title: Four-factor prothrombin complex concentrate for life-threatening bleeds or emergent surgery: A retrospective evaluation.
abstract: Previous trials investigating usage of four-factor prothrombin complex concentrate (4F-PCC) excluded patients with various thrombotic risk factors. The objective of this study was to evaluate the safety and effectiveness of 4F-PCC in a real-world setting based on an institutional protocol that does not have strict exclusion criteria.
  
  
  
  This was a retrospective study of adult patients who received 4F-PCC. The primary outcome was a confirmed thromboembolism within 14 days after 4F-PCC administration. Secondary outcomes included international normalized ratio (INR) correction to <1.5 at first draw and incidence of INR rebound for patients undergoing reversal of warfarin and hemostatic effectiveness for patients experiencing a bleed.
  
  
  
  Ninety-three patients received 4F-PCC. Sixty-three (67.7%) were reversed for bleeding and 30 (32.3%) for surgery. Eleven patients (11.8%) developed a thromboembolism within 14 days. The median (interquartile range) time to event was 5 (2-7) days. Significant risk factors were heparin-induced thrombocytopenia (P= .01) and major surgery within 14 days (P= .02), as well as the presence of >6 thrombotic risk factors (P= .01). For patients post-warfarin reversal, 45/63 (71.4%) achieved INR correction at first draw, 55/63 (87.3%) achieved INR correction within 24 hours, and 14/55 (25.5%) experienced INR rebound. Of these 14 patients, 8 (57.1%) did not receive concomitant vitamin K.
  
  
  
  4F-PCC was associated with a notable thromboembolic risk. All patient-specific risk factors should be considered prior to administration. 4F-PCC remains a useful agent for warfarin reversal. Lack of concomitant vitamin K may contribute to INR rebound.
authors.affiliation: NewYork-Presbyterian Hospital, Weill Cornell Medical Center, Department of Pharmacy, 525 East 68th Street, New York, NY 10065. Electronic address: rxjsin@gmail.com.
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Sin
authors.affiliation: NewYork-Presbyterian Hospital, Weill Cornell Medical Center, Department of Pharmacy, 525 East 68th Street, New York, NY 10065.
authors.forename: Karen
authors.initials: K
authors.lastname: Berger
authors.affiliation: NewYork-Presbyterian Hospital, Columbia University Medical Center, Department of Pharmacy, 630 West 168th Street, New York, NY 10032. Electronic address: cal9005@nyp.org.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Lesch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000009:adverse effects; D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D006348:Cardiac Surgical Procedures; D000069604:Dabigatran / Q000009:adverse effects; D004630:Emergencies; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000188:drug therapy; D016027:Heart Transplantation; D006470:Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D006490:Hemostatics / Q000009:adverse effects; D006493:Heparin / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D019934:International Normalized Ratio; D020300:Intracranial Hemorrhages / Q000139:chemically induced / Q000188:drug therapy; D007813:Laparotomy; D008297:Male; D008875:Middle Aged; D011300:Preoperative Care / Q000379:methods*; D011720:Pyrazoles / Q000009:adverse effects; D011728:Pyridones / Q000009:adverse effects; D012189:Retrospective Studies; D012307:Risk Factors; D000069552:Rivaroxaban / Q000009:adverse effects; D013514:Surgical Procedures, Operative; D013921:Thrombocytopenia / Q000139:chemically induced; D013923:Thromboembolism / Q000139:chemically induced*; D014812:Vitamin K / Q000627:therapeutic use*; D014859:Warfarin / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D000933:Antifibrinolytic Agents; D001779:Blood Coagulation Factors; D006490:Hemostatics; D011720:Pyrazoles; D011728:Pyridones; D014812:Vitamin K; C025667:prothrombin complex concentrates; C522181:apixaban; D014859:Warfarin; D006493:Heparin; D000069552:Rivaroxaban; D000069604:Dabigatran
keywords: anticoagulant reversal; anticoagulants; blood coagulation factors; prothrombin complex concentrates; thrombosis; vitamin K