A predictive clinical–genetic model of tissue plasminogen activator response in acute ischemic stroke

Río-Espínola, Alberto Del; Fernández‐Cadenas, Israel; Giralt, Dolors; Quiroga, Adoración G.; Gutiérrez‐Agulló, Maria; Quintana, Manuel; Fernández‐Álvarez, Patricia; Domingues‐Montanari, Sophie; Mendióroz, Maite; Delgado, Pilar; Turck, Natacha; Ruiz, Agustín; Ribó, Marc; Castellanos, Mar; Obach, Vı́ctor; Martínez, Santiago; Freijo, Mari Mar; Jiménez‐Conde, Jordi; Cuadrado-Godía, Elisa; Roquer, Jaume; Chacón, Pilar; Martí‐Fàbregas, Joan; Sánchez, Jean Charles; Montaner, Joan

doi:10.1002/ana.23664

Cited by 43 publications

(41 citation statements)

References 35 publications

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“…162 After stroke onset, early initiation of anticoagulants, heparin or enoxaparin increases the risk of HT. 163 The activated partial thromboplastin time is associated with HT, 156,164 and genetic mutations in coagulation factors (factor XII and factor XIII) have been associated with HT. 164,165 A mutation in collagen type IV, an important component of the BBB basal lamina, promotes cerebral hemorrhage related to anticoagulants.…”

Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

“…163 The activated partial thromboplastin time is associated with HT, 156,164 and genetic mutations in coagulation factors (factor XII and factor XIII) have been associated with HT. 164,165 A mutation in collagen type IV, an important component of the BBB basal lamina, promotes cerebral hemorrhage related to anticoagulants. 166 In ischemic stroke, collagen type IV is reduced in the basal lamina within the first 1 to 24 hours, thus it may contribute to coagulationrelated HT.…”

Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

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Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

446

369

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Hemorrhagic transformation (HT) is a common complication of ischemic stroke that is exacerbated by thrombolytic therapy. Methods to better prevent, predict, and treat HT are needed. In this review, we summarize studies of HT in both animals and humans. We propose that early HT (o18 to 24 hours after stroke onset) relates to leukocyte-derived matrix metalloproteinase-9 (MMP-9) and brain-derived MMP-2 that damage the neurovascular unit and promote blood-brain barrier (BBB) disruption. This contrasts to delayed HT (418 to 24 hours after stroke) that relates to ischemia activation of brain proteases (MMP-2, MMP-3, MMP-9, and endogenous tissue plasminogen activator), neuroinflammation, and factors that promote vascular remodeling (vascular endothelial growth factor and high-moblity-group-box-1). Processes that mediate BBB repair and reduce HT risk are discussed, including transforming growth factor beta signaling in monocytes, Src kinase signaling, MMP inhibitors, and inhibitors of reactive oxygen species. Finally, clinical features associated with HT in patients with stroke are reviewed, including approaches to predict HT by clinical factors, brain imaging, and blood biomarkers. Though remarkable advances in our understanding of HT have been made, additional efforts are needed to translate these discoveries to the clinic and reduce the impact of HT on patients with ischemic stroke.

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Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

Section: Clinical Factors Associated With Hemorrhagic Transformationmentioning

confidence: 99%

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Jickling

Liu

Stamova

et al. 2013

J Cereb Blood Flow Metab

446

369

View full text Add to dashboard Cite

show abstract

“…Higher serum uric acid level was significantly associated with lower HT rate and better outcome among stroke patients with rtPA administration [121]. This recent meta analysis of 8131 acute ischemic stroke patients reports that high uric acid serum level on admission should be regarded as good prognostic marker, suggesting its positive impact on BBB damage.…”

Section: Uric Acidmentioning

confidence: 88%

“…A2M was reported to play role in migration and degranulation of neutrophils as well. Elevated level of A2M in the CSF is a reliable sign of BBB disruption [121].…”

Section: Geneticsmentioning

confidence: 99%

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Hemorrhagic transformation of ischemic stroke

J¹,

Hortobágyi²

2017

Vascul Dis Ther

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The better understanding of the diverse mechanisms leading to the hemorrhagic transformation of an ischemic stroke is the crucial point in the prevention of this altogether common phenomenon. The different individual risk factors include the anatomical variability of collateral blood supply, age, genetics, body weight, etiology of the occlusion, side of the occluded vessel, renal status, stroke severity, history of high serum glucose or hypertension and hypertension or hyperglycemia at the onset of the stroke, ferritin level, INR, antiplatelet usage or the platelet count etc. All these might contribute to the process of hemorrhagic transformation. These risk factors have been identified by retrospective epidemiological studies and are useful to identify patients who are at high risk for hemorrhagic conversion and help the decision between conservative, thrombolytic or more advanced treatments such as thrombectomy. The modulations of potential molecular targets participating in the process seem to be promising in animal models, but human trials are lacking the breakthrough success so far, both in extending the time frame of the thrombolysis and in replacing the recombinant tissue plasminogen activator (rtPA) as thrombolytic agent.So far, the careful preselection of patients eligible for thrombolytic therapy is the best way to prevent hemorrhagic transformation. The intensive research in the field revealing small but important molecular details are continuously contributing to the better understanding of hemorrhagic transformation with the intention of finding new agents that co-administrated to the rtPA or completely replacing that could decrease the risk of secondary bleeding.The aim of this review is to give comprehensive insight into the process of hemorrhagic transformation of ischemic stroke, starting with basic overview of the penumbra concept and the collateral supply followed by discussion of the recanalisation-reperfusion-hemorrhagic transformation process after vessel occlusion also highlighting the importance of timing and ratio of recanalisation spontaneously and in case of thrombolytic agent administration. We overview the risk factors of hemorrhagic transformation, which may be helpful to physicians to identify high risk patients before rtPA administration. The last part of the work is dealing with future therapeutic possibilities based on the so far revealed molecular mechanisms of hemorrhagic transformation. With the aim to assess the rate and influencing factors on the recanalisation and reperfusion rate 381 patients with large-vessel occlusion was investigated. The patient group involved ones treated with rtPA or treated conservatively. Partial or complete recanalisation was achieved in 121 out of 210 (58%) patients after intravenous rtPA administration. The recanalisation success was more likely if the patient had atrial fibrillation [4] -maybe because cardioembolic clots consists more fibrin and are more likely to reopen by plasmin proteolysis than thrombosis of an atherosclerotic plaq...

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Universal probe amplification: Multiplex screening technologies for genetic variations

Park

Lee

et al. 2014

Biotechnology Journal

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In order to achieve multiplex screening of genetic variations, multiplex amplification of target genomic DNA is necessary. Universal amplification technology meets this requirement by simultaneously amplifying a number of different regions within the target genomic DNA using a single pair of universal primers and thus eliminating the limitations associated with the use of multiple pairs of primers. We comprehensively review universal probe amplification and its use with multiplex technologies for the identification of the most representative genetic variation, i. e. single nucleotide polymorphisms. The progress and key issues relating to universal probe amplification are discussed and the representative technologies are summarized with an emphasis on their application for the identification of susceptibility to human diseases.

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A predictive clinical–genetic model of tissue plasminogen activator response in acute ischemic stroke

Abstract: Two functional polymorphisms were consistently associated with t-PA safety. Our validated LR-based score predicts t-PA safety in the Spanish population.

Cited by 43 publications

References 35 publications

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Hemorrhagic Transformation after Ischemic Stroke in Animals and Humans

Hemorrhagic transformation of ischemic stroke

Universal probe amplification: Multiplex screening technologies for genetic variations

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