Utjecaj kromogene metode za određivanje aktivnosti koagulacijskog faktora IX na klasifikaciju i liječenje bolesnika s hemofilijom B

master's thesis

• Title (english): The impact of the chromogenic method for determining the activity of coagulation factor IX on the classification and treatment of patients with hemophilia B
• Author: Dora Rebrek
• Mentor: Dunja Rogić (mentor)
• Mentor: Desiree Coen Herak (mentor)
• Committee member: Ksenija Fumić (predsjednik povjerenstva)
• Committee member: Desiree Coen Herak (član povjerenstva)
• Committee member: Željka Vogrinc (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2023-07-28, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Hemofilija B je rijetki X-vezani nasljedni poremećaj zgrušavanja krvi uzrokovan potpunim ili djelomičnim
manjkom aktivnosti koagulacijskog faktora IX što rezultira povećanom sklonosti krvarenjima. S obzirom kako u
većini slučajeva ostatna aktivnost FIX dobro korelira s kliničkom slikom, pacijenti s hemofilijom B klasificiraju
se kao teški, umjereni ili blagi oblik na temelju aktivnosti FIX izmjerenih koagulacijskom metodom. S obzirom
na sve veću primjenu kromogene metode u dijagnostici hemofilije i njezinih prednosti u odnosu na koagulacijsku
metodu, ovim se istraživanjem nastojalo ispitati kakav utjecaj određivanje aktivnosti FIX kromogenom metodom
ima na klasifikaciju pacijenata s hemofilijom B i ispitati razlike u rezultatima terapijskog praćenja pacijenata
koagulacijskom i kromogenom metodom kako bi se utvrdilo koja je metoda prikladnija za praćenje učinkovitosti
lijekova te time doprinijelo boljoj skrbi i liječenju pacijenata s hemofilijom B. U istraživanje je bilo uključeno 45
ispitanika muškog spola (33 odrasla i 12 pedijatrijskih) koji boluju od hemofilije B, od kojih je pet u trenutku
ispitivanja primalo nadomjesnu terapiju te su oni promatrani kao zasebna skupina prilikom statističke obrade
rezultata. Svim je ispitanicima izmjereno APTV te aktivnosti FIX koagulacijskom metodom (FIXkgl) i
kromogenom metodom (FIXkr) upotrebom BIOPHENTM FIX komercijalnog testa (HYPHEN BioMed, Neuville
sur Oise, Francuska) na analizatoru Atellica COAG 360 (Siemens Healthcare, Marburg, Njemačka). U odnosu na
aktivnosti FIXkr, aktivnosti FIXkgl su bile značajno više u pacijenata s blagim i umjerenim oblikom hemofilije B
uz iznimku teškog oblika gdje su primijećene više vrijednosti FIXkr. Najviše je odstupanja u klasifikaciji s obje
metode uočeno kod teškog i umjerenog oblika hemofilije B dok je najmanje odstupanja u klasifikaciji zabilježeno
kod blagog oblika hemofilije. Također je uočena bolja povezanost kliničkog fenotipa s klasifikacijom prema
kromogenoj metodi. U skupini pacijenata na nadomjesnoj terapiji statističkom analizom nije uočena statistički
značajna razlika aktivnosti FIXkr odnosu na aktivnosti FIXkgl. Najveća odstupanja između rezultata FIXkr i
FIXkgl u skupini pacijenata na nadomjesnoj terapiji uočena su u području viših aktivnosti FIX. Rezultati ovog
istraživanja ukazali su na složenost diferencijalno-dijagnostičkog pristupa u dijagnostici hemofilije B, kao i na
neizostavnu ulogu koagulacijske i kromogene metode u dijagnostici i praćenju nadomjesne terapije. Nadalje,
uočene su prednosti i nedostaci pojedine metode te je osigurana osnova za potencijalnu primjenu kromogene
metode u klasifikaciji i terapijskom praćenju pacijenata s hemofilijom B.

Abstract (english)

Hemophilia B is a rare X-linked hereditary blood clotting disorder caused by a complete or partialy deficiency of
coagulation factor IX activity that results with increased bleeding tendency. Since residual FIX activity correlates
well with the clinical picture in most cases, hemophilia B patients are classified as severe, moderate or mild based
on FIX activity measured by the one-stage coagulation method. With regard to the increasing use of the
chromogenic method in the diagnosis of hemophilia and its advantages compared to the standard coagulation
method, the goal of this investigation was to examine the influence of the determination of FIX activity by the
chromogenic method on the classification of hemophilia B patients and to examine the differences in the results
of the therapeutic monitoring by coagulation and chromogenic methods in order to determine which method is
more suitable for monitoring the effectiveness of drugs and thereby contributes to better care and treatment of
hemophilia B patients. The investigation has included 45 male subjects (33 adults and 12 pediatric) suffering from
hemophilia B, of whom five were receiving replacement therapy at the time of the examination, and they were
obsereved as a separate group during the statistical analysis of results. APTT and FIX activities were measured by
using the coagulation method (FIXkgl) and chromogenic method (FIXkr) using the BIOPHENTM FIX commercial
test (HYPHEN BioMed, Neuville sur Oise, France) in all subjects on the Atellica COAG 360 analyzer (Siemens
Healthcare, Marburg, Germany). In relation to FIXkr activities, FIXkgl activities were significantly higher in mild
and moderate hemophilia B patients with the exception of the severe form where higher FIXkr values were
observed. The most discrepancies in classification with both methods were observed in severe and moderate
hemophilia B forms, while the least discrepancies in classification were observed in mild forms of hemophilia.
Moreover, a better correlation of the clinical phenotype with the classification according to the chromogenic
method was observed. In the group of patients on replacement therapy, statistically significant difference was not
found between the activities of FIXkr compared to FIXkgl activities. The largest discrepancies between the results
of FIXkr and FIXkgl in the group of patients on replacement therapy were observed in the area of higher FIX
activities. The results of this investigation indicated the complexity of the differential-diagnostic approach in the
diagnosis of hemophilia B and the indispensable role of the coagulation and chromogenic methods in the diagnosis
and monitoring of replacement therapy. Also, the advantages and disadvantages of each method were observed,
and the basis for the potential application of the chromogenic method in the classification and therapeutic
monitoring of patients with hemophilia B was provided.

• Keywords: koagulacijski faktor IX; hemofilija B; kromogena metoda; koagulacijska metoda; liječenje
• Keywords (english): coagulation factor IX; hemophilia B; chromogenic method; one-stage coagulation method; treatment
• Language: croatian
• URN:NBN: urn:nbn:hr:163:373749
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-11-21 13:35:29