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Functional clotting assay

Sven Van Poucke, Dana Huskens, Kurt Van der Speeten, Mark Roest, Bart Lauwereins, Ming-Hua Zheng, Seppe Dehaene, Joris Penders, Abraham Marcus, Marcus Lancé
BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal peroperative chemotherapy (HIPEC), indicated for patients with peritoneal metastases from digestive or gynecological malignancies alike, demonstrates a considerable impact on hemostatic metabolism, both on platelet and on coagulation level. The potential hemostatic interference in CRS and HIPEC is phase dependent. The hypothesis of this prospective cohort study is that the procedure exposed an increased thrombotic risk, resulting in a faster and increased thrombin generation and hyper platelet function...
2018: PloS One
Julia R Coleman, Ernest E Moore, Michael P Chapman, Anirban Banerjee, Christopher C Silliman, Arsen Ghasabyan, James Chandler, Jason M Samuels, Angela Sauaia
BACKGROUND: Several thrombelastography functional assays have been developed to guide transfusion in injured patients, but how this acceleration of thrombelastography affects its ability to predict massive transfusion is unknown. The objective of this study is to compare citrated native, citrated kaolin, and citrated rapid thromboelastographies for their prediction of massive transfusion after trauma. We hypothesized that citrated native thrombelastography best predicts massive transfusion...
June 11, 2018: Surgery
Kazuki Takeda, Yoshinori Ikenaka, Kazuyuki D Tanaka, Shouta M M Nakayama, Tsutomu Tanikawa, Hazuki Mizukawa, Mayumi Ishizuka
Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. There are two major mechanisms underlying this resistance, i.e., mutation of the target enzyme of warfarin, VKOR, and enhanced metabolism of warfarin...
June 2018: Pesticide Biochemistry and Physiology
Meiling Luo, Aiqiu Wei, Liqun Xiang, Jie Yan, Lin Liao, Xuelian Deng, Donghong Deng, Peng Cheng, Faquan Lin
We found a heterozygous dysfibrinogenemia caused by a substitution of AαArg16Cys. The proband suffered multiple cerebral infarctions. Routine coagulation tests revealed a prolonged thrombin time. The fibrinogen levels in the functional assays were considerably lower than the levels in the immunological assays. The polymerization of the purified fibrinogen was strongly impaired in the presence of calcium. As previously observed in other heterozygous Aα R16C variants, the release rate and amount of fibrinopeptide A (FPA) were lower in the proband than those in normal controls...
June 5, 2018: Journal of Thrombosis and Thrombolysis
Gary E Gilbert
Hemophilia A is caused by decreased or dysfunctional blood coagulation factor VIII (FVIII). Recent developments in the understanding of FVIII biology, in particular the nature of FVIII binding sites on platelets, may provide new insight into the limitations of current assays. Recent data suggest that the phospholipid vesicles, which represent nonphysiologic membranes of high phosphatidylserine (PS) content, poorly reflect functional FVIII binding sites critical to coagulation. This narrative review describes the function of FVIII in clotting and discusses our evolving understanding of FVIII binding sites and their clinical implications...
May 24, 2018: Blood Reviews
Kjersti Baksaas-Aasen, Susan Van Dieren, Kirsten Balvers, Nicole P Juffermans, Pål A Næss, Claire Rourke, Simon Eaglestone, Sisse R Ostrowski, Jakob Stensballe, Simon Stanworth, Marc Maegele, Carel Goslings, Pär I Johansson, Karim Brohi, Christine Gaarder
OBJECTIVE: Developing pragmatic data-driven algorithms for management of trauma induced coagulopathy (TIC) during trauma hemorrhage for viscoelastic hemostatic assays (VHAs). BACKGROUND: Admission data from conventional coagulation tests (CCT), rotational thrombelastometry (ROTEM) and thrombelastography (TEG) were collected prospectively at 6 European trauma centers during 2008 to 2013. METHODS: To identify significant VHA parameters capable of detecting TIC (defined as INR > 1...
May 23, 2018: Annals of Surgery
Liqing Zhu, Misheng Zhao, Mingshan Wang, Zhefeng Lou, Xiaoli Chen, Liangliang Pan, Dandan Yu, Wenli Xia, Han Wang, Bin Zhou, Shenmeng Gao
Hypodysfibrinogenemia is the least frequently reported congenital fibrinogen disorder, characterized by both quantity and quality defects of fibrinogen. In this study, we investigated the molecular basis of hypodysfibrinogenemia in a Chinese family. Functional fibrinogen was measured by Clauss method, and the antigenic fibrinogen was measured by immunoturbidimetry assay. All the exons and exon-intron boundaries of fibrinogen genes (FGA, FGB and FGG) were analysed by direct DNA sequencing. To further evaluate its molecular and functional characterizations, fibrinogen was purified from the plasma of propositus, then SDS-PAGE, fibrin polymerization, clot lysis, and electron microscopy scanning were all performed...
May 10, 2018: Journal of Thrombosis and Thrombolysis
M Levi
Several clinical conditions, in particular those associated with a systemic inflammatory response, can cause some degree of activation of coagulation but when the procoagulant stimulus is sufficiently severe and overcomes the natural anticoagulant mechanisms of coagulation, disseminated intravascular coagulation (DIC) may occur. The clinical manifestations of DIC encompass multiorgan dysfunction caused by fibrin-platelet clots in the microcirculation, and bleeding caused by consumption of platelets and coagulation factors...
May 2018: International Journal of Laboratory Hematology
Matthias Fröhlich, Nadine Schäfer, Michael Caspers, Julia K Böhm, Ewa K Stürmer, Bertil Bouillon, Marc Maegele
BACKGROUND: After severe polytrauma the dynamic process of coagulation may deteriorate towards a trauma-induced coagulopathy (TIC) promoting a dramatic increase in morbidity and mortality. Recent evidence suggests that microparticles (MPs) play a pivotal role at the interface between cellular and plasmatic coagulation systems. However, the impact of MPs on functional coagulation has not been clarified yet in the setting of traumatic injuries. We assessed the temporal patterns of circulating MP concentrations including their cellular origin in the context of clinical presentation and global coagulation assays...
April 27, 2018: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
E L Hethershaw, P J Adamson, K A Smith, W N Goldsberry, R J Pease, S E Radford, P J Grant, R A S Ariëns, M C Maurer, H Philippou
Essentials The roles of β-barrels 1 and 2 in factor XIII (FXIII) are currently unknown. FXIII truncations lacking β-barrel 2, both β-barrels, or full length FXIII, were made. Removing β-barrel 2 caused total loss of activity, removing both β-barrels returned 30% activity. β-barrel 2 is necessary for exposure of the active site cysteine during activation. SUMMARY: Background Factor XIII is composed of an activation peptide segment, a β-sandwich domain, a catalytic core, and, finally, β-barrels 1 and 2...
April 19, 2018: Journal of Thrombosis and Haemostasis: JTH
Zunjing Xia, Jie Lin, Lingping Lu, Chol Kim, Ping Yu, Ming Qi
: Hemophilia A is a bleeding disorder caused by coagulation factor VIII protein deficiency or dysfunction, which is classified into severe, moderate, and mild according to factor clotting activity. An overwhelming majority of missense and nonsense mutations occur in exons of F8 gene, whereas mutations in introns can also be pathogenic. This study aimed to investigate the effect of an intronic mutation, c.6430-3C>G (IVS22-3C>G), on pre-mRNA splicing of the F8 gene. We applied DNA and cDNA sequencing in a Chinese boy with hemophilia A to search if any pathogenic mutation in the F8 gene...
June 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
M C Kamaraj, S Mohan Raj, D Palani Selvam, S Subashchandrabose, A Kalaiselvan
The present investigations are phytochemical screening of Latex aqueous (Laq ) extract of C. sparsiflorus and study its role in homeostasis. It is being traditionally used for fresh cuts to stop bleeding immediately. To know the contents of extract, the quantitative phytochemical analysis were performed it showed the contents such as saponins (15.2%), alkaloids (7.61%), phenols (0.62%), tannins (1.1%), and flavonoids (0.224%). The in vitro and in vivo blood clotting mechanism was observed in Wister albino rats to understand the blood clotting activity...
March 27, 2018: Computational Biology and Chemistry
Sebastian Lickert, Simona Sorrentino, Jan-Dirk Studt, Ohad Medalia, Viola Vogel, Ingmar Schoen
Haemostatic platelet function is intimately linked to cellular mechanics and cytoskeletal morphology. How cytoskeletal reorganizations give rise to a highly contractile phenotype that is necessary for clot contraction remains poorly understood. To elucidate this process in vitro, we developed a morphometric screen to quantify the spatial organization of actin fibres and vinculin adhesion sites in single spread platelets. Platelets from healthy donors predominantly adopted a bipolar morphology on fibrinogen and fibronectin, whereas distinguishable, more isotropic phenotypes on collagen type I or laminin...
April 3, 2018: Scientific Reports
Kristin M Reddoch-Cardenas, Robbie K Montgomery, Crystal B Lafleur, Grantham C Peltier, James A Bynum, Andrew P Cap
BACKGROUND: Refrigeration of platelets (PLTs) in a PLT additive solution (PAS) reduces PLT activation compared to storage in plasma and preserves function for at least 15 days. Currently only two PASs are licensed by the Food and Drug Administration, each for use with only one apheresis platform. In this study, we compared the metabolic, functional, and activation status of PLTs collected on a Trima apheresis collection system and stored refrigerated in Isoplate (ISO) PAS to PLTs collected on an Amicus collection system and stored refrigerated in Intersol (INT) PAS...
March 30, 2018: Transfusion
Melanie Guerard, Christine Marchand, Jürgen Funk, Francois Christen, Michael Winter, Andreas Zeller
The potential of 4-chloro-ortho-toluidine (4-CloT), an aromatic amine substituted on the ortho- and para-position of the amine function, to induce DNA damage in male Wistar rats was evaluated with the micronucleus test (peripheral blood), Pig-a (peripheral blood) and comet assay (peripheral blood, liver, urinary bladder, jejunum) at several time points. In addition to those markers of DNA damage, i.e. gene mutation and clastogenicity, standard hematology, including methemoglobin (MetHb), histopathology and immunohistochemistry of γ-H2AX and Ki-67 in liver, jejunum and urinary bladder were performed...
March 20, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
A Gupta, P Mishra, H P Pati, S Tyagi, M Mahapatra, T Seth, R Saxena
INTRODUCTION: Hemostatic disorders are often missed in women with bleeding particularly menorrhagia. Preexisting hemostatic disorders are now known as common risk factor for postpartum hemorrhage and prolonged bleeding in puerperium. Females with bleeding complaints constitute an important population referred to hematology clinic. Hence, we aim to evaluate the type and frequency of hemostatic disorders among females presenting with bleeding in a tertiary care hospital and a basic hemostatic laboratory...
March 25, 2018: International Journal of Laboratory Hematology
V Chan, M Sarkari, R Sunderland, A E St John, N J White, C J Kastrup
Essentials Platelet transfusions can have limited efficacy during hemorrhage associated with coagulopathy. Thrombin can be shielded by encapsulation into nanoliposomes and delivered to platelets ex vivo. Loading platelets with liposomal thrombin improved several aspects of platelet coagulability. Platelets loaded with liposomal thrombin can overcome some coagulopathic deficiencies in vitro. SUMMARY: Background Platelets are integral to clot formation and are often transfused to stop or prevent bleeding...
June 2018: Journal of Thrombosis and Haemostasis: JTH
Helen V Wilmot, Jason Hockley, Peter Rigsby, Elaine Gray
Until recently, the role of factor XII (FXII) in hemostasis was not considered to be important since patients with FXII deficiency do not present with bleeding. The activation of FXII by agents including mast cells and platelet polyphosphates suggests that it may have a role in thrombogenesis. The inhibition of FXII therefore presents an option for antithrombotic therapy, and antibodies and inhibitors are already in development. Assays for FXII will be required to support these technologies, and an international standard (IS) for FXII would be useful for the development of these methods and for the clinical monitoring of patients...
2018: Frontiers in Medicine
Kankan Su, Xiaoxiao Cai, Wenli Xia, Yanhui Jin, Lihong Yang, Mingshan Wang
: The objective is to study a gene mutation (Tyr503Cys) found in a Chinese consanguineous marriage family with inherited factor XI (FXI) deficiency (cross-reacting material positive, type II). The FXI activity and FXI antigen were tested with clotting assay and ELISA, respectively. The FXI gene was amplified by PCR with direct sequencing. ClustalX-2.1-win and three online bioinformatics softwares were used to study the conservatism and harm of the mutation. The proband had reduced FXI: activity at 13%; three members had decreased to about 35%, all of whom had nomal FXI: antigen...
April 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
Jean Amiral, Maxime Laroche, Jerard Seghatchian
For many years, the importance of fibrinolysis has been recognized, first for its intravascular antithrombotic action, and more recently for its many extravascular activities, associated with matrix degradation and tissue remodeling. In the blood circulation system, fibrinolysis prevents thrombosis, and is associated with various biological and clinical situations: risk factors for cardio-vascular diseases in high risk clinical situations (type II diabetes, hypertension, triglycerides, high BMI, elevated glucose, etc...
February 2018: Transfusion and Apheresis Science
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