Thrombin generation capacity of prothrombin complex concentrate in an in vitro dilutional model

PLoS One. 2013 May 17;8(5):e64100. doi: 10.1371/journal.pone.0064100. Print 2013.

Abstract

Background: The use of PCC for the treatment of trauma-induced coagulopathy potentially increase the risk of thromboembolism and disseminated intravascular coagulation, which is addressed to an imbalance of both pro- and anticoagulants. As PCCs differ in composition, we used an in vitro dilutional approach to assess the overall thrombin generation of five different PCCs through various laboratory assays.

Methods: The vitamin K-dependent coagulation factors, heparin, and antithrombin were assessed in five commercially available PCCs. The procoagulant potential of the PCCs was assessed in plasma and whole blood from 4 healthy donors by means of classical coagulation assays, thrombin generation assay and thromboelastometry. In order to reflect coagulopathy, whole blood was diluted to 80, 60, 40, and 20% with Ringer's lactate solution.

Results: The five different PCCs were characterised by comparable levels of factors II, VII, IX and X (all around 20-30 IU/mL), whereas the heparin (0 to 17.6 IU/mL) and antithrombin (0.06 to 1.29 IU/mL) levels were remarkably different between manufactures. In vitro dilution of blood induced a prolongation of the PT and aPTT, and attenuation of thrombin generation and ExTem induced thromboelastometry. Overall, non- or low-heparin containing PCCs restored the in vitro dilutional coagulopathy, whereas PCCs containing heparin have an anticoagulant effect. The thrombin generation assay showed to be the most sensitive method for assessment of PCC effects.

Conclusions: This study shows that most available PCCs are not balanced regarding their pro- and anticoagulants. The effect of measured differences in thrombin generation among different PCCs requires further investigations to elaborate the clinical meaning of this finding in the treatment of trauma induced coagulopathy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation
  • Blood Coagulation Disorders / etiology
  • Blood Coagulation Factors / metabolism*
  • Blood Coagulation Tests
  • Hemostasis
  • Humans
  • Thrombin / biosynthesis*
  • Wounds and Injuries / complications

Substances

  • Blood Coagulation Factors
  • prothrombin complex concentrates
  • Thrombin

Grants and funding

This study was financed by the Maastricht University Medical Center and the RWTH Aachen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.