Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation

Blood Transfus. 2016 Jan;14(1):66-72. doi: 10.2450/2015.0030-15. Epub 2015 Jul 9.

Abstract

Background: Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway.

Materials and methods: Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7.

Results: The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations.

Discussion: The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.

MeSH terms

  • Blood Coagulation Tests
  • Blood Preservation / methods*
  • Cryopreservation / methods
  • Humans
  • Light
  • Methylene Blue / pharmacology*
  • Partial Thromboplastin Time*
  • Plasma / drug effects
  • Plasma / metabolism*
  • Plasma / radiation effects
  • Protein C / metabolism
  • Prothrombin Time*
  • Sterilization / methods*
  • Thrombin / metabolism*

Substances

  • Protein C
  • Thrombin
  • Methylene Blue