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Coagulation Factor Concentrates

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https://www.readbyqxmd.com/read/29475063/characterization-of-a-novel-selective-factor-xa-inhibitor-djt06001-which-reduces-thrombus-formation-with-low-risk-of-bleeding
#1
Xuefeng Hu, Ying Xiao, Chuan Yu, Yinglin Zuo, Wen Yang, Xinan Wang, Baohua Gu, Jing Li
Factor Xa (FXa) is a serine protease that plays key roles in linking the intrinsic and extrinsic coagulation pathways to the final common pathway. DJT06001 is an oral, highly specific and direct FXa inhibitor for the prevention and treatment of thromboembolic diseases. We characterized the compound in vitro and studied its in vivo activity in rat thrombosis models, as well as bleeding risk and Pharmacokinetics and Pharmacodynamics (PK/PD) relationship. DJT06001 inhibited free FXa with an inhibitory constant (Ki) of 0...
February 20, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29470366/impact-of-angiotensin-converting-enzyme-inhibition-on-platelet-tissue-factor-expression-in-stroke-prone-rats
#2
Marta Brambilla, Paolo Gelosa, Laura Rossetti, Laura Castiglioni, Chiara Zara, Paola Canzano, Elena Tremoli, Luigi Sironi, Marina Camera
OBJECTIVE: Hypertension is a well known risk factor for thrombotic events such as myocardial infarction and stroke. Platelets express tissue factor (TF), the key activator of blood coagulation and thrombus formation. The number of TF-positive platelets increases in pathological conditions characterized by thrombotic complications but whether this occurs in hypertension is unknown. Here we investigated whether platelet TF expression is increased in a hypertensive status through a mechanism acting on megakaryocytes; the phenomenon could be modulated by antihypertensive drug as captopril; angiotensin (AngII) influences platelet TF expression...
February 21, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29468977/the-development-of-new-factor-xa-inhibitors-based-on-amide-synthesis
#3
Dmitry Tarasov, Dmitry Tovbin, Dmitry Malakhov, Arseniy Aybush, Natalia Tserkovnikova, Marina Savelyeva, Dmitry Sychev, Natalia Drozd, Alla Savchenko
BACKGROUND: Factor Xa (FXa) is known to play a central role in a blood coagulation cascade and considered to be one of the most attractive targets for oral anticoagulants of new generation. OBJECTIVE: Our approach for the development of directly acting oral anticoagulants (DOAC), FXa inhibitors was demonstrated in this work. METHOD: Chemical synthesis is the base of our approach for the development of potential inhibitors. In this work, the substances like R1-(CONH)-R2-(CONH)-R3 are being developed, using previously described docking and screening methods, where R1, R2, R3 are some chemical groups, (CONH) are amid bonds connecting R1, R2 and R3...
February 14, 2018: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/29462691/factor-x-activating-atractaspis-snake-venoms-and-the-relative-coagulotoxicity-neutralising-efficacy-of-african-antivenoms
#4
Brice Oulion, James S Dobson, Christina N Zdenek, Kevin Arbuckle, Callum Lister, Francisco C P Coimbra, Bianca Op den Brouw, Jordan Debono, Aymeric Rogalski, Aude Violette, Rudy Fourmy, Nathaniel Frank, Bryan G Fry
Atractaspis snake species are enigmatic in their natural history, and venom effects are correspondingly poorly described. Bite reports are scarce but bites have been described as causing severe hypertension, profound local tissue damage leading to amputation, and deaths are on record. Clinical descriptions have largely concentrated upon tissue effects, and research efforts have focused upon the blood-pressure affecting sarafotoxins. However, coagulation disturbances suggestive of procoagulant functions have been reported in some clinical cases, yet this aspect has been uninvestigated...
February 17, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29458015/sulfenamide-and-sulfonamide-derivatives-of-metformin-can-exert-anti-coagulant-and-pro-fibrinolytic-properties
#5
Magdalena Markowicz-Piasecka, Kristiina M Huttunen, Łukasz Mateusiak, Elżbieta Mikiciuk-Olasik, Joanna Sikora
Type 2 diabetes mellitus (T2DM) is characterised not only by hyperglycaemia and insulin resistance but also an impaired balance between the processes of coagulation and fibrinolysis. The aim of this study was to examine the effects of metformin, a widely-used oral anti-diabetic drug, phenformin and eight sulfenamide and sulfonamide derivatives of metformin on several haemostasis parameters. Thrombin Time (TT) tests were performed according to the available commercial method. The activity of factor X was conducted based on deficient plasma factor X...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29439283/replacement-therapy-for-coronary-artery-bypass-surgery-in-patients-with-hemophilia-a-and-b
#6
REVIEW
Theoni Kanellopoulou, Efrosyni Nomikou
There are only a few cases of patients with hemophilia A and B who have undergone coronary artery bypass surgery. High levels of replacement therapy with factor concentrate either with bolus or continuous infusion are usually required pre-operatively and during the first post-operative days in order to maintain the coagulation deficient factor levels greater than 80% of normal. Heparinization during cardiopulmonary bypass appears to be safe and intra-operative blood salvage using cell saver techniques reduce the need for transfusions...
February 13, 2018: Journal of Cardiac Surgery
https://www.readbyqxmd.com/read/29438223/knockdown-of-tfpi-anchored-endothelial-cells-exacerbates-lipopolysaccharide-induced-acute-lung-injury-via-nf-%C3%AE%C2%BAb-signaling-pathway
#7
Bao Q Wang, Meng Shi, Jian P Zhang, Xie Wu, Mei J Chang, Zhi H Chen, Hua H Shen, Yuan L Song, Jian Zhou, Chun X Bai
BACKGROUND: As activation of the coagulation system is both a consequence and contributor to acute lung injury (ALI), pulmonary coagulopathy has become a potential target for therapeutic intervention in ALI patients. We investigated the effects and possible mechanisms of endothelial cell (EC)-anchored tissue factor pathway inhibitor (TFPI) on lipopolysaccharide (LPS)-induced ALI in mice. METHODS: To assess the effect of endothelial cell-anchored TFPI deletion on ALI indices, TFPI knockout (cKO) mice were generated...
February 12, 2018: Shock
https://www.readbyqxmd.com/read/29431889/coagulation-and-inflammation-in-long-term-cancer-survivors-results-from-the-adult-population
#8
Marina Panova-Noeva, Andreas Schulz, Natalie Arnold, Iris M Hermanns, Jürgen H Prochaska, Dagmar Laubert-Reh, Henri M Spronk, Maria Blettner, Manfred Beutel, Norbert Pfeiffer, Thomas Münzel, Karl J Lackner, Hugo Ten Cate, Philipp S Wild
BACKGROUND: The advancements in cancer treatment and detection of early cancer have resulted in steady increase of cancer survivors over the years. However, due to long term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular disease (CVD) is increasing in survivors. OBJECTIVES: This study investigates traditional cardiovascular risk factors (CVRFs), inflammation and coagulation profile in long-term cancer survivors (cancer diagnosis ≥ five years) from a large adult population-based study sample...
February 12, 2018: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/29430449/new-insights-into-the-mechanisms-of-pulmonary-edema-in-acute-lung-injury
#9
REVIEW
Raquel Herrero, Gema Sanchez, Jose Angel Lorente
Appearance of alveolar protein-rich edema is an early event in the development of acute respiratory distress syndrome (ARDS). Alveolar edema in ARDS results from a significant increase in the permeability of the alveolar epithelial barrier, and represents one of the main factors that contribute to the hypoxemia in these patients. Damage of the alveolar epithelium is considered a major mechanism responsible for the increased pulmonary permeability, which results in edema fluid containing high concentrations of extravasated macromolecules in the alveoli...
January 2018: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29426727/setting-the-stage-for-individualized-therapy-in-hemophilia-what-role-can-pharmacokinetics-play
#10
REVIEW
H C A M Hazendonk, I van Moort, R A A Mathôt, K Fijnvandraat, F W G Leebeek, P W Collins, M H Cnossen
Replacement therapy with clotting factor concentrates (CFC) is the mainstay of treatment in hemophilia. Its widespread application has led to a dramatic decrease in morbidity and mortality in patients, with concomitant improvement of quality of life. However, dosing is challenging and costs are high. This review discusses benefits and limitations of pharmacokinetic (PK)-guided dosing of replacement therapy as an alternative for current dosing regimens. Dosing of CFC is now primarily based on body weight and based on its in vivo recovery (IVR)...
January 31, 2018: Blood Reviews
https://www.readbyqxmd.com/read/29421956/olive-mill-wastewater-pretreatment-by-combination-of-filtration-on-olive-stone-filters-and-coagulation-flocculation
#11
Ghizlane Enaime, Abdelaziz Baçaoui, Abdelrani Yaacoubi, Marc Wichern, Manfred Lübken
In the present study a new combined process, comprising filtration of raw olive mill wastewater (OMWW) on two successive olive stone (OS) filters followed by a coagulation-flocculation, was developed in order to perform an efficient pretreatment of OMWW. The results show that the use of OS filter leads to a higher removal of total suspended solids (TSS) and fatty matter (FM) from the raw OMWW (about 82.5 and 73.8%, respectively) and a depletion of total phenolic compounds (TP) and chemical oxygen demand (COD) (11...
February 9, 2018: Environmental Technology
https://www.readbyqxmd.com/read/29416854/regulation-of-plasma-von-willebrand-factor
#12
REVIEW
Karl C Desch
Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding...
2018: F1000Research
https://www.readbyqxmd.com/read/29405633/state-of-the-art-vs-biological-variability-comparison-on-hematology-parameters-using-spanish-eqas-data
#13
A Molina, L Guiñon, A Perez, A Segurana, J L Bedini, J C Reverter, A Merino
INTRODUCTION: It is important for clinical laboratories to maintain under control the possible sources of error in its analytical determinations. The objective of this work is to perform an analysis of the total error committed by laboratories using the data extracted from the Spanish External Quality Assessment Program in Hematology and to compare them with the specifications based on the biological variability proposed by the Ricós group. MATERIAL AND METHODS: We analyzed a total of 3 89 000 results during the period 2015-2016 from the following quantitative schemes of Spanish External Quality Assessment Program: complete blood count, blood coagulation tests, differential leukocyte count, reticulocytes, hemoglobin A2 , antithrombin, factor VIII, protein C, and von Willebrand factor...
February 5, 2018: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/29404656/-hypovolemic-and-hemorrhagic-shock
#14
H Lier, M Bernhard, B Hossfeld
The term "shock" refers to a life-threatening circulatory failure caused by an imbalance between the supply and demand of cellular oxygen. Hypovolemic shock is characterized by a reduction of intravascular volume and a subsequent reduction in preload. The body compensates the loss of volume by increasing the stroke volume, heart frequency, oxygen extraction rate, and later by an increased concentration of 2,3-diphosphoglycerate with a rightward shift of the oxygen dissociation curve. Hypovolemic hemorrhagic shock impairs the macrocirculation and microcirculation and therefore affects many organ systems (e...
February 5, 2018: Der Anaesthesist
https://www.readbyqxmd.com/read/29403324/pharmacokinetics-based-clinical-management-of-acquired-von-willebrand-syndrome-a-case-report
#15
Candice M Baldeo, Candido E Rivera, Han W Tun, Prakash Vishnu
von Willebrand disease (VWD) is a common bleeding disorder caused by defective or low levels of von Willebrand factor (VWF). Although most cases of VWD are caused by genetic mutations, some are acquired due to various disease states. In managing VWD, the aim is to normalize plasma levels of both VWF and factor VIII (FVIII), as this aids in hemostasis. Desmopressin usually corrects VWF level in type 1 VWD by inducing the release of endogenous VWF. In cases where desmopressin is ineffective or cannot be used, transfusion of virally inactivated, plasma-derived VWF/FVIII concentrate or infusion of recombinant VWF (Vonvendi) is indicated...
2018: Journal of Blood Medicine
https://www.readbyqxmd.com/read/29401369/prophylactic-vitamin-k-for-the-prevention-of-vitamin-k-deficiency-bleeding-in-preterm-neonates
#16
REVIEW
Stephanie Ardell, Martin Offringa, Colleen Ovelman, Roger Soll
BACKGROUND: Vitamin K is necessary for the synthesis of coagulation factors. Term infants, especially those who are exclusively breast fed, are deficient in vitamin K and consequently may have vitamin K deficiency bleeding (VKDB). Preterm infants are potentially at greater risk for VKDB because of delayed feeding and subsequent delay in the colonization of their gastrointestinal system with vitamin K producing microflora, as well as immature hepatic and hemostatic function. OBJECTIVES: To determine the effect of vitamin K prophylaxis in the prevention of vitamin K deficiency bleeding (VKDB) in preterm infants...
February 5, 2018: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29396046/simultaneous-presence-of-hypercoagulation-and-increased-clot-lysis-time-due-to-il-1%C3%AE-il-6-and-il-8
#17
Janette Bester, Christina Matshailwe, Etheresia Pretorius
Circulating cytokines, and particularly the interleukin (IL)-family are known to play an important role in inflammation. These molecules circulate in the blood and therefore have a direct effect on the plasma molecules and the formed elements like the erythrocytes and platelets. Aberrant coagulation (hypercoagulation or blood clots that form too easily) and clot lyses (hypofibrinolysis, where clots do not dissolve properly, with an abnormally low rate of clot lysis time), are usually the hallmarks of many inflammatory conditions...
January 27, 2018: Cytokine
https://www.readbyqxmd.com/read/29395816/a-comparative-study-of-point-of-care-prothrombin-time-in-cardiopulmonary-bypass-surgery
#18
Shihoko Okabayashi, Satoru Ogawa, Kenichi A Tanaka, Takashi Nishiyama, Shusuke Takeshita, Yoshinobu Nakayama, Yasufumi Nakajima, Teiji Sawa, Toshiki Mizobe
OBJECTIVE: Point-of-care (POC) devices allow for prothrombin time/international normalized ratio (PT/INR) testing in whole blood (WB) and timely administration of plasma or prothrombin complex concentrate during cardiopulmonary bypass surgery. This study evaluated the sensitivities of a new POC PT test, a dry-hematology method with heparin neutralization technology (DRIHEMATO PT-S [DRI PT-S]; A&T Corporation, Kanagawa, Japan), and compared it with other POC tests currently available. DESIGN: Prospective, observational study...
December 29, 2017: Journal of Cardiothoracic and Vascular Anesthesia
https://www.readbyqxmd.com/read/29392436/prothrombin-complex-concentrate-reversal-of-coagulopathy-in-emergency-general-surgery-patients
#19
Moustafa Younis, Mohamed Ray-Zack, Nadeem N Haddad, Asad Choudhry, Matthew C Hernandez, Kevin Wise, Martin D Zielinski
BACKGROUND: Coagulopathy can delay or complicate surgical diseases that require emergent surgical treatment. Prothrombin complex concentrates (PCC) provide concentrated coagulation factors which may reverse coagulopathy more quickly than plasma (FFP) alone. We aimed to determine the time to operative intervention in coagulopathic emergency general surgery patients receiving either PCC or FFP. We hypothesize that PCC administration more rapidly normalizes coagulopathy and that the time to operation is diminished compared to FFP alone...
February 1, 2018: World Journal of Surgery
https://www.readbyqxmd.com/read/29383815/viral-safety-of-coagulation-factor-concentrates-memoirs-from-an-insider
#20
Pier Mannuccio Mannucci
The purpose of this essay is to recall the actions taken globally to improve the viral safety of coagulation factor concentrates, mainly in the years from 1985 to 1990, at a time of confusing and often contradictory information on bloodborne viral infections in multitransfused patients with hemophilia (PWH). I shall first recall the problem of the transmission and control of the hepatitis viruses and then that of the human immunodeficiency virus (HIV): not only for temporal reasons but also because understanding the progress of knowledge on hepatitis and the poor success of the early measures taken to tackle this problem in PWH is essential to understand how the problem of HIV transmission was ultimately dealt with success...
January 31, 2018: Journal of Thrombosis and Haemostasis: JTH
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