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Total 198 results found since Jan 2013.
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
Platelets induce apoptosis via membrane-bound FasL
After tissue injury, both wound sealing and apoptosis contribute to restoration of tissue integrity and functionality. Although the role of platelets (PLTs) for wound closure and induction of regenerative processes is well established, the knowledge about their contribution to apoptosis is incomplete. Here, we show that PLTs present the death receptor Fas ligand (FasL) on their surface after activation. Activated PLTs as well as the isolated membrane fraction of activated PLTs but not of resting PLTs induced apoptosis in a dose-dependent manner in primary murine neuronal cells, human neuroblastoma cells, and mouse embryoni...
Source: Blood - September 17, 2015 Category: Hematology Authors: Schleicher, R. I., Reichenbach, F., Kraft, P., Kumar, A., Lescan, M., Todt, F., Gobel, K., Hilgendorf, I., Geisler, T., Bauer, A., Olbrich, M., Schaller, M., Wesselborg, S., O'Reilly, L., Meuth, S. G., Schulze-Osthoff, K., Gawaz, M., Li, X., Kleinschnitz, Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Association between ENPP1 K173Q and stroke in a newborn cohort of 395 Brazilian children with sickle cell anemia
Source: Blood - September 3, 2015 Category: Hematology Authors: Belisario, A. R., Sales, R. R., Toledo, N. E., Velloso-Rodrigues, C., Silva, C. M., Viana, M. B. Tags: Pediatric Hematology, Sickle Cell Disease, Red Cells, Iron, and Erythropoiesis CORRESPONDENCE Source Type: research
Activated protein C {beta}-glycoform promotes enhanced noncanonical PAR1 proteolysis and superior resistance to ischemic injury
In this study, a recombinant APC variant (APCN329Q) mimicking the naturally occurring APC-β plasma glycoform was found to exhibit superior PAR1 proteolysis at a cleavage site that selectively mediates cytoprotective signaling. APCN329Q also enhanced integrin αMβ2-dependent PAR1 proteolysis to exert significantly improved antiinflammatory activity on macrophages compared with wild-type APC. Recent therapeutic applications of recombinant APC in ischemic stroke models have used APC variants with limited anticoagulant activity to negate potential bleeding side effects. Using a mouse model of ischemic stroke and...
Source: Blood - August 13, 2015 Category: Hematology Authors: Gleeson, E. M., Dichiara, M. G., Salicio, A., Quinn, L. M., Drakeford, C., Russell, S. E., Walsh, P. T., Orbe, J., Hermida, J., Smith, O. P., O'Donnell, J. S., Montes, R., Preston, R. J. S. Tags: Thrombosis and Hemostasis, Brief Reports Source Type: research
Targeted downregulation of platelet CLEC-2 occurs through Syk-independent internalization
Platelet aggregation at sites of vascular injury is not only essential for hemostasis, but may also cause acute ischemic disease states such as myocardial infarction or stroke. The hemi-immunoreceptor tyrosine-based activation motif–containing C-type lectinlike receptor 2 (CLEC-2) mediates powerful platelet activation through a Src- and spleen tyrosine kinase (Syk)–dependent tyrosine phosphorylation cascade. Thereby, CLEC-2 not only contributes to thrombus formation and stabilization but also plays a central role in blood-lymphatic vessel development, tumor metastasis, and prevention of inflammatory bleeding, m...
Source: Blood - June 25, 2015 Category: Hematology Authors: Lorenz, V., Stegner, D., Stritt, S., Vogtle, T., Kiefer, F., Witke, W., Schymeinsky, J., Watson, S. P., Walzog, B., Nieswandt, B. Tags: Thrombocytopenia, Platelets and Thrombopoiesis THROMBOSIS AND HEMOSTASIS Source Type: research
How I treat and manage strokes in sickle cell disease
Neurologic complications are a major cause of morbidity and mortality in sickle cell disease (SCD). In children with sickle cell anemia, routine use of transcranial Doppler screening, coupled with regular blood transfusion therapy, has decreased the prevalence of overt stroke from ~11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with SCD and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurologic deficit includes evaluation by...
Source: Blood - May 28, 2015 Category: Hematology Authors: Kassim, A. A., Galadanci, N. A., Pruthi, S., DeBaun, M. R. Tags: Sickle Cell Disease, How I Treat, Free Research Articles, Red Cells, Iron, and Erythropoiesis, Clinical Trials and Observations Source Type: research
Activated protein C: biased for translation
The homeostatic blood protease, activated protein C (APC), can function as (1) an antithrombotic on the basis of inactivation of clotting factors Va and VIIIa; (2) a cytoprotective on the basis of endothelial barrier stabilization and anti-inflammatory and antiapoptotic actions; and (3) a regenerative on the basis of stimulation of neurogenesis, angiogenesis, and wound healing. Pharmacologic therapies using recombinant human and murine APCs indicate that APC provides effective acute or chronic therapies for a strikingly diverse range of preclinical injury models. APC reduces the damage caused by the following: ischemia/rep...
Source: Blood - May 7, 2015 Category: Hematology Authors: Griffin, J. H., Zlokovic, B. V., Mosnier, L. O. Tags: Vascular Biology, Review Articles Source Type: research
Chronic and acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia
This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is ...
Source: Blood - March 5, 2015 Category: Hematology Authors: Bernaudin, F., Verlhac, S., Arnaud, C., Kamdem, A., Vasile, M., Kasbi, F., Hau, I., Madhi, F., Fourmaux, C., Biscardi, S., Epaud, R., Pondarre, C. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis Source Type: research
Chronic acute anemia and extracranial internal carotid stenosis are risk factors for silent cerebral infarcts in sickle cell anemia
This study includes 189 stroke-free patients with SCA from the Créteil newborn cohort (1992-2010) followed longitudinally by magnetic resonance imaging/MRA, including cervical MRA at the last assessment. All patients with abnormal TCD and/or intracranial stenoses were placed on a transfusion program. Mean follow-up was 9.9 years (range, 2.2-19.9 years; 1844 patient-years). Annual rates of clinical events were calculated. The cumulative risk for SCI was 39.1% (95% confidence interval [CI], 23.5%-54.7%) by age 18 years, with no plateau. We confirm that baseline hemoglobin level lower than 7 g/dL before age 3 years is ...
Source: Blood - March 5, 2015 Category: Hematology Authors: Bernaudin, F., Verlhac, S., Arnaud, C., Kamdem, A., Vasile, M., Kasbi, F., Hau, I., Madhi, F., Fourmaux, C., Biscardi, S., Epaud, R., Pondarre, C. Tags: Sickle Cell Disease, Free Research Articles, Red Cells, Iron, and Erythropoiesis Source Type: research
Platelet transfusions in platelet consumptive disorders are associated with arterial thrombosis and in-hospital mortality
This study utilized the Nationwide Inpatient Sample to evaluate the current in-hospital platelet transfusion practices and their association with arterial/venous thrombosis, acute myocardial infarction (AMI), stroke, and in-hospital mortality over 5 years (2007-2011). Age and gender-adjusted odds ratios (adjOR) associated with platelet transfusions were calculated. There were 10 624 hospitalizations with TTP; 6332 with HIT and 79 980 with ITP. Platelet transfusions were reported in 10.1% TTP, 7.1% HIT, and 25.8% ITP admissions. Platelet transfusions in TTP were associated with higher odds of arterial thrombosis (adjOR = 5....
Source: Blood - February 26, 2015 Category: Hematology Authors: Goel, R., Ness, P. M., Takemoto, C. M., Krishnamurti, L., King, K. E., Tobian, A. A. R. Tags: Thrombocytopenia, Transfusion Medicine, Free Research Articles, Platelets and Thrombopoiesis, Clinical Trials and Observations 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
Risk of venous and arterial thrombotic events in patients diagnosed with superficial vein thrombosis: a nationwide cohort study
We examined this in a nationwide population-based setting during a period when SVT was not treated routinely with anticoagulants. The Danish National Registry of Patients, covering all Danish hospitals, was used to identify 10 973 patients with a first-time diagnosis of SVT between 1980 and 2012. A comparison cohort of 515 067 subjects, matched by age, gender, and calendar year, was selected from the general Danish population. Outcomes were venous thromboembolism, acute myocardial infarction, ischemic stroke, and death. During median follow-up of 7 years, the incidence rate of venous thromboembolism was 18.0/1000 person-ye...
Source: Blood - January 8, 2015 Category: Hematology Authors: Cannegieter, S. C., Horvath-Puho, E., Schmidt, M., Dekkers, O. M., Pedersen, L., Vandenbroucke, J. P., Sorensen, H. T. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations 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
Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures
Using data from ARISTOTLE, we describe the periprocedural management of anticoagulation and rates of subsequent clinical outcomes among patients chronically anticoagulated with warfarin or apixaban. We recorded whether (and for how long) anticoagulant therapy was interrupted preprocedure, whether bridging therapy was used, and the proportion of patients who experienced important clinical outcomes during the 30 days postprocedure. Of 10 674 procedures performed during follow-up in 5924 patients, 9260 were included in this analysis. Anticoagulant treatment was not interrupted preprocedure 37.5% of the time. During the 30 day...
Source: Blood - December 11, 2014 Category: Hematology Authors: Garcia, D., Alexander, J. H., Wallentin, L., Wojdyla, D. M., Thomas, L., Hanna, M., Al-Khatib, S. M., Dorian, P., Ansell, J., Commerford, P., Flaker, G., Lanas, F., Vinereanu, D., Xavier, D., Hylek, E. M., Held, C., Verheugt, F. W. A., Granger, C. B., Lop Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Platelet 12-LOX is essential for Fc{gamma}RIIa-mediated platelet activation
In this study, we show for the first time that platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of FcRIIa-mediated thrombosis. Pharmacologic inhibition of 12-LOX in human platelets resulted in significant attenuation of FcRIIa-mediated aggregation. Platelet 12-LOX was shown to be essential for FcRIIa-induced phospholipase C2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin αIIbβ3. Additionally, platelets from transgenic mice expressing human FcR...
Source: Blood - October 2, 2014 Category: Hematology Authors: Yeung, J., Tourdot, B. E., Fernandez-Perez, P., Vesci, J., Ren, J., Smyrniotis, C. J., Luci, D. K., Jadhav, A., Simeonov, A., Maloney, D. J., Holman, T. R., McKenzie, S. E., Holinstat, M. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
