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Von Willebrand Factor

Michel W J Smeets, Ruben Bierings, Henriet Meems, Frederik P J Mul, Dirk Geerts, Alexander P J Vlaar, Jan Voorberg, Peter L Hordijk
[This corrects the article DOI: 10.1371/journal.pone.0173077.].
2018: PloS One
Pernille Just Vinholt, Anne B Alnor, Mads Nybo, Anne-Mette Hvas
: In thrombocytopenia, differences in haemostatic capacity may explain discrepancies in bleeding risk between patients with cancer and patients with liver cirrhosis. The objective was to compare the haemostatic capacity in different thrombocytopenic patient populations. We evaluated platelet aggregation using impedance aggregometry (Multiplate Analyzer), von Willebrand factor antigen (VWF:Ag), VWF:ristocetin-cofactor activity (VWF:RCo), activated partial thromboplastin time (aPTT), coagulation factor VIII, fibrinogen, and thrombin generation in adult hospitalized patients with platelet count less than 80 × 10/l...
March 19, 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Kristina Busygina, Janina Jamasbi, Till Seiler, Hans Deckmyn, Christian Weber, Richard Brandl, Reinhard Lorenz, Wolfgang Siess
Interaction of Von Willebrand factor (VWF) with platelet glycoprotein (GP) Ib and of collagen with GPVI is essential for thrombus formation on ruptured or eroded atherosclerotic plaques (atherothrombosis). GPIb and GPVI signal through Bruton tyrosine kinase (Btk) which can irreversibly be blocked by oral application of ibrutinib, an established therapy for chronic lymphocytic leukemia (CLL) with long term safety. We found that ibrutinib and the novel Btk-inhibitors acalabrutinib and ONO/GS-4059 block GPVI-dependent static platelet aggregation in blood exposed to human plaque homogenate and collagen but not to ADP or arachidonic acid...
March 20, 2018: Blood
Sallu Jabati, Jawed Fareed, Jeffrey Liles, Abigail Otto, Debra Hoppensteadt, Jack Bontekoe, Trung Phan, Amanda Walborn, Mushabbar Syed
The purpose of this study was to determine whether there are any differences in the levels of inflammatory, thrombotic, and collagen turnover biomarkers between individuals with atrial fibrillation (AF) and healthy volunteers. Circulating plasma levels of plasminogen activator inhibitor 1 (PAI-1), CD40-ligand (CD40-L), nucleosomes (which are indicators of cell death), C-reactive protein (CRP), procollagen III N-terminal propeptide (PIIINP), procollagen III C-terminal propeptide (PIIICP), procollagen I N-terminal propeptide, tissue plasminogen activator, and von Willebrand factor were analyzed as potential biomarkers of AF...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
Katrine Munk Begtrup, Johanne Andersen Hojbjerg, Birgitte Vrou Offersen, Anne-Mette Hvas
Cancer is associated with increased risk of venous thromboembolic disease. Venous thromboembolic disease accounts for a substantial addition to morbidity and mortality rates in cancer patients and is the second leading cause of death in cancer patients, exceeded only by the underlying cancer. Only few previous studies have investigated the influence of radiotherapy on hemostasis and whether radiotherapy in itself causes an increased risk of venous thromboembolic disease. The aim was to investigate if adjuvant radiotherapy affects hemostasis after surgery and chemotherapy in patients with breast cancer...
March 19, 2018: Platelets
Sonntana Seang, Prasit Pavasant, Chalida N Limjeerajarus
INTRODUCTION: Angiogenesis is a key determinant in dental pulp regeneration. Iloprost is a synthetic prostacyclin that promotes angiogenesis. A three-dimensional culture that mimics the in vivo condition has been used in tissue engineering. This study investigated the effect of iloprost on promoting dental pulp angiogenesis by using the tooth slice organ culture system. METHODS: Tooth slices with intact pulp tissue were cut from molars extracted from 12 patients...
March 14, 2018: Journal of Endodontics
Federico Moccetti, Craig C Weinkauf, Brian P Davidson, J Todd Belcik, Edmund R Marinelli, Evan Unger, Jonathan R Lindner
The aim of this study was to evaluate a panel of endothelium-targeted microbubble (MB) ultrasound contrast agents bearing small peptide ligands as a human-ready approach for molecular imaging of markers of high-risk atherosclerotic plaque. Small peptide ligands with established affinity for human P-selectin, VCAM-1, LOX-1 and von Willebrand factor (VWF) were conjugated to the surface of lipid-stabilized MBs. Contrast-enhanced ultrasound (CEUS) molecular imaging of the thoracic aorta was performed in wild-type and gene-targeted mice with advanced atherosclerosis (DKO)...
March 13, 2018: Ultrasound in Medicine & Biology
Kang An, Hang Yin, Ju Mei, Jiaquan Zhu, Min Tang
OBJECTIVES: We retrospectively analysed data from non-valvular atrial fibrillation (AF) patients who underwent minimally invasive surgical AF ablation at our centre. Our purpose was to explore the atrial endocardial expression of von Willebrand factor (vWF) and thrombomodulin (TM) and their association with rhythm results after the procedure. METHODS: From January 2014 to May 2015, 60 patients underwent minimally invasive surgical AF ablation at our centre. Left atrial appendage samples were obtained during the procedure and immunohistochemistry for endocardial markers including vWF and TM was performed and semi-quantitatively graded...
March 14, 2018: Interactive Cardiovascular and Thoracic Surgery
Cédric Garcia, Nicolas Montée, Julien Faccini, Jennifer Series, Olivier Meilhac, Anne-Valérie Cantero, Pauline Le Faouder, Meyer Elbaz, Bernard Payrastre, Cécile Vindis
BACKGROUND: While high-density lipoproteins (HDL) have anti-thrombotic effects by reducing platelet activation, the relationship between HDL levels and the risk of acute coronary syndrome (ACS) is unclear since HDL particles are heterogeneous in composition and biological properties OBJECTIVE: We characterized the effects of HDL2 and HDL3 subclasses from ACS patients and non-coronary artery disease (CAD) subjects on platelet activation. METHODS: We measured platelet aggregation and ex vivo thrombus formation, analyzed signaling pathways by flow cytometry and performed a targeted lipidomics analysis on HDL subclasses RESULTS: Analysis of human platelet aggregation in suspension, adhesion on von Willebrand factor and thrombus formation on collagen under arterial shear demonstrated that HDL2 subclass from ACS patients had a higher antiplatelet potency compared to ACS HDL3 particles and HDL subclasses from non-CAD subjects...
March 15, 2018: Journal of Thrombosis and Haemostasis: JTH
H-H Brackmann, G C White, E Berntorp, T Andersen, C Escuriola-Ettingshausen
Development of inhibitory antibodies to infused factor VIII (FVIII) concentrates continues to be the most serious complication of haemophilia A management. Induction of immune tolerance by administering high doses of FVIII concentrate (antigen) and prothrombin complex concentrates to control bleeding was originated in the 1970s in Bonn, Germany, by Dr Hans-Hermann Brackmann, and became known as the Bonn protocol. ITI transformed the life of the index patient, who was 19 years of age when he began treatment, and dramatically improved the medical landscape for all patients with haemophilia and inhibitors...
April 2018: Haemophilia: the Official Journal of the World Federation of Hemophilia
Chantal C Clark, Mirjam M Mebius, Steven de Maat, Aloysius G M Tielens, Philip G de Groot, Rolf T Urbanus, Rob Fijnheer, Bouke P C Hazenberg, Jaap J van Hellemond, Coen Maas
ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) cleaves von Willebrand Factor (VWF) multimers to control their thrombogenicity. The fibrinolytic enzyme plasmin can cleave VWF in a similar manner. However, plasmin can also cleave ADAMTS13, which ultimately inactivates it. This leaves the overall role of plasmin in primary haemostasis uncertain.We investigated the combined molecular effects of plasmin on VWF and ADAMTS13. We first identified that plasmin destroys FRETS-VWF73 substrate by cleaving the ADAMTS13 binding region in a buffered system...
March 2018: Thrombosis and Haemostasis
Keenan A Walker, Jeremy Walston, Rebecca F Gottesman, Anna Kucharska-Newton, Priya Palta, B Gwen Windham
Background: Evidence suggests systemic inflammation may have a mechanistic role in age-related frailty, yet prospective data is limited. We examined whether systemic inflammation during midlife was associated with late-life frailty within the community-based Atherosclerosis Risk in Communities Study. Methods: Plasma levels of four inflammatory markers (fibrinogen, von Willebrand factor, and Factor VIII, and white blood cell count) were measured during Visit 1 (1987-89; mean age: 52[5]), standardized into z-scores, and combined to create an inflammation composite score...
March 9, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Christina Brandenburger, Victoria Unislawski, Ulrich Budde, Armin Zittermann, Jan Gummert, Cornelius Knabbe, Ingvild Birschmann
No abstract text is available yet for this article.
March 12, 2018: Journal of Cardiovascular Surgery
Yuka Matsunaga, Masataka Ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shouichi Ohga
BACKGROUND: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. CASE PRESENTATION: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle...
February 7, 2018: Pediatrics and Neonatology
Peter D Sottile, David Albers, Marc M Moss
BACKGROUND: Neuromuscular blockade (NMB) is a therapy for acute respiratory distress syndrome (ARDS). However, the mechanism by which NMB may improve outcome for ARDS patients remains unclear. We sought to determine whether NMB attenuates biomarkers of epithelial and endothelial lung injury and systemic inflammation in ARDS patients, and whether the association is dependent on tidal volume size and the initial degree of hypoxemia. METHODS: We performed a secondary analysis of patients enrolled in the ARDS network low tidal volume ventilation (ARMA) study...
March 10, 2018: Critical Care: the Official Journal of the Critical Care Forum
Qizhen Shi
Gene therapy is an attractive approach for disease treatment. Since platelets are abundant cells circulating in blood with the distinctive abilities of storage and delivery and fundamental roles in hemostasis and immunity, they could be a unique target for gene therapy of diseases. Recent studies have demonstrated that ectopic expression of factor VIII (FVIII) in platelets under control of the platelet-specific promoter results in FVIII storage together with its carrier protein von Willebrand factor (VWF) in α-granules and the phenotypic correction of hemophilia A...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
Alfia Khaibullina, Elena A Adjei, Nowah Afangbedji, Andrey Ivanov, Namita Kumari, Luis E F Almeida, Zenaide M N Quezado, Sergei Nekhai, Marina Jerebtsova
Sickle cell disease patients are at increased risk of developing a chronic kidney disease. Endothelial dysfunction and inflammation associated with hemolysis lead to vasculopathy and contribute to the development of renal disease. Here we used a Townes sickle cell disease mouse model to examine renal endothelial injury. Renal disease in Townes mice was associated with glomerular hypertrophy, capillary dilation and congestion, and significant endothelial injury. We also detected substantial renal macrophage infiltration, and accumulation of macrophage stimulating protein 1 in glomerular capillary...
March 8, 2018: Haematologica
Yexiang Sun, Chunyu Yuan, Xulin Chen, Fei Wang, Congsong Sun, Zhi Gao, Sheng Liu
OBJECTIVE: To investigate the effect of different concentrations of hypertonic saline solution (HS) on intestine injury in rats at the early stage of severe burn. METHODS: 104 adult healthy female Sprague-Dawley (SD) rats were randomly divided into five groups: sham group (n = 8), lactated Ringer solution (LR) group (n = 24) and 200, 300, 400 mmol/L HS group (HS200 group, HS300 group, HS400 group, all n = 24). All the rats in LR group and different concentrations of HS groups were scalded for 30% total body surface area (TBSA) with III degree, after immediately, the rats were given burn resuscitation therapy by LR or corresponding concentrations of HS through the tail vein...
March 2018: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
Dalin Di, Lei Chen, Yingying Guo, Lina Wang, Chunling Zhao, Jiyu Ju
Breast cancer suppressor candidate-1 (BCSC-1; also termed von Willebrand factor A domain containing 5A and LOH11CR2A) is a newly identified candidate tumor suppressor gene that has been implicated in several types of cancer in previous studies. However, there have been few reports about the association between BCSC-1 and human breast cancer in recent years. In the present study, the expression of BCSC-1 in breast cancer was determined by immunohistochemistry (IHC) staining of tissue microarrays and clinical tissue specimens...
March 7, 2018: International Journal of Oncology
P Sasikumar, K S AlOuda, W J Kaiser, L M Holbrook, N Kriek, J A Unsworth, A P Bye, T Sage, R Ushioda, K Nagata, R W Farndale, J M Gibbins
OBJECTIVE: Heat shock protein 47 (HSP47) is an intracellular chaperone protein that is vital for collagen biosynthesis in collagen secreting cells. This protein has also been shown to be present on the surface of platelets. Given the importance of collagen and its interactions with platelets in triggering haemostasis and thrombosis, in this study we sought to characterise the role of HSP47 on these cells. APPROACH AND RESULTS: The deletion of HSP47 in mouse platelets or its inhibition in human platelets reduced their function in response to collagen and the GPVI agonist (CRP-XL), but responses to thrombin were unaltered...
March 7, 2018: Journal of Thrombosis and Haemostasis: JTH
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