aspiration and higher with separator, laser, and stent retriever. Rates of first-pass-recanalization (75%; 75%; and 45%) and embolic events (65%; 60%; and 75%) differed for red, white, and mixed thrombi. The mixed thrombus caused the highest number of embolized fragments, which was particularly high using the stent retriever. Conclusion Additional use of mechanical techniques significantly enhances the effectiveness of thrombectomy but simultaneously provokes more embolism. Laser seems to negatively alter the structure of a thrombus and thus diminishes the effectiveness, while provoking embolism. All techniques had lowest effectiveness, but highest embolism with the mixed thrombus. This was particularly striking when a stent retriever was used with the mixed thrombus.
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6

Kaesmacher, J., T. Boeckh-Behrens, S. Simon, et al. "Risk of Thrombus Fragmentation during Endovascular Stroke Treatment." American Journal of Neuroradiology 38, no. 5 (2017): 991–98. http://dx.doi.org/10.3174/ajnr.a5105.

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7

Price, G., and E. C. Martin. "A FLEXIBLE ULTRASONIC GUIDE WIRE FOR THROMBUS FRAGMENTATION." Investigative Radiology 24, no. 12 (1989): S125. http://dx.doi.org/10.1097/00004424-198912000-00209.

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8

Cordella, Alessia, Pascaline Pey, Nikolina Linta, et al. "Use of Contrast-Enhanced Ultrasonography for the Characterization of Tumor Thrombi in Seven Dogs." Animals 10, no. 9 (2020): 1613. http://dx.doi.org/10.3390/ani10091613.

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Tumors of adrenal and thyroid glands have been associated with vascular invasions—so-called tumor thrombi, both in humans and dogs. The detection and characterization of venous thrombi is an important diagnostic step in patients with primary tumors for both surgical planning and prognosis. The aim of this study was to describe the use of contrast-enhanced ultrasonography (CEUS) for the characterization of tumor thrombi. Dogs with tumor thrombus who underwent bi-dimensional ultrasound (B-mode US) and CEUS were included. Seven dogs were enrolled in this retrospective case series. On B-mode US, all thrombi were visualized, and vascular distension and thrombus-tumor continuity were seen in three and two cases, respectively. On color Doppler examination, all thrombi were identified, seemed non-occlusive and only two presented vascularity. On CEUS, arterial-phase enhancement and washout in the venous phase were observed in all cases. Non-enhancing areas were identified in the tumor thrombi most likely representing non-vascularized tissue that could potentially be embolized in the lungs after fragmentation of the tumor thrombi. On the basis of these preliminary study, CEUS appeared to be useful for the characterization of malignant intravascular invasion.
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9

Worku, Berhane, Kyle Blake, Iosif Gulkarov, Akhilesh Sista, and Arash Salemi. "Percutaneous Removal of Filter-Induced Iliocaval Thrombus Using the AngioVac Device." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 10, no. 3 (2015): 212–14. http://dx.doi.org/10.1097/imi.0000000000000156.

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Most percutaneous mechanical thrombectomy devices entail thrombolysis and/or thrombus fragmentation followed by subsequent aspiration, with the associated risks of bleeding and embolization. We describe the use of the AngioVac system (Angiodynamics, Latham, NY USA) for extraction of extensive iliocaval thrombus associated with an inferior vena cava filter followed by percutaneous inferior vena cava filter extraction in a patient with an absolute contraindication to thrombolysis. The AngioVac may be considered in this scenario as it does not require thrombolytics and can remove whole thrombus, thus overcoming some of the limitations of percutaneous mechanical thrombectomy devices in the setting of subacute and early chronic thrombus.
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10

Kutlu, Ramazan, Alpay Alkan, Ayhan Kocak, and Kaya Sarac. "Thrombolysis and Mechanical Fragmentation to Treat Massive Pulmonary Embolism in a Patient with an Anterior Communicating Artery Aneurysm." Journal of Endovascular Therapy 10, no. 2 (2003): 332–35. http://dx.doi.org/10.1177/152660280301000225.

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Purpose: To describe successful management of massive pulmonary embolism suffered by a patient with an unsecured intracranial aneurysm. Case Report: An anterior communicating artery aneurysm was found 10 days after a 50-year-old woman was admitted to the intensive care unit with subarachnoid hemorrhage. The patient developed severe acute dyspnea before planned surgery; imaging demonstrated thrombus in the right and left pulmonary arteries. Heparin was contraindicated, so an emergent coil embolization procedure was undertaken. In the same session, recombinant tissue plasminogen activator was administered directly into the thrombus. After 2 hours of thrombolysis and intermittent mechanical fragmentation, lung perfusion improved, and the patient's symptoms abated. Conclusions: Mechanical fragmentation together with fibrinolytic agent administration is a safe and effective treatment for pulmonary embolism after securing cerebral aneurysms.
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11

Zhang, Wei, Yong-Sheng Li, Michael A. Nardi, et al. "Dissolution of arterial platelet thrombi in vivo with a bifunctional platelet GPIIIa49-66 ligand which specifically targets the platelet thrombus." Blood 116, no. 13 (2010): 2336–44. http://dx.doi.org/10.1182/blood-2010-01-264358.

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Abstract Patients with HIV-1 immune-related thrombocytopenia have a unique antibody (Ab) against integrin GPIIIa49-66 capable of inducing oxidative platelet fragmentation via Ab activation of platelet nicotinamide adenine dinucleotide phosphate oxidase and 12-lipoxygenase releasing reactive oxygen species. Using a phage display single-chain antibody (scFv) library, we developed a novel human monoclonal scFv Ab against GPIIIa49-66 (named A11) capable of inducing fragmentation of activated platelets. In this study, we investigated the in vivo use of A11. We show that A11 does not induce significant thrombocytopenia or inhibit platelet function. A11 can prevent the cessation of carotid artery flow produced by induced artery injury and dissolve the induced thrombus 2 hours after cessation of blood flow. In addition, A11 can prevent, as well as ameliorate, murine middle cerebral artery stroke, without thrombocytopenia or brain hemorrhage. To further optimize the antithrombotic activity of A11, we produced a bifunctional A11-plasminogen first kringle agent (SLK), which homes to newly deposited fibrin strands within and surrounding the platelet thrombus, reducing effects on nonactivated circulating platelets. Indeed, SLK is able to completely reopen occluded carotid vessels 4 hours after cessation of blood flow, whereas A11 had no effect at 4 hours. Thus, a new antithrombotic agent was developed for platelet thrombus clearance.
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12

Gao, H., G. Y. Huang, L. L. Ma, and L. X. Wang. "Combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary embolism." Internal Medicine Journal 41, no. 9 (2011): 687–91. http://dx.doi.org/10.1111/j.1445-5994.2010.02205.x.

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13

Yi, Ho Jun, Jae Hoon Sung, and Dong Hoon Lee. "Bridging Intravenous Thrombolysis Before Mechanical Thrombectomy for Large Artery Occlusion May be Detrimental with Thrombus Fragmentation." Current Neurovascular Research 17, no. 1 (2020): 18–26. http://dx.doi.org/10.2174/1567202617666191223143831.

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Objective: We investigated whether intravenous thrombolysis (IVT) affected the outcomes and complications of mechanical thrombectomy (MT), specifically focusing on thrombus fragmentation. Methods: The patients who underwent MT for large artery occlusion (LAO) were classified into two groups: MT with prior IVT (MT+IVT) group and MT without prior IVT (MT-IVT) group. The clinical outcome, successful recanalization with other radiological outcomes, and complications were compared, between two groups. Subgroup analysis was also performed for patients with simultaneous application of stent retriever and aspiration. Results: There were no significant differences in clinical outcome and successful recanalization rate, between both groups. However, the ratio of pre- to peri-procedural thrombus fragmentation was significantly higher in the MT+IVT group (14.6% and 16.2%, respectively; P=0.004) compared to the MT-IVT group (5.1% and 6.8%, respectively; P=0.008). The MT+IVT group required more second stent retriever (16.2%), more stent passages (median value = 2), and more occurrence of distal emboli (3.9%) than the MT-IVT group (7.9%, median value = 1, and 8.1%, respectively) (P=0.004, 0.008 and 0.018, respectively). In subgroup analysis, the results were similar to those of the entire patients. Conclusion: Thrombus fragmentation of IVT with t-PA before MT resulted in an increased need for additional rescue therapies, and it could induce more distal emboli. The use of IVT prior to MT does not affect the clinical outcome and successful recanalization, compared with MT without prior IVT. Therefore, we need to reconsider the need for IVT before MT.
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Dovern, Elisabeth, Marlene R. Mende, Niels J. Elderson, Eelko Ronner, and Steven J. Sleeswijk Visser. "Successful treatment of massive pulmonary embolism using a pulmonary artery catheter during prolonged normothermic cardiopulmonary resuscitation." Acute Medicine Journal 13, no. 3 (2014): 118–20. http://dx.doi.org/10.52964/amja.0359.

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Massive pulmonary embolism has a high mortality rate. Standard treatment includes systemic thrombolysis. If this fails, surgical embolectomy or a percutaneous catheter-guided approach is advised in current guidelines. However, these treatment options might not be available in many non-tertiary care hospitals. We describe a case of a 25-year old woman with cardiac arrest from massive pulmonary embolism. She was treated with thrombus fragmentation using a pulmonary artery catheter and intra-pulmonary thrombolysis after failure of systemic thrombolysis along with 90 minutes of cardiopulmonary resuscitation (CPR). Neurological recovery was excellent and pulmonary pressure was normalized after one month. Besides catheter guided thrombus fragmentation and thrombolysis, we contribute the successful outcome to a combination of ultrasound-guided therapy, capnography-guided CPR, and “crew resource management” principles. Our case illustrates that a pulmonary artery catheter can be used successfully in a non-tertiary setting, to perform a percutaneous procedure during CPR and that full neurological recovery is possible after 90 minutes of CPR.
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Tennuci, Christopher, Gillian Pearce, Julian Wong, et al. "Comparison of the Effectiveness of Three Methods of Recanalization in a Model of the Middle Cerebral Artery: Thrombus Aspiration via a 4F Catheter, Thrombus Aspiration via the GP Thromboaspiration Device, and Mechanical Thrombectomy Using the Solitaire Thrombectomy Device." Stroke Research and Treatment 2011 (2011): 1–6. http://dx.doi.org/10.4061/2011/186424.

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Introduction. This paper compares different approaches to recanalization in a model of the middle cerebral artery (MCA).Methods. An occlusive thrombus (lamb's blood) was introduced into the MCA of a model of the cerebral circulation perfused with Hartmann's solution (80 pulsations/min, mean pressure 90 mm Hg). Three methods of clot retrieval were tested: thrombus aspiration via a 4F catheter (n=26), thrombus aspiration via the GP thrombus aspiration device (GPTAD) (n=30), and mechanical thrombectomy via the Solitaire Device (n=30).Results. Recanalization rate was similar for all 3 approaches (62%, 77%, and 85%). Time to recanalization was faster with aspiration devices (41 SD 42 s for 4F and 61 SD 21 s for GPTAD) than with the Solitaire (197 SD 64 sP<.05Kruksal-Wallis). Clot fragmentation was the same in the Solitaire (23%) and the GPTAD (23%), but higher with the 4F (53%,P<.05).Conclusion. In this model, thrombus aspiration was faster than mechanical thrombectomy, and similarly effective at recanalization. These results should be confirmedin vivo.
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Maegerlein, Christian, Sascha Prothmann, Kristin Elizabeth Lucia, Claus Zimmer, Benjamin Friedrich, and Johannes Kaesmacher. "Intraprocedural Thrombus Fragmentation During Interventional Stroke Treatment: A Comparison of Direct Thrombus Aspiration and Stent Retriever Thrombectomy." CardioVascular and Interventional Radiology 40, no. 7 (2017): 987–93. http://dx.doi.org/10.1007/s00270-017-1614-4.

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17

Alexandrov, Alexander, Dobrin Vassilev, Hristo F. Mateev, Iliana Petrova, and Elina Trendafilova. "TCT-510 Treating Patients With Massive Pulmonary Embolism By Local Fibrinolysis, Rotational Thrombus Fragmentation And Thrombus Aspiration." Journal of the American College of Cardiology 64, no. 11 (2014): B150. http://dx.doi.org/10.1016/j.jacc.2014.07.567.

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18

Noverike, Nikhen, Novi Kurnianingsih, Ardian Rizal, and Anna Fuji Rahimah. "Successful Management in Unprovoked Upper Extremity Deep Vein Thrombosis: Case Report." Heart Science Journal 5, no. 3 (2024): 76–79. http://dx.doi.org/10.21776/ub/hsj.2024.005.03.14.

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Background: One to four percent of all cases of deep vein thrombosis (DVT) occur in the upper extremities. Effective thrombolysis for upper extremity deep vein thrombosis (UEDVT) can be achieved with a combination of vascular interventions such as angioplasty, which is continued with catheter-directed thrombolysis (CDT) and anticoagulant therapy. Case Illustration: We presented the case of a 40-year-old man who developed sudden pain and swelling in his right upper extremity. The thrombus was located in the right subclavian vein, confirmed by duplex ultrasonography. Laboratory results were normal. The patient was diagnosed with unprovoked UEDVT. He underwent venography, which showed an acute-on-chronic lesion at the right subclavian vein. We decided to use double access, tried to inflate the balloon to fragment the thrombus, several times of thrombo-suction, and then continued with Catheter-directed thrombolysis (CDT) using Alteplase. The patient continued oral anticoagulant therapy with Rivaroxaban. After 6 months of follow-up, there wasn’t any complaint. Evaluation of Duplex ultrasonography showed normal results without any recurrent thrombus Conclusion: This case revealed how to treat acute-on-chronic lesions of unprovoked UEDVT with a comprehensive management method not only with balloon fragmentation and CDT but also anticoagulant therapy and showed a good outcome and no signs of bleeding complication. Keyword: Anticoagulant and Thrombolysis, Catheter-directed Thrombolysis, Unprovoked UEDVT; Upper Extermity Deep Vein Thrombosis.
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Noverike, Nikhen, Novi Kurnianingsih, Ardian Rizal, and Anna Fuji Rahimah. "Successful Management in Unprovoked Upper Extremity Deep Vein Thrombosis: Case Report." Heart Science Journal 5, no. 3 (2024): 76–79. http://dx.doi.org/10.21776/ub.hsj.2024.005.03.14.

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Background: One to four percent of all cases of deep vein thrombosis (DVT) occur in the upper extremities. Effective thrombolysis for upper extremity deep vein thrombosis (UEDVT) can be achieved with a combination of vascular interventions such as angioplasty, which is continued with catheter-directed thrombolysis (CDT) and anticoagulant therapy. Case Illustration: We presented the case of a 40-year-old man who developed sudden pain and swelling in his right upper extremity. The thrombus was located in the right subclavian vein, confirmed by duplex ultrasonography. Laboratory results were normal. The patient was diagnosed with unprovoked UEDVT. He underwent venography, which showed an acute-on-chronic lesion at the right subclavian vein. We decided to use double access, tried to inflate the balloon to fragment the thrombus, several times of thrombo-suction, and then continued with Catheter-directed thrombolysis (CDT) using Alteplase. The patient continued oral anticoagulant therapy with Rivaroxaban. After 6 months of follow-up, there wasn’t any complaint. Evaluation of Duplex ultrasonography showed normal results without any recurrent thrombus Conclusion: This case revealed how to treat acute-on-chronic lesions of unprovoked UEDVT with a comprehensive management method not only with balloon fragmentation and CDT but also anticoagulant therapy and showed a good outcome and no signs of bleeding complication. Keyword: Anticoagulant and Thrombolysis, Catheter-directed Thrombolysis, Unprovoked UEDVT, Upper Extermity Deep Vein Thrombosis.
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Worku, Berhane, Arash Salemi, Marcus D. D'Ayala, Robert F. Tranbaugh, Leonard N. Girardi, and Iosif M. Gulkarov. "The Angiovac Device: Understanding the Failures on the Road to Success." Innovations: Technology and Techniques in Cardiothoracic and Vascular Surgery 11, no. 6 (2016): 430–33. http://dx.doi.org/10.1097/imi.0000000000000310.

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Objective Current percutaneous thromboembolectomy techniques may obviate surgical intervention in high-risk patients with iliocaval thrombus or thrombus of the right side of the heart, but typically require thrombus fragmentation and thrombolysis with associated bleeding and thromboembolic complications. The AngioVac (Angiodynamics, Latham, NY USA) device uses a percutaneous venovenous bypass circuit to aspirate intact thrombus. A review of the literature was performed with regard to the AngioVac device to determine the factors correlating with successful thrombus extraction. Methods A literature search was performed with regard to use of the AngioVac device using the PubMed database. A meta-analysis was not performed given the small size and lack of statistical analysis of the individual reports included. Results Twenty-three reports describing 57 procedures in 56 patients were analyzed. Indications for thrombectomy included iliocaval thrombus in 53% (30), thrombus of the right side of the heart, in 49% (28), pulmonary embolus in 14% (8), and upper extremity venous/Glenn shunt thrombosis in 7% (4). The complete success rate, defined as removal of all thrombus, was 75% (43), with an 11% (6) partial success rate. In 14% (8) of cases, minimal or no thrombus was retrieved. When analyzed by indication, iliocaval thrombus and thrombus of the right side of the heart demonstrated 87% (26) and 82% (23) complete success rates, respectively. Pulmonary embolus demonstrated a significantly lower success rate at 12.5% [1; (P < .001)]. Complications occurred in 12% (7), including six hematomas and one retroperitoneal bleed. Conclusions The AngioVac device offers an excellent alternative to surgical thrombectomy for patients presenting with iliocaval or intracardiac thrombus, with success rates of more than 80%, although it seems that pulmonary emboli are less amenable. Appropriate patient selection can lead to improved outcomes. Larger numbers are needed to make more definite conclusions.
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Rosenov, Alexander, Axel Haine, Laura Naëmi Walti, Debora Capiaghi, Marc Schindewolf, and Iris Baumgartner. "Upside-down positioning of a peri-interventional cava filter during endovascular thrombectomy of a septic superior vena cava thrombosis." SAGE Open Medical Case Reports 10 (January 2022): 2050313X2211173. http://dx.doi.org/10.1177/2050313x221117333.

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A 43-year-old male patient with advanced colon carcinoma presented with disseminated staphylococcus aureus bacteremia and central venous catheter associated septic thrombosis of the superior vena cava. Despite appropriate antimicrobial therapy and surgical debridement of distant foci, bacteremia persisted, so an endovascular thrombectomy was performed. Contrary to the usual application, the Capturex® peri-interventional cava filter was positioned upside down, in the direction of the blood flow, in the superior vena cava to prevent septic embolism during mechanical thrombectomy. The wall-adherent septic thrombus was mechanically detached using a RAT fragmentation basket® followed by Aspirex® rotational thrombectomy. Final phlebography showed complete thrombus removal. Small thrombus fragments could be demonstrated in the filter after retrieval. The adapted technique of a reverse positioning of the Capturex® filter in the superior vena cava seems feasible and effective.
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Li, Zongdong, Michael Nardi, Ruimin Pan, Herman Yee, and Simon Karpatkin. "A New Mechanism of Platelet Activation and Oxidative Death Induced by ADAMTS-18 and Regulating Bleeding Time." Blood 110, no. 11 (2007): 133. http://dx.doi.org/10.1182/blood.v110.11.133.133.

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Abstract Anti-platelet integrin GPIIIa49-66 Ab obtained from HIV-ITP patients (or raised in rabbits) induces complement-independent platelet oxidative fragmentation and death by activating platelet 12-lipoxygenase (generation of 12(S)-HETE) and NADPH oxidase (JCI, 113:973, 2004). Platelet oxidative fragmentation is measured by flow cytometry of generated microparticles as well as intracellular DCFH oxidation. We now report that oxidative fragmentation in human platelets is preceded by Ca++ flux and P-selectin activation, n=6. However, the activation mechanism is different from classic platelet activation in that it is not inhibited by PGE1 or dibutryl cyclic AMP and is operative with Gαq−/− mouse platelets, whereas under these conditions, thrombin-induced platelet activation is completely inhibited, n=5–6. We chose to identify putative physiologic ligands that behave similarly to the GPIIIa49-66 Ab, and are therefore capable of regulating platelet reactive oxygen species (ROS) as well as arterial thrombus formation. The GPIIIa49-66 platelet peptide was used as bait to screen a 7-mer peptide phage display library. A peptide was found with 70% homology at the C-terminal position of ADAMTS-18, an ‘orphan’ disintegrin and metalloproteinase with thrombospondin (TSR)-like motifs, with unknown substrate. We have found it present in HUVEC as well as human pulmonary artery endothelial cells, on fixed sections of pathology specimens employing immunohistochemistry with a specific rabbit Ab raised against a C-terminal 18 mer peptide ADAMTS-18 (no staining with preimmune Ab). Recombinant ADAMTS-18 was produced in HEK 293 T cells and shown to induce ROS and oxidative platelet fragmentation in an identical kinetic fashion as anti-GPIIIa49-66 Ab. HUVEC ADAMTS-18 activity could be inhibited by a human scFv Ab raised against its C-terminal 18 mer peptide, as well as the ADAMTS-18 peptide itself, but not by a rabbit Ab against the N-terminal domain or an irrelevant peptide. Endothelial cell secretion and activation of ADAMTS-18 was optimally induced with 0.5 u/ml thrombin at 2 – 4 hrs, n=3–4. The truncated 385 amino acid C-terminal rADAMTS-18 fragment containing the 4 TSR motifs (produced in E.coli) had full activity at (<0.3 uM) whereas the C-terminal 66 amino acid fragment not containing the 18-mer binding site was inactive at 65 fold higher concentration, n=4. The physiologic significance of ADAMTS-18 was supported by demonstrating its secretion into plasma following iv injection of 4–16 u/ml thrombin into mice. Wild type mice have no detectable ADAMTS-18 in their plasma, with a sensitive ELISA assay (1 ng detectability). Thrombin stimulated mice secrete ADAMTS-18 in a concentration dependent manner. Platelet aggregates produced ex vivo with ADP and fibrinogen were destroyed with ADAMTS-18 as documented by LDH release at 1, 2 and 4 hrs of 83, 241 and 260 fold respectively, of PBS buffer control. In vivo tail vein bleeding time was shortened 4.5 fold with 1 hr prior infusion of 25 ug of a polyclonal rabbit IgG against ADAMTS-18, but not with preimmune IgG, n=10. Thus, a new mechanism is proposed for platelet activation, ROS release, death and platelet thrombus regulation, via platelet membrane oxidative fragmentation induced by thrombin-induced secretion and activation of ADAMTS-18.
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Li, Zongdong, Michael A. Nardi, Steven J. Feinmark, and Simon Karpatkin. "A New Mechanism of Platelet Activation, Oxidation and Death Induced by ADAMTS-18." Blood 106, no. 11 (2005): 652. http://dx.doi.org/10.1182/blood.v106.11.652.652.

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Abstract Anti-platelet GPIII49–66 Ab obtained from HIV-1-ITP patients (or raised in rabbits) induces platelet oxidation, fragmentation and death by activating platelet 12-lipoxygenase (generating 12(S)-HETE) and NADPH-oxidase with exposure of membrane fragment phosphatidyl serine and thrombin-generating capacity (Cell106:551, 2001; JCI113: 973, 2004). Our recent studies reveal that activation of oxidative platelet death requires classic Ca++ flux (fura-2, AM) (completely inhibited by 100uM EGTA or 10uM BAPTA), and is associated with mild GPIIIa activation (PAC Ab binding) and prominent P-selectin release (n=4). However, robust activation of oxidative fragmentation/death is induced in the presence of 1uM PGE1, 10uM dibutyrl cyclic AMP (n=6) and occurs in Gαq KO mouse platelets (all conditions which inhibit ADP, collagen or thrombin-induced platelet activation). We have also observed that platelet oxidation/fragmentation can be induced independently of anti-GPIIIa49–66 by 10mM A23187, a Ca++ ionophore or 0.4uM PMA, a PKC activator. Both A23187 and PMA induce oxidation of platelets loaded with the oxidative fluorochrome, DCFH. Their reactivity is inhibited by the oxidation scavengers catalase (H2O2) and DPI (inhibitor of NADPH oxidase) and is absent in NADPH oxidase gp91phox(−/−) KO as well as 12-LO(−/−) KO mouse platelets (n=4). Thus, anti-GPIIIa49–66 could be inducing the intracellular effects of ionophore and PMA. We next looked for a possible physiologic mechanism. Platelet GPIIIa49–66 was panned with a phage-peptide display library. Twenty 7-mer peptide clones were found which reacted with GPIIIa49–66. One of these peptides (VHCVQLY) had 70% homology with ADAMTS-18, a disintegrin and metalloprotease with thrombospondin (TSP)-like motifs, constitutively secreted by endothelial cells. An 18-mer peptide of ADAMTS-18 was therefore synthesized from the C-terminal TSP motif and conjugated to biotin, Bio-VQTRSVHCVQQGRPSSSC-OH. The peptide alone had no effect on platelet oxidation/fragmentation. However, an anti-biotin Ab employed to cluster the peptide did induce oxidation/fragmentation (n=6). Recombinant ADAMTS 18 was then made with the expression vector pBudCE4.1 in 293T cells. It induced platelet 12(S)-HETE and oxidation/fragmentation in an identical kinetic fashion as anti-GPIIIa49–66 Ab. Both expressed rADAMTS-18 and HUVEC conditioned media ADAMTS-18 could be activated by thrombin (0.5 u/ml and then neutralized with hirudin) with optimum effect at 1 hr (n=4). HUVEC ADAMTS-18 was inactive in the absence of thrombin. ADAMTS-18 induced oxidation/fragmentation could be inhibited ~50% by an scFV Ab raised against the ADAMTS-18 (18-mer) peptide as well as GPIIIa49–66 peptide, as well as RGDS (GPIIIa ligand binding site) (n=7). Both peptides GPIII49–66 and RGDS were synergistic (~75% inhibited) when combined at optimum individualized concentration, suggesting 2 binding sites on platelet GPIIIa. Thus a mechanism is proposed for platelet thrombus clearance, induced by platelet membrane oxidative fragmentation leading to thrombin generation and activation of constitutively secreted endothelial cell ADAMTS-18.
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Schubert, Franziska, Masashi Tamura, Sophie Bezela, et al. "Comparison of Aspiration Catheters with Modified Standard Catheters for Treatment of Large Pulmonary Embolism Using an In-vitro Patho-Physiological Model." CardioVascular and Interventional Radiology 45, no. 1 (2021): 112–20. http://dx.doi.org/10.1007/s00270-021-02987-y.

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Abstract Purpose The presented in-vitro study provides a comparison of various catheters for mechanical treatment of large-burden pulmonary embolism (PE) under standardized conditions, using a new test rig. Dedicated aspiration catheters (JETi®, Penumbra Indigo®, Aspirex®) were compared with standard catheters (Pigtail, Multi-Purpose, Balloon Catheter) applied for embolus fragmentation. Materials and Methods Emboli prepared from porcine blood were washed into the test rig which consists of anatomical models of the pulmonary artery (PA) and of the right heart in combination with a pulsatile drive system. For all catheters, the duration of the recanalization procedure and the weight percentage (wt%) of the remaining, removed and washed-down clot fractions were evaluated. For aspiration catheters, the aspirated volume was measured. Results All catheters achieved full or partial recanalization. The aspiration catheters showed a significantly (p < 0.05) lower procedure time (3:15 min ± 4:26 min) than the standard fragmentation catheters (7:19 min ± 4:40 min). The amount of thrombus removed by aspiration was significantly (p < 0.001) higher than that by fragmentation, averaging 86.1 wt% ± 15.6 wt% and 31.7 wt% ± 3.8 wt%, respectively. Nonetheless, most of the residue was fragmented into pieces of ≥ 1 mm and washed down. Only in 2 of 36 tests, a residual thrombus of 11.9 wt% ± 5.1 wt% remained in the central PA. Conclusion Comparison under standardized in-vitro patho-physiological conditions showed that embolus fragmentation with standard catheters is clearly inferior to aspiration with dedicated catheters in the treatment of large-burden PE, but can still achieve considerable success. Level of Evidence No level of evidence, experimental study.
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Kasirajan, Karthikeshwar, Venkatesh G. Ramaiah, and Edward B. Diethrich. "The Trellis Thrombectomy System in the Treatment of Acute Limb Ischemia." Journal of Endovascular Therapy 10, no. 2 (2003): 317–21. http://dx.doi.org/10.1177/152660280301000223.

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Purpose: To report the use of a new percutaneous mechanical thrombectomy device in the treatment of acute limb-threatening ischemia. Technique: The Trellis Thrombectomy System is a 7-F drug dispersion catheter that features a treatment segment isolated by proximal and distal occlusion balloons, which help prevent distal embolization and systemic release of the infused thrombolytic agent. After inflating the distal balloon, the thrombolytic agent is infused and held at the target site by inflation of the proximal balloon. An oscillating dispersion wire optimizes dispersal of the thrombolytic agent as the thrombus is mechanically fragmented. The liquefied thrombus is then aspirated. Four consecutive patients with acute lower extremity ischemia secondary to bypass graft thrombosis were treated with the Trellis thrombectomy catheter. Overall, 95% of thrombus was successfully removed from the treatment zone, with no device-related complications. Only one patient required adjunctive thrombolytic therapy after thrombectomy with the Trellis device. Conclusions: The Trellis thrombectomy device is a safe and effective technique to isolate the infused thrombolytic agent in association with mechanical fragmentation for rapid blood flow restoration.
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Kаrnаushkinа, M. А., and R. S. Dаnilov. "Clinical case of pulmonary embolism in a patient with eosinophilic phenotype of chronic obstructive pulmonary disease." Medical alphabet 3, no. 29 (2019): 40–45. http://dx.doi.org/10.33667/2078-5631-2019-3-29(404)-40-45.

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Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality in the world. Exacerbations of COPD is considered an independent risk factor for pulmonary embolism (PE). PE is also significant problem of modern medicine, because mortality in PE remains at a high level. Exacerbations of COPD are heterogeneous as by etiology as by phenotype of the inflammatory response. It is presents the clinical case of PE in patient with acute exacerbation of COPD with eosinophilic phenotype of inflammation. It was the presence of a floating venous thrombus in the patient, which could become a source of repeated PE at any time. The patient underwent endovascular intervention — thrombus fragmentation and thromboaspiration. Given the signs of eosinophilic inflammation, systemic glucocorticosteroids have also been prescribed. The result of the intervention was a regression of respiratory failure and pulmonary hypertension.
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Wei, Ming, Zhiqiang Wei, Xin Li, and Hong Li. "Retrograde semi-retrieval technique for combined stentriever plus aspiration thrombectomy in acute ischemic stroke." Interventional Neuroradiology 23, no. 3 (2017): 285–88. http://dx.doi.org/10.1177/1591019916689053.

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The endovascular treatment of acute ischemic stroke has become a standard procedure. The combination of multiple neuroendovascular devices provides more possibilities for the improvement of the thrombectomy technique. We describe a modified retrieval technique using a distal intracranial catheter (DIC) for the semi-retrieval of stentriever during the thrombectomy procedure. The retrograde semi-retrieval technique involves completely unfolding the stent retriever by pulling a Navien catheter and the partial re-sheath of a retrievable stent forming a tapered configuration by pushing the Navien catheter, which results in the thrombi being embedded into the strut, securing the clot within the stent and there being a shorter distance for the clot to travel. This technique may lessen the occurrence of thrombus fragmentation and injury to the vessel wall. The retrograde semi-retrieval technique is an optional thrombectomy technique that may improve the efficiency of this procedure in the treatment of acute ischemic stroke.
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Lau, Kelly, Irwin White-Gittens, Jonathan Schor, and Mina Guerges. "COVID-19-associated ischaemic stroke due to underlying carotid artery thrombosis in a healthy young woman." BMJ Case Reports 14, no. 8 (2021): e244396. http://dx.doi.org/10.1136/bcr-2021-244396.

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SARS-CoV-2 has proven its versatility in host presentations; one such presentation is a hypercoagulable state causing large-vessel thrombosis. We report a case on a previously asymptomatic COVID-19-positive patient presenting with an acute ischaemic stroke and an incidental left internal carotid artery thrombus. The patient’s medical, social and family history and hypercoagulability screening excluded any other explanation for the left carotid thrombus or stroke, except for testing positive for the COVID-19. This case explores the known hypercoagulable state associated with COVID-19 and the effect of the virus on the host’s immune response. It also questions whether administration of recombinant tissue plasminogen activator (t-PA), according to the American Heart Association guidelines, following a negative head CT for haemorrhagic stroke is safe without prior extended imaging in this patient population. We recommend, in addition to obtaining a non-contrast CT scan of the brain, a CT angiogram or carotid duplex of the neck be obtained routinely in patients with COVID-19 exhibiting stroke symptoms before t-PA administration as the effects may be detrimental. This recommendation will likely prevent fragmentation and embolisation of an undetected carotid thrombus.
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Hill, B., and T. J. Fogarty. "The Use of the Fogarty Catheter in 1998." Cardiovascular Surgery 7, no. 3 (1999): 273–78. http://dx.doi.org/10.1177/096721099900700301.

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Catheter-mediated thromboembolectomy has evolved over the last three decades along with changes in vascular disease patterns. As in situ arterial thrombosis has become more common both in natural arteries and prosthetic grafts, changes in mechanical thromboembolectomy have been necessary to optimize treatment strategies. A variety of devices and techniques are now available for transluminal clot removal including the original thromboembolectomy catheter, newer adherent clot catheters, graft thrombectomy catheters, thru-lumen balloon catheters and methods that involve fragmentation and removal of fresh thrombus by hydrodynamic means.
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Del Rosario, Timothy, Mafdy Basta, and Shvetank Agarwal. "AngioVac Suction Thrombectomy Complicated by Thrombus Fragmentation and Distal Embolization Leading to Hemodynamic Collapse." A & A Case Reports 8, no. 8 (2017): 206–9. http://dx.doi.org/10.1213/xaa.0000000000000469.

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Baek, Jang-Hyun, Ji Hoe Heo, Hyo Suk Nam, Byung Moon Kim, Dong Joon Kim, and Young Dae Kim. "Preprocedural D-Dimer Level as a Predictor of First-Pass Recanalization and Functional Outcome in Endovascular Treatment of Acute Ischemic Stroke." Journal of Clinical Medicine 12, no. 19 (2023): 6289. http://dx.doi.org/10.3390/jcm12196289.

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We aimed to evaluate the association between preprocedural D-dimer levels and endovascular and clinical outcomes. We retrospectively reviewed patients with acute intracranial large-vessel occlusion who underwent mechanical thrombectomy. Plasma D-dimer levels were measured immediately before the endovascular procedure. Endovascular outcomes included successful recanalization, first-pass recanalization (first-pass effect (FPE) and modified FPE (mFPE)), thrombus fragmentation, and the number of passes of the thrombectomy device. Clinical outcomes were assessed at 3 months using the modified Rankin Scale. A total of 215 patients were included. Preprocedural D-dimer levels were lower in patients with FPE (606.0 ng/mL [interquartile range, 268.0–1062.0]) than in those without (879.0 ng/mL [437.0–2748.0]; p = 0.002). Preprocedural D-dimer level was the only factor affecting FPE (odds ratio, 0.92 [95% confidence interval, 0.85–0.98] per 500 ng/mL; p = 0.022). D-dimer levels did not differ significantly based on successful recanalization and thrombus fragmentation. The number of passes of the thrombectomy device was higher (p = 0.002 for trend) and the puncture-to-recanalization time was longer (p = 0.044 for trend) as the D-dimer levels increased. Patients with favorable outcome had significantly lower D-dimer levels (495.0 ng/mL [290.0–856.0]) than those without (1189.0 ng/mL [526.0–3208.0]; p < 0.001). Preprocedural D-dimer level was an independent factor for favorable outcome (adjusted odds ratio, 0.88 [0.81–0.97] per 500 ng/mL; p = 0.008). In conclusion, higher preprocedural D-dimer levels were significantly associated with poor endovascular and unfavorable functional outcomes.
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Barman, Bapi, and Pankaj Sharma. "Catheter-directed Therapy to Treat High-risk Pulmonary Thromboembolism." NMO Journal 18, no. 2 (2024): 99–102. https://doi.org/10.4103/jnmo.jnmo_7_24.

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Abstract Acute pulmonary thromboembolism (PTE) is one of the leading causes of morbidity and mortality worldwide. We describe a case of high-risk PTE in a patient with a history of recent major abdominal surgery, who presented to the emergency department with hypotension, requiring vasopressor support. She had a right ventricular strain on electrocardiogram and computed tomography. The patient was treated with catheter-directed therapy, including thrombus fragmentation and targeted thrombolysis with technical success and good early clinical outcome. This case highlights the importance of timely percutaneous interventional radiology treatment of high-risk PTE, when there is contraindication to systemic thrombolysis.
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Dimitrova, V., B. Vodenicharova, D. Dimitrov, and P. Krastev. "Combined thrombus fragmentation and catheter-directed thrombolysis in the treatment of pulmonary thromboembolism in high- and moderate-risk patients." Bulgarian Cardiology 30, no. (3) (2024): 59–70. https://doi.org/10.3897/bgcardio.30.e135697.

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<em>Introduction:</em> In recent years with the increase in the incidence of pulmonary embolism (PE) worldwide and the rapid development of new devices in interventional cardiology, there has been a tendency to expand the indications for the endovascular treatment of acute PE. Systemic thrombolysis significantly reduces mortality in patients without contraindications for the procedure but at the cost of an increased risk of bleeding. High mortality with a conservative approach in patients with high-risk PE and contraindications for fibrinolysis, as well as moderate-risk patients with a lack of clinical response to optimal anticoagulant therapy, requires a more selective treatment approach to ensure an inevitable positive hemodynamic response. Catheter-based therapy (CBT), including mechanical thrombus fragmentation and selective thrombolysis, is a combined approach with potentially increased efficacy and safety over systemic thrombolysis. In the published literature there is a lack of sufficient data on the application of this therapeutic strategy as a first-line treatment for PE. Large, randomized trials are needed to confirm the value of CBT in these patient groups and to establish precise criteria and recommendations for the initial and follow-up monitoring during treatment. <em>Aim:</em> To evaluate the safety and efficacy of CBT in high- and moderate-risk patients with acute PE as an initial treatment strategy at one-year follow-up. <em>Material and methods:</em> For the period of May 2021- 2024, a total of 35 patients with acute PE were treated in our clinic. In this retrospective study, 23 patients were included, in which a decision was made to conduct CBT as a primary strategy, (in one case there is not a long enough follow-up at this stage). The remaining 8 patients were treated conservatively with low-molecular-weight heprain (LMWH), and the systemic thrombolysis in three of patients was administered. Demographic indicators, history of deep venous thrombosis (DVT), hemodynamic status on admission, non-invasive and invasive parameters of right ventricular burden, contraindications for fibrinolysis, fatal and non-fatal post-procedural complications were recorded. The clinical follow-up is in-hospital conditions, at 6 and 12 months in terms of mortality, manifestations of heart failure, bleeding and hospitalization for PE relapse. All patients in the study group underwent right heart catheterization according to a standardized protocol. CBT includes defragmentation of the thrombi using a Pigtail catheter and selective fibrinolysis with recombinant tissue plasminogen activator /r-TPA, alteplase/ with a dosage of 0.3 mg/kg. <em>Results:</em> The PESI score, which evaluates 30-day mortality in patients with acute pulmonary thromboembolism based on 11 clinical criteria, was used for risk assessment The studied cohort included patients with very high and moderately high risk and an estimated PESI score in the III-V range. CBT was technically successful in 100% (n = 23) of patients. The overall clinical success of the procedure, defined as haemodynamic stability, reversal of hypoxia, reduction of respiratory rate and improvement of peripheral perfusion was achieved in 90.4% of patients. During the hospital stay, 2 deaths were registered (8.69%), the fatal outcome being due to treatment-refractory cardiogenic shock in the first case (the patient died 24 hours after admission) (4.35%) and haemorrhagic stroke in the second (4.35%). In the remaining patients, not a single haemorrhagic incident as well as serious periprocedural complications, were detected. The comparative analysis between echocardiography and invasively assessed pulmonary artery pressure (PAP) before and after the CBT shows that the decrease in the mean PAP (m-PAP) after the treatment is statistically significant - on average 10 mm Hg, which suggests a positive effect of the treatment. During the 6-month follow-up, two more deceased patients were registered &ndash; an 81-year-old woman with previous melena before treatment for PE, and with a new episode and a large drop in haemoglobin, sent for treatment to a gastroenterology department, and a second patient with an unclear cause of death - probable sudden cardiac death (SCD). (Mortality at 6 months is 8.6%). Up to 12 months, no other adverse cardiovascular events were observed in the remaining patients. <em>Conclusion:</em> Our experience in endovascular therapy of acute PE showed that the methodology is both therapeutically and prognostically effective, but also low-risk for the patient. A large, randomized trial is needed before the technique can be recommended as a first-line treatment.
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Horie, Kenji, Hirotada Suzuki, Akihide Ohkuchi, Shigeki Matsubara, Tomokazu Ikemoto, and Mitsuaki Suzuki. "Thrombus just beneath a retrievable inferior vena cava filter in a pregnant woman with deep vein thrombosis: Its removal requiring catheter thrombus fragmentation with fibrinolysis." Journal of Obstetrics and Gynaecology Research 40, no. 2 (2013): 590–94. http://dx.doi.org/10.1111/jog.12169.

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Liu, Bing, MingYuan Liu, LiHong Yan, et al. "Percutaneous mechanical thrombectomy combined with catheter-directed thrombolysis in the treatment of acute pulmonary embolism and lower extremity deep venous thrombosis: A novel one-stop endovascular strategy." Journal of International Medical Research 46, no. 2 (2017): 836–51. http://dx.doi.org/10.1177/0300060517729898.

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Objective This study was performed to evaluate the efficacy and feasibility of percutaneous mechanical thrombectomy (PMT) combined with catheter-directed thrombolysis (CDT) in patients with acute pulmonary embolism (APE) and lower extremity deep venous thrombosis (LEDVT). Methods In total, 20 consecutive patients with APE and LEDVT were prospectively selected for PMT combined with CDT. Mechanical thrombus fragmentation and aspiration using a pigtail rotation catheter followed by CDT was performed in each patient. Details regarding the patients’ clinical presentation and outcome, pulmonary status parameters (pulmonary arterial pressure, partial pressure of oxygen in arterial blood, Miller score, thigh and calf circumference, and shock index), and lower extremity parameters (thrombus-lysis grade and Villalta scale score) were recorded. Results All 20 patients’ clinical manifestations significantly improved. Both the clinical success rate and technical success rate were 100%. No major adverse events occurred during hospitalization. Four patients developed iliac vein compression syndrome and underwent stent implantation in the iliac vein. No pulmonary embolism recurred within 16.5±6.8 months of follow-up. Conclusions The combination of PMT and CDT is a safe and effective treatment for APE and LEDVT with good short- and intermediate-term clinical outcomes.
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Stock, Klaus Wilhelm, Augustinus Ludwig Jacob, Karl Jakob Schnabel, Georg Bongartz, and Wolfgang Steinbrich. "Massive Pulmonary Embolism: Treatment with Thrombus Fragmentation and Local Fibrinolysis with Recombinant Human-Tissue Plasminogen Activator." CardioVascular and Interventional Radiology 20, no. 5 (1997): 364–68. http://dx.doi.org/10.1007/s002709900169.

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Wang, Jianrong, Junxue Wang, Jianzhu Wang, Ziliang Qian, Wensheng Xu, and Xiaofeng Hang. "Combination treatment for advanced hepatocellular carcinoma with portal vein tumour thrombus: A case report." Journal of International Medical Research 49, no. 2 (2021): 030006052199440. http://dx.doi.org/10.1177/0300060521994406.

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We present a case of a 43-year-old man with advanced hepatocellular carcinoma (HCC) with portal vein tumour thrombus. Initially, transcatheter arterial chemoembolization (TACE) was performed. Although alpha-fetoprotein (AFP) levels decreased, circulating tumour DNA (ctDNA) levels showed an upward trend, and abdominal magnetic resonance imaging (MRI) showed that tumours in the portal vein had increased. Based on ctDNA profiling, apatinib and anti-programmed cell death protein 1 (anti-PD-1) antibodies and were sequentially administered. Approximately three months later, intrahepatic tumours had significantly diminished and AFP and ctDNA levels had reduced. The response was sustained at the 23-month follow-up and the patient was in good health. Combination treatment of TACE, apatinib and anti-PD-1 antibodies was effective, and profiling of ctDNA fragmentation may be beneficial in the therapeutic management of patients with HCC.
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Alekseeva, Ya V., E. V. Vyshlov, V. A. Markov, and S. V. Demyanov. "DEFERRED STENT IMPLANTATION IN PATIENTS WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION AND MASSIVE CORONARY THROMBOSIS." Siberian Medical Journal 33, no. 2 (2018): 16–20. http://dx.doi.org/10.29001/2073-8552-2018-33-2-16-20.

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By researches it is proved that the phenomenon of no-reflow is an independent predictor of remodeling of the left ventricle at the moment. Particular importance in formation of this phenomenon is the fragmentation of a thrombus with distal embolization of small vessels, which often arise as a complication of the percutaneous coronary intervention during the destruction of a thrombus. Attempts to prevent the development of microvascular obstruction led to the creation of delayed stenting.The Purpose:assessing the efficacy and safety of deferred stent implantation in patients with ST-segment elevation myocardial infarction and massive coronary thrombosis.Material and Methods.12 patients with STEMI are included in a research. In the course of emergency coronary angiography was performed a massive thrombosis of the infarct-related coronary artery was observed with TIMI 2–3 blood flow. The emergency stenting wasn’t carried out to these patients, but continued anti-thrombotic therapy within 24 hours. After one day, repeated the coronary angiography was performed and, according to the indications, performed stenting of residual stenosis.Results.Development of the phenomenon of no-reflow, deaths and coronary events due to reocclusion of the infarctrelated coronary artery at all patients wasn’t observed. Also, all patients had a positive angiographic result in the form of regurgitation of the thrombus as a result of repeated the coronary angiography.Conclusion.Two-stage revascularization with delayed-on-day stenting with massive thrombosis of the infarct-related coronary artery in patients with acute myocardial infarction combined with aggressive antithrombotic therapy may be use in clinical practice to reduce the risk of developing the no-reflow phenomenon.
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Haas, Nikolaus A. "Successful Revascularization of a Completely Occluded Right Coronary Artery by Local Thrombus Fragmentation, Thrombolysis, Thrombus Aspiration and Balloon Angioplasty in a Patient with Atypical Kawasaki Disease." Journal of Structural Heart Disease 2, no. 5 (2016): 224–30. http://dx.doi.org/10.12945/j.jshd.2016.011.15.

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Bala, Fouzi, Manon Kappelhof, Johanna Ospel, et al. "Association des caractéristiques radiologiques du thrombus et des détails du traitement avec le risque de fragmentation et d'embolisation distale du thrombus au cours des thrombectomie mécaniques." Journal of Neuroradiology 50, no. 2 (2023): 117. http://dx.doi.org/10.1016/j.neurad.2023.01.028.

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Sénémaud, Jean N., Quentin D. Pellenc, Yves H. Castier, and Arnaud K. Roussel. "Aneurysm mural thrombus fragmentation and cerebral embolism: a rare complication of femoro-femoral extracorporeal membrane oxygenation support." Interactive CardioVascular and Thoracic Surgery 29, no. 1 (2019): 162. http://dx.doi.org/10.1093/icvts/ivy365.

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Han, Mei, Qiang Liu, Baihai Su, Shudong Sun, and Changsheng Zhao. "Bioinspired Polyethersulfone Membrane Design via Blending with Functional Polyurethane." International Journal of Polymer Science 2017 (2017): 1–10. http://dx.doi.org/10.1155/2017/2158124.

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Polyurethanes (PUs) are currently considered to be biocompatible materials but limited by a low resistance to thrombus. We therefore design a heparin-like PU (HLPU) to modify polyethersulfone (PES) membranes approaching integrated antifouling and antithrombotic properties by bioinspiration of heparin structure. Poly(vinyl pyrrolidone)-HLPU (PVP-HLPU) was synthesized via reversible addition-fragmentation chain transfer polymerization of VP using PU as a macroinitiator and then sulfonated by concentrated H2SO4. FTIR and NMR results demonstrated the successful synthesis of PVP-HLPU. By incorporation of PVP-HLPU, the cross-sectional structure of PES composite membranes altered from finger-like structure to sponge-like structure resulting in tunable permeability. The increased hydrophilicity verified by water contact angles benefited both the permeability and antifouling property. As a consequence, the composite membranes showed good blood compatibility, including decreased protein adsorption, suppressed platelet adhesion, lowered thrombin-antithrombin III generation, reduced complement activation, and prolonged clotting times. Interestingly, the PVP-capped HLPU showed better blood compatibility compared to polyethyleneglycol-capped and citric acid-capped HLPUs. The results demonstrated the enhanced antifouling and antithrombotic properties of PES hemodialysis membranes by the introduction of functional HLPUs. Also, the proposed method may forward the fabrication of hemocompatible membranes via bioinspired surface design.
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Ozsancak Ugurlu, Aylin, Ozlem Cinar, Ismail Caymaz, Halime Cevik, and Burcak Gumus. "Combined catheter thrombus fragmentation and percutaneous thrombectomy in a patient with massive pulmonary emboli and acute cerebral infarct." Anadolu Kardiyoloji Dergisi/The Anatolian Journal of Cardiology 15, no. 1 (2015): 72–74. http://dx.doi.org/10.5152/akd.2014.5765.

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44

El-Bouri, Wahbi K., Andrew MacGowan, Tamás I. Józsa, Matthew J. Gounis, and Stephen J. Payne. "Modelling the impact of clot fragmentation on the microcirculation after thrombectomy." PLOS Computational Biology 17, no. 3 (2021): e1008515. http://dx.doi.org/10.1371/journal.pcbi.1008515.

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Many ischaemic stroke patients who have a mechanical removal of their clot (thrombectomy) do not get reperfusion of tissue despite the thrombus being removed. One hypothesis for this ‘no-reperfusion’ phenomenon is micro-emboli fragmenting off the large clot during thrombectomy and occluding smaller blood vessels downstream of the clot location. This is impossible to observe in-vivo and so we here develop an in-silico model based on in-vitro experiments to model the effect of micro-emboli on brain tissue. Through in-vitro experiments we obtain, under a variety of clot consistencies and thrombectomy techniques, micro-emboli distributions post-thrombectomy. Blood flow through the microcirculation is modelled for statistically accurate voxels of brain microvasculature including penetrating arterioles and capillary beds. A novel micro-emboli algorithm, informed by the experimental data, is used to simulate the impact of micro-emboli successively entering the penetrating arterioles and the capillary bed. Scaled-up blood flow parameters–permeability and coupling coefficients–are calculated under various conditions. We find that capillary beds are more susceptible to occlusions than the penetrating arterioles with a 4x greater drop in permeability per volume of vessel occluded. Individual microvascular geometries determine robustness to micro-emboli. Hard clot fragmentation leads to larger micro-emboli and larger drops in blood flow for a given number of micro-emboli. Thrombectomy technique has a large impact on clot fragmentation and hence occlusions in the microvasculature. As such, in-silico modelling of mechanical thrombectomy predicts that clot specific factors, interventional technique, and microvascular geometry strongly influence reperfusion of the brain. Micro-emboli are likely contributory to the phenomenon of no-reperfusion following successful removal of a major clot.
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45

Jyoti, Dhrubo, Daniel Reeves, Scott Gordon-Wylie, Clifford Eskey, and John Weaver. "Improving Stroke Treatment Using Magnetic Nanoparticle Sensors to Monitor Brain Thrombus Extraction." Sensors 25, no. 3 (2025): 672. https://doi.org/10.3390/s25030672.

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(1) Background: Mechanical thrombectomy (MT) successfully treats ischemic strokes by extracting the thrombus, or clot, using a stent retriever to pull it through the blood vessel. However, clot slippage and/or fragmentation can occur. Real-time feedback to a clinician about attachment between the stent and clot could enable more complete removal. We propose a system whereby antibody-targeted magnetic nanoparticles (NPs) are injected via a microcatheter to coat the clot, oscillating magnetic fields excite the particles, and a small coil attached to the catheter picks up a signal that determines the proximity of the clot to the stent. (2) Methods: We used existing simulation code to model the signal from NPs distributed on a hemispherical clot with three orthogonally applied magnetic fields. An in vitro apparatus was built that applied fields and read out signals from a 1.5 mm pickup coil at a variable distance and orientation angle from a sample of 100 nm iron oxide core/shell NPs. (3) Results: Our simulations suggest that the sum of the voltages induced in the pickup coil from three orthogonal applied fields could localize a clot to within 180 µm, regardless of the exact orientation of the pickup coil, with further precision added via rotation-correction formulae. Our experimental system validated simulations; we estimated an in vitro distance recovery precision of 41 µm with a pickup coil 1 mm from the clot. (4) Conclusions: Magnetic NP sensing could be a safe and real-time method to estimate whether a clot is attached to the stent retriever during MT.
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46

Zhang, Wei, Dawei Bu, Suying Dang, Tao Hong, and Thomas Wisniewski. "Adamts-18 Is a Novel Candidate Gene Of Vascular Development That Is Related To Aggravated Thrombosis: Evidence From a Adamts-18 Knock Out Mice." Blood 122, no. 21 (2013): 31. http://dx.doi.org/10.1182/blood.v122.21.31.31.

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Abstract HIV-ITP patients have a unique antibody (Ab) against platelet GPIIIa49-66 which induces oxidative platelet fragmentation in the absence of complement (Cell 106: 551, 2001; JCI 113: 973, 2004). The search for a physiologic ligand that could induce this reaction was undertaken by panning the GPIIIa49-66 peptide with a phage surface display 7-mer peptide library. From 20 positive clones, 1 had 70% identity with a C-terminal region of ADAMTS-18 (a disintegrin and metalloproteinase with thrombospondin (TSR)-like motif 18), which is secreted by endothelial cell (EC). The recombinant C-terminal fragment of ADAMTS-18 can completely dissolve platelet aggregates formed in vitro. Moreover, this fragment lyses thrombi formed in the cerebral artery of mice and reduces infarction and neurologic impairment in murine ischemic stroke model (Blood 113: 6051, 2009). However, whether ADAMTS-18 represents the dominant physiologic mechanism controlling thrombus dissolution in vivo remains to be clarified. Here, we used ADAMTS-18-deficient (ADAMTS-18-/-) mice to study the contributions of ADAMTS-18 to thrombus formation in vivo. To investigate possible functional differences between WT and ADAMTS-18-/- platelets, we tested WT and ADAMTS-18-/- platelets in a model of pulmonary thromboembolism induced by infusion of a mixture of platelet agonist collagen (25 µg per mouse) and epinephrine (1 µg per mouse). In lung tissue Hematoxylin and eosin-stained (HE) slides, the mean number of thrombi per lung was same in the ADAMTS-18-/- group compared with WT group (163.7 ±14.38 vs 174.9 ±11.73, n=30/group, P=0.5480). In vitro, there is no difference between WT and ADAMTS-18-/- platelet aggregation trace and activation initiated by various platelet agonists ADP (10 µM) or collagen (2 µg/mL). No difference was noted on WT and ADAMTS-18-/- platelet adhesion on immobilized ligand (fibrinogen). These results indicated ADAMTS-18 had no effect on platelet function. We next evaluate the effect of ADAMTS-18 on thrombus formation in a second well-established carotid artery thrombosis model, which is induced by 10% FeCl3 patch. In the process of surgical operation, we unexpectedly observed that all ADAMTS-18-/- mice have premature common carotid artery bifurcation compared with WT mice. A Doppler flow monitor showed ADAMTS-18-/- mice exhibited significantly reduced carotid artery blood flow than WT mice (ADAMTS-18-/- vs WT, 0.5 ± 0.11 vs 0.75 ± 0.21 mL/min, n=7/group, P=0.0298), which results in shortened time of thrombus formation (ADAMTS-18-/- vs WT, 452.17 ± 68.88 vs 611.43 ± 92.02 sec, n=7/group, P=0.0005 ). Immunohistochemistry staining showed that the common carotid artery of ADAMTS-18-/- mice had increased adventitial collagen deposition compared with WT mice. In vivo matrigel plug assay demonstrated that ADAMTS-18-/- mice had significantly lower density of blood vessels compared to the WT mice. Since the middle cerebral artery arises from the internal carotid artery, we conjecture that ADAMTS-18-/- mice would have aggravated brain infarction for the less cerebral blood flow supplying. This proved to be true. In transient middle cerebral artery occlusion (tMCAO) model, the infarction size in ADAMTS-18-/- mice was significantly larger than in WT mice (mean infarction %, 25.68 ± 4.13 vs 17.41 ± 3.24, n=8, P=0.0012). Taken together, these observations suggest vasculature is the potential site of action of ADAMTS-18. To our knowledge, this is the first validation study of linkage and association of ADAMTS-18 as a pro-vasculature gene that is related to aggravated thrombosis. Disclosures: No relevant conflicts of interest to declare.
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47

Dimitrova, V., B. Vodenicharova, D. Dimitrov, and P. Krastev. "Combined thrombus fragmentation and catheter-directed thrombolysis in the treatment of pulmonary thromboembolism in high- and moderate-risk patients." Bulgarian Cardiology 30, no. 3 (2024): 59–70. https://doi.org/10.3897/bgcardio.30.e135697.

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Introduction: In recent years with the increase in the incidence of pulmonary embolism (PE) worldwide and the rapid development of new devices in interventional cardiology, there has been a tendency to expand the indications for the endovascular treatment of acute PE. Systemic thrombolysis significantly reduces mortality in patients without contraindications for the procedure but at the cost of an increased risk of bleeding. High mortality with a conservative approach in patients with high-risk PE and contraindications for fibrinolysis, as well as moderate-risk patients with a lack of clinical response to optimal anticoagulant therapy, requires a more selective treatment approach to ensure an inevitable positive hemodynamic response. Catheter-based therapy (CBT), including mechanical thrombus fragmentation and selective thrombolysis, is a combined approach with potentially increased efficacy and safety over systemic thrombolysis. In the published literature there is a lack of sufficient data on the application of this therapeutic strategy as a first-line treatment for PE. Large, randomized trials are needed to confirm the value of CBT in these patient groups and to establish precise criteria and recommendations for the initial and follow-up monitoring during treatment. Aim: To evaluate the safety and efficacy of CBT in high- and moderate-risk patients with acute PE as an initial treatment strategy at one-year follow-up. Material and methods: For the period of May 2021- 2024, a total of 35 patients with acute PE were treated in our clinic. In this retrospective study, 23 patients were included, in which a decision was made to conduct CBT as a primary strategy, (in one case there is not a long enough follow-up at this stage). The remaining 8 patients were treated conservatively with low-molecular-weight heprain (LMWH), and the systemic thrombolysis in three of patients was administered. Demographic indicators, history of deep venous thrombosis (DVT), hemodynamic status on admission, non-invasive and invasive parameters of right ventricular burden, contraindications for fibrinolysis, fatal and non-fatal post-procedural complications were recorded. The clinical follow-up is in-hospital conditions, at 6 and 12 months in terms of mortality, manifestations of heart failure, bleeding and hospitalization for PE relapse. All patients in the study group underwent right heart catheterization according to a standardized protocol. CBT includes defragmentation of the thrombi using a Pigtail catheter and selective fibrinolysis with recombinant tissue plasminogen activator /r-TPA, alteplase/ with a dosage of 0.3 mg/kg. Results: The PESI score, which evaluates 30-day mortality in patients with acute pulmonary thromboembolism based on 11 clinical criteria, was used for risk assessment The studied cohort included patients with very high and moderately high risk and an estimated PESI score in the III-V range. CBT was technically successful in 100% (n = 23) of patients. The overall clinical success of the procedure, defined as haemodynamic stability, reversal of hypoxia, reduction of respiratory rate and improvement of peripheral perfusion was achieved in 90.4% of patients. During the hospital stay, 2 deaths were registered (8.69%), the fatal outcome being due to treatment-refractory cardiogenic shock in the first case (the patient died 24 hours after admission) (4.35%) and haemorrhagic stroke in the second (4.35%). In the remaining patients, not a single haemorrhagic incident as well as serious periprocedural complications, were detected. &amp;nbsp;The comparative analysis between echocardiography and invasively assessed pulmonary artery pressure (PAP) before and after the CBT shows that the decrease in the mean PAP (m-PAP) after the treatment is statistically significant - on average 10 mm Hg, which suggests a positive effect of the treatment. During the 6-month follow-up, two more deceased patients were registered &amp;ndash; an 81-year-old woman with previous melena before treatment for PE, and with a new episode and a large drop in haemoglobin, sent for treatment to a gastroenterology department, and a second patient with an unclear cause of death - probable sudden cardiac death (SCD). (Mortality at 6 months is 8.6%). Up to 12 months, no other adverse cardiovascular events were observed in the remaining patients. Conclusion: Our experience in endovascular therapy of acute PE showed that the methodology is both therapeutically and prognostically effective, but also low-risk for the patient. A large, randomized trial is needed before the technique can be recommended as a first-line treatment.&amp;nbsp;
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48

Endicott, Kendal M., Charles B. Drucker, Hakan Orbay, et al. "Intraoperative Fragmentation and Retention of Endovascular Devices: Clinical Consequences and Preventative Strategies." Vascular and Endovascular Surgery 54, no. 2 (2019): 118–25. http://dx.doi.org/10.1177/1538574419886193.

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Background: Expanded applications and increasing volumes of complex endovascular procedures have increased the risk of unintended intraoperative fragmentation and retention of catheters and sheaths. We describe a series of retained or fragmented endovascular devices, a quality improvement program to address this unmet need for improved detection of catheter fragmentation, and the results of this program. Methods: Cases utilizing endovascular devices that resulted in a retained catheter fragment were identified and analyzed during divisional quality improvement review. One consistent area of concern was operating room (OR) staff unfamiliarity with verifying the integrity of an endovascular device. In response, a slide-based training protocol of focused, endovascular nursing education was implemented. Following perceived lack of improvement after this approach, we developed a handheld visual reference display of the tips of common catheters and sheaths. Staff was surveyed before and after intervention to assess the educational value of the display and the impact on staff device familiarity. Results: All 4 described cases resulted in an unplanned return to the OR for retrieval of the fragmented catheter or sheath. No thromboembolic complications were observed, although associated intra-arterial thrombus was noted in 2 cases. Thirty-four OR nurses were polled to trial the visual reference display initiative, with 70% of those reporting primary surgical assignments outside of cardiovascular ORs. Introduction of the new visual reference display improved staff confidence in their ability to identify a broken device (2.4-3.7, P &lt; .001). This improvement was most significant in OR staff with primary assignments in noncardiovascular services. Conclusion: Current OR standard operating procedures fail to address the potential for unintentionally retained catheters and wires during endovascular procedures. Our novel visual reference display of common endovascular items rather than conventional in-service training improved the ability of staff to identify device fragmentation at the time of the index procedure.
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49

Zhang, Wei, Suying Dang, and Thomas Wisniewski. "Synergistic Effects of Bifunctional Antibodies Against beta3 Integrin on Dissolution of Platelet Thrombus,." Blood 118, no. 21 (2011): 3350. http://dx.doi.org/10.1182/blood.v118.21.3350.3350.

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Abstract Abstract 3350 HIV-ITP patients have a unique Ab against platelet GPIIIa49-66 which induces oxidative platelet fragmentation in the absence of complement (Cell 106: 551, 2001; JCI 113: 973, 2004). Using a phage display single-chain antibody (scFv) library, we developed a novel human monoclonal scFv Ab against GPIIIa49-66 (named A11), which act similarly to the parental Ab (JBC 283: 3224, 2008). We then produced a bifunctional GPIIIa49-66 agent (named SLK), that targets newly deposited fibrin strands within and surrounding the platelet thrombus and has reduced effects on non-activated circulating platelets (Blood 116: 2336, 2010). In this study, we produced another bifunctional GPIIIa49-66 agent (named APAC), which homes to activated platelets. Like SLK, APAC destroys platelet aggregates ex vivo in an identical fashion with ∼85% destruction of platelet aggregates at 2 hrs. Platelet aggregate dissolution with a combination of SLK and APAC was ∼2 fold greater than either agent alone at 0.025 μM. Platelet-rich clot lysis experiments demonstrated the time required for 50% platelet-rich fibrin clot lysis (T50%) by APAC (95±6.1 min) was significantly longer than that by APAC+SLK (65±7.6 min) at a final concentration of 0.025 μM (APAC+SLK vs APAC, p&lt;0.01). In comparison with APAC alone, the T50% of APAC+SLK was shortened by 1.56, 1.67 and 2.1 fold at the concentrations of 0.025, 0.5 and 0.1μM, respectively. Thus these low concentrations of a combination of both agents are likely to be more effective and less toxic when used therapeutically in vivo. Disclosures: No relevant conflicts of interest to declare.
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50

Duval, Cédric, Adomas Baranauskas, Tímea Feller та ін. "Elimination of fibrin γ-chain cross-linking by FXIIIa increases pulmonary embolism arising from murine inferior vena cava thrombi". Proceedings of the National Academy of Sciences 118, № 27 (2021): e2103226118. http://dx.doi.org/10.1073/pnas.2103226118.

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The onset of venous thromboembolism, including pulmonary embolism, represents a significant health burden affecting more than 1 million people annually worldwide. Current treatment options are based on anticoagulation, which is suboptimal for preventing further embolic events. In order to develop better treatments for thromboembolism, we sought to understand the structural and mechanical properties of blood clots and how this influences embolism in vivo. We developed a murine model in which fibrin γ-chain cross-linking by activated Factor XIII is eliminated (FGG3X) and applied methods to study thromboembolism at whole-body and organ levels. We show that FGG3X mice have a normal phenotype, with overall coagulation parameters and platelet aggregation and function largely unaffected, except for total inhibition of fibrin γ-chain cross-linking. Elimination of fibrin γ-chain cross-linking resulted in thrombi with reduced strength that were prone to fragmentation. Analysis of embolism in vivo using Xtreme optical imaging and light sheet microscopy demonstrated that the elimination of fibrin γ-chain cross-linking resulted in increased embolization without affecting clot size or lysis. Our findings point to a central previously unrecognized role for fibrin γ-chain cross-linking in clot stability. They also indirectly indicate mechanistic targets for the prevention of thrombosis through selective modulation of fibrin α-chain but not γ-chain cross-linking by activated Factor XIII to reduce thrombus size and burden, while maintaining clot stability and preventing embolism.
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