Utjecaj novih oralnih antikoagulacijskih lijekova na probirne pretrage hemostaze

master's thesis

• Title (english): Impact of direct oral anticoagulants on routine haemostasis assays
• Author: Jelena Buben
• Mentor: Sandra Šupraha Goreta (mentor)
• Committee member: Sandra Šupraha Goreta (predsjednik povjerenstva)
• Committee member: Sandra Margetić (član povjerenstva)
• Committee member: Ivana Ćelap (član povjerenstva); MBZ: 36516
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2020-12-01, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy

Abstract

Izravni oralni antikoagulansi (engl. direct oral anticoagulants, DOAC) posljednjih se godina sve više primjenjuju u prevenciji i liječenju tromboembolijskih bolesti. Terapija DOAC lijekovima se, zahvaljujući njihovoj predvidljivoj farmakokinetici, provodi u fiksnim dozama pa ne zahtijevaju rutinsko laboratorijsko praćenje. S druge strane, DOAC lijekovi zbog izravnog inhibicijskog djelovanja na aktivnost određenog segmenta hemostatstkog sustava, imaju utjecaj na rezultate brojnih pretraga hemostaze, kako probirnih tako i specijalističkih. Poznavanje utjecaja DOAC lijekova na pojedine pretrage hemostaze od izuzetne je važnosti zbog pravilne interpretacije rezultata te sprečavanja lažno pozitivnih ili lažno negativnih rezultata koji bi mogli imati negativan utjecaj na samo liječenje bolesnika. Cilj provedenog istraživanja bio je ispitati utjecaj tri DOAC lijeka, dabigatrana, rivaroksabana i apiksabana, na rezultate probirnih pretraga hemostaze: PV, APTV, TV i fibrinogen. U uzorcima bolesnika liječenih DOAC lijekovima, dabigatranom (n=248), rivaroksabanom (n=294) i apiksabanom (n=142), određene su vršne (2 sata nakon primjene zadnje doze) i minimalne koncentracije (neposredno prije slijedeće doze) DOAC lijeka te probirne pretrage hemostaze PV, APTV, TV i fibrinogen. Rezultati provedenog ispitivanja pokazali su da DOAC lijekovi utječu na rezultate probirnih pretraga hemostaze. Taj se utjecaj značajno razlikuje ovisno o vrsti lijeka i vremenu uzorkovanja u odnosu na zadnju dozu lijeka. Utjecaj DOAC lijekova na navedene pretrage značajno je veći kod vršnih koncentracija lijeka u cirkulaciji u odnosu na minimalne. Dabigatran značajno utječe na rezultate pretrage TV i APTV te u manjoj mjeri na PV, a nema utjecaja na fibrinogen. Rivaroksaban utječe na PV i APTV, ali samo kod vršnih koncentracija lijeka te nema utjecaja na TV i fibrinogen. Apiksaban ima najmanji utjecaj na rezultate probirnih pretraga hemostaze, a vrijednosti svih ispitanih pretraga su unutar referentnog intervala i kod vršnih i kod minimalnih koncentracija lijeka. Ovo ispitivanje upućuje da probirne pretrage hemostaze nisu prikladne za procjenu antikoagulacijskog učinka i/ili koncentracije odgovarajućeg DOAC lijeka, ali i da je poznavanje utjecaja DOAC lijekova na pojedine probirne pretrage preduvjet pravilne interpretacije rezultata ovih pretragau svakodnevnoj laboratorijskoj i kliničkoj praksi.

Abstract (english)

Direct oral anticoagulants (DOACs) have been increasingly used in the recent years for the prevention and treatment of thromboembolic disease. Due to their predictable pharmacokinetics, DOAC drug therapy is performed in fixed doses and does not require routine laboratory monitoring. On the other hand, due to their direct inhibitory effect on the activity of a certain segment of the haemostatic system, DOACs have a significant impact on the results of numerous haemostasis assays, both screening and specific. Understanding the influence of DOACs on a particular haemostasis assay is extremely important for correct interpretation of the results, as well as prevention of false positive or false negative results that could have a negative impact on the patient treatment. The aim of this study was to examine the effect of three DOACs, dabigatran, rivaroxaban and apixaban, on the results of routine screening haemostasis tests; PV, APTV, TV and fibrinogen. In the samples of patients treated with DOACs, dabigatran (n = 248), rivaroxaban (n = 294) and apixaban (n = 142), peak (2 hours after administration of the last dose) and trough concentrations (shortly before taking the next dose) of a certain DOAC were determined and screening haemostasis tests, PV, APTV, TV and fibrinogen, were conducted. The results of the conducted study showed that DOACs affect the results of haemostasis screening tests. This effect differs significantly depending on the type of DOAC used and the time of blood sampling in relation to the time of the administration of the last dose. The influence of DOACs on these assays is significantly larger at peak plasma concentrations of the drug when compared to the trough drug concentration. Dabigatran significantly affects TV and APTV test results and to a lesser extent PV, whilst it has no effect on fibrinogen assay. Rivaroxaban affects PV and APTV, but only at peak drug concentrations and has no effect on TV and fibrinogen. Apixaban has the lowest effect on the results of haemostasis screening tests, and the obtained values of all examined samples were within the reference interval at both peak and trough drug concentrations. This study indicates that haemostasis screening tests are not suitable for assessment of the anticoagulant effect and/or the concentration of a certain DOAC, whereas understanding the impact of DOACs on individual screening tests is essential for proper interpretation of obtained test results in everyday laboratory and clinical practice.

• Keywords: oralni antikoagulansi; DOAC lijekovi; rutinske pretrage; hemostaze; PV; APTV; TV; fibrinogen
• Keywords (english): direct oral anticoagulants; DOAC drugs; routine assays; hemostasis; PV; APTV; TV; fibrinogen
• Language: croatian
• URN:NBN: urn:nbn:hr:163:251227
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-05-12 13:22:16