title: Reversibility of Apixaban Anticoagulation with a Four-Factor Prothrombin Complex Concentrate in Healthy Volunteers.
abstract: It was hypothesized that the four-factor prothrombin complex concentrate (4F-PCC) Kcentra 25 unit/kg would reverse impairment of thrombin generation in healthy volunteers dosed with apixaban to steady state. In this randomized, two-period crossover, assessor-blinded trial, 12 healthy subjects received 5 mg apixaban every 12 h. Three h after the fifth dose, four-factor prothrombin complex concentrate (4F-PCC) 25 unit/kg or saline were infused. Serial blood samples were assessed for thrombin generation using PPP-reagent and PPP-reagent low, anti-Xa, PT, and PTT assays. Geometric mean ratio was calculated at 30 min postinfusion, and at 24, 48, and 72 h. Peak thrombin generation was 76% higher at 30 min postinfusion with 4F-PCC (p = 0.025). The difference declined to 24% at 24 h and resolved by 48 h. Other thrombin generation parameters were also partially normalized. There was no difference between 4F-PCC and saline in anti-Xa assessment at 30 min or later time points.
authors.affiliation: Department of Medicine, Division of Hematology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nagalla
authors.affiliation: Thomas Jefferson University Hospital Pharmacy, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: L
authors.initials: L
authors.lastname: Thomson
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Oppong
authors.affiliation: Department of Medicine, Division of Hematology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: B
authors.initials: B
authors.lastname: Bachman
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: I
authors.initials: I
authors.lastname: Chervoneva
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: W K
authors.initials: WK
authors.lastname: Kraft
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D023381:Endpoint Determination; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010919:Placebos; D011517:Prothrombin Time; D011720:Pyrazoles / Q000494:pharmacology*; D011728:Pyridones / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D010919:Placebos; D011720:Pyrazoles; D011728:Pyridones; C025667:prothrombin complex concentrates; C522181:apixaban; D013917:Thrombin; D015951:Factor Xa