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Blood clotting factors

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https://www.readbyqxmd.com/read/28920906/clotchip-a-microfluidic-dielectric-sensor-for-point-of-care-assessment-of-hemostasis
#1
Debnath Maji, Michael A Suster, Erdem Kucukal, Ujjal D S Sekhon, Anirban Sen Gupta, Umut A Gurkan, Evi X Stavrou, Pedram Mohseni
This paper describes the design, fabrication, and testing of a microfluidic sensor for dielectric spectroscopy of human whole blood during coagulation. The sensor, termed ClotChip, employs a three-dimensional, parallel-plate, capacitive sensing structure with a floating electrode integrated into a microfluidic channel. Interfaced with an impedance analyzer, the ClotChip measures the complex relative dielectric permittivity, ϵ Tr, of human whole blood in the frequency range of 40 Hz to 100 MHz. The temporal variation in the real part of the blood dielectric permittivity at 1 MHz features a time to reach a permittivity peak, Tpeak, as well as a maximum change in permittivity after the peak, ∆εr,max, as two distinct parameters of ClotChip readout...
September 12, 2017: IEEE Transactions on Biomedical Circuits and Systems
https://www.readbyqxmd.com/read/28918098/identifying-novel-factor-xiia-inhibitors-with-pca-ga-svm-developed-vhts-models
#2
Jonathan Jun Feng Chen, Donald P Visco
There currently is renewed interest in blood clotting Factor XII as a potential target for thrombosis inhibition. Historically untargeted, there is little drug information with which to start drug candidate searches. Typical high-throughput screening can identify potential drug candidates, but is inefficient. Virtual high-throughput screening can be used to raise efficiency by focusing experimental efforts on compounds predicted to be active and is applied here to identify new Factor XIIa inhibitors. We combine principal component analysis, genetic algorithm and support vector machine to create the models used in the virtual high-throughput screening...
September 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28915711/vitamin-k-and-its-analogs-potential-avenues-for-prostate-cancer-management
#3
REVIEW
Subramanyam Dasari, Syed M Ali, Guoxing Zheng, Aoshuang Chen, Venkata Satish Dontaraju, Maarten C Bosland, Andre Kajdacsy-Balla, Gnanasekar Munirathinam
Epidemiological studies have demonstrated a relationship between cancer incidence and dietary habits. Especially intake of certain essential nutrients like vitamins has been shown to be beneficial in experimental studies and some clinical trials. Vitamin K (VK) is an essential nutrient involved in the blood clotting cascade, and there are considerable experimental data demonstrating its potential anticancer activity in several cancer types including prostate cancer. Previous in vitro and in vivo studies have focused mainly on anti-oxidative effects as the underlying anticancer mechanism of VK...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914800/effect-of-clotting-duration-and-temperature-on-bdnf-measurement-in-human-serum
#4
Patrizia Amadio, Leonardo Sandrini, Alessandro Ieraci, Elena Tremoli, Silvia Stella Barbieri
Brain-derived neurothrophic factor (BDNF) is a neurotrophin expressed in different tissues and cells, including neurons, endothelial cells, leukocytes, megakaryocytes and platelets. Modifications of BDNF in plasma and/or in serum are associated with neurodegenerative and psychiatric disorders, cardiovascular diseases, metabolic syndrome and with mortality risk. Indeed, changes in blood levels of BDNF may reflect those of its tissue of origin and/or promote pathological dysfunctions. The measurement of BDNF amount in plasma or in serum has been characterized with particular attention in the impact of different anti-coagulants, clotting duration, temperature (≤21 °C) and delay in blood sample centrifugation as well as in stability of storage...
September 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28912777/class-a-cpg-oligonucleotide-priming-rescues-mice-from-septic-shock-via-activation-of-platelet-activating-factor-acetylhydrolase
#5
Yoshinari Yamamoto, Ryu Sugimura, Takafumi Watanabe, Suguru Shigemori, Takuma Okajima, Shireen Nigar, Fu Namai, Takashi Sato, Tasuku Ogita, Takeshi Shimosato
Sepsis is a life-threatening, overwhelming immune response to infection with high morbidity and mortality. Inflammatory response and blood clotting are caused by sepsis, which induces serious organ damage and death from shock. As a mechanism of pathogenesis, platelet-activating factor (PAF) induces excessive inflammatory responses and blood clotting. In this study, we demonstrate that a Class A CpG oligodeoxynucleotide (CpG-A1585) strongly induced PAF acetylhydrolase, which generates lyso-PAF. CpG-A1585 rescued mice from acute lethal shock and decreased fibrin deposition, a hallmark of PAF-induced disseminated intravascular coagulation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28905885/long-term-correction-of-hemophilia-a-mice-following-lentiviral-mediated-delivery-of-an-optimized-canine-factor-viii-gene
#6
J M Staber, M J Pollpeter, C-G Anderson, M Burrascano, A L Cooney, P L Sinn, D T Rutkowski, W C Raschke, P B McCray
Current therapies for hemophilia A include frequent prophylactic or on-demand intravenous factor treatments which are costly, inconvenient and may lead to inhibitor formation. Viral vector delivery of factor VIII (FVIII) cDNA has the potential to alleviate the debilitating clotting defects. Lentiviral-based vectors delivered to murine models of hemophilia A mediate phenotypic correction. However, a limitation of lentiviral-mediated FVIII delivery is inefficient transduction of target cells. Here, we engineer a feline immunodeficiency virus (FIV) -based lentiviral vector pseudotyped with the baculovirus GP64 envelope glycoprotein to mediate efficient gene transfer to mouse hepatocytes...
September 14, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28904343/engineered-factor-xa-variants-retain-procoagulant-activity-independent-of-direct-factor-xa-inhibitors
#7
Daniël Verhoef, Koen M Visscher, C Ruben Vosmeer, Ka Lei Cheung, Pieter H Reitsma, Daan P Geerke, Mettine H A Bos
The absence of an adequate reversal strategy to prevent and stop potential life-threatening bleeding complications is a major drawback to the clinical use of the direct oral inhibitors of blood coagulation factor Xa. Here we show that specific modifications of the substrate-binding aromatic S4 subpocket within the factor Xa active site disrupt high-affinity engagement of the direct factor Xa inhibitors. These modifications either entail amino-acid substitution of S4 subsite residues Tyr99 and/or Phe174 (chymotrypsinogen numbering), or extension of the 99-loop that borders the S4 subsite...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28900369/the-local-clinical-validation-of-a-new-lithium-heparin-tube-with-a-barrier-bd-vacutainer%C3%A2-barricor-lh-plasma-tube
#8
Fatma Demet Arslan, Inanc Karakoyun, Banu Isbilen Basok, Merve Zeytinli Aksit, Anil Baysoy, Yasemin Kilic Ozturk, Yusuf Adnan Guclu, Can Duman
INTRODUCTION: Although serum-providing blood tubes with a barrier are still widely used due to their significant advantages, the use of blood tubes with a barrier to provide plasma is becoming widespread. We compared 22 analytes in a BD Vacutainer® Barricor LH Plasma tube for local clinical validation of this new lithium heparin tube with a barrier. MATERIALS AND METHODS: Samples from 44 volunteers were collected in different tubes (Becton Dickinson and Company): Z tube without additive (reference), clot-activator tube with gel (SST), lithium heparin tube without gel (LiH), and lithium heparin tube with barrier (Barricor)...
October 15, 2017: Biochemia Medica: časopis Hrvatskoga Društva Medicinskih Biokemičara
https://www.readbyqxmd.com/read/28899852/identification-of-extant-vertebrate-myxine-glutinosa-vwf-evolutionary-conservation-of-primary-hemostasis
#9
Marianne A Grant, David L Beeler, Katherine C Spokes, Junmei Chen, Harita Dharaneeswaran, Tracey E Sciuto, Ann M Dvorak, Gianluca Interlandi, José A Lopez, William C Aird
Hemostasis in vertebrates involves both a cellular and protein component. Previous studies in jawless vertebrates (cyclostomes) suggest that the protein response, which involves thrombin-catalyzed conversion of a soluble plasma protein, fibrinogen, into a polymeric fibrin clot, is conserved in all vertebrates. However, similar data are lacking for the cellular response, which in gnathostomes, is regulated by von Willebrand factor (VWF), a glycoprotein that mediates the adhesion of platelets to the subendothelial matrix of injured blood vessels...
September 12, 2017: Blood
https://www.readbyqxmd.com/read/28876572/haemoperitoneum-secondary-to-snake-bite
#10
S Rahim
BACKGROUND: Literature supports that very rarely the venom of "Hemotoxic Snake" (Russell's Vipers) affect haemostasis by secreting thrombin-like enzyme which promotes formation of unstable clots. Such clots could lead to fibrin deposition in micro circulation that in turn consume platelets and coagulation factors (consumption coagulopathy). Clinical presentation is mainly spontaneous bleeding and coagulopathy. In this case the significant effects of altered coagulation were observed in retropetitoneum and the patient presented in casuality as acute abdomen...
September 2017: South African Journal of Surgery. Suid-Afrikaanse Tydskrif Vir Chirurgie
https://www.readbyqxmd.com/read/28871021/effectiveness-of-two-psychological-interventions-for-pain-management-emotional-regulation-and-promotion-of-quality-of-life-among-adult-portuguese-men-with-haemophilia-psy-haemopeq-study-protocol-for-a-single-centre-prospective-randomised-controlled-trial
#11
Patrícia Ribeiro Pinto, Ana Cristina Paredes, Patrício Costa, Manuela Carvalho, Manuela Lopes, Susana Fernandes, Susana Pedras, Armando Almeida
INTRODUCTION: Haemophilia is a bleeding disorder associated with significant pain, emotional distress, quality of life (QoL) impairment and considerable healthcare costs. Psychosocial health and effective pain management are considered essential end points for optimal haemophilia care, but there is a significant gap in evidence-based treatments targeting these outcomes in people with haemophilia (PWH). Psychological interventions are cost-effective in promoting emotional well-being, QoL and pain control, although these have been scarcely used in haemophilia field...
September 3, 2017: BMJ Open
https://www.readbyqxmd.com/read/28844307/clinical-evidence-for-regenerative-endodontic-procedures-immediate-versus-delayed-induction
#12
Tatiana M Botero, Xianli Tang, Richard Gardner, Jan C C Hu, James R Boynton, G Rex Holland
Clinicians face many challenges when treating immature permanent teeth in young patients. Immediate blood clot induction can be a successful option as described by some case reports. No experimental studies or clinical trials have addressed this question. We have designed a clinical trial in which we hypothesized that there is no difference in success between immediate or delayed induction protocols. After confirmation of pulpal necrosis, patients were randomized. In the delayed group, 15 teeth were treated following the American Association of Endodontists guidelines, and calcium hydroxide was used as the intracanal medication...
September 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28837614/mice-deficient-in-the-anti-haemophilic-coagulation-factor-viii-show-increased-von-willebrand-factor-plasma-levels
#13
Klytaimnistra Kiouptsi, Alexandra Grill, Amrit Mann, Mareike Döhrmann, Maren Lillich, Sven Jäckel, Frano Malinarich, Henning Formes, Davit Manukyan, Saravanan Subramaniam, Avinash Khandagale, Cornelia Karwot, Serge C Thal, Markus Bosmann, Inge Scharrer, Kerstin Jurk, Christoph Reinhardt
Von Willebrand factor (VWF) is the carrier protein of the anti-haemophilic Factor VIII (FVIII) in plasma. It has been reported that the infusion of FVIII concentrate in haemophilia A patients results in lowered VWF plasma levels. However, the impact of F8-deficiency on VWF plasma levels in F8-/y mice is unresolved. In order to avoid confounding variables, we back-crossed F8-deficient mice onto a pure C57BL/6J background and analysed VWF plasma concentrations relative to C57BL/6J WT (F8+/y) littermate controls...
2017: PloS One
https://www.readbyqxmd.com/read/28834179/human-pancreatic-tumors-grown-in-mice-release-tissue-factor-positive-microvesicles-that-increase-venous-clot-size
#14
Y Hisada, C Ay, A C Auriemma, B C Cooley, N Mackman
BACKGROUND: Pancreatic cancer patients have a high rate of venous thromboembolism. Human pancreatic tumors and cell lines express high levels of tissue factor (TF) and release TF-positive microvesicles (TF+MVs). In pancreatic cancer patients, tumor-derived TF+MVs are present in blood and increased levels are associated with venous thromboembolism and decreased survival. Previous studies have shown that mice with orthotopic human or murine pancreatic tumors have circulating tumor-derived TF+MVs, an activated clotting system, and larger clots than controls in an inferior vena cava stenosis model...
August 22, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28833193/coagulation-and-fibrinolysis-in-gastric-cancer
#15
REVIEW
Ombretta Repetto, Valli De Re
Coagulation is a highly conserved process occurring after an injury to a blood vessel and resulting in hemostasis. In the thrombus microenvironment, finely orchestrated events restore vessel integrity through platelet activation, adhesion, and aggregation (primary hemostasis), followed by the coagulation cascades, thrombin generation, and fibrin clot deposition (secondary hemostasis). Several studies on cancer have provided insight into dramatic changes to coagulation-related events (i.e., fibrin clot deposition, fibrinolysis) during tumor pathogenesis, progression, and metastasis, in addition to a tumor-driven systemic activation of hemostasis and thrombosis (Trousseau's syndrome)...
August 22, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28831047/flow-induced-elongation-of-von-willebrand-factor-precedes-tension-dependent-activation
#16
Hongxia Fu, Yan Jiang, Darren Yang, Friedrich Scheiflinger, Wesley P Wong, Timothy A Springer
Von Willebrand factor, an ultralarge concatemeric blood protein, must bind to platelet GPIbα during bleeding to mediate hemostasis, but not in the normal circulation to avoid thrombosis. Von Willebrand factor is proposed to be mechanically activated by flow, but the mechanism remains unclear. Using microfluidics with single-molecule imaging, we simultaneously monitored reversible Von Willebrand factor extension and binding to GPIbα under flow. We show that Von Willebrand factor is activated through a two-step conformational transition: first, elongation from compact to linear form, and subsequently, a tension-dependent local transition to a state with high affinity for GPIbα...
August 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28821815/epac1-deficient-mice-have-bleeding-phenotype-and-thrombocytes-with-decreased-gpib%C3%AE-expression
#17
Gyrid Nygaard, Lars Herfindal, Kathrine S Asrud, Ronja Bjørnstad, Reidun K Kopperud, Eystein Oveland, Frode S Berven, Lene Myhren, Erling A Hoivik, Turid Helen Felli Lunde, Marit Bakke, Stein O Døskeland, Frode Selheim
Epac1 (Exchange protein directly activated by cAMP 1) limits fluid loss from the circulation by tightening the endothelial barrier. We show here that Epac1(-/-) mice, but not Epac2(-/-) mice, have prolonged bleeding time, suggesting that Epac1 may limit fluid loss also by restraining bleeding. The Epac1(-/-) mice had deficient in vitro secondary hemostasis. Quantitative comprehensive proteomics analysis revealed that Epac1(-/-) mouse platelets (thrombocytes) had unbalanced expression of key components of the glycoprotein Ib-IX-V (GPIb-IX-V) complex, with decrease of GP1bβ and no change of GP1bα...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820035/changes-in-heparin-dose-response-slope-during-cardiac-surgery-possible-result-in-inaccuracy-in-predicting-heparin-bolus-dose-requirement-to-achieve-target-act
#18
Junko Ichikawa, Tetsu Mori, Mitsuharu Kodaka, Keiko Nishiyama, Makoto Ozaki, Makiko Komori
INTRODUCTION: The substantial interpatient variability in heparin requirement has led to the use of a heparin dose response (HDR) technique. The accuracy of Hepcon-based heparin administration in achieving a target activated clotting time (ACT) using an HDR slope remains controversial. METHODS: We prospectively studied 86 adult patients scheduled for cardiac surgery requiring cardiopulmonary bypass. The total dose of calculated heparin required for patient and pump priming was administered simultaneously to achieve a target ACT of 450 s for HDR on the Hepcon HMS system...
September 2017: Perfusion
https://www.readbyqxmd.com/read/28819614/acute-compartment-syndrome-after-an-olecranon-fracture-in-a-patient-with-mild-hemophilia-b
#19
John M Reynolds, Christy Christophersen, Mary K Mulcahey
INTRODUCTION: Compartment syndrome is a serious condition characterized by compartmental pressures within 20 mmHg of diastolic blood pressure, or clinical signs of pain, paresthesia, pallor, and lack of pulses. Often a surgical intervention is necessary. Increased surveillance for compartment syndrome is important when a patient with a bleeding disorder sustains a traumatic injury. CASE REPORT: We present a case of forearm compartment syndrome in a patient with mild hemophilia B who sustained an olecranon fracture...
March 2017: Journal of Orthopaedic Case Reports
https://www.readbyqxmd.com/read/28815418/availability-of-angiography-and-therapeutic-embolization-for-the-treatment-of-acute-bleeding-in-patients-with-hemophilia
#20
Mi Jin Kim, Ji Young Oh, Young Shil Park
Clotting factor replacement therapy alone is often inadequate for acute bleeding in hemophilia patients, and surgery for such patients poses significant clinical challenges. Arterial angiographic intervention is used to control bleeding in local blood vessels. In the present study, we examined the clinical course and prognosis of hemophilia patients with bleeding who had undergone angiography, and evaluated the validity of diagnostic angiography and therapeutic embolization in these patients. Angiography was performed in five hemophilia patients, who experienced bleeding that was difficult to control even after treatment with clotting factor replacement or bypassing agent therapy...
August 16, 2017: International Journal of Hematology
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