Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Katogiannis Konstantinos
Dissertation committee:
Ευστάθιος Ηλιοδρομίτης, Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Δημήτριος Αλεξόπουλος, Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Ιωάννης Παρίσης, Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αργυρή Γιαλεράκη, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών, Επιβλέπουσα
Αργύριος Τσαντές, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Ιγνάτιος Οικονομίδης, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Στυλιανή Κοκόρη, Επίκουρη Καθηγήτρια, Ιατρική Σχολή, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
Αξιολόγηση των σφαιρικών δοκιμασιών της αιμόστασης στην ex vivo μελέτη της αντιπηκτικής και αντιαιμοπεταλιακής δράσης των νεότερων από του στόματος αντιπηκτικών και της ασενοκουμαρόλης σε ασθενείς με μη βαλβιδική κολπική μαρμαρυγή.
Translated title:
Evaluation of the global hemostatic assays in the ex vivo study of the anticoagulant and antiplatelet effect of the novel oral anticoagulants and acenocoumarol in patients with non-valvular atrial fibrillation.
Summary:
Background/Aim:
There is a shortage of data in clinical practice about the anticoagulant effects of direct oral anticoagulants (DOACs). Our aim was to estimate the intensity of anticoagulant activity induced by DOACs among patients with nonvalvular atrial fibrillation (NVAF) and to investigate the interaction of DOACs with platelet function.
Methods:
We studied 80 patients with NVAF and 20 sex and age matched controls (20 treated with dabigatran 110 mg bid, 20 treated with rivaroxaban 20 mg qd, 20 with apixaban 5 mg bid, 20 treated with acenocoumarol). We performed conventional coagulation tests (PT/INR, APTT, FIB), global assays reflecting the hemostatic profile [thrombin generation (TG), thromboelastometry (ROTEM)] as well as the gold standard assay for the estimation of platelet activation [epinephrine-induced light transmission aggregometry (LTA)] in all 80 patients and 20 controls. Hemoclot Thrombin Inhibitor assay (HTI) was performed to measure dabigatran plasma levels and Factor Xa Direct Inhibitor (DiXaI) assay was used to measure rivaroxaban and apixaban plasma levels, respectively.
Results:
Patients on dabigatran 110 mg, show a marginally insignificant decrease in platelet aggregation, compared to those on acenocoumarol (p=0.068) and a significant decrease compared to those on rivaroxaban (p = 0.045) according to LTA results.
Patients receiving dabigatran 110 mg, compared with those treated with acenocoumarol show significantly lower lysis time at 60 min (p=0.011), while no significant difference was noticed between the rivaroxaban and apixaban group of patients (p=0.499).
Acenocoumarol affects more pronouncedly thrombin generation compared to dabigatran 110 mg, (area under the curve [AUC], p<0.001) as suggested by ETP. Similar findings were noticed after comparing rivaroxaban and apixaban with acenocoumarol (p<0.001). Additionally, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban (p<0.003). Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban.
Moreover, statistically significant associations were detected between dabigatran 110 mg, levels, as determined by the HTI assay, and almost all parameters of ETP assay (AUC, p< 0.001). Similarly, significant correlations were observed between rivaroxaban plasma concentrations and kinetic parameters of TG assay (Tlag, p=0.045; Tmax, p=0.016; and Cmax, p=0.003). Moreover, a statistically significant, strong inverse correlation was noticed between apixaban plasma concentrations and ETP (AUC, p < 0.001) was observed.
Conclusion:
Based on ROTEM, TG assays and LTA, the anticoagulant effects induced by DOACs given in the specific dose regimens in real-world patients are the following: i) dabigatran 110 mg, seems to affect platelet activity and to enhance fibrinolysis, additionally to thrombin inhibition, which might partly explain risk of bleeding, ii) apixaban seems to imply a safer profile based on the results of ETP measurements iii) DOAC maximum levels correlate with TGA parameters (but not with ROTEM parameters), suggesting a role of TGA in DOAC monitoring.
Main subject category:
Health Sciences
Keywords:
Atrial fibrillation, Anticoagulant activity per os anticoagulants, Thrombin generation assay, Thromboelastometry, Aggregometry, DOAC plasma levels
Number of references:
131
