L´hemostàsia primària en la trombosi venosa. Biomolècules implicades en la formació del coàgul plaquetari: paper de VAMP8, SERT, SEROTONINA, ADAMTS13 i Factor von Willebrand

Autor: Llobet i Lorente, Ma. Dolors
Přispěvatelé: Fontcuberta i Boj, Jordi, Souto Andrés, Juan Carlos, Carbonell i Camós, Teresa, Universitat de Barcelona. Facultat de Biologia
Rok vydání: 2020
Předmět:
Zdroj: TDX (Tesis Doctorals en Xarxa)
TDR: Tesis Doctorales en Red
CBUC, CESCA
Dipòsit Digital de la UB
Universidad de Barcelona
TDR. Tesis Doctorales en Red
instname
Popis: [cat] La patologia associada a l’hemostàsia primària ha estat clàssicament relacionada amb diàtesi hemorràgica (malaltia de von Willebrand, Síndrome de Bernard- Soulier, malaltia de Glanzmann, trombopènia, etc) on s’ha valorat el paper de les plaquetes i del factor von Willebrand en una defectuosa agregació i/o adhesió plaquetària. També ha estat àmpliament estudiat el paper de les plaquetes en la trombosi arterial. Ja que el paper de les plaquetes és fonamental en l’inici i la formació del coàgul és possible que tinguin un paper important en la patogènia de la trombosi venosa. Treballs experimentals en ratolins demostren que les plaquetes i el FvW juguen un paper molt important en l’inici i el desenvolupament de la trombosi venosa [7]. En aquesta tesi es vol investigar sobre el paper d’aquests paràmetres en patologia trombòtica venosa humana. Recentment s’ha introduït el concepte d’hiperagregabilitat plaquetària on trobem individus amb plaquetes que agreguen a dosis molt petites d’inductor (ADP o/i Epinefrina). La agregabilitat a dosis baixes d’epinefrina (EPI) i/o d’ADP en la població normal dona lloc a dues poblacions diferenciades: individus amb hiperreactivitat plaquetària (agregació >60%) i individus amb hiporreactivitat plaquetària (agregació
[eng] The role of platelet in bleeding has been studied widely but little is known about their role in venous thrombosis (VT). Recently, platelet hyperreactivity has been described as associated with thrombotic risk. Platelet hyperreactivity is measured by aggregation in platelet rich plasma (platelet hyper-aggregability) or through test with whole blood as PFA-100® system. Recently, our group found that platelet function (measured by PFA-100® system) was associated with VT. The objective of my research is to evaluate the role of platelets in VT and the role of plasmatic biomolecules in primary hemostasis as human vesicle associated membrane protein 8 (VAMP8), serotonin, serotonin transporter (SERT), a disintegrin and metalloproteinase with thrombospodin-1-like domains (ADAMTS13) and von Willebrand factor (vWf). The main conclusions in the first article were that platelet hyper-aggregability is not independently associated with VT risk. The correlation between platelet hyper-aggregability and platelet function was modest (only 12% of PFA-100® values was estimated to be due to platelet aggregation). Although, no association was found between platelet hyper-aggregability and VT, however our group found an association between platelet hyperreactivity (measured by PFA-100® system) and VT. This finding motivated us to examine platelet hyperreactivity following treatment with some biomolecules related to this phenotype and platelet aggregation as VAMP8, SERT and serotonin. In the second article we reported that VAMP8 and SERT levels were independently associated with VT in women. We did not find a correlation between these biomolecules and PFA-100® values. Endothelium plays an important role in primary hemostasis. Endothelial cell and platelets synthesize vWf that is necessary for platelet adhesion. ADAMTS13 is the regulator of vWf. Both are associated with arterial thrombosis but little is known about their relation with VT. The third article reports that low levels of ADAMTS13 were associated with high VT risk in women and that vWf levels were blood group dependant while ADAMTS13 were not. Finally, the fourth article reports that a genome-wide association study (GWAS) identified susceptibility loci for PFA-100® phenotypes. Our results suggest that ABO locus is the main determinant of PFA-100® phenotypes.
Databáze: OpenAIRE
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