Introduction: Coagulation factor products are costly and can cause adverse outcomes when used inappropriately. Active stewardship may reduce the risk of inappropriate use, increase the likelihood of safe and effective use, and help control costs. Such goals may be met when these products are dispensed from an inpatient pharmacy. After multidisciplinary discussions of unmet clinical needs and pharmacoeconomic concerns, coagulation factor product guidelines for use were established at our institution and a multidisciplinary stewardship program was implemented.
Objective: The purpose of this quality improvement initiative was to implement a multidisciplinary coagulation factor stewardship program and ascertain its impact on the use of coagulation factor products after dispensing them from inpatient pharmacy instead of the blood bank.
Methods: We compared the utilization of 4-Factor prothrombin complex concentrate (4F-PCC) and recombinant factor VIIa (rVIIa) from the period of 7/1/16 to 5/31/17, 6 months prior to and 6 months after implementation of the stewardship program. Prior to implementation, pharmacists, hematologists, surgeons, anesthesiologists, and intensivists met to develop hospital-wide guidelines and order sets for 4F-PCC and rVIIa. The guidelines include indications for which 4F-PCC can be dispensed without hematology consultation and the requirement for hematology consultation for approval of requests outside of these guidelines. The Pharmacy & Therapeutics Committee approved all guidelines, order sets and the hematology service stewardship. Data about approval, administration, cost, and outcomes were obtained retrospectively for the 6 months prior and prospectively for the 6 months after implementation of the stewardship program.
Results: Pre-implementation, 30 patients received 4F-PCC and 7 received rFVIIa. Warfarin reversal prior to emergent surgery (n=18, 60%) was the most common indication for 4F-PCC, followed by warfarin reversal for major bleeding (n=9, 30%) and direct oral anticoagulant (DOAC) reversal (n=3, 10%). Vitamin K was administered to 78% of the patients requiring warfarin reversal. The indications for rFVIIa included FVII deficiency (n=3, 42%), hemophilia with inhibitors (n=2, 29%), and refractory major bleeding (n=2, 29%). Of all patients, 7 (19%) died before discharge, but not within 72 hours and 1 (3%) had a thrombotic event within 72 hours. The cost of 4F-PCC and rFVIIa during the 6 months preceding the stewardship program was $261,880.
After stewardship was implemented, 34 patients received 4F-PCC and 3 received rFVIIa. Indications for 4F-PCC included warfarin reversal prior to emergent surgery (n=21, 62%), warfarin reversal for major bleeding (n=5, 15%), DOAC reversal (n=4, 12%), and peri-operative management of other coagulopathies (n=4, 12%). Vitamin K was administered to 88% of patients requiring warfarin reversal. The pharmacy dispensed the products according to institutional guidelines in 88% of cases, and without hematology consultation when it should have been obtained in 12% of cases. Hematology was consulted for stewardship in 6 cases; 2 were approved and 4 were denied for disseminated intravascular coagulation (DIC) (n=2), factor V deficiency without active bleeding (n=1), and surgical bleeding (n=1). Of all patients, 10 (24%) died before discharge, including the 2 with DIC who were denied product. Three (7%) died within 72 hours and 2 (5%) had thrombotic events within 72 hours. The cost for 4F-PCC and rFVIIa was $160,144 after stewardship was implemented.
Conclusions: Dispensing 4F-PCC and rFVIIa from the inpatient pharmacy with stewardship has resulted in similar utilization and efficacy as existed in the pre-implementation period but with cost savings of $101,000 during the first 6 months of stewardship. Furthermore, implementation of a multidisciplinary coagulation factor stewardship program with standardized institutional guidelines, streamlined dispensing from the inpatient pharmacy, as well as use of expert hematologic consultation when indicated, has enhanced the culture of safety in our institution. The experience has also enriched the training of hematology fellows, residents and pharmacists.
Fongemie: Bristol Myers Squibb: Speakers Bureau. Comenzo: Janssen: Consultancy, Research Funding; Prothena: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Research Funding.
Asterisk with author names denotes non-ASH members.