title: Comparison of Fresh-Frozen Plasma, Four-Factor Prothrombin Complex Concentrates, and Recombinant Factor VIIa to Facilitate Procedures in Critically Ill Patients with Coagulopathy from Liver Disease: A Retrospective Cohort Study.
abstract: To evaluate fresh-frozen plasma (FFP), four-factor prothrombin complex concentrates (PCCs), and recombinant factor VIIa (rFVIIa) for lowering international normalized ratio (INR) and facilitating procedures in critically ill patients with hepatic impairment.
  
  
  
  Retrospective cohort study.
  
  
  
  Intensive care units at a large university-affiliated teaching hospital.
  
  
  
  Forty-five adults with hepatic impairment who were admitted between September 1, 2011, and December 31, 2015, and had an admission INR of 1.5 or greater, required an invasive intervention or minor surgical procedure, and received FFP alone (15 patients), PCCs (15 patients), or rFVIIa (15 patients).
  
  
  
  The primary outcomes were rates of achieving an INR less than 1.5 at the time of the procedure and an absolute change in INR from 12 hours before the procedure to the time of the procedure. Secondary outcomes were the time to the procedure, blood product use, bleeding rates, and adverse events. The mean ± SD doses of FFP, PCCs, and rFVIIa were 1.1 ± 0.5 units, 2523 ± 861 units, and 2.6 ± 0.9 mg, respectively, administered 2.1 ± 1.4 hours (p<0.05, FFP vs PCCs or rFVIIa), 1.3 ± 0.5 hours, and 1.3 ± 0.6 hours before the procedure, respectively. Achieving an INR less than 1.5 was more likely to occur with PCCs (80%, p=0.03) and rFVIIa (87%, p=0.01) compared with FFP (27%). INR reduction was greater with PCCs (1.6 ± 0.9, p<0.05) and rFVIIa (1.8 ± 0.7, p<0.01) compared with FFP (0.5 ± 0.8). Use of blood products (FFP, cryoprecipitate, packed red blood cells, and platelets) was significantly greater in the FFP group both before and after the procedural intervention. Hypervolemia was less likely to occur in the PCCs (40%, p=0.02) or rFVIIa (33%, p<0.01) groups than in the FFP group (93%). Overall, 33 (73%) of the 45 patients experienced minor bleeding. Three patients (7%) experienced clotting of a central line or dialysis filter, and all were in the PCCs or rFVIIa groups.
  
  
  
  Unlike FFP, PCCs and rFVIIa effectively and safely reduced INR in critically ill patients with coagulopathy associated with liver impairment to expedite interventions. The amount of blood products used was significantly lower in the PCC and rFVIIa groups, possibly reducing the risk of hypervolemia. Bleeding rates, however, were similar across groups.
authors.affiliation: University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado.
authors.forename: Jennifer O
authors.initials: JO
authors.lastname: Kwon
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado. Rob.MacLaren@ucdenver.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: MacLaren
mesh_terms: D000328:Adult; D001778:Blood Coagulation Disorders / Q000209:etiology / Q000628:therapy*; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D015331:Cohort Studies; D016638:Critical Illness; D015942:Factor VIIa / Q000008:administration & dosage*; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology; D006801:Humans; D019934:International Normalized Ratio; D008107:Liver Diseases / Q000150:complications; D008297:Male; D008875:Middle Aged; D010949:Plasma; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa
keywords: coagulopathy; factor VII; hemorrhage; liver; plasma; procoagulant; prothrombin complex concentrate