Povezanost prokoagulacijskih i fibrinolitičkih čimbenika s ukupnim trombinskim potencijalom i fenotipskim izražajem u bolesnika s hemofilijom A

doctoral thesis

• Title (english): Association of procoagulant and fibrinolytic factors with thrombin potential and hemophilia A phenotype
• Author: Marija Miloš
• Mentor: Renata Zadro (mentor)
• Committee member: Tihana Žanić Grubišić (predsjednik povjerenstva)
• Committee member: Renata Zadro (član povjerenstva)
• Committee member: Dubravka Čvorišćec (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2012-06-01, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry
• Universal decimal classification (UDC): 615 - Pharmacology. Therapeutics. Toxicology

Abstract

Hemofilija A je rijetki nasljedni poremećaj zgrušavanja krvi koji nastaje zbog manjka FVIII u cirkulaciji i dijeli
se na teški, srednje teški i blagi oblik. Kod teškog oblika bolesti javljaju se spontana krvarenja, koja su kod
blažih oblika rijetka. Literaturni podaci ukazuju na heterogenost kliničkog izražaja hemofilije A. Cilj ovog
istraživanja bio je utvrditi mogući utjecaj drugih prokoagulacijskih i fibrinolitičkih čimbenika, osim FVIII, na
endogeni trombinski potencijal i na klinički... More izražaj bolesti. Ispitana je vrijednost analize reakcijske krivulje
APTV-a i analize stvaranja trombina u dijagnostici hemofilije A jer se ovim metodama mjeri ukupni hemostatski
potencijal plazme. Dobiveni rezultati potvrđuju povećanu aktivnost fibrinolitičkog sustava kod hemofilije A u
odnosu na zdravu populaciju, koja je izraženija kod teškog oblika bolesti. Pojačana fibrinoliza kod bolesnika s
težom kliničkom slikom nije nedvojbeno potvrđena. Potvrđena je vrijednost analize reakcijske krivulje APTV-a
u dijagnostici hemofilije A. Pokazana je dobra korelacija sa standardnim laboratorijskim metodama i kliničkim
pokazateljima te dobro razlikovanje stupnja bolesti. Jednostavnost i cijena metode, koja zahtijeva samo mjerenje
APTV-a, dodatne su prednosti. Ispitivanjem analize stvaranja trombina dobivena je slabija korelacija sa
standardnim laboratorijskim metodama i kliničkim pokazateljima, te slabije razlikovanje stupnja bolesti. U
postojećoj izvedbi metoda nije primjenjiva u rutinskoj laboratorijskoj dijagnostici hemofilije A. Less

Abstract (english)

Hemophilia A is a rare X-linked bleeding disorder characterized by decreased FVIII activity, and is classified as
severe, moderate or mild. The clinical phenotype of severe hemophilia A consists of spontaneous bleeding
episodes that are rare in non-severe types. Heterogeneity in bleeding pattern has been observed, but mechanisms
are poorly understood. The aim of this study was to identify whether activities of common prothrombotic and
fibrinolytic factors are associated with clinical... More phenotypes. New laboratory methods were evaluated that assess
overall clotting function, clot waveform analysis and thrombin generation test. Results showed enhanced
fibrinolytic activity in patients as compared to healthy subjects, as well as in severe hemophilia A patients
compared to those with mild disease. The enhanced fibrinolytic activity in patients with severe phenotype was
not confirmed with certainity. By using waveform analysis, good correlation was obtained to standard laboratory
methods and clinical parameters, as well as good discrimination of disease severity. Simplicity and cost benefit
of this method make this approach a promising tool for assessing coagulation in hemophilia patients. The
correlation to routine laboratory methods and clinical parameters in thrombin generation test was weaker and this
method did not fulfill the goals expected for a routine laboratory method. Less

• Keywords: hemofilija A; FVIII; prokoagulacijski čimbenici; fibrinolitički čmbenici; fenotipski izražaj hemofilije A; analiza reakcijske krivulje APTV-a; analiza stvaranja trombina
• Keywords (english): hemophilia A; FVIII; procoagulant factors; fibrinolytic factors; hemophilia A phenotype; aPTT waveform analysis; thrombin generation test
• Language: croatian
• URN:NBN: urn:nbn:hr:163:075077
• Study programme: Title: Pharmacy and biochemistry; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor znanosti (doktor znanosti)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-11-17 14:45:41