title: How the direct oral anticoagulant apixaban affects thrombin generation parameters.
abstract: OBJECTIVE
  Apixaban is a direct oral anticoagulant (DOAC) targeting factor Xa and thus quenching thrombin generation and clot formation. However, little information is available on the influence that apixaban may have on the parameters of thrombin generation.
  
  
  METHODS
  Aliquots of a pooled normal plasma have been added with increased concentrations of purified apixaban and were used to assess the degree of modification brought about by the drug on the basic tests of coagulation prothrombin and activated partial thromboplastin time (PT and APTT) and on thrombin generation parameters.
  
  
  RESULTS
  The study shows that while apixaban has little effect on PT or APTT it does affect all the parameters of thrombin generation, including the lag-time (which is increased), the endogenous thrombin potential (ETP) and thrombin-peak (both decreased although to a different extent), and the velocity index (decreased). Interestingly, the above effects were more pronounced when the measurements were recorded in the presence of thrombomodulin, thus making the ratio (with/without thrombomodulin) to decrease consistently as a function of the apixaban concentrations.
  
  
  CONCLUSIONS
  These findings support the antithrombotic properties of apixaban and can help to understand the mechanism(s) of action of this drug. Thrombin generation could be used as a convenient laboratory tool to assess the anticoagulant activity of other drugs and to make between-DOAC comparison.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, MiIano, ltaly; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy. Electronic address: armando.tripodi@unimi.it.
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, MiIano, ltaly; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
authors.forename: Lidia
authors.initials: L
authors.lastname: Padovan
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, MiIano, ltaly; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
authors.forename: Chantarangkul
authors.initials: C
authors.lastname: Veena
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, MiIano, ltaly; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Scalambrino
authors.affiliation: Haemostasis Thrombosis Center, General Hospital, Cremona, Italy.
authors.forename: Sophie
authors.initials: S
authors.lastname: Testa
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, MiIano, ltaly; IRCCS Cà Granda Maggiore Hospital Foundation, Milano, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milano, Italy.
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D065427:Factor Xa Inhibitors / Q000737:chemistry; D006801:Humans; D010314:Partial Thromboplastin Time; D011517:Prothrombin Time; D011720:Pyrazoles / Q000008:administration & dosage*; D011728:Pyridones / Q000008:administration & dosage*; D013917:Thrombin / Q000096:biosynthesis*; D018180:Thrombomodulin / Q000737:chemistry; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011720:Pyrazoles; D011728:Pyridones; D018180:Thrombomodulin; C522181:apixaban; D013917:Thrombin
keywords: Anticoagulants; Partial thromboplastin time; Prothrombin time; Thrombomodulin; Thrombosis