Long-term storage multicenter study of fresh frozen plasma at -40 degrees C. A multicenter study on the stability of labile coagulation factors over a period of 3 years

Background. Fresh frozen plasma (FFP) is exposed to numerous factors affect ing the quality and stability of coagulation factors during blood collectio n, preparation and storage. In 1995 the European 'Guide to the preparation, use and quality assurance of blood components' extended the shelf-life of FFP from 12 to 24 months and concurrently reduced the storage temperature f rom -30 to -40 degreesC. Four years later, the European guidelines amended the storage regulations and permitted a 24-month shelf-life at -30 degreesC . This new regulation of FFP led us to the question whether storage over 3 years at -40 degreesC could be performed without relevant loss in coagulati on factor activity. Due to missing data, a multicenter study was carried ou t in 7 different quality control (QC) laboratories of the Bavarian Red Cros s Blood Transfusion Service. The aim of our study was to obtain selected st ability data of the coagulation factors FV, FVIII:C and FXI as well as of t he major inhibitor antithrombin III (AT III) over a storage period of more than 3 years at -40 degreesC. Material and Methods: 12 plasma units - 3 of each ABO blood group - derived from CPD whole blood were processed accordin g to current national and European guidelines. The plasma units were aliquo ted and frozen within 18 h after donation at below -30 degreesC. The storag e temperature was held between -38 and -42 degreesC during the total storag e period of 37 months. In the long-term storage, 4 parameters of the coagul ation system were determined in aliquots in 7 different QC laboratories. On e-stage coagulometric methods were used to determine coagulation factors, a nd the determination of AT III inhibitor activity was done by a chromogenic method. After the 1st month of storage, each plasma was tested for specifi c activity. Thereafter, follow-up testing was performed in 4-month periods. Results. The evaluated coagulation parameters show an acceptable stability during the total storage period if ABO blood groups are not taken into con sideration. There was no statistically significant loss in activity for FXI and AT III at the end of the storage period in comparison to the initial v alues, 101.5% for FXI (P-FXI = 0.17) and 101% for AT III (p(AT III) = 0.66) . The loss in FV and in FVIII:C activities was 0.6 and 9%, respectively. Bo th results indicate a statistically significant reduction (t test: P-Fv = 0 .048; P-FvII:C = 0.033). Similar results were obtained taking ABO blood gro uping into account, with the exceptions of blood group A where AT III showe d an increase of 11% over baseline values and of blood group 0 where FXI sh owed an increase of 11.2% over average coagulation activities. There were n o differences in the coagulation activities of blood groups B and AB over t he storage period. Conclusions: The results show that, under these storage conditions, the recovery of coagulation parameters in FFP is not reduced be low 70% of the starting activity and stays in acceptable ranges. For FXI an d AT III we did not find any significant reduction. However, for FV and FVI II:C a significant reduction was found, although total activities were not dramatically low. With regard to the guidelines for therapeutic plasma, our findings show that an extended storage for up to 3 years at -40 degreesC s hould be possible without clinically relevant loss of efficacy.