Pathophysiologic and Therapeutic Perspectives Based on Thrombus Histology in Stroke

Heo, Ji Hoe; Nam, Hyo Suk; Kim, Young Dae; Choi, Jin Kyo; Kim, Byung Moon; Kim, Dong Joon; Kwon, Il

doi:10.5853/jos.2019.03440

Cited by 56 publications

(73 citation statements)

References 74 publications

(122 reference statements)

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“…Moreover, patients treated with tPA who underwent thrombectomy presented higher platelet fraction in thrombi. This fact has not been previously described but has been suggested in some studies ( 43 ). A paradoxical platelet activation has been reported secondary to fibrinolysis ( 44 ) as responsible for delayed thrombosis in some patients with tPA-resistant thrombi causing reocclusion and rethrombosis ( 45 ).…”

Section: Discussionsupporting

confidence: 57%

Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

et al. 2021

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Background: Actual clinical management of ischemic stroke (IS) is based on restoring cerebral blood flow using tissue plasminogen activator (tPA) and/or endovascular treatment (EVT). Mechanical thrombectomy has permitted the analysis of thrombus structural and cellular classic components. Nevertheless, histological assessment of hemostatic parameters such as thrombin-activatable fibrinolysis inhibitor (TAFI) and matrix metalloproteinase 10 (MMP-10) remains unknown, although their presence could determine thrombus stability and its response to thrombolytic treatment, improving patient's outcome.Methods: We collected thrombi (n = 45) from large vessel occlusion (LVO) stroke patients (n = 53) and performed a histological analysis of different hemostatic parameters [TAFI, MMP-10, von Willebrand factor (VWF), and fibrin] and cellular components (erythrocytes, leukocytes, macrophages, lymphocytes, and platelets). Additionally, we evaluated the association of these parameters with plasma levels of MMP-10, TAFI and VWF activity and recorded clinical variables.Results: In this study, we report for the first time the presence of MMP-10 and TAFI in all thrombi collected from LVO patients. Both proteins were localized in regions of inflammatory cells, surrounded by erythrocyte and platelet-rich areas, and their content was significantly associated (r = 0.41, p < 0.01). Thrombus TAFI was lower in patients who died during the first 3 months after stroke onset [odds ratio (OR) (95%CI); 0.59 (0.36–0.98), p = 0.043]. Likewise, we observed that thrombus MMP-10 was inversely correlated with the amount of VWF (r = −0.30, p < 0.05). Besides, VWF was associated with the presence of leukocytes (r = 0.37, p < 0.05), platelets (r = 0.32, p < 0.05), and 3 months mortality [OR (95%CI); 4.5 (1.2–17.1), p = 0.029]. Finally, plasma levels of TAFI correlated with circulating and thrombus platelets, while plasma MMP-10 was associated with cardiovascular risk factors and functional dependence at 3 months.Conclusions: The present study suggests that the composition and distribution of thrombus hemostatic components might have clinical impact by influencing the response to pharmacological and mechanical therapies as well as guiding the development of new therapeutic strategies.

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Section: Discussionsupporting

confidence: 57%

Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

et al. 2021

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“…It is worth noting that thrombus composition plays a crucial role in recanalization therapy in LAO patients ( 13 ). We found that the percentage of fibrin in the VHD group was significantly higher than that in the other groups, and the contents of red blood cells and WBCs were lower.…”

Section: Discussionmentioning

confidence: 99%

Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques

et al. 2020

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Background and Purpose: Acute ischemic stroke (AIS) with large artery occlusion (LAO) may lead to severe disability or death if not promptly treated. To determine the source of cerebral artery occlusion thrombosis, we studied the pathological components of cerebral artery thrombosis with different etiological classifications to guide clinical formulation of preventive treatment. Materials and Methods: Eighty-eight thrombi from AIS patients with LAO, 12 atrial thrombi from patients with valvular heart disease (VHD), and 11 plaques obtained by carotid endarterectomy (CEA) from patients with carotid artery stenosis were included in this retrospective study. The hematoxylin and eosin–stained specimens were quantitatively analyzed for erythrocytes, white blood cells (WBCs) and fibrin; platelets were shown by immunohistochemistry for CD31. Results: The thrombi of VHD showed the highest percentage of fibrin, followed by those of cardioembolism (CE) and stroke of undetermined etiology (SUE), and these values were higher than those of the other groups. Plaques obtained by CEA showed the highest erythrocyte number, followed by the large artery atherosclerosis (LAA) thrombi, and showed significantly noticeable differences between other stroke subtypes. The proportions of fibrin and erythrocytes in the thrombi of CE and SUE were most similar to those in the thrombi of VHD, and the LAA thrombi were the closest to those obtained by CEA. CE thrombi and CEA plaques had a higher percentage of WBCs than thrombi of other stroke thrombus subtypes and VHD. Conclusions: CE and most cryptogenic thrombi may originate from the heart, and the formation of carotid atherosclerotic plaques may be related to atherosclerotic cerebral embolism. Inflammation may be involved in their formation.

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“…The pathomechanism of NBTE remains unknown. Autopsy studies in patients with NBTE have shown that cardiac vegetation is mainly composed of platelets [ 21 ], and examinations of thrombi retrieved during mechanical thrombectomy in stroke patients with NBTE have indicated very high platelet and low erythrocyte fractions [ 11 , 22 ]. These studies suggest that platelet-mediated mechanisms play a key role in the development of cancer-associated NBTE.…”

Section: Discussionmentioning

confidence: 99%

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis

et al. 2020

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Background and Purpose Nonbacterial thrombotic endocarditis (NBTE) is a cause of stroke in cancer. However, clinical characteristics and outcomes in stroke patients with cancer-associated NBTE are not well known.<br/>Methods We included consecutive patients with stroke and active cancer over a 9-year period who underwent echocardiography. We retrospectively compared clinical characteristics and presence of metastasis between patients with NBTE, those with cryptogenic etiologies, and those with determined etiologies. We also investigated mortality and stroke events during the 6-month follow-up.<br/>Results Among the 245 patients, 20 had NBTE, 96 had cryptogenic etiologies, and 129 had determined etiologies. Metastasis was seen in all 20 patients (100%) with NBTE, 69.8% in patients with cryptogenic etiology, and 48.8% in patients with or determined etiology. During the 6-month follow-up, 127 patients (51.8%) developed stroke and/or died (death in 110 [44.9%] and stroke events in 55 [22.4%]). Patients with NBTE showed significantly higher mortality (80%) and stroke occurrence (50%) than those with cryptogenic etiologies (mortality 54.2%, stroke 25.0%, log-rank P=0.006) and determined etiologies (mortality 32.6%, stroke 16.3%, log-rank P<0.001). In a multivariate Cox proportional hazard analysis, the presence of NBTE was independently associated with composite outcomes of mortality and stroke events (hazard ratio, 1.941; 95% confidence interval, 1.052 to 3.690).<br/>Conclusions NBTE should be suspected as a potential cause of stroke in patients with metastatic cancer. Patients with NBTE have a high risk of recurrent stroke and mortality. Future studies are necessary to determine strategies to reduce stroke recurrence in patients with NBTE.

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Pathophysiologic and Therapeutic Perspectives Based on Thrombus Histology in Stroke

Cited by 56 publications

References 74 publications

Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

Inside the Thrombus: Association of Hemostatic Parameters With Outcomes in Large Vessel Stroke Patients

Differences in Pathological Composition Among Large Artery Occlusion Cerebral Thrombi, Valvular Heart Disease Atrial Thrombi and Carotid Endarterectomy Plaques

Outcome of Stroke Patients with Cancer and Nonbacterial Thrombotic Endocarditis

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