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

Abstract

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 The administration of prothrombin complex concentrates is useful in approved and off-label indications for life-threatening bleeding and should be incorporated in massive bleeding protocols. 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.

Prothrombin Complex Concentrate Utilization in Children's Hospitals

“…7 In a retrospective case study of more than 300 adults receiving PCCs for either VKA reversal or coagulopathy bleeding, investigators found that PCC use demonstrated clinically effective bleeding control, albeit with less pronounced improvement in INR reduction compared with the VKA reversal group. 17 The incidence of thrombosis in this cohort was low (3%), and importantly, there was no difference between the groups. Notably, the thrombosis rate in our cohort was much higher (17.0%) and is a factor that should be analyzed in future studies.…”

Covid-19’da Anti̇koagülan Tedavi̇

“…Mutlak kullanım endikasyonu varsa veya daha önceden kullanan bir hastada kesilemiyorsa, kanama açısından çok dikkatli şekilde takip yapılması önerilmektedir. Pandemi öncesi yapılan bir çalışmada, bu ajanlara bağlı kanamada, 4 faktör protrombin kompleks konsantratı ile %88.9 hastada direkt oral antikoagülan etkisinin kırılabilmesi sağlanmıştır (29). Bu nedenle 4 faktör protrombin kompleks konsantratı, kanama durumunda, kullanılabilecek bir ajandır.…”