Safety and effectiveness of a prothrombin complex concentrate in approved and off-label indications
Objective To evaluate the effectiveness and safety of prothrombin complex concentrates (PCCs) in approved and off-label indications. Background PCCs are approved for the urgent reversal of vitamin K antagonists (VKAs). Data concerning the efficacy, safety and dosing for off-label indications are limited, but they are included in massive bleeding protocols. Methods This was a retrospective review of cases treated with four-factor PCCs (4F-PCCs) between January 2009 and 2016. Efficacy end-points include: (i) VKA reversal efficacy assessed by international normalised ratio (INR) normalisation (<1 center dot 5) and (ii) clinical efficacy as bleeding cessation and/or decreased number of transfused blood components and 24-h mortality in bleeding coagulopathy. The safety end-point is the incidence of thromboembolic events. Results A total of 328 patients were included (51 center dot 8% male, median age 78 years old). Indications were as follows: VKA reversal (66 center dot 6%), bleeding coagulopathy (30 center dot 5%) and direct anticoagulant (DOAC) reversal due to bleeding (2 center dot 5%). VKA reversal was effective in 97 center dot 1% of patients, and 76 center dot 5% demonstrated complete reversal (INR < 1 center dot 5); only 34 center dot 3% patients needed hemoderivatives. Prior to emergency procedures, PCCs achieved global responses in 83% of patients, with no bleeding complication during intervention. DOAC reversal was effective in 88 center dot 9% of patients. Bleeding cessation was associated with the dose administered (P = 0 center dot 002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56 center dot 7% of massive bleeding events and in 42 center dot 5% of other coagulopathies; 24-h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3 center dot 1%). Conclusion 4F-PCC was effective as adjuvant treatment with an acceptable safety profile, not only for the emergent reversal of VKAs but also for refractory coagulopathy associated with major bleeding.