Safety and effectiveness of a prothrombin complex concentrate in approved and off‐label indications

• Published in: Transfusion medicine (Oxford, England) Vol. 29; no. 4; pp. 268 - 274
• Main Authors: Marcos‐Jubilar, M., García Erce, J. A., Martínez‐Calle, N., Páramo, J. A., Martínez Virto, A., Quintana‐Díaz, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2019
• Subjects: Aged; Aged, 80 and over; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Blood Coagulation Factors - administration & dosage; Blood Coagulation Factors - adverse effects; Disseminated Intravascular Coagulation - blood; Disseminated Intravascular Coagulation - drug therapy; Disseminated Intravascular Coagulation - mortality; Female; Hemorrhage - blood; Hemorrhage - chemically induced; Hemorrhage - drug therapy; Hemorrhage - mortality; Humans; Incidence; International Normalized Ratio; Male; massive bleeding; Middle Aged; Off-Label Use; prothrombin complex concentrate; Retrospective Studies; Safety; Thromboembolism - blood; Thromboembolism - chemically induced; Thromboembolism - mortality; transfusion practice; Vitamin K - antagonists & inhibitors; massive bleeding; transfusion practice; prothrombin complex concentrate
• ISSN: 0958-7578; 1365-3148
• DOI: 10.1111/tme.12621

Summary 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 (<1·5) 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 (51·8% male, median age 78 years old). Indications were as follows: VKA reversal (66·6%), bleeding coagulopathy (30·5%) and direct anticoagulant (DOAC) reversal due to bleeding (2·5%). VKA reversal was effective in 97·1% of patients, and 76·5% demonstrated complete reversal (INR < 1·5); only 34·3% 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 88·9% of patients. Bleeding cessation was associated with the dose administered (P = 0·002). In coagulopathy bleeding, haemorrhage cessation, established by the International Society of Thrombosis and Haemostais (ISTH) definition, occurred in 56·7% of massive bleeding events and in 42·5% of other coagulopathies; 24‐h mortality was 30%, mainly related to active bleeding. Ten thrombotic episodes were observed (3·1%). 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.