Abstract:
:Fibrinogen is a hexameric glycoprotein consisting of two sets of three polypeptides (the Aα, Bβ, and γ chains, encoded by the three genes FGA, FGB, and FGG). It is involved in the final phase of the coagulation process, being the precursor of the fibrin monomers necessary for the formation of the hemostatic plug. Rare inherited fibrinogen disorders can manifest as quantitative deficiencies, qualitative defects, or both. In particular, dysfibrinogenemia and hypo-dysfibrinogenemia are characterized by reduced functional activity associated with normal or reduced antigen levels, and are usually determined by heterozygous mutations affecting any of the three fibrinogen genes. In this study, we investigated the genetic basis of dys- and hypo-dysfibrinogenemia in seven unrelated patients. Mutational screening disclosed six different variants, two of which novel (FGB-p.Asp185Asn and FGG-p.Asn230Lys). The molecular characterization of the FGG-p.Asn230Lys mutation, performed by transient expression experiments of the recombinant mutant protein, demonstrated that it induces an almost complete impairment in fibrinogen secretion, according to a molecular mechanism often associated with quantitative fibrinogen disorders. Conversely, the FGB-p.Asp185Asn variant was demonstrated to be a gain-of-glycosylation mutation leading to a hyperglycosylation of the Bβ chain, not affecting fibrinogen assembly and secretion. To our knowledge, this is the second gain-of-glycosylation mutation involving the FGB gene.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Asselta R,Robusto M,Platé M,Santoro C,Peyvandi F,Duga Sdoi
10.1016/j.thromres.2015.05.007subject
Has Abstractpub_date
2015-07-01 00:00:00pages
168-74issue
1eissn
0049-3848issn
1879-2472pii
S0049-3848(15)00234-0journal_volume
136pub_type
杂志文章abstract::In this study, we investigated the effects of a 3-min insulin incubation both at physiological and at supraphysiological concentrations on platelet aggregation and intraplatelet cyclic guanosine monophosphate (cGMP) levels both in the absence and in the presence of phosphodiesterase inhibition. We observed that insuli...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(96)00051-5
更新日期:1996-04-01 00:00:00
abstract::Fluorescein Dextran (FD) was shown to be transported at increased rates through partially denuded endothelial monolayer. Platelet binding to the partially denuded monolayer lowered transport rates to those comparable with intact endothelium. Inhibition of transport by platelet binding was not affected by the addition ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90191-c
更新日期:1992-05-01 00:00:00
abstract::Cooperative effects of PAF-acether and arachidonic acid in blood platelet activation were studied in human platelet-rich plasma. Using a combination of low concentrations of PAF-acether and subthreshold amounts of exogenous arachidonic acid an enhancement of aggregation and an increased formation of malondialdehyde ar...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90080-x
更新日期:1984-02-15 00:00:00
abstract::Platelet membrane glycoprotein V (GPV) was hydrolyzed during thrombin-induced platelet aggregation releasing a fragment GPVfl into the supernatant. Hydrolysis of GPV required catalytically active thrombin and was diminished by chemical modification of the fibrinogen binding site of thrombin. Half-maximal liberation of...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90207-5
更新日期:1985-06-15 00:00:00
abstract::Cancer is frequently associated with activation of blood coagulation, which in turn has been suggested to promote tumor growth and metastasis. Indeed, low molecular weight heparin treatment significantly prolongs the survival of a wide variety of patients with cancer. Based on this notion that anticoagulant treatment ...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(12)70022-1
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVE:The present cohort study was performed to investigate the impact of the factor 5 rs6025 [F5] and the factor 2 rs1799963 [F2] mutations on high-titer inhibitor development [HRI] in patients with severe/moderate-severe hemophilia A [HA]. PATIENTS AND METHODS:216 patients with F8<2% born between 1980 and 2011 w...
journal_title:Thrombosis research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.thromres.2014.01.005
更新日期:2014-04-01 00:00:00
abstract::A simple and discriminating assay for the determination of the fast-acting plasminogen activator inhibitor (PAI) activity in human plasma is described. The method is based on the inhibition of purified tissue plasminogen activator (tPA) by plasma diluted with a PAI-depleted plasma and the subsequent measurement of res...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90250-8
更新日期:1989-11-01 00:00:00
abstract::Four novel polymorphisms were identified in the fibrinogen gene cluster. Three of them were localized in the promoter regions of the Aalpha-chain (alpha -128 C/G, alpha -58 G/A) or the gamma-chain (gamma -239 A/G) gene, while the remaining one was identified in intron 9 of the gamma-chain gene (gamma 7792 C/T). Genoty...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(01)00329-2
更新日期:2001-08-15 00:00:00
abstract::The use of oral contraceptives (OCs) has been associated with vascular complications. The mechanism(s) by which OCs predispose to thrombotic events remains unclear. Recent studies have demonstrated that postmenopausal (PM) women who take estrogen replacement therapy (ERT) have a decreased incidence of myocardial infar...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90043-n
更新日期:1993-01-15 00:00:00
abstract::Thrombocytopenia is a common finding in cancer patients and can have different and/or multifactorial pathogenesis. While in solid tumors it occurs often as a consequence of chemotherapy treatment, it is frequently observed at diagnosis in patients with hematological malignancies being aggravated to a potentially life-...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2018.02.001
更新日期:2018-04-01 00:00:00
abstract::Generation of active Factor XII (FXIIa) triggers blood clotting on artificial surfaces and may also enhance intravascular thrombosis. We developed a patterned kaolin (0 to 0.3 pg/μm(2))/type 1 collagen fibril surface for controlled microfluidic clotting assays. Perfusion of whole blood (treated only with a low level o...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2014.09.030
更新日期:2014-12-01 00:00:00
abstract::Atherothrombosis is the leading cause of morbidity and mortality in patients with diabetes mellitus. Several mechanisms contribute to the diabetic prothrombotic state, including endothelial dysfunction, coagulative activation and platelet hyper-reactivity. In particular, diabetic platelets are characterised by dysregu...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2011.11.052
更新日期:2012-03-01 00:00:00
abstract::Severe bleeding took place in a patient when abdominal aneurysm was removed by operation. Bleeding continued after infusion of heparin, antithrombin III (ATIII), fresh platelets and fresh blood. Infusion of tranexamic acid resulted in an immediate cessation of bleeding and improvement of his general condition. Sometim...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90167-b
更新日期:1990-04-15 00:00:00
abstract::The use of platinum based chemotherapy in ovarian malignancy and other cancer types is known to be associated with deep vein thrombosis. In a prospective study of 47 patients with ovarian cancer of International Federation of Gynecology and Obstetrics stage Ib-IV, serial rheological parameters were determined (plasma ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(98)00022-x
更新日期:1998-04-15 00:00:00
abstract:BACKGROUND:Variability in platelet response to clopidogrel and its clinical relevance have been well described. However, the underlying mechanisms remain unclear. Recently, the T744C polymorphism of the P2Y12 receptor gene has been associated with enhanced platelet aggregation in healthy volunteers, suggesting a possib...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2007.01.012
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:The treatment of venous thromboembolism (VTE) in cancer patients remains controversial. PURPOSE:The Italian Society for Thrombosis and Haemostasis (SISET) commissioned a project to develop clinical practice guidelines for the therapy of VTE in patients with malignancies. METHODS:Key questions about the tre...
journal_title:Thrombosis research
pub_type: 杂志文章,实务指引
doi:10.1016/j.thromres.2009.08.006
更新日期:2009-11-01 00:00:00
abstract::A new model of arterial thrombosis in rats was based on a combination of a localizing hemodynamic factor /partial mechanical constriction of aorta/, generalized mild endothelial lesion /i.v.hypotonic saline/ and a humoral factor/i.v. serotonin/. The resulting aortic occlusion was indicated by measuring rectal temperat...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90362-2
更新日期:1986-03-01 00:00:00
abstract:INTRODUCTION:Aspirin is a common antiplatelet drug used in the prevention of ischemic stroke due to its inhibitory effect on platelet cyclooxygenase-1 (Cox-1). Patients can be categorized as either aspirin 'responders' or 'non-responders' depending on whether they are protected against a secondary stroke event or not. ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2003.12.005
更新日期:2003-01-01 00:00:00
abstract::We evaluate the anti-platelet and anti-thrombotic effects of cilostazol using Multiplate® and PFA-100® in vitro and ex vivo with freshly isolated rat whole blood and in vivo venous and arterial thrombosis models in the same species, in an effort to assess the sensitivity of the whole blood aggregometer assays without ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2011.02.004
更新日期:2011-06-01 00:00:00
abstract:BACKGROUND:Postthrombotic intraluminal tissue causing postthrombotic syndrome (PTS) has not been well described. This study defines its histological characteristics and assess whether tissue function evolves over time. METHODS:Specimens from 18 common femoral veins (CFV) from 16 patients obtained during CFV endovenect...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2015.02.026
更新日期:2015-05-01 00:00:00
abstract::Amino sugars and basic amino acids inhibit platelet aggregation and the activity of the endogenous platelet lectin, yet, relatively high concentrations (approximately 30 mM) are required for the inhibition. If cooperative interactions are involved in these platelet surface activities, oligomers of primary amines shoul...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(84)90160-9
更新日期:1984-02-01 00:00:00
abstract::One of the primary and most serious treatment-related complications in haemophilia A is the formation of anti-factor VIM (FVIII) antibodies, which significantly impacts patient care. For these patients, immunomodulatory therapy becomes important to induce immunological tolerance to FVIII. Immune tolerance induction (I...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/S0049-3848(08)70003-3
更新日期:2008-01-01 00:00:00
abstract::Plasma antithrombin III (AT-III) levels were measured in 61 patients undergoing general surgery. The patients were randomly allocated to a test or a control group. The test group received 5000iu of subcutaneous heparin two hours before operation and then twelve hourly for seven days. The control group received subcuta...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(86)90102-7
更新日期:1986-09-15 00:00:00
abstract::A synthetic pentasaccharide, representing the critical sequence required in heparin for binding to antithrombin III (AT III), produces strong anti-factor Xa activity in vitro in the presence of AT III and is devoid of any activity directed towards thrombin. This pentasaccharide provides a unique tool to study the ques...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(87)90280-5
更新日期:1987-04-15 00:00:00
abstract::An in vitro test system was developed to examine the effects of red blood cells (RBC) on shear-induced platelet adhesion (SIPAD) and platelet aggregation (SIPAG). Suspensions of human platelets labeled with Mepacrine and suspended in citrated plasma were exposed to single, continuous or repetitive (120-300x) one secon...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(98)00160-1
更新日期:1998-12-15 00:00:00
abstract::Resveratrol (3, 4', 5-trihydroxystilbene), a natural polyphenol, is found in some plants that are used in human nutrition. Grapes are a major source for resveratrol, and a significant amount can also be found in red wine. Several experimental studies have demonstrated biological properties of resveratrol, especially i...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(02)00273-6
更新日期:2002-08-15 00:00:00
abstract::Von Willebrand disease (VWD) is classified into three primary subtypes; type 1 includes partial quantitative deficiency, type 2 (A, B, M and N) includes qualitative defects and type 3 includes virtually complete deficiency of von Willebrand factor (VWF). Type 2A includes variants with decreased platelet adhesion cause...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2007.03.014
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Use of antiplatelet therapy in combination with oral anticoagulants remains controversial. The purpose of this article is to review current consensus recommendations for antithrombotic therapy, to evaluate risks for bleeding among patients taking combination antithrombotic therapy, and lastly to review singl...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2008.08.011
更新日期:2008-01-01 00:00:00
abstract::Enzymatic treatment used for passaging of endothelial cells may induce release of von Willebrand factor (vWF). Decreased ability to replenish intracellular stores results in decreased secretion of vWF in later passages of cells. Since both trypsin and pancreatin complex have been used for passaging endothelial cells, ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00401-1
更新日期:2001-02-15 00:00:00
abstract::SK, t-PA or APSAC were incubated in human plasma (adjusted to 300,000 platelets/mm3), in vitro, for up to 90 minutes using concentrations which were equivalent to those achieved in the treatment of AMI patients. Aggregation was measured in response to ADP and collagen. SK inhibited platelet aggregation after a 60 minu...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90105-l
更新日期:1990-11-15 00:00:00