Kaleb Morris, PharmD,
PGY2 Emergency Medicine Pharmacy Resident
Jackson Memorial Hospital
Conyers, Georgia
Disclosure information not submitted.
Melanie Condeni, BCCCP, BCPS, PharmD
Pharmacist
MUSC Health of Medical University of South Carolina
Charleston, SC, United States
Disclosure information not submitted.
Carolyn Bell, BCCCP, PharmD
Pharmacist
MUSC Health of Medical University of South Carolina
Charleston, South Carolina, United States
Disclosure information not submitted.
Title: 4 Factor Prothrombin Complex Concentrate for Reversal of Coagulopathy in Liver Failure
Introduction: Coagulopathy in acute and acute on chronic liver failure (AACLF) secondary to impaired synthetic function presents a challenge to health care providers, especially regarding use of procoagulant agents to potentially lower bleeding risk. The goal of this study is to determine the efficacy and safety of 4 Factor Prothrombin Complex Concentrate (4F-PCC) for treating coagulopathy in patients with AACLF.
Methods: A single center retrospective analysis from February 2015 to December 2020 of patients ≥ 18 years receiving 4F-PCC for coagulopathy secondary to AACLF was performed. Patients were identified by ICD-9 and ICD-10 codes and medication order for 4F-PCC. Patient charts were reviewed for dose, time, and indication of 4F-PCC, a pre-4F-PCC and post-4F-PCC international normalized ratio (INR) and administration of blood products within 24 hours. Reversal of coagulopathy was defined as a post-dose INR of < 1.5. For safety, bleeding and thrombotic events were reviewed within 10 days of 4F-PCC administration. Bleeding was assessed using the International Society of Thrombosis and Haemostasis (ISTH) definitions.
Results: Of 67 patients reviewed, reversal of coagulopathy secondary to AACLF was done in 25 patients, representing a total of 33 doses of 4F-PCC. In all, 12 patients received 4F-PCC for bleeding,15 pre-procedure and 2 received a dose for each indication. The patients were predominantly male (80%) and Caucasian (72%) with a median age of 60 years. One patient met the primary outcome of an INR < 1.5 with a pre-4F-PCC INR of 1.62 and post-4F-PCC INR of 1.49 after receiving 22.86 units/kg of 4F-PCC. The overall median (IQR) INR reduction was 0.67 (-0.19 to 8.17) with a median (IQR) dose of 22.8 units/kg (8.88 to 59.36 units/kg). Of the included patients, 12 (48%) received fresh frozen plasma prior to 4F-PCC. Most patients, 18 (72%), experienced major bleeding after 4F-PCC administration, only 2 (8%) experienced a thrombotic event. Observed in-hospital mortality was high at 76%.
Conclusions: In this study the use of 4F-PCC provided minimal benefit in lowering the INR with only one post-4F-PCC INR < 1.5. Furthermore, 72% of patients still experienced major bleeding after 4F-PCC administration, indicating minimal clinical benefit. However, only 8% of patients experienced a thromboembolic event.