Novel antiplatelet strategies targeting VWF and GPIb.
Authors: Prasannan N, Scully M Abstract Von Willebrand factor has a pivotal role in primary hemostasis. Its role in thrombotic microangiopathies (TMA), as well as cardiovascular disease, has been demonstrated. Thrombotic thrombocytopenic purpura (TTP), a thrombotic microangiopathy, is a life-threatening condition with a high mortality rate if untreated. Current management strategies comprise plasma exchange to remove autoantibodies and replenish ADAMTS13, along with immunosuppressive agents in immune TTP. This review focuses on novel antiplatelet strategies that target VWF and GPIb. The benefits of the nanobody cap...
Source: Platelets - July 4, 2020 Category: Hematology Tags: Platelets Source Type: research
Changes of plasma Von Willebrand factor and Von Willebrand factor-cleaving protease levels in pregnancy-induced hypertension.
Authors: Zhang TT, Yu ZK, Xiu CF, Bai YT, Peng M, Guo ZH PMID: 32608221 [PubMed - as supplied by publisher] (Source: Journal of Biological Regulators and Homeostatic Agents)
Source: Journal of Biological Regulators and Homeostatic Agents - July 3, 2020 Category: Biomedical Science Tags: J Biol Regul Homeost Agents Source Type: research
Cancers, Vol. 12, Pages 1746: Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding
Gurnari Over the past decade, new insights have emerged on the pathophysiology of essential thrombocythemia (ET), its clinical management, and associated thrombohemostatic disturbances. Here, we review the latest diagnostic and risk stratification modalities of ET and its therapeutics. Moreover, we discuss the clinical evidence-based benefits, deriving from major clinical trials, of using cytoreductive therapy and antiplatelet agents to lower the risk of fatal vascular events. Also, we focus on the condition of extreme thrombocytosis (&gt;1000 &times; 109/L) and bleeding risk, the development and pathog...
Source: Cancers - June 30, 2020 Category: Cancer & Oncology Authors: Hassan Awada Maria Teresa Voso Paola Guglielmelli Carmelo Gurnari Tags: Review Source Type: research
Perioperative cardiovascular complications rate and activity of coagulation and fibrinolysis among patients undergoing vascular surgery for peripheral artery disease and abdominal aortic aneurysm.
Szczeklik W Abstract OBJECTIVES: To compare preoperative coagulation and fibrinolysis activity and incidence of perioperative complications between patients undergoing vascular procedures for peripheral artery disease and abdominal aortic aneurysm. METHODS: This is a substudy of a prospective observational cohort study (VISION; NCT00512109) in which we recruited patients aged ≥45 years, undergoing surgery for peripheral artery disease and abdominal aortic aneurysm. Blood samples were obtained 24 h preoperatively to measure platelet count, concentrations of coagulation coagulation (fibrinogen,...
Source: Vascular - June 29, 2020 Category: Surgery Authors: Polok K, Górka J, Fronczek J, Iwaniec T, Górka K, Szczeklik W Tags: Vascular Source Type: research
Type 2B Von Willebrand Disease in Pregnancy: A Systematic Literature Review [36K]: Correction.
Authors: PMID: 32590717 [PubMed - as supplied by publisher] (Source: Obstetrics and Gynecology)
Source: Obstetrics and Gynecology - June 28, 2020 Category: OBGYN Tags: Obstet Gynecol Source Type: research
Caplacizumab: an anti-von Willebrand factor antibody for the treatment of thrombotic thrombocytopenic purpura.
CONCLUSION: Caplacizumab is a first-in-class von Willebrand factor inhibitor approved for the treatment of adults with acquired TTP. PMID: 32588878 [PubMed - as supplied by publisher] (Source: American Journal of Health-System Pharmacy : AJHP)
Source: American Journal of Health-System Pharmacy : AJHP - June 26, 2020 Category: Drugs & Pharmacology Authors: Hollifield AL, Arnall JR, Moore DC Tags: Am J Health Syst Pharm Source Type: research
Navigating the Myriad of von Willebrand Factor Assays.
Abstract von Willebrand factor (VWF) represents a large and complex adhesive plasma protein whose main function is to provide a bridge between blood platelets and damaged endothelium, and thus facilitate primary hemostasis. VWF also binds to FVIII, preventing early proteolysis, and delivers this cargo to sites of vascular injury, thereby promoting clot formation and secondary hemostasis. An absence, deficiency, or defect in VWF can lead to a bleeding diathesis called von Willebrand disease (VWD), considered the most common inherited bleeding disorder. Contemporary laboratory assays used in VWD diagnosis/exclusion ...
Source: Hamostaseologie - June 26, 2020 Category: Hematology Authors: Favaloro EJ Tags: Hamostaseologie Source Type: research
Reference range for ADAMTS13 antigen, activity and anti-ADAMTS13 antibody in the healthy adult Singapore population.
CONCLUSION: TTP and TMAs are encountered in a wide range of specialties. The availability of new assays in Singapore will aid clinicians in the timely management of these conditions. Standardising reference ranges established for Singapore, against World Health Organization standards, allows the harmonisation of measurements between laboratories and for future research collaborations. PMID: 32588586 [PubMed - as supplied by publisher] (Source: Singapore Medical Journal)
Source: Singapore Medical Journal - June 26, 2020 Category: General Medicine Authors: Tso ACY, Sum CLL, Ong KH Tags: Singapore Med J Source Type: research
Comparative Analysis of Risk Factors in Declined Kidneys from Donation after Brain Death and Circulatory Death.
Conclusions: Similar characteristics of DCD were shown in comparison with DBD kidneys. Importantly, the additional warm ischemic time in DCD appeared to have no further detectable adverse effects on tissue injury, inflammation and complement activation. vWF, C4d and C3 might be potential biomarkers facilitating the evaluation of donor kidneys. PMID: 32604873 [PubMed - in process] (Source: Medicina (Kaunas))
Source: Medicina (Kaunas) - June 26, 2020 Category: Universities & Medical Training Authors: Zwaini Z, Patel M, Stover C, Dormer J, Nicholson ML, Hosgood SA, Yang B Tags: Medicina (Kaunas) Source Type: research
Comparison of von Willebrand factor platelet-binding activity assays: ELISA overreads type 2B with loss of HMW multimers.
CONCLUSIONS: Different assay principles may lead to discrepant results for certain VWD types or mutations. Therefore, a more extensive study for a large number of patients is needed to better characterise the incidence and relevance of such assay specific differences. PMID: 32573891 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - June 23, 2020 Category: Hematology Authors: Szederjesi A, Baronciani L, Budde U, Castaman G, Colpani P, Lawrie AS, Liu Y, Montgomery R, Peyvandi F, Schneppenheim R, Patzke J, Bodó I Tags: J Thromb Haemost Source Type: research
Von Willebrand Factor and Cancer; metastasis and coagulopathies.
Abstract Von Willebrand factor (VWF) is a multimeric procoagulant plasma glycoprotein that mediates platelet adhesion along the endothelium. In addition to its role maintaining normal haemostasis, more recently novel biological functions for VWF have been described, including inflammation, angiogenesis and metastasis. Significantly increased plasma VWF levels have been reported across a variety of cancer patient cohorts. Given that VWF is established as a risk factor for venous thrombosis, this is of direct clinical importance. Moreover, elevated VWF has also been observed localized within the tumour microenvironm...
Source: Thrombosis and Haemostasis - June 23, 2020 Category: Hematology Authors: Patmore S, Dhami SPS, O'Sullivan JM Tags: J Thromb Haemost Source Type: research
Role of von Willebrand Factor and ADAMTS-13 in the Pathogenesis of Thrombi in SARS-CoV-2 Infection: Time to Rethink.
PMID: 32575136 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - June 23, 2020 Category: Hematology Authors: Morici N, Bottiroli M, Fumagalli R, Marini C, Cattaneo M Tags: Thromb Haemost Source Type: research
Clinical management and follow-up of relapsed immune thrombotic thrombocytopenic purpura during pregnancy: A case report
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare thrombotic microangiopathic (TMA) disorder that may be life-threatening if not appropriately managed. iTTP is caused by autoantibodies inhibiting ADAMTS-13 activity, thus preventing the cleavage of ultra-large von Willebrand factor (vWF) multimers, which facilitate the formation of platelet-rich microthrombi localized to arteriocapillary junctions of multiple organs. Although the cause of the autoantibody is unknown, pregnancy is considered a risk factor and the incidence of iTTP is higher in pregnant women than in the general population . (Source: Thrombosis Research)
Source: Thrombosis Research - June 19, 2020 Category: Hematology Authors: Shally Marcellini Antonio, Sandra Valencia Castillo, Jos é Díaz Valdés, Ana Torres Tienza, Esther Zato Hernández, Aránzazu García Mateo, M. Dolores Llorente Melgar, M. Carmen Olivier Cornacchia, José Antonio Queizán Hernández Tags: Letter to the Editors-in-Chief Source Type: research
Identification of potential key genes and key pathways related to clear cell renal cell carcinoma through bioinformatics analysis.
In this study, we conducted a bioinformatics analysis on three Gene Expression Omnibus datasets and identified 437 differentially expressed genes (DEGs) related to ccRCC development and prognosis, of which 311 and 126 genes are respectively down-regulated and up-regulated. The protein-protein interaction network of these DEGs consists of 395 nodes and 1872 interactions and 2 prominent modules. The Staphylococcus aureus infection and complement and coagulation cascades are significantly enriched in module 1 and are likely involved in ccRCC progression. Forty-two hub genes were screened, of which von Willebrand factor, TIMP ...
Source: Acta Biochimica et Biophysica Sinica - June 19, 2020 Category: Biochemistry Authors: Zhai W, Lu H, Dong S, Fang J, Yu Z Tags: Acta Biochim Biophys Sin (Shanghai) Source Type: research
The acquired von Willebrand syndrome focused for hematologists.
Abstract The acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike the inherited disease, the AVWS occurs in persons with no personal or family history of bleeding and is often associated with a variety of underlying diseases, most frequently lymphoproliferative, myeloproliferative and cardiovascular disorders. After the presentation of a typical case, in this narrative review we discuss the more recent data on the pathophysiology, clinical, laboratory and therapeutic aspects of this acquired bleeding syndr...
Source: Haematologica - June 18, 2020 Category: Hematology Authors: Franchini M, Mannucci PM Tags: Haematologica Source Type: research
Identification of genes associated with gastric cancer survival and construction of a nomogram to improve risk stratification for patients with gastric cancer.
Authors: Ding Y, Chen Y, Wu M, Li L, Huang Y, Wang H, Wang H, Yu X, Xu N, Teng L Abstract The present study aimed to identify genes associated with gastric cancer survival and improve risk stratification for patients with gastric cancer. Transcriptomic and clinicopathological data from 443 gastric cancer samples were retrieved from The Cancer Genome Atlas database. The DESeq R package was applied to screen for differentially expressed genes between Tumor-Node-Metastasis (TNM) stage (I vs. IV) and histological grade (G3 vs. G1 and G2). A total of seven genes were common to both comparisons; spondin 1 (SPON1); thromb...
Source: Oncology Letters - June 17, 2020 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Factor VIII binding affects the mechanical unraveling of the A2 domain of von Willebrand factor.
CONCLUSIONS: Our results suggest that binding of FVIII to D'D3 and/or A2 may alter the mechanical property in the central A2 domain. The findings provide novel insight into the molecular mechanism underlying FVIII-dependent regulation of VWF proteolysis by ADAMTS13 under mechanical force. PMID: 32544272 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - June 16, 2020 Category: Hematology Authors: Cao W, Cao W, Zhang W, Zheng XL, Zhang XF Tags: J Thromb Haemost Source Type: research
Human adipose-derived stem cell spheroids incorporating platelet-derived growth factor (PDGF) and bio-minerals for vascularized bone tissue engineering.
Abstract Stem cells with mineralized materials have been used for bone regeneration; however, engineering the complex vascularized structure of the natural bone remains a challenge. Here, we developed platelet-derived growth factor (PDGF) and bio-mineral coated fibers which were then assembled with human adipose-derived stem cells (hADSCs) to form spheroids as building blocks for vascularized bone regeneration. The PDGF incorporated within the spheroid increased the proliferation of hADSCs, which was characterized by Ki-67 staining and DNA contents. Furthermore, the PDGF enhanced not only osteogenic differentiatio...
Source: Biomaterials - June 12, 2020 Category: Materials Science Authors: Lee J, Lee S, Ahmad T, Madhurakkat Perikamana SK, Lee J, Kim EM, Shin H Tags: Biomaterials Source Type: research
Inherited Bleeding Disorders in Pediatric Patients; experience of the national referral center in Iraq
AbstractBackgroundInherited bleeding disorders can lead to lifelong bleeding; they are mainly caused by quantitative or qualitative defect of coagulation factors, von Willebrand factor (VWF) or platelets. No published data are available about the different types of inherited bleeding disorders in Iraq.ObjectivesTo describe types, severity and presentation of inherited bleeding disorders in pediatric patients in the major referral center in Iraq.Patients and MethodsThis is a cohort prospective descriptive study conducted at the National Center of Hematology, a referral center for bleeding disorders in Baghdad-Iraq, from Jan...
Source: Indian Journal of Hematology and Blood Transfusion - June 10, 2020 Category: Hematology Source Type: research
Use of Tranexamic Acid for the Treatment of Mittelschmerz in a Patient with Type 1 von Willebrand Disease and Recurrent Hemorrhagic Cysts.
CONCLUSION: We report that the use of mid-cycle tranexamic acid in patients with recurrent haemorrhagic cysts can lower ovulation-associated pain. PMID: 32482469 [PubMed - as supplied by publisher] (Source: Journal of Obstetrics and Gynaecology Canada : JOGC)
Source: Journal of Obstetrics and Gynaecology Canada : JOGC - June 4, 2020 Category: OBGYN Tags: J Obstet Gynaecol Can Source Type: research
Unraveling mucin domains in cancer and metastasis: when protectors become predators
AbstractA dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called mucins. Mucins, broadly grouped into transmembrane and secreted mucins, are the first responders to any mechanical or chemical insult to the epithelia and help maintain tissue homeostasis. However, their intrinsic properties to protect and repair the epithelia are exploited during oncogenic processes, where mucins are metamorphosed to aid the tumor cells in their malignant journey. Diverse domains, like the variable number tandem repeats (VNTR), sea...
Source: Cancer and Metastasis Reviews - June 2, 2020 Category: Cancer & Oncology Source Type: research
von Willebrand factor increases in experimental cerebral malaria but is not essential for late-stage pathogenesis in mice.
CONCLUSIONS: Our study suggests that increased VWF concentration is a hallmark of ECM. However, VWF does not have a major influence in modulating late-stage ECM pathogenesis. PMID: 32485089 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - June 2, 2020 Category: Hematology Authors: Kraisin S, Martinod K, Desender L, Pareyn I, Verhenne S, Deckmyn H, Vanhoorelbeke K, Van den Steen PE, De Meyer SF Tags: J Thromb Haemost Source Type: research
ABO blood group, glycosyltransferase activity and risk of venous thromboembolism
ABO blood group influence the risk of venous thromboembolism (VTE) by modifying A and B glycosyltransferases (AGT and BGT) activities that further modulates Factor VIII (FVIII) and von Willebrand Factor (VWF) plasma levels. The aim of this work was to evaluate the association of plasma GTs activities with VWF/FVIII plasma levels and VTE risk in a case-control study. (Source: Thrombosis Research)
Source: Thrombosis Research - June 1, 2020 Category: Hematology Authors: Manal Ibrahim Kosta, Pascal Bailly, Monique Silvy, Noemie Saut, Pierre Suchon, Pierre-Emmanuel Morange, Jacques Chiaroni, David-Alexandre Tr égouët, Louisa Goumidi Tags: Full Length Article Source Type: research
968 a multi-center study of left ventricular assist device (lvad)-related bleeding
Continuous left ventricular assist devices (LVAD) offer comprehensive hemodynamic support in advanced decompensated heart failure, but their use is complicated by the high incidence of gastrointestinal (GI) bleeding events that are often poorly tolerated in these patients with significant medical co-morbidities. Many of these bleeding events are thought to be a consequence of non-pulsatile flow with resultant acquired von-Willebrand disease. Prior studies have explored this phenomenon, but have largely been smaller, single-center investigations focused primarily on the low rates of endoscopic yield. (Source: Gastrointestinal Endoscopy)
Source: Gastrointestinal Endoscopy - June 1, 2020 Category: Gastroenterology Authors: Joseph Dailey, Long H. Nguyen, Arushi Kohli, Jasmine Ha, Michael B. Russell, Rohit Dhingra, Molly Thomas, Michael S. Kiernan, Erin C. Coglianese, Mark J. Sterling, Robert F. Yacavone, Nikola Natov, James Richter Tags: Oral abstracts Source Type: research
Renal denervation improves vascular endothelial dysfunction by inducing autophagy via AMPK/mTOR signaling activation in a rat model of type 2 diabetes mellitus with insulin resistance
ConclusionsRDN may not only increase the expression of ACE2 in the vascular endothelium, but also can via ACE2 activate p-AMPK and inhibit p-mTOR, thus promoting autophagy and improving endothelial dysfunction. (Source: Acta Diabetologica)
Source: Acta Diabetologica - June 1, 2020 Category: Endocrinology Source Type: research
von Willebrand Factor and Factor VIII Clearance in Perioperative Hemophilia A Patients.
roup Abstract BACKGROUND: von Willebrand factor (VWF) is crucial for optimal dosing of factor VIII (FVIII) concentrate in hemophilia A patients as it protects FVIII from premature clearance. To date, it is unknown how VWF behaves and what its impact is on FVIII clearance in the perioperative setting. AIM: To investigate VWF kinetics (VWF antigen [VWF:Ag]), VWF glycoprotein Ib binding (VWF:GPIbM), and VWF propeptide (VWFpp) in severe and moderate perioperative hemophilia A patients included in the randomized controlled perioperative OPTI-CLOT trial. METHODS: Linear mixed effects modeling...
Source: Thrombosis and Haemostasis - June 1, 2020 Category: Hematology Authors: van Moort I, Bukkems LH, Heijdra JM, Schutgens REG, Laros-van Gorkom BAP, Nieuwenhuizen L, van der Meer FJM, Fijnvandraat K, Ypma P, de Maat MPM, Leebeek FWG, Meijer K, Eikenboom J, Mathôt RAA, Cnossen MH, OPTI-CLOT Study Group Tags: Thromb Haemost Source Type: research
Von Willebrand factor as a thrombotic and inflammatory mediator in critical illness.
Abstract The endothelial exocytosis of high-molecular-weight multimeric von Willebrand factor (vWF) may occur in critical illness states, including trauma and sepsis, leading to the sustained elevation and altered composition of plasma vWF. These critical illnesses involve the common process of sympathoadrenal activation and loss of the endothelial glycocalyx. As a prothrombotic and proinflammatory molecule that interacts with the endothelium, the alterations exhibited by vWF in critical illness have been implicated in the development and damaging effects of downstream pathologies, such as disseminated intravascul...
Source: Transfusion - June 1, 2020 Category: Hematology Authors: Plautz WE, Matthay ZA, Rollins-Raval MA, Raval JS, Kornblith LZ, Neal MD Tags: Transfusion Source Type: research
In silico features of ADAMTS13 contributing to plasmatic ADAMTS13 levels in neonates with congenital heart disease
Risk factors contributing to heightened thrombosis in pediatric congenital heart disease (CHD) patients are not fully understood. Among the neonatal CHD population, those presenting with single ventricular physiology are at the highest risk for perioperative thrombosis. The von Willebrand factor and ADAMTS13 interactions have emerged as causative risk factors for pediatric stroke and could contribute to heightened thrombosis in CHD neonates. (Source: Thrombosis Research)
Source: Thrombosis Research - May 31, 2020 Category: Hematology Authors: Upendra K. Katneni, David D. Holcomb, Nancy E. Hernandez, Nobuko Hamasaki-Katagiri, Ryan C. Hunt, Haim Bar, Juan C. Ibla, Chava Kimchi-Sarfaty Tags: Full Length Article Source Type: research
The leucine-rich repeat domain of human peroxidasin 1 promotes binding to laminin in basement membranes.
In this study, we probed the interactions of four PXDN constructs with different domain compositions with components of a basement membrane extract by immunoprecipitation. Strong binding of the LRR-containing construct was detected with the major ECM protein laminin. Analysis of these interactions by surface plasmon resonance spectroscopy revealed similar kinetics and affinities of binding of the LRR-containing construct to human and murine laminin-111, with calculated dissociation constants of 1.0 and 1.5 μM, respectively. The findings are discussed with respect to the recently published in-solution structures of the...
Source: Archives of Biochemistry and Biophysics - May 30, 2020 Category: Biochemistry Authors: Sevcnikar B, Schaffner I, Chuang CY, Gamon L, Paumann-Page M, Hofbauer S, Davies MJ, Furtmüller PG, Obinger C Tags: Arch Biochem Biophys Source Type: research
Acquired von Willebrand Syndrome and Platelet Function Defects during Extracorporeal Life Support (Mechanical Circulatory Support).
Abstract Patients with ventricular assist devices (VADs) and extracorporeal membrane oxygenation (ECMO) suffer from an increased risk for thromboembolic events as well as for hemorrhages. High shear stress in the mechanical device results in acquired von Willebrand syndrome (AVWS), characterized by a loss of high-molecular-weight multimers of von Willebrand factor (VWF) leading to an increased bleeding risk. Onset of AVWS occurs within hours, persists during the whole period of mechanical support, and subsides rapidly after explantation. Patients with the older HeartMate II exhibit more severe AVWS than those with...
Source: Hamostaseologie - May 29, 2020 Category: Hematology Authors: Schlagenhauf A, Kalbhenn J, Geisen U, Beyersdorf F, Zieger B Tags: Hamostaseologie Source Type: research
Treatment of gastrointestinal bleeding in left ventricular assist devices: A comprehensive review.
Abstract Left ventricular assist devices (LVAD) are increasingly become common as life prolonging therapy in patients with advanced heart failure. Current devices are now used as definitive treatment in some patients given the improved durability of continuous flow pumps. Unfortunately, continuous flow LVADs are fraught with complications such as gastrointestinal (GI) bleeding that are primarily attributed to the formation of arteriovenous malformations. With frequent GI bleeding, antiplatelet and anticoagulation therapies are usually discontinued increasing the risk of life-threatening events. Small bowel bleeds ...
Source: World Journal of Gastroenterology : WJG - May 28, 2020 Category: Gastroenterology Authors: Vedachalam S, Balasubramanian G, Haas GJ, Krishna SG Tags: World J Gastroenterol Source Type: research
Inflammatory markers in thrombosis associated with primary antiphospholipid syndrome
AbstractThe role of inflammation in thrombotic complications of primary antiphospholipid syndrome (PAPS) is controversial. The aim of this study was to evaluate levels of inflammation and coagulation markers in patients with thrombotic PAPS (t-PAPS). Patients with t-PAPS and individuals with no history of thrombosis were enrolled. The association of t-PAPS with levels of tumor necrosis factor (TNF)- α, C-reactive protein (hs-CRP), interferon (IFN)-α, interleukins (IL)-6, -8, factor VIII (FVIII), von Willebrand factor (VWF) and tissue factor (TF) was evaluated by regression models. The levels of these markers we...
Source: Journal of Thrombosis and Thrombolysis - May 27, 2020 Category: Hematology Source Type: research
Anticoagulant treatment and bleeding complications in patients with left ventricular assist devices.
Authors: den Exter PL, Beeres SLMA, Eikenboom J, Klok FA, Huisman MV Abstract INTRODUCTION: The treatment options for advanced heart failure patients drastically changed with the introduction of left ventricular assist devices (LVADs), either as bridge to transplant or as destination therapy for patients ineligible for transplant. Despite major benefits in terms of survival, functional status and quality of life, managing patients with LVADs comes with several challenges. The most significant challenge is balancing between the risks of thrombotic and bleeding complications. AREAS COVERED: The present review des...
Source: Expert Review of Cardiovascular Therapy - May 26, 2020 Category: Cardiology Tags: Expert Rev Cardiovasc Ther Source Type: research
[A case of "juvenile" self-healing cutaneous mucinosis in an adult].
CONCLUSION: The form of SHJCM described in pediatric populations may occur in rare cases in adults. Should the name of juvenile mucinosis still be used in this event? PMID: 32466850 [PubMed - as supplied by publisher] (Source: Annales de Dermatologie et de Cenereologie)
Source: Annales de Dermatologie et de Cenereologie - May 25, 2020 Category: Dermatology Authors: Lecanu P, Haidar D, Lafargue O, Comoz F, Guillemain JL, Fraitag S, Dompmartin A Tags: Ann Dermatol Venereol Source Type: research
Tspan18 is a novel regulator of thrombo-inflammation
AbstractThe interplay between thrombosis and inflammation, termed thrombo-inflammation, causes acute organ damage in diseases such as ischaemic stroke and venous thrombosis. We have recently identified tetraspanin Tspan18 as a novel regulator of thrombo-inflammation. The tetraspanins are a family of 33 membrane proteins in humans that regulate the trafficking, clustering, and membrane diffusion of specific partner proteins. Tspan18 partners with the store-operated Ca2+ entry channel Orai1 on endothelial cells. Orai1 appears to be expressed in all cells and is critical in health and disease. Orai1 mutations cause human immu...
Source: Medical Microbiology and Immunology - May 23, 2020 Category: Microbiology Source Type: research
Management of von Willebrand disease with a factor VIII-poor von Willebrand factor concentrate: results from a prospective observational post-marketing study.
CONCLUSIONS: Results from this PMS increase the clinical experience of a FVIII-poor pdVWF in patients of all ages and VWD types including those with thrombotic risk factors and emphasize that giving FVIII is not always mandatory to effectively treat patients with severe VWD. PMID: 32445594 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 23, 2020 Category: Hematology Authors: Goudemand J, Bridey F, Claeyssens S, Itzhar-Baïkian N, Harroche A, Desprez D, Négrier C, Chamouni P, Chambost H, Henriet C, Susen S, Borel-Derlon A Tags: J Thromb Haemost Source Type: research
ADAMTS13 activity, von Willebrand factor, factor VIII and D-dimers in COVID-19 inpatients
Emmental Hospital, situated in the rural town of Burgdorf in Switzerland, has treated a low volume of inpatients with COVID-19. Of the 13 admissions prior to 30th April 2020, 4 required treatment in the intensive care unit (ICU). Here we report on 3 consecutive inpatients with severe COVID-19, following the unexpected death of our first patient with severe COVID-19 from pulmonary embolism. (Source: Thrombosis Research)
Source: Thrombosis Research - May 22, 2020 Category: Hematology Authors: R. Escher, N. Breakey, B. L ämmle Tags: Letter to the Editors-in-Chief Source Type: research
Involvement of ADAMTS13 and von Willebrand factor in thromboembolic events in patients infected with SARS-CoV-2.
PMID: 32441844 [PubMed - as supplied by publisher] (Source: International Journal of Laboratory Hematology)
Source: International Journal of Laboratory Hematology - May 22, 2020 Category: Hematology Authors: Huisman A, Beun R, Sikma M, Westerink J, Kusadasi N Tags: Int J Lab Hematol Source Type: research
Traumatic injury results in prolonged circulation of ultralarge von Willebrand factor and a reduction in ADAMTS13 activity.
CONCLUSION: Traumatic injury is associated with acute coagulopathy that is characterized by increased UL-VWF multimers and reduction in ADAMTS13, which correlates with blood loss, transfusion requirement, and injury severity. These findings suggest the potential for future trials targeting ADAMTS13 repletion to enhance clearance of VWF multimers. PMID: 32441353 [PubMed - as supplied by publisher] (Source: Transfusion)
Source: Transfusion - May 22, 2020 Category: Hematology Authors: Dyer MR, Plautz WE, Ragni MV, Alexander W, Haldeman S, Sperry JL, Guyette FX, Zuckerbraun BS, Rollins-Raval MA, Raval JS, Neal MD, A TACTIC Publication Tags: Transfusion Source Type: research
D-dimer and mortality in COVID-19: a self-fulfilling prophecy or a pathophysiological clue?
We present the case of a patient who was diagnosed with a pulmonary thrombotic complication during inpatient care for COVID-19. The haemostasis parameters we observed, including increased levels of von Willebrand factor and factor VIII, point towards a relevant involvement of endothelial cells in patients with severe COVID-19. We suggest that it is possible to hypothesise a spectrum of secondarily acquired, prothrombotic coagulopathy mediated by the endothelial interaction with SARS-CoV-2 as a cause of mortality in a subset of patients with a complicated clinical course of COVID-19. We support the recommendation of thrombo...
Source: Swiss Medical Weekly - May 18, 2020 Category: General Medicine Authors: Breakey N, Escher R Tags: Swiss Med Wkly Source Type: research
Direct Rivaroxaban-Induced Factor XA Inhibition Proves to be Cardioprotective in Rats
Background: Acute myocardial infarction is a leading cause of death worldwide. Though highly beneficial, reperfusion of myocardium is associated with reperfusion injury. While indirect inhibition of Factor Xa has been shown to attenuate myocardial ischemia-reperfusion (I/R) injury, the underlying mechanism remains unclear. Our study sought to evaluate the effect of rivaroxaban (RIV), a direct inhibitor of Factor Xa, on myocardial I/R injury and determine its cellular targets. Experimental Approach: We used a rat model of 40-min coronary ligation followed by reperfusion. RIV (3 mg/kg) was given per os 1 h before repe...
Source: Shock - May 16, 2020 Category: Emergency Medicine Tags: Basic Science Aspects Source Type: research
Flow-diverting stent and delayed intracranial bleeding: the case for discussing acquired von Willebrand disease.
Authors: Oran I Abstract A unique feature of the flow-diverting stent (FDS) has rendered it useful in the endovascular treatment of selected intracranial aneurysms for the last decade. Delayed aneurysmal rupture and intracranial parenchymal bleeding are two leading hemorrhagic complications after FDS. It has recently been shown for the first time that there is a relationship between FDS and reduced level of vWF activity in patients undergoing endovascular cerebral aneurysm treatment. Here, the current literature is reviewed in the context of this novel finding to propose an illustrative scenario that conceptually l...
Source: Platelets - May 16, 2020 Category: Hematology Tags: Platelets Source Type: research
Thrombin-induced miRNA-24-1-5p upregulation promotes angiogenesis by targeting prolyl hydroxylase domain 1 in intracerebral hemorrhagic rats.
This study aimed to determine if miRNAs might be involved in thrombin-induced angiogenesis after ICH by targeting HIF-1α or its upstream prolyl hydroxylase domains (PHDs). METHODS: The study was divided into two parts. In part 1, rats received an injection of thrombin into the right globus pallidus. An miRNA array combined with miRNA target prediction, luciferase activity assay, and miRNA mimic/inhibitor transfection were used to identify candidate miRNAs and target genes. Part 2 included experiments 1 and 2. In experiment 1, rats were randomly divided into the sham group, ICH group, and ICH+hirudin-treated (thr...
Source: Journal of Neurosurgery - May 15, 2020 Category: Neurosurgery Authors: Cui H, Yang A, Zhou H, Wang Y, Luo J, Zhou J, Liu T, Li P, Zhou J, Hu E, He Z, Hu W, Tang T Tags: J Neurosurg Source Type: research
Baicalein mediates protection against Staphylococcus aureus-induced pneumonia by inhibiting the coagulase activity of vWbp.
Abstract The emergence and spread of multidrug-resistant Staphylococcus aureus (S. aureus) necessitate the research on therapeutic tactics which are different from classical antibiotics in overcoming resistance andtreatinginfections. In S. aureus, von Willebrand factor-binding protein (vWbp) is one of the key virulence determinants because it mediates not only the activation of thrombin to convert fibrinogen to fibrin, thereby enabling S. aureus to escape from the host immune clearance, but also the adhesion of S. aureus to host cells. Thus, vWbp is regarded as a promising druggable target to treat S. aureus-assoc...
Source: Biochemical Pharmacology - May 12, 2020 Category: Drugs & Pharmacology Authors: Zhang H, Luan Y, Jing S, Wang Y, Gao Z, Yang P, Ding Y, Wang L, Wang D, Wang T Tags: Biochem Pharmacol Source Type: research
Effects of coal-fired PM2.5 on the expression levels of atherosclerosis-related proteins and the phosphorylation level of MAPK in ApoE-/- mice.
CONCLUSION: Coal-derived PM2.5 exacerbated the formation of atherosclerosis in mice, increased the expression levels of atherosclerosis-related proteins in mice serum, and promoted the phosphorylation of proteins relevant to MAPK signaling pathway. Thus, MAPK signaling pathway may play a role in the atherosclerosis pathogenesis induced by Coal-derived PM2.5. PMID: 32384920 [PubMed - as supplied by publisher] (Source: BMC Pharmacology and Toxicology)
Source: BMC Pharmacology and Toxicology - May 11, 2020 Category: Drugs & Pharmacology Tags: BMC Pharmacol Toxicol Source Type: research
Coexistence of Von Willebrand Disease and Gastrointestinal stromal tumor (G.I.S.T): Case report of a rare and challenge association
We report herein on the management of a patient affected by VWD2B with severe GI bleeding secondary to gastrointestinal stromal tumor (GIST) complicated by deep vein thrombosis (DVT). The current case demonstrated that the hemostatic balance, in RBDs under specific circumstances, can range from a tendency toward a hemorrhagic to normal or prothrombotic state. (Source: Transfusion and Apheresis Science)
Source: Transfusion and Apheresis Science - May 11, 2020 Category: Hematology Authors: Simona Raso, Mariasanta Napolitano, Francesca Mansueto, Mercurio Paola, Gianfranco Cocorullo, Marco Santoro, Vincenzo Accurso, Salvatrice Mancuso, Sergio Siragusa Source Type: research
The potential roles of Von Willebrand factor and neutrophil extracellular traps in the natural history of hypertrophic and hypertensive cardiomyopathy
Inflammation is often applied broadly to human disease. Despite its general familiarity, inflammation is highly complex. There are numerous injurious, immune and infectious determinants, functional elements and signaling pathways, ranging from genetic to epigenetic, environmental, racial, molecular and cellular that participate in disease onset and progression, phenotypic heterogeneity, and treatment selection and response. In addition, inflammation can be tissue and organ specific, adding a layer of complexity to achieving a detailed and translatable understanding of its role in health and disease. (Source: Thrombosis Research)
Source: Thrombosis Research - May 7, 2020 Category: Hematology Authors: Richard C. Becker, A. Phillip Owens, Sakthivel Sadayappan Tags: Review Article Source Type: research
Orchestration of Primary Hemostasis by Platelet and Endothelial Lysosome-Related Organelles.
Abstract Megakaryocyte-derived platelets and endothelial cells store their hemostatic cargo in α- and δ-granules and Weibel-Palade bodies, respectively. These storage granules belong to the lysosome-related organelles (LROs), a heterogeneous group of organelles that are rapidly released following agonist-induced triggering of intracellular signaling pathways. Following vascular injury, endothelial Weibel-Palade bodies release their content into the vascular lumen and promote the formation of long VWF (von Willebrand factor) strings that form an adhesive platform for platelets. Binding to VWF strings as...
Source: Arteriosclerosis, Thrombosis and Vascular Biology - May 7, 2020 Category: Cardiology Authors: Karampini E, Bierings R, Voorberg J Tags: Arterioscler Thromb Vasc Biol Source Type: research
Bleeding symptoms in patients diagnosed as type 3 Von Willebrand Disease: results from 3WINTERS-IPS, an international and collaborative cross-sectional study.
Fernandez MF, Mannucci PM, Mazzucconi MG, Morfini M, Oldenburg J, Peake I, Parra Lòpez R, Peyvandi F, Schneppenheim R, Tiede A, Toogeh G, Trossaert M, Zekavat O, Zetterberg EMK, Federici AB Abstract BACKGROUND: Type 3 von Willebrand's disease (VWD) patients present markedly reduced levels of von Willebrand factor and factor VIII. Because of its rarity, the bleeding phenotype of type 3 VWD is poorly described, as compared to type 1 VWD. AIMS: To evaluate the frequency and the severity of bleeding symptoms across age and sex groups in type 3 patients and to compare these with those observed in type 1 VW...
Source: Thrombosis and Haemostasis - May 7, 2020 Category: Hematology Authors: Tosetto A, Badiee Z, Baghaipour MR, Baronciani L, Battle J, Berntorp E, Bodó I, Budde U, Castaman G, Eikenboom JCJ, Eshghi P, Ettorre C, Goodeve A, Goudemand J, Charles Richard Morris H, Hoorfar H, Karimi M, Keikhaei B, Lassila R, Leebeek FWG, Lopez Fern Tags: J Thromb Haemost Source Type: research
Non-additive effect on thrombin generation when a plasma-derived factor VIII/ von Willebrand factor (FVIII/VWF) is combined with emicizumab in vitro.
CONCLUSIONS: pdFVIII/VWF showed a non-additive effect on TG when combined in vitro with emicizumab. This finding suggests that emicizumab has limited ability to promote factor X activation in the presence of pdFVIII/VWF, thus reducing the risk of thrombotic events. PMID: 32379931 [PubMed - as supplied by publisher] (Source: Thrombosis and Haemostasis)
Source: Thrombosis and Haemostasis - May 7, 2020 Category: Hematology Authors: Bravo MI, Raventós A, Pérez A, Costa M, Willis T Tags: J Thromb Haemost Source Type: research