title: An international, multicenter, prospective study of a prothrombin complex concentrate, Prothromplex Total®, in anticoagulant reversal.
abstract: BACKGROUND
  Prothrombin complex concentrates (PCCs) are a common treatment option for the reversal of oral anticoagulation with vitamin K antagonists (VKAs). This study assessed efficacy and safety of Prothromplex Total®.
  
  
  METHODS
  Patients (≥18 years) with acquired prothrombin complex coagulation factor deficiency (international normalized ratio [INR] ≥ 2 at screening) due to oral VKAs, requiring reversal of anticoagulation, were treated with 25, 35, or 50 IU/kg BW PCC. After infusion, efficacy was assessed for 72 ± 4 hours. Adverse events (AEs) were captured for 15 days.
  
  
  RESULTS
  Sixty-one subjects, 48 requiring interventional procedures and 13 with acute bleeds, received a single infusion of PCC. Of 59 subjects analyzed, all achieved normalization of INR (≤ 1.3) within 30 ± 5 minutes of infusion, demonstrating effective anticoagulant reversal. IVRs of factors II, VII, IX, and X ranged from 1.12-2.03 IU/dL:IU/kg. Median INRs remained between 1.00 and 1.18 for up to 6 hours. Overall efficacy of treatment was rated "excellent" for 60 subjects. Three AEs were deemed possibly related to treatment: 1 serious AE (SAE) of acute myocardial infarction (rated severe), 1 SAE of deep vein thrombosis (rated mild), and 1 AE of pyrexia (rated mild). Thrombotic adverse events (2/61, 3.3%) reported here are comparable to rates observed in other PCC studies.
  
  
  CONCLUSIONS
  While there is a risk of thromboembolic events following treatment with PCC products, the number of events reported here was low and could have occurred without PCC treatment. The individualized, INR-based dosing of PCC used here for VKA anticoagulant reversal produces rapid normalization of INR to ≤ 1.3 within 30 minutes.
authors.affiliation: Department of Surgery, Saint George University Teaching Hospital, Székesfehérvár, Hungary.
authors.forename: Áron
authors.initials: Á
authors.lastname: Altorjay
authors.affiliation: Pediatric Department, Veszprém County Hospital, Veszprém, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Szabó
authors.affiliation: Department of Internal Medicine, Thrombosis and Hemostasis Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Boda
authors.affiliation: 1st Department of Medicine with Gastroenterology, Wien-Hietzing Hospital, Vienna, Austria.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Kramer
authors.affiliation: Baxter Healthcare Corporation, Westlake Village, CA, USA.
authors.forename: Leock Y
authors.initials: LY
authors.lastname: Ngo
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Engl
authors.affiliation: Baxter Innovations GmbH, Vienna, Austria.
authors.forename: Clair L
authors.initials: CL
authors.lastname: Firth
authors.affiliation: Baxter Healthcare Corporation, Westlake Village, CA, USA.
authors.forename: Erik R
authors.initials: ER
authors.lastname: Ahlstrom
authors.affiliation: Baxter Healthcare Corporation, Westlake Village, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Gelmont
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria. Electronic address: ingrid.pabinger@meduniwien.ac.at.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Pabinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced / Q000517:prevention & control; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; D006490:Hemostatics; D014812:Vitamin K; C025667:prothrombin complex concentrates
keywords: Anticoagulant reversal; Oral anticoagulant; Prothrombin complex concentrate; Prothromplex total; Vitamin K antagonists