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Total 198 results found since Jan 2013.
Reduced ADAMTS13 activity during TTP remission is associated with stroke in TTP survivors
In conclusion, stroke is common after recovery from TTP and is associated with reduced ADAMTS13 activity during remission.
Source: Blood - September 25, 2019 Category: Hematology Authors: Upreti, H., Kasmani, J., Dane, K., Braunstein, E. M., Streiff, M. B., Shanbhag, S., Moliterno, A. R., Sperati, C. J., Gottesman, R. F., Brodsky, R. A., Kickler, T. S., Chaturvedi, S. Tags: Thrombosis and Hemostasis, Clinical Trials and Observations 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
Results from the Displace Consortium: Practice Patterns on the Use of Transcranial Doppler Screening for Risk of Stroke in Children with Sickle Cell Anemia
Conclusions: Nearly all DISPLACE sites order TCD screening annually, as recommended in the guidelines, with some ordering screening more frequently. A few sites did not report initiation of CRCT per STOP protocol for abnormal TCD results; however, over half of the sites reported following up with an MRI/MRA, which may suggest evaluating for vasculopathy prior to CRCT. Some sites reported beginning HU therapy for abnormal results; this may reflect consideration of patients for whom CRCT is not possible, but data were not collected for confirmation. Interestingly, results suggest a reliance on MRI/MRA since sites commonly re...
Source: Blood - November 21, 2018 Category: Hematology Authors: Phillips, S., Mueller, M., Schlenz, A. M., Melvin, C., Adams, R. J., Kanter, J. Tags: 901. Health Services Research-Non-Malignant Conditions: Poster III 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
Low Hemoglobin Increases Risk for Stroke, Kidney Disease, Elevated Estimated Pulmonary Artery Systolic Pressure, and Premature Death in Sickle Cell Disease: A Systematic Literature Review and Meta-Analysis
Conclusions: In conclusion, comprehensive evaluation of peer-reviewed literature published over the past 20 years demonstrates a significant relationship between chronic anemia and worse clinical outcomes in individuals with SCD. Meta-analyses further demonstrate that even relatively modest differences in hemoglobin are important and support hemoglobin increase by ≥1 g/dL as a relevant therapeutic target. These results suggest that interventions that reduce hemolytic anemia may confer clinical benefit in this patient population.DisclosuresAtaga: Novartis: Consultancy, Honoraria; Bioverativ: Honoraria, Membership on an e...
Source: Blood - November 21, 2018 Category: Hematology Authors: Ataga, K. I., Gordeuk, V. R., Allen, I. E., Colby, J., Gittings, K., Agodoa, I. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
Stroke in a Pediatric Immune Thrombocytopenia Case
Conclusion: Stroke in the immune thrombocytopenic clinic is a rare but hard to manage condition. Although its mechanism not understand well, the clinician should be identify and manage it carefully.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - November 21, 2018 Category: Hematology Authors: Leblebisatan, G., Cil, M., Sasmaz, H. I., Kilinc, Y., Soyupak, S. Tags: 311. Disorders of Platelet Number or Function 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
Innovative thrombolytic strategy using a heterodimer diabody against TAFI and PAI-1 in mouse models of thrombosis and stroke
In conclusion, administration of a bispecific inhibitor against TAFI and PAI-1 results in a prominent profibrinolytic effect in mice without increased bleeding.
Source: Blood - February 19, 2015 Category: Hematology Authors: Wyseure, T., Rubio, M., Denorme, F., Martinez de Lizarrondo, S., Peeters, M., Gils, A., De Meyer, S. F., Vivien, D., Declerck, P. J. Tags: 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
Outcomes in Children with Severe Vasculopathy from Sickle Cell Anemia after Treatment with Chronic Transfusion, Surgical Revascularization and/or Allogenic Hematopoetic Stem Cell Transplantation
Conclusions: The risk for cerebral infarction and/or vasculopathy progression after initiation of treatment with either chronic transfusion, HSCT or EDAS is still a major concern. Our data suggest HSCT and surgical revascularization with chronic transfusion provide the greatest benefit in reducing stroke risk and HSCT reduces risk for progression of a severe vasculopathy. Additional, large population studies are needed to clarify the risk.DisclosuresMajumdar: NIMHD: Research Funding. Campbell: Functional Fluitics: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on ...
Source: Blood - November 21, 2018 Category: Hematology Authors: Johnson, C. W., Majumdar, S., Campbell, A. D., Magge, S., Darbari, D. S., Webb, J., Diab, Y. A., Nickel, R. S., Speller-Brown, B., Carpenter, J., Abraham, A. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Poster I Source Type: research
SOD3-Mimetic As a Complement for Genetic Therapy in Sickle Cell Disease
Conclusions:The present results support development of SanFlow, delivered through continuous infusion, for anemic SCD children to prevent the development of blood transfusion dependency in order to avoid stroke and painful vaso-occlusive crisis (VOC). These results also demonstrated that SanFlow can be used safely and effectively in the elimination of serious painful vaso-occlusive crisis and protect silent and major strokes. Clinical trials of SanFlow in SCD children, prior to their transfusion dependence, as well as in transfusion-dependent teenagers and adults with SCD patients are warranted. By extension, ß-Thala...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hsia, C. J., Ma, L. Tags: 113. Hemoglobinopathies, Excluding Thalassemia-Basic and Translational Science: Poster II Source Type: research
Central nervous system complications and management in sickle cell disease
With advances in brain imaging and completion of randomized clinical trials (RCTs) for primary and secondary stroke prevention, the natural history of central nervous system (CNS) complications in sickle cell disease (SCD) is evolving. In order of current prevalence, the primary CNS complications include silent cerebral infarcts (39% by 18 years), headache (both acute and chronic: 36% in children with sickle cell anemia [SCA]), ischemic stroke (as low as 1% in children with SCA with effective screening and prophylaxis, but ~11% in children with SCA without screening), and hemorrhagic stroke in children and adults with SCA ...
Source: Blood - February 18, 2016 Category: Hematology Authors: DeBaun, M. R., Kirkham, F. J. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis, Review Articles, Review Series, Clinical Trials and Observations Source Type: research
Incidence of Bleeding in Patients with Sickle Cell Disease: A Population Based Study
Conclusion:The findings from our study indicate that SCD patients have a high cumulative incidence of bleeding. While the increased incidence of intracranial, urological, and retinal bleeding has been previously described and are confirmed here, we present the novel finding that SCD patients also have a high incidence of GI bleeding, the majority of which are from an upper GI source. The association of hemorrhagic stroke with a history of ischemic stroke is also confirmed. The association of bleeding with VTE is likely due, at least in part, to anticoagulation. Further studies on the causes and risk factors for GI bleeding...
Source: Blood - November 21, 2018 Category: Hematology Authors: Hariharan, N., Brunson, A. M., Keegan, T. H. M., Wun, T. Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
