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The Potential of Plants as Treatments for Venous Thromboembolism
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Lilitha L. Denga, Namrita Lall
The tenase complex proteolytically creates more FXa by activating additional FX (Autin et al. 2004). FXa then forms the prothrombinase complex with FVa. The prothrombinase complex rapidly converts prothrombin to thrombin, which further amplifies the cascade and converts soluble fibrinogen to insoluble fibrin (Smith, Travers, and Morrissey 2015).
Haemostasis
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The propagation phase begins formation with the tenase (IXa–VIIIa) complex on platelet surfaces. The tenase complex generates large amounts of factor Xa that interacts with factor Va, forming the prothrombinase (factors Va–Xa) complex, which catalyses the conversion of prothrombin (factor II) to thrombin (factor IIa). Thrombin converts fibrinogen into fibrin monomers, which polymerize to form a stable fibrin clot. This burst of thrombin generation also produces a positive feedback by activating factors V, VIII and XI (Figure 53.4).
Phospholipids and the Clotting Process
Published in E. Nigel Harris, Thomas Exner, Graham R. V. Hughes, Ronald A. Asherson, Phospholipid-Binding Antibodies, 2020
Robert F. A. Zwaal, Edouard M. Bevers, Jan Rosing
Most of the studies on the phospholipid requirements of blood coagulation have been performed with coagulation tests or assays with purified coagulation factors in which the activity of the prothrombinase complex is determined. Much less is known about the phospholipid requirements of the tenase complex. Studies using coagulation assays do not provide explicit information about the phospholipids required for optimal activity of the tenase complex because these assays are always dependent on the prothrombinase complex as well. However, the large similarities between the prothrombinase and the tenase complex suggests that the phospholipid requirement of both complexes is very similar.
High-molecular-weight fucosylated glycosaminoglycan induces human platelet aggregation depending on αIIbβ3 and platelet secretion
Published in Platelets, 2021
Lisha Lin, Lian Yang, Jun Chen, Lutan Zhou, Sujuan Li, Na Gao, Jinhua Zhao
Fucosylated glycosaminoglycan (FG) is found, so far, exclusively in body wall of sea cucumber (Echinodermata, Holothuroidea). FG is characterized in the sulfated fucose (FucS) branches that link to its chondroitin sulfate (CS)-like glycosaminoglycan backbone [1,2]. Multiple bioactivities of FGs have been reported, including anticoagulant, anti-inflammatory, anticancer, antiviral, and pro-angiogenic activities [3–5]. Particularly, FG is a promising lead compound for anticoagulation by inhibiting intrinsic tenase (iXase, composed by FIXa-FVIIIa-Ca2+-phospholipid) [6–8]. However, FG from natural source lacks pharmacological selectivity, in that, it has both serpin-independent and serpin-dependent anticoagulant mechanisms, and that the undesired effects of FXII activation and platelet aggregation which potentially poses risks [9,10].
TEG®6s system measures the contributions of both platelet count and platelet function to clot formation at the site-of-care
Published in Platelets, 2020
Joao D. Dias, Carlos G Lopez-Espina, Kevin Bliden, Paul Gurbel, Jan Hartmann, Hardean E Achneck
The small but statistically significant reductions in reaction time parameters (CK.R, CKH.R, and CRT.ACT) with increasing platelet counts are consistent with the cell-based model of hemostasis [1]. Accelerated clot formation at higher platelet concentrations may be due to the increased number of phospholipid membranes providing a substrate for tenase and prothrombinase complexes [1]. During the propagation phase of the hemostatic process, tenase and prothrombinase complexes are assembled on the platelet surface, and large-scale thrombin generation takes place. A lower platelet count decreases the speed of this process. Unlike platelet count, changes in platelet function did not affect reaction time parameters in our study. This may be explained by the fact that provision of surfaces for the hemostatic process by platelets is independent of their function. Alternatively, it is possible that abciximab, through steric hindrance and conformational changes, prevents binding to the αIIbβ3 receptor, blocking secondary platelet activation, but not the initial platelet activation. This would mean that platelets continue to be activated and generate thrombin, leading to a feedback loop increasing the number of available platelets. When the effects of both MA and reaction time parameters are combined, the TEG®6s analyzer can be used to accurately monitor functional platelets at any count.
Emerging PEGylated non-biologic drugs
Published in Expert Opinion on Emerging Drugs, 2019
Eun Ji Park, Jiyoung Choi, Kang Choon Lee, Dong Hee Na
Pegnivacogin, a 37-nucleotide RNA aptamer conjugated to 40 kDa-branched PEG (Figure 3), is an anticoagulant that selectively inhibits the activated coagulation factor IXa [85]. It reduces the formation of the tenase complex (factor IXa and VIIIa) and the subsequent downstream conversion of factor X to factor Xa, which thereby reduces the generation of thrombin [86]. In the aptamer-based anticoagulation system (REG1, Regado Biosciences), pegnivacogin (RB006) was designed to work in conjunction with anivamersen (RB007), which is an antidote oligonucleotide to pegnivacogin that specifically binds to pegnivacogin and rapidly reverses the anticoagulation effect of pegnivacogin in a dose-dependent manner [27].