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      Early changes in fibrinogen after administration of alteplase are associated with the short-term efficacy of thrombolysis

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          Abstract

          The authors aimed to determine whether early changes in fibrinogen were associated with the efficacy of intravenous thrombolysis at 24 hours after alteplase infusion. The authors retrospectively reviewed a consecutive series of 56 patients with acute ischemic stroke treated with alteplase in the clinical database. The fibrinogen levels were monitored at the first and fourth hours after alteplase infusion. Additionally, the National Institutes of Health Stroke Scale (NIHSS) scores were recorded to define the short-term efficacy of intravenous thrombolysis before and 24 hours after alteplase infusion. The patients were distributed into amelioration, deterioration, and inefficiency groups according the short-term efficacy of intravenous thrombolysis. One-way ANOVA and post hoc analysis were used to compare the differences in the clinical characteristics among these groups. The relationships among changes in the fibrinogen levels, other potential risk factors, and NIHSS scores were examined using logistic regression analysis. Fifty-two patients (mean age, 65.71 ± 11.04 years; male, 57.7%) were finally enrolled in the study. The median NIHSS of these patients was 11 (range, 2–23), and the mean time from symptom onset to thrombolysis was 187.17 ± 67.53 minutes. The frequency of hypertension in the deterioration group was significantly higher than that in the inefficiency group ( P = .01). Changes in the fibrinogen level were more significant in the amelioration group than in the other groups ( P < .05). Logistic regression analysis revealed that changes in the fibrinogen levels between the first and fourth hours were positively associated with the short-term efficacy of alteplase infusion (odds ratio, 3.98; 95% confidence interval, 1.56–10.16; P = .004). Early changes in fibrinogen levels may be a potential predictor for the short-term efficacy of alteplase treatment in acute ischemic stroke. Additionally, these changes may be helpful for determining the short-term efficacy of alteplase treatment and early therapeutic strategies in clinical practice.

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          Factors influencing haemorrhagic transformation in ischaemic stroke.

          Haemorrhagic transformation (HT) of ischaemic infarction occurs when an area of brain infarction is stained with blood products, mainly red blood cells. An abnormally permeable blood-brain barrier resulting from ischaemia of the capillary endothelium allows this extravasation of blood products. HT is part of the natural history of some forms of ischaemic infarction, especially cerebral embolism, but it can be precipitated or enhanced by therapeutic interventions used in the acute phase of ischaemic stroke. The old view of HT after cerebral embolism as a generally asymptomatic change in a tissue that is already necrotic has been challenged by observations from therapeutic thrombolysis that suggest that HT can have a negative effect on patients' outcomes. Understanding of the risk factors for and the underlying mechanisms and clinical variability of HT in the context of acute therapeutic interventions in ischaemic stroke could help in the early detection of this complication, in determining the safety of recanalisation approaches, and in setting the stage for future research into the prevention or treatment of HT in patients with acute ischaemic stroke. Copyright © 2013 Elsevier Ltd. All rights reserved.
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            Using recombinant tissue plasminogen activator to treat acute ischemic stroke in China: analysis of the results from the Chinese National Stroke Registry (CNSR).

            Little is known about intravenous recombinant tissue plasminogen activator (rtPA) use in China. By accessing the Chinese National Stroke Registry (CNSR), the rate of intravenous rtPA use was reviewed. We specifically examined the issues of prehospital and in-emergency department delay and compared them with the published data from developed countries. Funded by Chinese government, CNSR is the only nationwide stroke registry that includes 132 urban hospitals. All patients eligible for intravenous rtPA were included for analysis. We then compared the onset-to-needle time and door-to-needle time in the emergency department in China with those in developed countries. From September 2007 to August 2008, 14,702 patients with ischemic stroke were entered into CNSR. Among 11,675 patients with known time of stroke onset, 2514 (21.5%) presented to the emergency department within 3 hours, 1469 (12.6%) were eligible for thrombolytic treatment, and 284 (2.4%) were finally treated, 181 (1.6%) of them with intravenous rtPA. The median onset-to-needle time was 180 (interquartile range, 150 to 228) minutes; the median door-to-needle time was 116 (interquartile range, 70 to 150) minutes; the median imaging-to-needle time was 90 (interquartile range, 60 to 129) minutes. Patients who were younger, presented to the emergency department quicker, with higher National Institutes of Health Stroke Scale scores, having higher income, and better education had a better chance of receiving intravenous rtPA. Approximately 1 in 5 patients with stroke presenting within 3 hours received thrombolytic therapy. The onset-to-needle time, door-to-needle time, and especially imaging-to-needle time were significantly longer than those in developed countries. Reducing prehospital and in-emergency department response time would help increase intravenous rtPA use in China.
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              Causal relationship between hyperfibrinogenemia, thrombosis, and resistance to thrombolysis in mice.

              Epidemiologic studies have correlated elevated plasma fibrinogen (hyperfibrinogenemia) with risk of cardiovascular disease and arterial and venous thrombosis. However, it is unknown whether hyperfibrinogenemia is merely a biomarker of the proinflammatory disease state or is a causative mechanism in the etiology. We raised plasma fibrinogen levels in mice via intravenous infusion and induced thrombosis by ferric chloride application to the carotid artery (high shear) or saphenous vein (lower shear); hyperfibrinogenemia significantly shortened the time to occlusion in both models. Using immunohistochemistry, turbidity, confocal microscopy, and elastometry of clots produced in cell and tissue factor-initiated models of thrombosis, we show that hyperfibrinogenemia increased thrombus fibrin content, promoted faster fibrin formation, and increased fibrin network density, strength, and stability. Hyperfibrinogenemia also increased thrombus resistance to tenecteplase-induced thrombolysis in vivo. These data indicate that hyperfibrinogenemia directly promotes thrombosis and thrombolysis resistance and does so via enhanced fibrin formation and stability. These findings strongly suggest a causative role for hyperfibrinogenemia in acute thrombosis and have significant implications for thrombolytic therapy. Plasma fibrinogen levels may be used to identify patients at risk for thrombosis and inform thrombolytic administration for treating acute thrombosis/thromboembolism.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                March 2018
                30 March 2018
                : 97
                : 13
                : e0241
                Affiliations
                [a ]Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou
                [b ]Department of Neurology and Stroke Center, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi, China.
                Author notes
                []Correspondence: Hong Yang, Department of Neurology and Stroke Center, The Fourth Affiliated Hospital of Guangxi Medical University, Guangxi 518000, China (e-mail: 2308516579@ 123456qq.com ).
                Article
                MD-D-17-06367 00241
                10.1097/MD.0000000000010241
                5895368
                29595678
                6103623d-e11b-43cc-aa8a-dea96fbb5c83
                Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

                History
                : 15 October 2017
                : 28 February 2018
                : 1 March 2018
                Categories
                5300
                Research Article
                Observational Study
                Custom metadata
                TRUE

                acute ischemic stroke,alteplase,fibrinogen,short-term efficacy

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