1,721,206 research outputs found
La benedizione dei genitori (Greg. Naz. epitaph. 101-102 = Anth. Pal. 8,75-76)
No full textEsame della tradizione manoscritta degli epitaffi 101 e 102 di Gregorio Nazianzeno (= Anth. Pal. 8,75-76
Modulators of Von Willebrand factor (VWF) multimers size in thrombotic processes
No full textSUMMARY : during this doctorate, we evaluated how the presence of von Willebrand factor (VWF) multimers in plasma is regulated and how this process might influence the onset of thrombotic thrombocytopenic purpura (TTP) and myocardial infarction (MI). We demonstrated that: - salts, and particularly anions, in physiological conditions determine an inhibition of VWF cleavage by ADAMTS-13, causing a conformational change of the VWF. Finally we demonstrated the presence of a negative association between the GpIb or ristocetin binding and ions binding to VWF; - TSP-1 display a inhibiting effect on ADAMTS-13 activity and the entire A1A2A3 region is necessary to achieve an optimal inhibition. The A3 domain plays a central role, although its effect is dependent on the allosteric role of the A1 domain; - an association between the N700S polymorphism in the Tsp-1 gene and the development of MI. Nevertheless this association can be hardly explained by an alteration of TSP-1 reductase activity, that, differently from previous data, was not confirmed. In conclusion the obtained results allowed to identifying new modulators of the VWF multimers size in vitro (chloride ions and TSP-1) and to deepen their modes of action, increasing the knowledge of this physiological process that remains indeed very complex. The understanding of all involved mechanisms might clarify the pathogenesis of both thrombotic and haemorrhagic diseases, improve diagnosis and treatment , mainly for a rare but highly disabling disease, such as TT
Rare bleeding disorders: worldwide efforts for classification, diagnosis, and management
No full textRare bleeding disorders (RBDs) comprise the inherited deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI, and FXIII, and are usually transmitted as autosomal recessive disorders. RBDs are characterized by a wide variety of symptoms from mild to severe; however, due to their rarity, only little information is available on the adequate management of patients affected with these deficiencies. Moreover, the limitations of laboratory assays and the lack of a definitive consensus concerning their classification have prevented adoption of optimal approaches to their individual management. To overcome these limitations, new strategies are therefore necessary, such as the establishment of global collaborations and networks among treatment centers, as well as increasing support provided by public health organizations
European registry of rare bleeding disorders
No full textRare bleeding disorders (RBDs) are autosomal recessive diseases including the deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV+FVIII, FVII, FX, FXI and FXIII. Their prevalence in the general population varies from 1 in 500.000 for FVII and FXI deficiency up to 1 in 2 million for FXIII deficiency. As a consequence of their rarity, the type and severity of bleeding symptoms, and the management of bleeding episodes, are not well established. A definition of clinical severity in RBDs is lacking and a large heterogeneity of clinical manifestations is observed in different RBDs. We tried to describe the general features of RBDs based on data from previously reported literature and on the results of three years of collaboration between 11 European treatment centers in the frame of a project funded in the European Union, entitled “Establishment of a European Network of Rare Bleeding Disorders: EN-RBD.” Our results might help to provide novel information on the clinical severity of the different RBDs and on its correlation to the laboratory phenotyp
Two adjacent homozygous mutations on EGF2 domain of factor X (FX) gene lead to severe FX deficiency
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Rare bleeding disorders: diagnosis and treatment
No full textDespite the worldwide prevalence of rare bleeding disorders (RBDs), knowledge of these conditions and their management is suboptimal; health care professionals often have little diagnostic and treatment experience with variable access to diagnostic modalities required for accurate identification. Therefore, patients often experience morbidity and mortality due to delayed diagnosis. As RBDs represent a small potential commercial market, few, if any, specific therapies exist for these conditions. As a result, affected individuals commonly face delayed diagnosis, incomplete laboratory evaluation, and limited treatment options. Standardization and customization of coagulation assays, full genome sequencing, and global clotting assays will significantly improve diagnosis of patients with RBDs. In addition, new therapeutic modalities, both recombinant and plasma derived, are emerging, at least in developed countries. Registries and clinical trials have demonstrated decreased bleeding and improved outcomes when patients are appropriately diagnosed and properly treated. Expansion and harmonization of international registries has been initiated to correlate genotype, laboratory, and clinical phenotypes including bleeding severity to improve the diagnosis and therapeutic approach. This review focuses on the latest advances in our understanding, diagnosis, and treatment of RBDs
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