Ventre, itala (2020) From unfractionated heparin to pentasaccharide: paradigm of rigorous science growing in the understanding of the in vivo thrombin generation. [Tesi di dottorato]

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Tipologia del documento: Tesi di dottorato
Lingua: English
Titolo: From unfractionated heparin to pentasaccharide: paradigm of rigorous science growing in the understanding of the in vivo thrombin generation
Autori:
AutoreEmail
Ventre, italaventre.itala@fbfbn.it
Data: 2020
Numero di pagine: 47
Istituzione: Università degli Studi di Napoli Federico II
Dipartimento: Medicina Clinica e Chirurgia
Dottorato: Terapie avanzate medico-chirurgiche
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
nomeemail
Di Minno, Giovannigiovanni.diminno@unina.it
Tutor:
nomeemail
Di Minno, Giovanni[non definito]
Data: 2020
Numero di pagine: 47
Parole chiave: NATURAL POLYSACCHARIDES . HEPARIN HISTORY.PENTASACCHARIDE .ANTICOAGULATION. DEEP VENOUS THROMBOSIS. MECHANISM OF ACTION.
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/09 - Medicina interna
Depositato il: 22 Mar 2020 10:40
Ultima modifica: 28 Ott 2021 12:36
URI: http://www.fedoa.unina.it/id/eprint/13245

Abstract

Following a chance discovery made a medical student who was searching for a clot-proming activity in tissue extracts, it took 15-20 years to attain the therapeutic use of standard unfractioned heparin (UHF),DUE TO PROBLEM WITH THE PURIFICATION AND EXTRACTION OF THE ACTIVE MATERIAL.Soon it was found that: 1) thrombin inactivation by UFH was associated with the formation of molecular complex between antithrombin and the activeted forms of factor x(FXa) and thrombin ,2) low-molecular-weight fractions of HFU lose their antithrombin activity while still interacting with FXa, 3) a pentasaccharide sequence of UHF increase FXa ( but non thrombin) inactivation by antithrombin. Low- molecular-weight heparins (LMWHs) with little effect on thrombin and strongly active versus FXa were then developed. In patients, LMWHs (and the pentasaccharide sequence ) came up as a useful class of drug to prevent and treat thrombinosis, their greatest advantage over UFHbeing the convenience of once/twise daily subcutaneus injections at a fixed dose without any laboratory monitoring . In addition to providing major information on vivo modulation of thrombin generation, the haparin saga served as a paradigm to support an alternative coagulation scheme that plateles and tissue factor as integral parts of model.Forthcoming work with this scheme-also supported by studies in haemophilia and rare bnleeding disorder - is expected to provide major hints for underatandin why some patients benefit more than Others from the small amount of thrombin they form and directions to tailor prevention and treatment of thrombotic disorder

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