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Source: Blood
Condition: Thrombosis
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Total 98 results found since Jan 2013.
Only severe thrombocytopenia results in bleeding and defective thrombus formation in mice
Platelets are essential mediators of hemostasis and thrombosis. Platelet counts (PCs) in humans average 250 platelets/nL, but it is not entirely clear how platelet numbers affect hemostasis and occurrence of thrombotic events. Mice, displaying PCs of ~1000 platelets/nL, are widely used to assess platelet function in (patho-)physiology, but also in this species, the significance of PC for hemostasis and thrombotic disease is not established. We reduced PCs in mice to defined ranges between 0 and 1000 platelets/nL by platelet-depleting antibodies and challenged them in different arterial thrombosis models: the transient midd...
Source: Blood - June 13, 2013 Category: Hematology Authors: Morowski, M., Vogtle, T., Kraft, P., Kleinschnitz, C., Stoll, G., Nieswandt, B. Tags: Thrombocytopenia, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Increased risk of CVD after VT is determined by common etiologic factors
In conclusion, individuals with VT had an increased risk of CVD. This could be explained by common etiologic factors.
Source: Blood - June 13, 2013 Category: Hematology Authors: Roach, R. E. J., Lijfering, W. M., Flinterman, L. E., Rosendaal, F. R., Cannegieter, S. C. Tags: Free Research Articles, Thrombosis and Hemostasis Source Type: research
Reperfusion of cerebral artery thrombosis by the GPIb-VWF blockade with the Nanobody ALX-0081 reduces brain infarct size in guinea pigs
Thrombolytic therapy is the cornerstone of treatment of acute atherothrombotic ischemic stroke but is associated with brain hemorrhage; antiplatelet therapy has limited efficacy and is still associated with intracranial bleeding. Therefore, new antithrombotic approaches with a better efficacy/safety ratio are required. We have assessed the effect of ALX-0081, a Nanobody against the A1 domain of von Willebrand factor (VWF) that blocks VWF binding to GPIb, of the thrombolytic agent recombinant tissue plasminogen activator (rtPA), and of the GPIIb/IIIa antagonist tirofiban, in a middle cerebral artery (MCA) thrombosis model i...
Source: Blood - June 20, 2013 Category: Hematology Authors: Momi, S., Tantucci, M., Van Roy, M., Ulrichts, H., Ricci, G., Gresele, P. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
Antithrombotic actions of statins involve PECAM-1 signaling
Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment of coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Because several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1 (platelet endothelial cell adhesion molecule-1), we investigated a potential connection between the influence of statins on platelet f...
Source: Blood - October 31, 2013 Category: Hematology Authors: Moraes, L. A., Vaiyapuri, S., Sasikumar, P., Ali, M. S., Kriek, N., Sage, T., Gibbins, J. M. Tags: Platelets and Thrombopoiesis Source Type: research
Spontaneous heparin-induced thrombocytopenia syndrome: 2 new cases and a proposal for defining this disorder
We describe 2 new cases presenting with thrombotic stroke/thrombocytopenia: one following shoulder hemi-arthroplasty (performed without heparin) and the other presenting to the emergency room without prior hospitalization, heparin exposure, or preceding infection. Both patients tested strongly positive for anti-platelet factor 4 (PF4)/heparin immunoglobulin (Ig)G in 2 different immunoassays and in the platelet serotonin-release assay. Crucially, both patients’ sera also caused strong (>80%) serotonin release in the absence of heparin, a serologic feature characteristic of delayed-onset HIT (ie, where heparin use p...
Source: Blood - June 5, 2014 Category: Hematology Authors: Warkentin, T. E., Basciano, P. A., Knopman, J., Bernstein, R. A. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Brief Reports Source Type: research
Lower risk for serious adverse events and no increased risk for cancer after PBSC vs BM donation
In conclusion, SAEs after donation are rare but more often occurred in BM donors and women. In addition, there was no evidence of increased risk for cancer, autoimmune illness, and stroke in donors receiving granulocyte colony-stimulating factor during this period of observation.
Source: Blood - June 5, 2014 Category: Hematology Authors: Pulsipher, M. A., Chitphakdithai, P., Logan, B. R., Navarro, W. H., Levine, J. E., Miller, J. P., Shaw, B. E., O'Donnell, P. V., Majhail, N. S., Confer, D. L. Tags: Transfusion Medicine, Transplantation Source Type: research
Targeted mutagenesis of zebrafish antithrombin III triggers disseminated intravascular coagulation and thrombosis, revealing insight into function
Pathologic blood clotting is a leading cause of morbidity and mortality in the developed world, underlying deep vein thrombosis, myocardial infarction, and stroke. Genetic predisposition to thrombosis is still poorly understood, and we hypothesize that there are many additional risk alleles and modifying factors remaining to be discovered. Mammalian models have contributed to our understanding of thrombosis, but are low throughput and costly. We have turned to the zebrafish, a tool for high-throughput genetic analysis. Using zinc finger nucleases, we show that disruption of the zebrafish antithrombin III (at3) locus result...
Source: Blood - July 3, 2014 Category: Hematology Authors: Liu, Y., Kretz, C. A., Maeder, M. L., Richter, C. E., Tsao, P., Vo, A. H., Huarng, M. C., Rode, T., Hu, Z., Mehra, R., Olson, S. T., Joung, J. K., Shavit, J. A. Tags: Thrombosis and Hemostasis 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
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
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
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
How I treat patients with inherited bleeding disorders who need anticoagulant therapy
Situations that ordinarily necessitate consideration of anticoagulation, such as arterial and venous thrombotic events and prevention of stroke in atrial fibrillation, become challenging in patients with inherited bleeding disorders such as hemophilia A, hemophilia B, and von Willebrand disease. There are no evidence-based guidelines to direct therapy in these patients, and management strategies that incorporate anticoagulation must weigh a treatment that carries a risk of hemorrhage in a patient who is already at heightened risk against the potential consequences of not treating the thrombotic event. In this paper, we rev...
Source: Blood - July 13, 2016 Category: Hematology Authors: Martin, K., Key, N. S. Tags: How I Treat, Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism
Recent genome-wide association studies (GWAS) have confirmed known risk mutations for venous thromboembolism (VTE) and identified a number of novel susceptibility loci in adults. Here we present a GWAS in 212 nuclear families with pediatric VTE followed by targeted next-generation sequencing (NGS) to identify causative mutations contributing to the association. Three single nucleotide polymorphisms (SNPs) exceeded the threshold for genome-wide significance as determined by permutation testing using 100 000 bootstrap permutations (P < 10–5). These SNPs reside in a region on chromosome 6q13 comprising the genes smal...
Source: Blood - February 8, 2017 Category: Hematology Authors: Rühle, F., Witten, A., Barysenka, A., Huge, A., Arning, A., Heller, C., Krümpel, A., Mesters, R., Franke, A., Lieb, W., Riemenschneider, M., Hiersche, M., Limperger, V., Nowak-Göttl, U., Stoll, M. Tags: Thrombosis and Hemostasis Source Type: research
Murine systemic thrombophilia and hemolytic uremic syndrome from a factor H point mutation
We describe here that disruption of FH function on the cell surface can also lead to disseminated complement-dependent macrovascular thrombosis. By gene targeting, we introduced a point mutation (W1206R) into murine FH that impaired its interaction with host cells but did not affect its plasma complement-regulating activity. Homozygous mutant mice carrying this mutation developed renal TMA as well as systemic thrombophilia involving large blood vessels in multiple organs, including liver, lung, spleen, and kidney. Approximately 30% of mutant mice displayed symptoms of stroke and ischemic retinopathy, and 48% died premature...
Source: Blood - March 1, 2017 Category: Hematology Authors: Ueda, Y., Mohammed, I., Song, D., Gullipalli, D., Zhou, L., Sato, S., Wang, Y., Gupta, S., Cheng, Z., Wang, H., Bao, J., Mao, Y., Brass, L., Zheng, X. L., Miwa, T., Palmer, M., Dunaief, J., Song, W.-C. Tags: Immunobiology, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research
