Analysis of Using Low Dose 3 Factor PCC (Bebulin®) for INR Reversal in Patients with Warfarin Induced Severe/Life-Threatening Bleeding

Background: 3 Factor Prothrombin Complex Concentrates have been used off label with plasma products for effective and timely reversal of INR in patients on Warfarin presenting with severe bleeding. The exact dosage required for this purpose has yet to be determined.

Methods: We conducted a retrospective review of all patients taking Warfarin who presented to our institution between January 1, 2013 to June 30, 2014 who received 3 Factor Prothrombin Complex Concentrate (PCC) Bebulin® for INR reversal for significant/lifethreatening bleeding. The dose of Bebulin was determined by clinical judgment by the blood bank and the treating physician in accordance with the patient’s weight, bleeding location and the presenting INR.

Results: A total of 116 patients were treated. Mean age was 72 years. Forty-two (36.21%) of patients were female. Most common bleeding site was intracranial (n=61), followed by systemic hemorrhage (n=24), GI bleeding (n=16), trauma (n=10) and other bleed (n=5). Some patients were also on other anticoagulants besides Warfarin – 28 patients (24%) were on Aspirin and 9 (7.8%) on Plavix. The mean INR prior to Bebulin treatment was 3.62 which dropped to 2.05 at an average of 2.2 hours post-treatment. Mean level at 12 hour post-Bebulin dropped to 1.57. The average patient received 2 units of plasma and 1 unit of packed red cell transfusions. The average Bebulin dose administered was 959 IU (SD +/-465 IU) with average patient weight of 82.9 kg (SD +/- 27kg). Based on this the average Bebulin dose administered was 11.57 IU/kg. Eighty-eight patients (76%) were able to be discharged home or to a skilled nursing facility.

Thirty-six patients (31.1%) required more than one dose of Bebulin®. Mean INR at presentation in this group of patients were not similar to the remainder of the group. Mean INR at average of 2.5 hours post-Bebulin in this group was 2.18 which dropped further to an average of 1.75 at 9 hours. The total average Bebulin dose incrementally administered was similar in both groups.

Conclusion: Low dose Bebulin at doses of approximately 12 IU/kg with 2 Units of plasma was effective in timely reversal of INR in majority of patients who presented with Warfarin induced bleeding.