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Source: Blood
Condition: Ischemic Stroke
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Total 64 results found since Jan 2013.
Elevated Levels of CD64 MFI on Monocyte Subsets Are Associated with a History of Stroke in Sickle Cell Disease
Conclusion: Levels of monocyte subsets have been shown to correlate with clinical outcomes in non-SCD stroke, but to our knowledge this is the first study to examine their roles in ischemic stroke in SCD. The pathophysiology of stroke in SCD is unique and the role of monocytes in it deserves separate study from the role of monocytes in non-SCD stroke. We saw that while monocyte subsets were associated with a history of ischemic stroke, CD64 MFI on all monocyte subsets showed a strong association. We wonder if this may be due to CD64 MFI being a marker for cells which are more adherent to endothelium as has been shown in pr...
Source: Blood - November 21, 2018 Category: Hematology Authors: Curtis, S. A., Balbuena-Merle, R., Devine, L., Zelterman, D., Roberts, J. D., Dearborn-Tomazos, J., Sansing, L., Hendrickson, J. E. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis
Conclusions: Our results suggest that inherited thrombophilias including FVL, PTM, PCD, and PSD are associated with an increased risk of arterial ischemic stroke, particularly in young patients. The association with FVL and PTM is stronger in the homozygous than in the heterozygous state, suggesting a potential dose-response relationship and causal role for inherited thrombophilias. The implications of these findings with respect to the evaluation and management of patients with ischemic stroke require further investigation.DisclosuresCrowther: Alnylam: Equity Ownership; Daiichi Sankyo: Membership on an entity's Board of D...
Source: Blood - November 21, 2018 Category: Hematology Authors: Chiasakul, T., De Jesus, E., Tong, J., Chen, Y., Crowther, M., Garcia, D. A., Chai-Adisaksopha, C., Messe, S. R., Cuker, A. Tags: 331. Pathophysiology of Thrombosis: Poster II Source Type: research
Vascular Proteomics Reveals Critical Roles of ADAMTS18 in Stroke Associated with Imbalanced Level of Von Willebrand Factor Versus ADAMTS13
Conclusion and Significance-Results of this first vascular proteomic study of Adamts18 KO mice establish a substantial new resource for investigation of how ADAMTS gene affects cellular phenotypes of stroke. These new findings contribute to inform novel prevention strategies and direct therapeutic development for stroke.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Zhu, R., Pan, Y.-H., Lu, T., Dang, S., Liao, C.-C., Zhang, W. Tags: 301. Vascular Wall Biology, Endothelial Progenitor Cells, and Platelet Adhesion, Activation, and Biochemistry: Poster III Source Type: research
Low ADAMTS13 activity is associated with an increased risk of ischemic stroke
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin motif repeats 13) has antithrombotic properties because it cleaves von Willebrand factor (VWF) in smaller, less active multimers. The aim of our study was to investigate prospectively the association between ADAMTS13 activity and ischemic stroke. We included 5941 individuals ≥55 years without a history of stroke or transient ischemic attack (TIA) of the Rotterdam Study, a population-based cohort study. ADAMTS13 activity was measured at inclusion with the FRETS-VWF73 assay and VWF antigen (VWF:Ag) levels by enzyme-linked immunosorbent assay. We assessed ...
Source: Blood - December 17, 2015 Category: Hematology Authors: Sonneveld, M. A. H., de Maat, M. P. M., Portegies, M. L. P., Kavousi, M., Hofman, A., Turecek, P. L., Rottensteiner, H., Scheiflinger, F., Koudstaal, P. J., Ikram, M. A., Leebeek, F. W. G. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Thrombophilia risk is not increased in children after perinatal stroke
Perinatal stroke causes cerebral palsy and lifelong disability. Specific diseases are definable, but mechanisms are poorly understood. Evidence suggests possible associations between arterial perinatal stroke and prothrombotic disorders, but population-based, controlled, disease-specific studies are limited. Understanding thrombophilia in perinatal stroke informs pathogenesis models and clinical management. We conducted a population-based, prospective, case-control study to determine the association of specific perinatal stroke diseases with known thrombophilias. Children with idiopathic magnetic resonance imaging–cl...
Source: Blood - May 18, 2017 Category: Hematology Authors: Curtis, C., Mineyko, A., Massicotte, P., Leaker, M., Jiang, X. Y., Floer, A., Kirton, A. Tags: Pediatric Hematology, Free Research Articles, Thrombosis and Hemostasis, Vascular Biology, CME article Source Type: research
A Genetic Variant in GOLGB1 Affects Golgi Function and Stroke Risk in Patients with Sickle Cell Disease
Conclusions: Our study has shown that a coding variant in GOLGB1, identified as protective against risk of stroke in patients with SCD, has significant effects on Golgi function in SCD samples. We observed that having the GOLGB1 Y1212C variant resulted in more compact and less fragmented Golgi apparatus. Proteomic analysis showed that SCD patients with the GOLGB1 variant also had significantly lower levels of proteins involved in platelet activation and Golgi trafficking. Our findings suggest a novel role for the Golgi apparatus in controlling protein flux that modulates risk of stroke in SCD.DisclosuresNo relevant conflic...
Source: Blood - November 21, 2018 Category: Hematology Authors: Kotu, V., Dubrelle, J., Baker, J., Jenson, K., Flanagan, J. M. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster III Source Type: research
Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation
L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher ...
Source: Blood - March 10, 2016 Category: Hematology Authors: Shen, M.-Y., Chen, F.-Y., Hsu, J.-F., Fu, R.-H., Chang, C.-M., Chang, C.-T., Liu, C.-H., Wu, J.-R., Lee, A.-S., Chan, H.-C., Sheu, J.-R., Lin, S.-Z., Shyu, W.-C., Sawamura, T., Chang, K.-C., Hsu, C. Y., Chen, C.-H. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
ADAMTS13-mediated thrombolysis of t-PA-resistant occlusions in ischemic stroke in mice
Rapid vascular recanalization forms the basis for successful treatment of cerebral ischemia. Currently, tissue plasminogen activator (t-PA) is the only approved thrombolytic drug for ischemic stroke. However, t-PA does not always result in efficient thrombus dissolution and subsequent blood vessel recanalization. To better understand thrombus composition, we analyzed thrombi retrieved from ischemic stroke patients and found a distinct presence of von Willebrand factor (VWF) in various samples. Thrombi contained on average 20.3% ± 10.1% VWF, and this was inversely correlated with thrombus red blood cell content. We h...
Source: Blood - May 11, 2016 Category: Hematology Authors: Denorme, F., Langhauser, F., Desender, L., Vandenbulcke, A., Rottensteiner, H., Plaimauer, B., Francois, O., Andersson, T., Deckmyn, H., Scheiflinger, F., Kleinschnitz, C., Vanhoorelbeke, K., De Meyer, S. F. Tags: Thrombosis and Hemostasis Source Type: research
Recurrent Stroke: The Role of Thrombophilia in a Large International Pediatric Stroke Population
CONCLUSIONS:Identifying children at increased for recurrent AIS events is important in intensifying preventative measures. Among 894 Canadian, English and German pediatric stroke patients, 17.9% experienced recurrent AIS at a median of 3.1 months after the index stroke. The presence of more than one prothrombotic risk factor is associated with AIS recurrence in childrenDisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Deveber, G., Kirkham, F. J., Shannon, K., Brandao, L. R., Strater, R., Kenet, G., Clausnizer, H., Moharir, M., Kausch, M., Askalan, R., MacGregor, D., Stoll, M., Torge, A., Dlamini, N., Ganesan, V., Prengler, M., Singh, J., Nowak Goettl, U. Tags: 331. Pathophysiology of Thrombosis: Poster III Source Type: research
ADAMTS13 controls vascular remodeling by modifying VWF reactivity during stroke recovery
Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)–cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) break...
Source: Blood - July 6, 2017 Category: Hematology Authors: Xu, H., Cao, Y., Yang, X., Cai, P., Kang, L., Zhu, X., Luo, H., Lu, L., Wei, L., Bai, X., Zhu, Y., Zhao, B.-Q., Fan, W. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research
PAR1 biased signaling is required for activated protein C in vivo benefits in sepsis and stroke
Activated protein C (APC) cleaves protease-activated receptor 1 (PAR1) in vitro at R46 to initiate beneficial cell signaling; however, thrombin and APC can cleave at R41. To elucidate PAR1-dependent aspects of the pharmacologic in vivo mechanisms of APC, we generated C57BL/6 mouse strains carrying QQ41 or QQ46 point mutations in PAR1 (F2r gene). Using these strains, we determined whether or not recombinant murine signaling-selective APC mutants would reduce septic death or provide neuroprotection against ischemic stroke when mice carried PAR1-homozygous mutations that prevent cleavage at either R41 or R46. Intercrossing PA...
Source: Blood - March 15, 2018 Category: Hematology Authors: Sinha, R. K., Wang, Y., Zhao, Z., Xu, X., Burnier, L., Gupta, N., Fernandez, J. A., Martin, G., Kupriyanov, S., Mosnier, L. O., Zlokovic, B. V., Griffin, J. H. Tags: Plenary Papers, Thrombosis and Hemostasis, Vascular Biology Source Type: research
Regulatory T cells are strong promoters of acute ischemic stroke in mice by inducing dysfunction of the cerebral microvasculature
We have recently identified T cells as important mediators of ischemic brain damage, but the contribution of the different T-cell subsets is unclear. Forkhead box P3 (FoxP3)–positive regulatory T cells (Tregs) are generally regarded as prototypic anti-inflammatory cells that maintain immune tolerance and counteract tissue damage in a variety of immune-mediated disorders. In the present study, we examined the role of Tregs after experimental brain ischemia/reperfusion injury. Selective depletion of Tregs in the DEREG mouse model dramatically reduced infarct size and improved neurologic function 24 hours after stroke a...
Source: Blood - January 24, 2013 Category: Hematology Authors: Kleinschnitz, C., Kraft, P., Dreykluft, A., Hagedorn, I., Gobel, K., Schuhmann, M. K., Langhauser, F., Helluy, X., Schwarz, T., Bittner, S., Mayer, C. T., Brede, M., Varallyay, C., Pham, M., Bendszus, M., Jakob, P., Magnus, T., Meuth, S. G., Iwakura, Y., Tags: Thrombosis and Hemostasis Source Type: research
SLAP/SLAP2 prevent excessive platelet (hem)ITAM signaling in thrombosis and ischemic stroke in mice
In this study, we show that platelets expressed both SLAP isoforms and that overexpression of either protein in a heterologous cell line almost completely inhibited glycoprotein VI and C-type lectin-like receptor 2 signaling. In mice, single deficiency of SLAP or SLAP2 had only moderate effects on platelet function, whereas double deficiency of both adapters resulted in markedly increased signal transduction, integrin activation, granule release, aggregation, procoagulant activity, and thrombin generation in response to (hem)ITAM-coupled, but not G protein-coupled, receptor activation. In vivo, constitutive SLAP/SLAP2 knoc...
Source: Blood - January 1, 2015 Category: Hematology Authors: Cherpokova, D., Bender, M., Morowski, M., Kraft, P., Schuhmann, M. K., Akbar, S. M., Sultan, C. S., Hughes, C. E., Kleinschnitz, C., Stoll, G., Dragone, L. L., Watson, S. P., Tomlinson, M. G., Nieswandt, B. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Platelet-derived VWF is not essential for normal thrombosis and hemostasis but fosters ischemic stroke injury in mice
Von Willebrand factor (VWF) is a key hemostatic protein synthesized in both endothelial cells and megakaryocytes. Megakaryocyte-derived VWF is stored in α-granules of platelets and is enriched in hyperactive "ultra-large" VWF multimers. To elucidate the specific contribution of platelet VWF in hemostasis and thrombosis, we performed crossed bone marrow transplantations between C57BL/6J and Vwf–/– mice to generate chimeric mice. Chimeric mice specifically lacking platelet VWF showed normal tail bleeding and carotid artery thrombosis, similar to wild-type mice. Chimeric mice with VWF present only in platele...
Source: Blood - October 1, 2015 Category: Hematology Authors: Verhenne, S., Denorme, F., Libbrecht, S., Vandenbulcke, A., Pareyn, I., Deckmyn, H., Lambrecht, A., Nieswandt, B., Kleinschnitz, C., Vanhoorelbeke, K., De Meyer, S. F. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
A genome-wide association study identifies new loci for factor VII and implicates factor VII in ischemic stroke etiology
Factor VII (FVII) is an important component of the coagulation cascade. Few genetic loci regulating FVII activity and/or levels have been discovered to date. We conducted a meta-analysis of 9 genome-wide association studies of plasma FVII levels (7 FVII activity and 2 FVII antigen) among 27 495 participants of European and African ancestry. Each study performed ancestry-specific association analyses. Inverse variance weighted meta-analysis was performed within each ancestry group and then combined for a trans-ancestry meta-analysis. Our primary analysis included the 7 studies that measured FVII activity, and a secondary an...
Source: Blood - February 28, 2019 Category: Hematology Authors: de Vries, P. S., Sabater-Lleal, M., Huffman, J. E., Marten, J., Song, C., Pankratz, N., Bartz, T. M., de Haan, H. G., Delgado, G. E., Eicher, J. D., Martinez-Perez, A., Ward-Caviness, C. K., Brody, J. A., Chen, M.-H., de Maat, M. P. M., Franberg, M., Gill Tags: Thrombosis and Hemostasis Source Type: research
