title: Dabigatran but not rivaroxaban or apixaban treatment decreases fibrinolytic resistance in patients with atrial fibrillation.
abstract: BACKGROUND
  Most anticoagulants stimulate fibrinolysis in vitro through mechanisms dependent on and independent of thrombin activatable fibrinolysis inhibitor (TAFI). We evaluated the effect of dabigatran, rivaroxaban and apixaban treatment on plasma fibrinolysis in patients with non-valvular atrial fibrillation.
  
  
  RESULTS
  Patients treated with dabigatran etexilate (n=22), rivaroxaban (n=24) or apixaban (n=22) were studied. Plasma was obtained before (trough) and 2h after drug intake (peak). Fibrinolytic resistance of clots exposed to exogenous tissue plasminogen activator was significantly lower in peak than in trough samples and correlated with drug concentration only in dabigatran group. Moreover, fibrinolytic resistance at peak was lower in dabigatran than in rivaroxaban and apixaban groups. This difference disappeared if the TAFI pathway was inhibited. Thrombin generation and TAFI activation were markedly lower in peak than in trough samples in all three groups. However, TAFIa levels in trough and peak samples were significantly lower in dabigatran group than in rivaroxaban and apixaban groups. Circulating levels of prothrombin fragment F1+2 (reflecting in vivo thrombin generation) and plasmin-antiplasmin complex (reflecting plasmin generation) were not or barely influenced by drug levels in all groups.
  
  
  CONCLUSIONS
  Our data suggest that dabigatran, contrary to rivaroxaban and apixaban, reduces fibrinolytic resistance by virtue of its greater impact on TAFI activation. The profibrinolytic effect of dabigatran may play a role locally, at sites of fibrin formation, by making the nascent thrombus more susceptible to plasminogen-dependent degradation.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of General and Experimental Pathology, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Semeraro
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of General and Experimental Pathology, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Incampo
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of General and Experimental Pathology, University of Bari "Aldo Moro", Bari, Italy.
authors.forename: Concetta T
authors.initials: CT
authors.lastname: Ammollo
authors.affiliation: Haemostasis and Thrombosis Center, Department of Clinical Pathology, AO Istituti Ospitalieri, Cremona, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dellanoce
authors.affiliation: Haemostasis and Thrombosis Center, Department of Clinical Pathology, AO Istituti Ospitalieri, Cremona, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Paoletti
authors.affiliation: Haemostasis and Thrombosis Center, Department of Clinical Pathology, AO Istituti Ospitalieri, Cremona, Italy.
authors.forename: Sophie
authors.initials: S
authors.lastname: Testa
authors.affiliation: Department of Biomedical Sciences and Human Oncology, Section of General and Experimental Pathology, University of Bari "Aldo Moro", Bari, Italy. Electronic address: mario.colucci@uniba.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Colucci
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use*; D000991:Antithrombins / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000097:blood / Q000378:metabolism; D000069604:Dabigatran / Q000627:therapeutic use*; D065427:Factor Xa Inhibitors / Q000627:therapeutic use; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D011720:Pyrazoles / Q000627:therapeutic use*; D011728:Pyridones / Q000627:therapeutic use*; D000069552:Rivaroxaban / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban; D000069552:Rivaroxaban; D025901:Carboxypeptidase B2; D013917:Thrombin; D000069604:Dabigatran
keywords: Anticoagulants; Coagulation; Fibrinolysis; Thrombin; Thrombin activatable fibrinolysis inhibitor