title: How the direct oral anticoagulant apixaban affects hemostatic parameters. Results of a multicenter multiplatform study.
abstract: BACKGROUND
  Apixaban is a newly developed direct oral anticoagulant targeting activated factor X (FXa). The degree of interference of apixaban with coagulation parameters has not been thoroughly investigated.
  
  
  METHODS
  Increasing amounts of apixaban were added to aliquots of a pooled normal plasma (PNP) to mimic a large range of concentrations (n=8) that are observed in treated patients. Upon preparation, samples were stored frozen and tested for a vast array of coagulation parameters (including procoagulant and anticoagulant factors) in three laboratories, using three widely used coagulation platforms (reagent/coagulometer combinations).
  
  
  RESULTS
  Results for each parameter were expressed as ratios of the value corresponding to each apixaban concentration to the value corresponding to the PNP without apixaban. By definition, ratios higher or lower than the unity define overestimation or underestimation, respectively. Prothrombin and activated partial thromboplastin times were barely prolonged by apixaban 200 ng/mL (ratios <1.29 or <1.19, respectively). Conversely, antithrombin was considerably overestimated when the measurement was made with FXa as target enzyme (ratios up to 1.43). Protein C and protein S were overestimated when measured as anticoagulant activities (ratios up to 1.20 or 1.95, respectively), and most measurements for individual coagulation factors (except fibrinogen) were considerably underestimated (ratios from 0.62 to 1.01).
  
  
  CONCLUSIONS
  This large multicenter multiplatform study investigating a common set of test plasmas shows that apixaban interferes with the measurement of most coagulation parameters requested for investigation of hemostasis and highlights the need for a careful interpretation of results obtained in patients under treatment.
authors.forename: Armando
authors.initials: A
authors.lastname: Tripodi
authors.forename: Lidia
authors.initials: L
authors.lastname: Padovan
authors.forename: Sophie
authors.initials: S
authors.lastname: Testa
authors.forename: Cristina
authors.initials: C
authors.lastname: Legnani
authors.forename: Veena
authors.initials: V
authors.lastname: Chantarangkul
authors.forename: Erica
authors.initials: E
authors.lastname: Scalambrino
authors.forename: Silvia
authors.initials: S
authors.lastname: Ludovici
authors.forename: Laura
authors.initials: L
authors.lastname: Bassi
authors.forename: Flora
authors.initials: F
authors.lastname: Peyvandi
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D064368:Healthy Volunteers; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D011720:Pyrazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D000925:Anticoagulants; D011720:Pyrazoles; D011728:Pyridones; C522181:apixaban