von Willibrand disease

BACKGROUND: Growth hormone deficiency (GHD) has been implicated in increased cardiovascular and cerebrovascular disease risk seen in hypopituitarism, however the mechanism remains speculative. We hypothesise that platelet abnormalities may play a contributory role. Herein we examined platelet behaviour in GHD hypopituitary patients, pre- and post-growth hormone (GH) replacement. METHODS: This study utilizes a physiological flow-based assay to quantify platelet function in whole blood from patient cohorts under arterial shear...

INTRODUCTION: Patients with inherited bleeding disorders (IBDs) can experience challenges in accessing dental care. The COVID-19 pandemic saw the cessation of routine dentistry in England. This study aims to highlight whether access to dental care for patients with IBDs was impacted by the pandemic, and whether the severity of their IBD impacts patients experience of dental care. METHODS: Patients over the age of 18 with Haemophilia A and B, Von Willibrands (VWD), Bernard-Soulier syndrome (BSS) and Glanzmann's disease were recruited...

Type 2N von Willebrand disease is caused by mutations in the factor VIII (FVIII) binding site of von Willibrand factor (VWF), resulting in dysfunctional VWF with defective binding capacity for FVIII. Here we developed a novel type 2N mouse model using CRISPR/Cas9 technology. In homozygous VWF2N/2N mice, plasma VWF levels were normal (1167±257 mU/ml) but the VWF was completely incapable of binding FVIII, resulting in 53±23 mU/ml of plasma FVIII levels that were similar to those in VWF deficient (VWF-/-) mice...

SARS-CoV-2 infection can cause compromised respiratory function and thrombotic events. SARS-CoV-2 binds to and mediates downregulation of angiotensin converting enzyme 2 (ACE2) on cells that it infects. Theoretically, diminished enzymatic activity of ACE2 may result in increased concentrations of pro-inflammatory molecules, angiotensin II, and Bradykinin, contributing to SARS-CoV-2 pathology. Using immunofluorescence microscopy of lung tissues from uninfected, and SARS-CoV-2 infected individuals, we find evidence that ACE2 is highly expressed in human pulmonary alveolar epithelial cells and significantly reduced along the alveolar lining of SARS-CoV-2 infected lungs...

OBJECTIVE: Despite the importance of reactive oxygen species (ROS) and NOX (nicotinamide adenine dinucleotide phosphate [NADPH] oxidase) 2 in platelet activation and in vivo thrombosis, it is unclear how ROS and NOX2 play a role in platelet activation and why NOX2 deficiencies in humans and mice do not affect hemostasis. Outside-in signaling of integrin αIIb β3 mediates platelet response to shear stress, secondary platelet activation, and thrombus expansion and is critical to thrombosis but dispensable for hemostasis...

Microphysiological systems (MPS), or "organ-on-a-chip" platforms, aim to recapitulate in vivo physiology using small-scale in vitro tissue models of human physiology. While significant efforts have been made to create vascularized tissues, most reports utilize primary endothelial cells that hinder reproducibility. In this study, we report the use of human induced pluripotent stem cell-derived endothelial cells (iPS-ECs) in developing three-dimensional (3D) microvascular networks. We established a CDH5-mCherry reporter iPS cell line, which expresses the vascular endothelial (VE)-cadherin fused to mCherry...

Edible bird's nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period...

OBJECTIVE: To investigate the methods for assessing angiogenesis in experimental liver fibrosis. METHODS: Male C57BL/6 mice were randomly divided into a normal (unmodeled) group and a liver fibrosis model group.The model was established by a 4-week course of 10% CCl4 solution (in olive oil) intraperitoneal injection. Liver vasculature was observed by magnetic resonance (MR),computed tomography (CT),synchrotron radiation X-ray,and von Willibrand factor(vWF) immunofluorescence staining...

AIM: To determine the relationship of hemostatic disorders to the direct impact of Coxiella burnetii on platelets as one of the key mechanisms of the pathogenesis of Q fever. SUBJECTS AND METHODS; Platelet functional activity, plasma hemostatic parameters, von Willibrand factor (vWF) were investigated; and polymerase chain reaction assay was used to determine C. burnetii DNA in the leukocyte and platelet sediments of 41 patients aged 39.9 +/- 0.8 years diagnosed with Q fever at the Astrakhan Regional Clinical Hospital in 2009 to 2010...

BACKGROUND: Oral leukoplakia is the best-known precursor lesion. Although a morphologic feature of oral epithelial dysplasia is well described, less is known about the pathobiologic changes within the cells and over the cell surfaces for malignant transformation. AIMS: The present study is aimed at comparing and correlating the mast cell density (MCD) and micro vascular density (MVD) in Normal Mucosa (NM) and different grades of dysplasia and to analyze their role in disease progression...

The 'A-disintegrin and metalloproteinase' ( ADAM ) and 'A-disintegrin and metalloproteinase with thrombospondin motifs' ( ADAMTS ) genes make up two similar, yet distinct, gene families. The human and mouse genomes contain 21 and 24 putatively functional protein-coding ADAM genes, respectively, and 24 versus 32 putatively functional protein-coding ADAMTS genes, respectively. Analysis of evolutionary divergence shows that both families are unique. Each of the two families can be separated, if need be, into groups of more closely related members: six subfamilies for ADAM , four subfamilies for ADAMTS...

A 43-year-old black male was brought to hospital with complaints of confusion and fever. He was noted to have petechial lesions, thrombocytopenia (platelet count 7,200/ml), schistocytes on peripheral smear, and serum creatinine 1.7 mg/dl (150.28 micromol/L). He was diagnosed to have thrombotic thrombocytopenic purpura (TTP) and started on high dose IV steroids and plasmapheresis. Attempts at steroid withdrawal following plasmapheresis were unsuccessful as his platelet count started to decrease. He subsequently was started on rituximab given as 4 weekly infusions...

Thrombotic microangiopathies are a relatively rare group of congenital and inherited disorders caused by defects in processing the ultra large forms of von Willibrand factor which pathologically give rise to platelet rich microthrombi in the micro arterial circulation leading to end organ damage particularly in the brain, heart and kidneys. Identification of the ADAMTS 13 gene has led to the definition of congenital deficiency of its activity or failure of activity due to the development of an inhibitory IgG antibody...

BACKGROUND/AIM: It has been reported that adipose tissue contain progenitor cells with angiogenic potential and that therapy based on adipose tissue-derived progenitor cells administration may constitute a promising cell therapy in patients with ischemic disease. In this study we evaluated the effect of culture-expanded mesenchymal stem cells (MSC) derived from adipose tissue on neovascularization and blood flow in an animal model of limb ischemia in immunodeficient mice. METHODS: MSC were cultured from human adipose tissue by collagenase digestion...

Secondary thrombosis may contribute to cerebral ischemia caused by traumatic brain injury (TBI). In this study, we sought to investigate the temporal and spatial profiles of intravascular thrombosis and to evaluate the effect of atorvastatin, a beta-hydroxy-beta-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitor, on thrombosis after TBI. Young male Wistar rats weighing 350-400 g were subjected to controlled cortical impact injury, and were sacrificed at 1 and 4 h, and 1, 3, 8, and 15 days after TBI (5 rats/time point), respectively...

Release of unusually large von Willibrand factor (UL vWF) multimers and a deficiency of vWF metalloprotease may result in thrombotic thrombocytopenic purpura (TTP), a life threatening disease. Surgery has been associated with TTP, probably by releasing massive amounts of UL vWF. An association between TTP and orthopedic surgery has never been reported in the literature. We report a case of TTP following a total knee replacement surgery in which prior use of ticlopidine might have played a role.

AIMS: Raised homocysteine (hcy) levels are associated with premature coronary artery disease, but the underlying vascular mechanism and the extent to which hcy affects small vessel vasodilator responses (especially non-nitric oxide mediated pathways) are unclear. METHODS: This double-blind, placebo-controlled crossover study in 14 healthy male subjects evaluated the effects of single-dose oral methionine 15 g (to induce acute hyperhomocysteinaemia) on cutaneous microvascular vasodilator responses to incremental-dose iontophoretic administration of acetylcholine (Ach) and sodium nitroprusside (SNP) using laser Doppler fluximetry (LDF), and the effects on von Willibrand factor (vWF) levels and systemic haemodynamics...

BACKGROUND: In virtually all patients with advanced prostate cancer, the disease metastasizes to bone and causes osteoblastic growth. However, the mechanisms that contribute to bone metastasis are poorly understood. It has been hypothesized that the bone provides a favorable growth environment for prostate cancer cells, which nonselectively seed the bone marrow from the bloodstream. Alternatively, prostate cancer cells may preferentially bind to bone marrow endothelial cells. We developed an in vitro model of bone endothelium and tested the hypothesis that prostate cancer cells adhere preferentially to bone marrow endothelial cells...

The diagnosis and management of ENT patients with coincidental bleeding dyscrasias presents special difficulties, which include diagnosis of the disorder, arrest of the bleeding when unexpected, and the conservative and surgical care of affected children with ENT diseases. The dyscrasias most often found in childhood are haemophilia, von Willibrand's disease and ideopathic thrombocytopenic purpura. The clinical presentation and course of these disorders are described. Present day treatment is effective in arrest of the haemorrhage such that a fatality can almost always be avoided...