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Source: Blood
Condition: Thrombosis
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Total 98 results found since Jan 2013.
Tissue-type plasminogen activator regulates macrophage activation and innate immunity
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires low-density lipoprotein receptor-related protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IBα phosphorylation. tPA independently induced transient IBα phosphorylation and extracellular signal-regulated kinase 1/2 (ERK1/2) activation in macrophages; however, these events did not trigger inflam...
Source: Blood - September 14, 2017 Category: Hematology Authors: Mantuano, E., Azmoon, P., Brifault, C., Banki, M. A., Gilder, A. S., Campana, W. M., Gonias, S. L. Tags: Immunobiology and Immunotherapy, Phagocytes, Granulocytes, and Myelopoiesis, Thrombosis and Hemostasis 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
Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin
Venous thromboembolism occurs in up to one-third of patients with primary brain tumors. Spontaneous intracranial hemorrhage (ICH) is also a frequent occurrence in these patients, but there is limited data on the safety of therapeutic anticoagulation. To determine the rate of ICH in patients treated with enoxaparin, we performed a matched, retrospective cohort study with blinded radiology review for 133 patients with high-grade glioma. After diagnosis of glioma, the cohort that received enoxaparin was 3 times more likely to develop a major ICH than those not treated with anticoagulation (14.7% vs 2.5%; P = .036; hazard rati...
Source: Blood - June 22, 2017 Category: Hematology Authors: Mantia, C., Uhlmann, E. J., Puligandla, M., Weber, G. M., Neuberg, D., Zwicker, J. I. Tags: Free Research Articles, Thrombosis and Hemostasis, Clinical Trials and Observations Source Type: research
Intracranial hemorrhage in patients with atrial fibrillation receiving anticoagulation therapy
We investigated the frequency and characteristics of intracranial hemorrhage (ICH), the factors associated with the risk of ICH, and outcomes post-ICH overall and by randomized treatment. We identified patients with ICH from the overall trial population enrolled in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial who received ≥1 dose of the study drug (n = 18 140). ICH was adjudicated by a central committee. Cox regression models were used to identify factors associated with ICH. ICH occurred in 174 patients; most ICH events were spontaneous (71.7%) versus traumatic (28.3...
Source: Blood - June 1, 2017 Category: Hematology Authors: Lopes, R. D., Guimaraes, P. O., Kolls, B. J., Wojdyla, D. M., Bushnell, C. D., Hanna, M., Easton, J. D., Thomas, L., Wallentin, L., Al-Khatib, S. M., Held, C., Gabriel Melo de Barros e Silva, P., Alexander, J. H., Granger, C. B., Diener, H.-C. 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
Plasma kallikrein mediates brain hemorrhage and edema caused by tissue plasminogen activator therapy in mice after stroke
Thrombolytic therapy using tissue plasminogen activator (tPA) in acute stroke is associated with increased risks of cerebral hemorrhagic transformation and angioedema. Although plasma kallikrein (PKal) has been implicated in contributing to both hematoma expansion and thrombosis in stroke, its role in the complications associated with the therapeutic use of tPA in stroke is not yet available. We investigated the effects of tPA on plasma prekallikrein (PPK) activation and the role of PKal on cerebral outcomes in a murine thrombotic stroke model treated with tPA. We show that tPA increases PKal activity in vitro in both muri...
Source: Blood - April 20, 2017 Category: Hematology Authors: Simao, F., Ustunkaya, T., Clermont, A. C., Feener, E. P. Tags: Thrombosis and Hemostasis Source Type: research
Platelet secretion is crucial to prevent bleeding in the ischemic brain but not in the inflamed skin or lung in mice
Platelets maintain hemostasis after injury, but also during inflammation. Recent studies have shown that platelets prevent inflammatory bleeding through (hem) immunoreceptor tyrosine-based activation motif-dependent mechanisms irrespective of aggregation during skin and lung inflammation. Although the exact mechanisms underlying this process remain unknown, it was speculated that mediators released from platelet granules might be involved. Maintaining cerebral hemostasis during stroke treatment is of high clinical relevance because hemorrhage may aggravate the disease state and increase mortality. Although it was shown tha...
Source: Blood - March 23, 2017 Category: Hematology Authors: Deppermann, C., Kraft, P., Volz, J., Schuhmann, M. K., Beck, S., Wolf, K., Stegner, D., Stoll, G., Nieswandt, B. Tags: Platelets and Thrombopoiesis, Thrombosis and Hemostasis, Brief Reports Source Type: research
Platelets and von Willebrand factor in atherogenesis
The role of platelet adhesion, activation, and aggregation in acute atherothrombotic events such as myocardial infarction and stroke is well established. There is increasing evidence that platelet-endothelial interactions also contribute to early atherosclerotic plaque initiation and growth. Through these interactions, platelet-derived factors can contribute to the proinflammatory and mitogenic status of resident mural cells. Among the many putative mechanisms for platelet-endothelial interactions, increased endothelial-associated von Willebrand factor, particularly in a multimerized form, which interacts with platelet gly...
Source: Blood - March 15, 2017 Category: Hematology Authors: Wu, M. D., Atkinson, T. M., Lindner, J. R. Tags: Hematopoiesis and Stem Cells, Thrombosis and Hemostasis, Vascular Biology, Blood Spotlight 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
Factor XI deficiency is associated with lower risk for cardiovascular and venous thromboembolism events
Factor XI deficiency is one of the rare inherited coagulation factor deficiencies. However, its incidence is high within the Ashkenazi Jewish community. Because factor XI displays both procoagulant and antifibrinolytic activities, it has been postulated that an underlying cardiovascular benefit may exist with factor XI deficiency. This historical cohort study was performed using the electronic database of Clalit Health Services, the largest health care provider in Israel. All adults tested for factor XI activity between 2002 and 2014 were included in the study. Factor XI activity was classified into 3 categories: normal (a...
Source: Blood - March 1, 2017 Category: Hematology Authors: Preis, M., Hirsch, J., Kotler, A., Zoabi, A., Stein, N., Rennert, G., Saliba, W. Tags: 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
How I use anticoagulation in atrial fibrillation
Atrial fibrillation is the most common cardiac arrhythmia and conveys a significant risk of morbidity and mortality due to related stroke and systemic embolism. Oral anticoagulation (OAC) is the mainstay of thromboembolism prevention, and management of anticoagulation can be challenging. For patients without significant valvular disease, decisions around anticoagulation therapy are first based on the presence of additional stroke risk factors, as measured by the CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75, diabetes, prior stroke or transient ischemic attack, vascular disease, age 65–74, and sex c...
Source: Blood - December 21, 2016 Category: Hematology Authors: Steinberg, B. A. Tags: How I Treat, Free Research Articles, 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
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
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
