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

Transfus Med. 2019 Aug;29(4):268-274. doi: 10.1111/tme.12621. Epub 2019 Jul 25.

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 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.

Keywords: massive bleeding; prothrombin complex concentrate; transfusion practice.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • 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
  • Middle Aged
  • Off-Label Use*
  • Retrospective Studies
  • Safety*
  • Thromboembolism / blood
  • Thromboembolism / chemically induced
  • Thromboembolism / mortality
  • Vitamin K / antagonists & inhibitors*

Substances

  • Anticoagulants
  • Blood Coagulation Factors
  • Vitamin K
  • prothrombin complex concentrates