title: Four-Factor Prothrombin Complex Concentrate for Coagulopathy Reversal in Patients With Liver Disease.
abstract: A 4-factor prothrombin complex concentrate (4F-PCC, Kcentra®) was recently approved in the United States for the reversal of vitamin K antagonist-associated major bleeding, but it is often used to reverse coagulopathy in patients with liver disease (LD). This single-center, retrospective study analyzed the efficacy and safety of 4F-PCC administered in patients with and without LD. Prothrombin time/International Normalized Ratio (PT/INR) reversal with 4F-PCC was attempted in 85 patients; LD was documented in 31 patients. Coagulopathy reversal and hemostasis with 4F-PCC were inferior in patients with LD compared to patients without LD. Coagulopathy reversal, defined as INR = 1.5 after 4F-PCC administration, was achieved in 6 (19.4%) LD patients, compared to 44 (81.5%) non-LD patients ( p < 0.01). Hemostasis was achieved in 6 LD patients (19.4%) compared to 23 non-LD patients (42.6%) ( p = 0.03). Thromboembolic events occurred in 1 LD patient (3.2%) and 8 non-LD patients (14.8%) ( p = 0.15). Mortality was 51.6% in LD patients and 18.5% in non-LD patients ( p < 0.01). These observations suggest that the efficacy of 4F-PCC is suboptimal to correct coagulopathy and hemostasis in patients with LD, who have high rates of in-hospital mortality due to sequelae of LD. The incidence of thromboembolic events appeared comparable, suggesting that 4F-PCC does not cause undue thromboembolism in LD patients. In conclusion, 4F-PCC appears to be safe in LD patients when administered judiciously; however, further studies are necessary to optimize its use and elucidate its hemostatic potential in this patient population.
authors.affiliation: 1 UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA.
authors.forename: Wan-Ting
authors.initials: WT
authors.lastname: Huang
authors.affiliation: 1 UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Cang
authors.affiliation: 1 UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Derry
authors.affiliation: 1 UC San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, San Diego, CA, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Lane
authors.affiliation: 2 Department of Medicine, Hemophilia and Thrombosis Treatment Center, University of California San Diego, San Diego, CA, USA.|3 The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: von Drygalski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001778:Blood Coagulation Disorders / Q000188:drug therapy* / Q000401:mortality; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged
chemical_list: D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates
keywords: anticoagulants; bleeding; blood coagulation factors; clinical pharmacology; hemostasis