γD318Y fibrinogen shows no fibrin polymerization due to defective “A-a” and “B-b” interactions, whereas that of γK321E fibrinogen is nearly normal

Kamijo, Tomu; Mukai, Saki; Taira, Chiaki; Higuchi, Yumiko; Okumura, Nobuo

doi:10.1016/j.thromres.2019.08.017

Cited by 3 publications

(3 citation statements)

References 28 publications

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“…Afterwards thrombin is activated on surface of platelets and fibrinogen is converted into insoluble fibrin [19]. The last step in the blood clotting cascade necessary for hemostasis and thrombosis is the conversion of fibrinogen to fibrin [20]. Fibrinogen's conversion to fibrin stops bleeding by providing the insoluble matrix of the blood clot [21].…”

Section: Fibrinogen's Role In the Pathophysiology Of Thrombosis And B...mentioning

confidence: 99%

Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Brunclíková

Šimurda

Žolková

et al. 2022

JCM

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Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen’s structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype–phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event.

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Section: Fibrinogen's Role In the Pathophysiology Of Thrombosis And B...mentioning

confidence: 99%

Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Brunclíková

Šimurda

Žolková

et al. 2022

JCM

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“…Fibrinogen contains both high and low Ca 2+ -binding sites; three high-and 8-10 low-affinity calcium binding sites (Weisel and Litvinov, 2017). Of the high-affinity Ca 2+ binding sites in the γ chains, γ1, is associated with amino acid residues γAsp318, γAsp320, γGly324, and γPhe322 and coordinated with two strongly bound water molecules (Spraggon et al, 1997;Kamijo et al, 2019). The remaining high-affinity Ca 2+ binding sites (named β1) are located at the β-nodules within loop β381-385 and both have a coordinating water molecule (Everse et al, 1998).…”

Section: The Effect Of Ca 2+ On Blood Clotsmentioning

confidence: 99%

Current Application of Beta-Tricalcium Phosphate in Bone Repair and Its Mechanism to Regulate Osteogenesis

Zhou

et al. 2021

Front. Mater.

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Large segmental bone loss and bone resection due to trauma and/or the presence of tumors and cysts often results in a delay in healing or non-union. Currently, the bone autograft is the most frequently used strategy to manage large bone loss. Nevertheless, autograft harvesting has limitations, namely sourcing of autograft material, the requirement of an invasive procedure, and susceptibility to infection. These disadvantages can result in complications and the development of a bone substitute materials offers a potential alternative to overcome these shortcomings. Among the biomaterials under consideration to date, beta-tricalcium phosphate (β-TCP) has emerged as a promising material for bone regeneration applications due to its osteoconductivity and osteoinductivity properties as well as its superior degradation in vivo. However, current evidence suggests the use β-TCP can in fact delay bone healing and mechanisms for this observation are yet to be comprehensively investigated. In this review, we introduce the broad application of β-TCP in tissue engineering and discuss the different approaches that β-TCP scaffolds are customized, including physical modification (e.g., pore size, porosity and roughness) and the incorporation of metal ions, other materials (e.g., bioactive glass) and stem cells (e.g., mesenchymal stem cells). 3D and 4D printed β-TCP-based scaffolds have also been reviewed. We subsequently discuss how β-TCP can regulate osteogenic processes to aid bone repair/healing, namely osteogenic differentiation of mesenchymal stem cells, formation of blood vessels, release of angiogenic growth factors, and blood clot formation. By way of this review, a deeper understanding of the basic mechanisms of β-TCP for bone repair will be achieved which will aid in the optimization of strategies to promote bone repair and regeneration.

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“…Fibrinogen is a 340 kDa glycoprotein composed of six polypeptide chains 2Aα, 2Bβ, and 2 γ [ 2 , 3 ]. The N-termini of all six chains are formed in the E domain, whereas the D domain is composed mainly of the C-termini of the Bβ and γ chains [ 4 ]. Fibrinogen is present in the blood at a concentration of 2–4 mg/mL [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Fungi Fibrinolytic Compound 1 Plays a Core Role in Modulating Fibrinolysis, Altering Plasma Clot Structure, and Promoting Susceptibility to Lysis

Gao,

Bao,

Bao

et al. 2023

Pharmaceutics

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Fibrin clot structure and function are major determinants of venous and arterial thromboembolic diseases, as well as the key determinants of the efficiency of clot lysis. Studies have revealed that fungi fibrinolytic compound 1 (FGFC1) is a novel marine pyranisoindolone natural product with fibrinolytic activity. Here, we explore the impacts of FGFC1 on clot structure, lysis, and plasminogen activation in vitro using turbidimetric, enzyme-linked immunosorbent assay, confocal and electron microscopy, urokinase, or plasmin chromogenic substrate. Clots formed in the presence of FGFC1 expressed reduced fibrin polymerization rate and maximum turbidity; however, they did not influence the lag phase of fibrin polymerization. In the absence of scu-PA (single-chain urokinase plasminogen activator), microscopy revealed that FGFC1 increased the number of protofibrils within fibrin fiber and the pore diameter between protofibrils, inducing clots to form a region of thinner and looser networks separated by large pores. The effects of FGFC1 on scu-PA-mediated plasma clot structure were similar to those in the absence of scu-PA. In addition, FGFC1 promoted the lysis of clots and increased the D-dimer concentration in lysate. FGFC1 increased the generation rate of p-nitroaniline in plasma. These results show that FGFC1 has fibrinolytic activity in plasma, leading to interference with the release of fibrinopeptide B to affect lateral aggregation of protofibrils and increase clot susceptibility to fibrinolysis by altering its structure.

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γD318Y fibrinogen shows no fibrin polymerization due to defective “A-a” and “B-b” interactions, whereas that of γK321E fibrinogen is nearly normal

Cited by 3 publications

References 28 publications

Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis

Current Application of Beta-Tricalcium Phosphate in Bone Repair and Its Mechanism to Regulate Osteogenesis

Fungi Fibrinolytic Compound 1 Plays a Core Role in Modulating Fibrinolysis, Altering Plasma Clot Structure, and Promoting Susceptibility to Lysis

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