Prothrombin Complex Concentrate Versus Fresh Frozen Plasma for Vitamin K Antagonist Reversal in Acutely Bleeding Patients: A Retrospective Study

Introduction

Vitamin K antagonist (VKA) drugs require immediate reversal in VKA-treated patients with major bleeding or requiring urgent surgery. 4-factor prothrombin complex concentrates (PCCs)are approved for urgent VKA reversalbecause they reverse the international normalized ratio (INR) more rapidly than fresh frozen plasma (FFP). Studies comparing the clinical benefits of PCC and FFP have focused on VKA reversal prior to urgent surgery. Few data comparing laboratory and clinical outcomes of patients receiving PCC or FFP for major hemorrhage have been published, and these pertain to intracranial hemorrhage (ICH) only. Given the complexity of performing randomized studies in this setting, observational studies are relevant to inform on this issue.

AIMS

To compare the effects of PCC versus FFP on patient outcomes in VKA-associated major hemorrhage. The primary outcomes were the rate of INR reversal and blood product utilization. The secondary outcome was duration of intensive care and total hospital admission.

Methods

We performed a retrospective, single-center study of consecutive unselected patients receiving a 4-factor PCC for VKA reversal because of hemorrhage between January 2012 and April 2015 compared to consecutive unselected patients treated with FFP for the same indication from January 2010-December 2011, a period prior to introduction of PCC at the Meir Medical Center. Patients were identified by review of clinical and blood bank electronic medical records. We analyzed patient demographics, indication for VKA, underlying illnesses, aspirin use, site and severity of hemorrhage, INR pre- and post reversal, rate of INR reversal, transfusion requirements and duration of hospitalization, treatment.

Results

56 patients received PCC and were compared to 56 patients treated with FFP. In the PCC group 17 patients had ICH and 25 had gastrointestinal hemorrhage compared to 17 and 31 patients respectively in the FFP group. Patients were adjusted for age, sex, presence of renal failure, active cancer, aspirin use, site of hemorrhage, pre-treatment INR and hemoglobin concentration and hemorrhagic shock at presentation. Outcomes: Median time to INR of ≤1.3 was 0.5 (range 0.5-1.5) vs 15.5 (range 5-96) hours for PCC vs FFP respectively, P<0.001). Packed red cell transfusion did not differ between the groups: median =1(range 0-13) in the PCC group and median= 2(range=2-10) in the FFP group (P=0.3), but more FFP was transfused in the FFP vs PCC group median =0(range 0-8) in the PCC group and median= 4(range=2-8) in the FFP group (P<0.001). Duration of hospital admission was longer in the FFP (median=7 days, range 1-93) vs PCC patients (median =6 days, range=1-35) (P=0.04).

Conclusion

This is the first observational study comparing PCC and FFP for VKA-related hemorrhage to our knowledge and the first study of PCC versus FFP for extracranial VKA-related hemorrhage. PCC was more effective than FFP in for reversal of the INR and was associated with less overall FFP use but not packed red cell transfusion. Similarly hospital admission duration was shorter among the PCC patients. Larger studies are required to determine whether PCC confers other clinical benefits over FFP for VKA reversal in acutely bleeding patients.