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Seminars in Thrombosis and Hemostasis
Thieme Medical Publishers
Seminars in Thrombosis and Hemostasis

Thieme Medical Publishers

0094-6176

Seminars in Thrombosis and Hemostasis/Journal Seminars in Thrombosis and HemostasisSCIISTP
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    2021 Eberhard F. Mammen Award Announcements: Part II—Young Investigator Awards

    Emmanuel J. Favaloro
    9页
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Hemostasis and Neuroscience—Hemostasis and Fibrinolysis Involved in Brain Pathology and Brain Disorders

    Christine Lodberg HvasHau C. KwaanAnne-Mette Hvas
    3页
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Neurocoagulation from a Mechanistic Point of View in the Central Nervous System

    Shani BerkowitzShany Guly GofritKeren AltmanNitai Weinberg...
    11页
    查看更多>>摘要：Coagulation mechanisms are critical for maintaining homeostasis in the central nervous system (CNS). Thrombin, an important player of the coagulation cascade, activates protease activator receptors (PARs), members of the G-protein coupled receptor family. PAR1 is located on neurons and glia. Following thrombin activation, PAR1 signals through the extracellular signal-regulated kinase pathway, causing alterations in neuronal glutamate release and astrocytic morphological changes. Similarly, the anticoagulation factor activated protein C (aPC) can cleave PAR1, following interaction with the endothelial protein C receptor. Both thrombin and aPC are expressed on endothelial cells and pericytes in the blood-brain barrier (BBB). Thrombin-induced PAR1 activation increases cytosolic Ca2+ concentration in brain vessels, resulting in nitric oxide release and increasing F-actin stress fibers, damaging BBB integrity. aPC also induces PAR1 activation and preserves BBB vascular integrity via coupling to sphingosine 1 phosphate receptors. Thrombin-induced PAR1 overactivation and BBB disruption are evident in CNS pathologies. During epileptic seizures, BBB disruption promotes thrombin penetration. Thrombin induces PAR1 activation and potentiates N-methyl-D-aspartate receptors, inducing glutamate-mediated hyperexcitability. Specific PAR1 inhibition decreases status epilepticus severity in vivo. In stroke, the elevation of brain thrombin levels further compromises BBB integrity, with direct parenchymal damage, while systemic factor Xa inhibition improves neurological outcomes. In multiple sclerosis (MS), brain thrombin inhibitory capacity correlates with clinical presentation. Both thrombin inhibition by hirudin and the use of recombinant aPC improve disease severity in an MS animal model. This review presents the mechanisms underlying the effects of coagulation on the physiology and pathophysiology of the CNS.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease

    Tamara K. StevensonShannon J. MooreDaniel A. LawrenceGeoffrey G. Murphy...
    13页
    查看更多>>摘要：Tissue plasminogen activator's (tPA) fibrinolytic function in the vasculature is well-established. This specific role for tPA in the vasculature, however, contrasts with its pleiotropic activities in the central nervous system. Numerous physiological and pathological functions have been attributed to tPA in the central nervous system, including neurite outgrowth and regeneration; synaptic and spine plasticity; neurovascular coupling; neurodegeneration; microglial activation; and blood–brain barrier permeability. In addition, multiple substrates, both plasminogen-dependent and -independent, have been proposed to be responsible for tPA's action(s) in the central nervous system. This review aims to dissect a subset of these different functions and the different molecular mechanisms attributed to tPA in the context of learning and memory. We start from the original research that identified tPA as an immediate-early gene with a putative role in synaptic plasticity to what is currently known about tPA's role in a learning and memory disorder, Alzheimer's disease. We specifically focus on studies demonstrating tPA's involvement in the clearance of amyloid-β and neurovascular coupling. In addition, given that tPA has been shown to regulate blood–brain barrier permeability, which is perturbed in Alzheimer's disease, this review also discusses tPA-mediated vascular dysfunction and possible alternative mechanisms of action for tPA in Alzheimer's disease pathology.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Clinical Significance of Vascular Occlusive Events following Moderate-to-Severe Traumatic Brain Injury: An Observational Cohort Study

    Alexander Fletcher-Sandersj??Charles TatterJonathan TjerkaskiJiri Bartek Jr...
    8页
    查看更多>>摘要：Preventing hemorrhage progression is a potential therapeutic opportunity in traumatic brain injury (TBI) management, but its use has been limited by fear of provoking vascular occlusive events (VOEs). However, it is currently unclear whether VOE actually affects outcome in these patients. The aim of this study was to determine incidence, risk factors, and clinical significance of VOE in patients with moderate-to-severe TBI. A retrospective observational cohort study of adults (≥15 years) with moderate-to-severe TBI was performed. The presence of a VOE during hospitalization was noted from hospital charts and radiological reports. Functional outcome, using the Glasgow Outcome Scale (GOS), was assessed at 12 months posttrauma. Univariate and multivariate logistic regressions were used for endpoint assessment. In total, 848 patients were included, with a median admission Glasgow Coma Scale of 7. A VOE was detected in 54 (6.4%) patients, of which cerebral venous thrombosis was the most common (3.2%), followed by pulmonary embolism (1.7%) and deep vein thrombosis (1.3%). Length of ICU stay (p?<?0.001), body weight (p?=?0.002), and skull fracture (p?=?0.004) were independent predictors of VOE. VOE development did not significantly impact 12-month GOS, even after adjusting for potential confounders using propensity score matching. In conclusion, VOE in moderate-to-severe TBI patients was relatively uncommon, and did not affect 12-month GOS. This suggests that the potential benefit of treating bleeding progression might outweigh the risks of VOE.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Cerebral Venous Thrombosis

    Anne Hege AamodtThor H?kon Skatt?r
    9页
    查看更多>>摘要：Cerebral venous thrombosis (CVT) is a rare form of stroke that often affects younger age groups, especially reproductive age group females. CVT is a potentially fatal neurological condition that can be frequently overlooked due to the vague nature of its clinical and radiological presentation. Headache is the most common presenting symptom. However, a wide range of symptoms can be present and the symptom onset can be acute, subacute, or chronic. Neuroimaging is mandatory in cases where CVT is suspected. Both magnetic resonance venography and computed tomography venography can confirm a diagnosis of CVT. Anticoagulation with low-molecular-weight heparin is the mainstay of treatment. Intracranial hemorrhage is not considered a contraindication to the use of anticoagulants in CVT. Endovascular intervention is still controversial but can be a treatment option for patients with neurological deterioration or thrombus progression, despite the use of anticoagulation or with development of new or worsening intracerebral hemorrhage. Patients with CVT have an increased risk of recurrence of CVT and other types of venous thromboembolism. This review provides an overview of the epidemiology, diagnosis, and treatment of CVT in adults. Commentary about increased presentation of CVT in patients with coronavirus disease 2019 (COVID-19), or after immunization against COVID-19, is also provided.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Venous Thromboembolism Risk and Thromboprophylaxis in Pediatric Neurosurgery and Spinal Injury: Current Trends and Literature Review

    Dimitrios PanagopoulosPloutarchos KarydakisGeorgios NoutsosMarios Themistocleous...
    5页
    查看更多>>摘要：Although the entities of venous thromboembolism (VTE), deep venous thrombosis, pulmonary embolus, and thromboprophylaxis in adult patients undergoing brain tumor and spine surgery, traumatic brain injury and elective neurosurgical procedures are widely elucidated, the same is not valid when pediatric patients are under consideration. An attempt to review the peculiarities of these patients through a comprehensive bibliographic review is undertaken. We performed a narrative summary of the relevant literature dedicated to pediatric patients, centered on traumatic brain injury, the general incidence of thromboembolic disease in this patient population, the role of low molecular weight heparin (LMWH) in the treatment and prophylaxis of VTE, and its role in elective neurosurgical procedures, including spinal operations. Additionally, the risk of deep venous thrombosis in elective neurosurgical procedures is reviewed. Due to inherent limitations of the current studies, particularly a restricted number of patients, our data are underpowered to give a definitive protocol and guidelines for all the affected patients. Our current conclusions, based only on pediatric patients, argue that there is limited risk of VTE in pediatric patients suffering from brain tumors and that the possibility of VTE is very low in children undergoing elective neurosurgical procedures. There is no consensus regarding the exact incidence of VTE in traumatic brain injury patients. LMWH seems to be a safe and effective choice for the “at risk” pediatric patient population defined as being older than 15 years, venous catheterization, nonaccidental trauma, increased length of hospital stays, orthopaedic (including spinal) surgery, and cranial surgery.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    New Insights in Coagulation and Fibrinolysis in Patients with Primary Brain Cancer: A Systematic Review

    Anne Winther-LarsenBirgitte Sandfeld-PaulsenAnne-Mette Hvas
    15页
    查看更多>>摘要：Patients with primary brain tumors have a high incidence of thrombosis and hemorrhage. The underlying mechanism is believed to be derangement of their hemostatic system. To get nearer a clarification of this, we aimed to systematically review the existing literature regarding primary and secondary hemostasis as well as fibrinolysis in patients with primary brain tumor. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases PubMed, Embase, and Web of Science were searched on December 15, 2020, without time restrictions. Studies were included if they evaluated at least one blood coagulation and/or fibrinolysis parameter in patients with primary brain cancer. In total, 26 articles including 3,288 patients were included. Overall, increased activity of secondary hemostasis was observed as increased prothrombin fragment 1?+?2 and endogenous thrombin generation levels were found in glioma patients compared with controls. Furthermore, data showed a state of hypofibrinolysis with increased plasminogen activator inhibitor 1 and prolonged clot lysis time in glioma patients. In contrast, no consistent increase in the primary hemostasis was identified; however, data suggested that increased sP-selectin could be a biomarker of increased venous thromboembolism risk and that increased platelet count may be prognostic for survival. Lastly, data indicated that fibrinogen and D-dimer could hold prognostic value. In conclusion, this review indicates that an increased activity of secondary hemostasis and impaired fibrinolysis could be important players in the pathogeneses behind the high risk of thromboembolisms observed in brain cancer patients. Thus, long-term thromboprophylaxis may be beneficial and additional studies addressing this issue are wanted.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Nonhematologic and Hematologic Factors in Spontaneous Intracerebral Hemorrhage

    Hau C. Kwaan
    6页
    查看更多>>摘要：Spontaneous intracerebral hemorrhage is defined as nontraumatic bleeding into the brain without vascular malformations or presence of tumor. It occurs in about a third of all strokes and has a high mortality and morbidity. Risk factors that determine the outcome are incompletely understood. Known factors include older age, male gender, Asian ethnicity, hypertension, and comorbidity such as inherited or acquired bleeding diathesis and use of antithrombotic drugs. Likewise, the clinical characteristics of the hematoma such as location and volume of the hematoma and other imaging features are also important. Hematoma extension or expansion is a complication with an unfavorable outcome. Recognition of risk factors for hematoma expansion and measures to prevent it, such as blood pressure lowering, will improve the outcome. Enhanced diagnostic methods, especially in imaging techniques developed over the past decade, have not only led to a better understanding of the pathophysiology of spontaneous intracerebral hemorrhage but also of the factors that influence hematoma expansion. An improved knowledge is essential to better management, minimizing hematoma expansion and leading to a healthier outcome.
      原文链接:
    • NSTL
    • Thieme Medical Publishers

    Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders

    Kamand HaeriOmid Baradarian GhanbariAbbas AhmadiAkbar Dorgalaleh...
    12页
    查看更多>>摘要：Intracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV–FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.
      原文链接:
    • NSTL
    • Thieme Medical Publishers