4-Factor Prothrombin Complex Concentrate Reduces Time to Procedure in Vitamin K Antagonist-Treated Patients Experiencing Gastrointestinal Bleeding

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Introduction: Gastrointestinal (GI) bleeding is one of the most common complications in patients anticoagulated with vitamin K antagonists (VKAs), and is associated with significant morbidity and mortality. In severe GI bleeding, VKA-anticoagulated patients require rapid anticoagulation reversal to enhance hemostasis and expedite endoscopic or surgical intervention. Restoration of vitamin K-dependent factors can be accomplished by infusion of plasma or prothrombin complex concentrate. This analysis evaluated the impact of non-activated four-factor prothrombin complex concentrate (4F-PCC; Kcentra®) vs plasma infusion on time to procedure in VKA-anticoagulated patients with GI bleeding who required an urgent surgical or invasive procedure. Methods: This post hoc analysis included a subgroup of patients with GI bleeding from two pivotal non-inferiority multicenter phase 3b clinical trials comparing 4F-PCC with plasma in patients requiring urgent VKA reversal owing to acute major bleeding or prior to an urgent invasive procedure. Data from two large trial sites were used to compare 4F-PCC and plasma in terms of volume and infusion times, times from both admission and start of study treatment to procedure, and hospital stay duration. Adverse events (AEs) and serious adverse events (SAEs) were recorded up to days 10 and 45, respectively.Table 1Results: Data from 42 patients were analyzed (4F-PCC, n=22; plasma, n=20). Infusion volumes were approximately 8-fold greater for plasma (median [range] 870 [594, 1500] mL) than 4F-PCC (103 [50, 210] mL; P< 0.0001). Infusion times were approximately 13-fold longer for plasma (210 [82, 735] minutes) than 4F-PCC (16 [10, 60] minutes; P< 0.0001). Median times from start of study treatment to first procedure were longer for the plasma group (23.9 [1.8, 115.7] hours) than for 4F-PCC (17.5 [−0.4, 70.1] hours; P=0.037); full details of timings are shown in the Table. Incidence of fluid overload events was higher for plasma than 4F-PCC (20% vs 5%, respectively), though none of these events were considered treatment-related. There were no deaths, and only one SAE (respiratory failure in the plasma group) was considered treatment-related by the investigator. Conclusion: In VKA-anticoagulated patients with GI bleeding requiring urgent reversal of anticoagulation, use of 4F-PCC was associated with smaller infusion volumes, shorter infusion times and reduced time to procedure, compared with plasma.